Haematology

Question 1

What is tumour lysis syndrome?

Answer 1

Tumour lysis syndrome is a common oncological emergency.

It is associated with rapid cell death, causing release of uric acid, on starting chemotherapy and is common in tumours which are rapidly proliferating.

The uric acid can form crystals in the interstitial tissue and tubules of the kidneys and causes acute kidney injury.

These are classically haematological malignancies such as leukaemia and lymphoma.

Question 2

What happens physiologically in tumour lysis syndrome?

Answer 2

It results in an increase in serum urate, potassium and phosphate, precipitating renal failure.

Question 3

Symptoms of tumour lysis syndrome?

Answer 3

Nausea
Vomiting
Muscle pain

Question 4

Prevention of tumour lysis syndrome?

Answer 4

Management focuses on preventing this from occurring through giving:

Prophylactic allopurinol

In some cases a recombinant urate oxidase rasburicase is given

Good hydration should be maintained.

Question 5

What is lymphadenopathy and what are the general causes?

Answer 5

Lymphadenopathy refers to enlarged lymph nodes. There are a long list of causes of enlarged lymph nodes, which can be generally grouped into:

Reactive lymph nodes (e.g., swelling caused by viral upper respiratory tract infections, dental infection or tonsillitis)

Infected lymph nodes (e.g., tuberculosis, HIV or infectious mononucleosis)

Inflammatory conditions (e.g., systemic lupus erythematosus or sarcoidosis)

Malignancy (e.g., lymphoma, leukaemia or metastasis)

Question 6

Lymphadenopathy - features suggesting malignancy?

Answer 6

Unexplained (e.g., not associated with an infection)

Persistently enlarged (particularly over 3cm in diameter)

Abnormal shape (normally oval shaped where the length is more than double the width)

Hard or “rubbery”

Non-tender

Tethered or fixed to the skin or underlying tissues

Associated symptoms, such as night sweats, weight loss, fatigue or fevers

Question 7

Lymphadenopathy of which of the cervical lymph nodes are most concerning for malignancy?

Answer 7

Supraclavicular - . They may be caused by malignancy in the chest or abdomen and require further investigation.

Question 8

Infectious mononucleosis is a cause of lymphadenopathy. What cause is it and what are the features?

Answer 8

It is caused by infection with the Epstein Barr virus (EBV) and most often affects teenagers and young adults. It is found in the saliva of infected individuals and may be spread by kissing or sharing cups, toothbrushes and other equipment that transmits saliva.

It presents with

Fever
Sore throat
Fatigue
Lymphadenopathy

Mononucleosis can present with an intensely itchy maculopapular rash in response to amoxicillin or cefalosporins.

The first-line investigation is the Monospot test. It is also possible to test for IgM (acute infection) and IgG (immunity) to the Epstein Barr virus.

Management is supportive. Patients should avoid alcohol (risk of liver impairment) and contact sports (risk of splenic rupture).

Question 9

What are lymphomas and how do they cause lymphadenopathy?

Answer 9

Lymphomas are a group of cancers that affect the lymphocytes inside the lymphatic system. These cancerous cells proliferate within the lymph nodes and cause the lymph nodes to become abnormally large

Question 10

What are the two categories of lymphoma and which is more common?

Answer 10

Hodgkin’s lymphoma (1/5) and non-Hodgkin’s lymphoma (4/5).

Hodgkin’s lymphoma is a specific disease and non-Hodgkins lymphoma encompasses all the other lymphomas.

Question 11

What causes Hodgkin’s lymphoma (physiologically, in simple terms)?

Answer 11

Proliferation of lymphocytes

Question 12

In which ages does lymphoma most commonly present?

Answer 12

bimodal age distribution with peaks around aged 20 and 75 years

Question 13

Typical presentation of Hodgkin’s lymphoma?

Answer 13

Lymphadenopathy: key presenting symptom

The enlarged lymph node or nodes might be in the neck, axilla (armpit) or inguinal (groin) region.

They are characteristically non-tender and feel “rubbery”.

Some patients will experience pain in the lymph nodes when they drink alcohol.

B symptoms are the systemic symptoms of lymphoma:

Fever
Weight loss
Night sweats

Fatigue
Itching
Cough
Shortness of breath
Abdominal pain
Recurrent infections

Question 14

What are B symptoms?

Answer 14

B symptoms are the systemic symptoms of lymphoma:

Fever
Weight loss
Night sweats

Question 15

What is the key finding from lymph node biopsy in patients with Hodgkin’s lymphoma.

Answer 15

The Reed-Sternberg cell

Question 16

What staging system is used for lymphoma?

Answer 16

The Ann Arbor staging system is used for both Hodgkins and non-Hodgkins lymphoma.

Question 17

The presentation of leukaemia is quite non-specific.
Some typical features are what?

Answer 17

Fatigue

Fever

Pallor due to anaemia

Petechiae and abnormal bruising due to thrombocytopenia

Failure to thrive (children)

Abnormal bleeding

Lymphadenopathy

Hepatosplenomegaly

Question 18

What is leukaemia and how is it classified?

Answer 18

Leukaemia is the name for cancer of a particular line of the stem cells in the bone marrow.

This causes the unregulated production of certain types of blood cells.

They can be classified depending on how rapidly they progress (chronic is slow and acute is fast) and the cell line that is affected (myeloid or lymphoid) to make four main types:

Acute myeloid leukaemia
Acute lymphoblastic leukaemia
Chronic myeloid leukaemia
Chronic lymphocytic leukaemia

Question 19

What are the components of blood and serum?

Answer 19

Blood is made up of plasma (the liquid of the blood) that contains red blood cells, white blood cells and platelets. The plasma also contains lots of clotting factors such as fibrinogen.

Once the clotting factors are removed from the blood what is left is called the serum. Serum contains:

Glucose
Electrolytes such as sodium and potassium
Proteins such as immunoglobulins and hormones

Question 20

Where do blood cells develop from?

Answer 20

Bone marrow

Question 21

Where is bone marrow mostly found?

Answer 21

Pelvis
Vertebrae
Ribs
Sternum

Question 22

What are Pluripotent Haematopoietic Stem Cells and what do they become?

Answer 22

These are undifferentiated cells that have the potential to transform into a variety of blood cells. They initially become:

Myeloid Stem Cells
Lymphoid Stem Cells
Dendritic Cells (via various intermediate stages)

Question 23

Reticulocyte vs red blood cell?

Answer 23

Red blood cells (RBCs) develop from reticulocytes that comes from the myeloid stem cells.

Reticulocytes are immature red blood cells that are slightly larger than standard erythrocytes (RBCs) and still have RNA material in them. The RNA has a reticular (“mesh like”) appearance inside the cell. It is normal to have about 1% of red blood cells as reticulocytes.

Question 24

Where do reticulocytes come from?

Answer 24

Myeloid stem cells

Question 25

RBC lifespan?

Answer 25

120 days

Question 26

Platelet lifespan?

Answer 26

10 days

Question 27

What are platelets made by?

Answer 27

Megakaryocytes

Question 28

What is the role of platelets

Answer 28

Their role is to clump together (platelet aggregation) and plug gaps where blood clots need to form

Question 29

What can promyelocytes become?

Answer 29

Monocytes then macrophages
Neutrophils
Eosinophils
Mast Cells
Basophils

Question 30

What do myeloid stem cells become?

Answer 30

Promyelocytes

Question 31

What do myeloid stem cells become?

Answer 31

Promyelocytes

Question 32

Where do lymphocytes come from?

Answer 32

Lymphoid stem cells

Question 33

What do lymphocytes become?

Answer 33

B cells or T cells

Question 34

Where do B lymphocytes mature?

Answer 34

Bone marrow

Question 35

Where do T lymphocytes mature?

Answer 35

Thymus gland

Question 36

What do B lymphocytes differentiate into?

Answer 36

After maturing in the bone marrow:

Plasma Cells
Memory B cells

Question 37

What do T lymphocytes differentiate into?

Answer 37

After maturing in the thymus gland

CD4 cells (T helper cells)
CD8 cells (Cytotoxic T Cells)
Natural Killer Cells

Question 38

What is a blood film?

Answer 38

A blood film involves a specialist examining the blood using a microscope to manually check for abnormal shapes, sizes and contents of the cells and note abnormal inclusions in the blood

Question 39

Blood film findings: what is anisocytosis and when might it be seen?

Answer 39

Variation in size of red blood cells

Myelodysplastic syndrome, some types of anaemia

Question 40

Blood film findings: what are target cells and when might they be seen?

Answer 40

RBC that have a central pigmented area, surrounded by a pale area, surrounded by a ring of thicker cytoplasm on the outside. This makes it look like a bull’s eye target.

These can be seen in iron deficiency anaemia and post-splenectomy.

Question 41

What is seen here and why might it be present?

Answer 41

Anisocytosis refers to a variation in size of the red blood cells. These can be seen in myelodysplasic syndrome as well as some forms of anaemia

Question 42

What are seen here and why might they be present?

Answer 42

Target cells - have a central pigmented area, surrounded by a pale area, surrounded by a ring of thicker cytoplasm on the outside. This makes it look like a bull’s eye target. These can be seen in iron deficiency anaemia and post-splenectomy.

Question 43

What are seen here and why might they be present?

Answer 43

Howell-Jolly bodies are individual blobs of DNA material seen inside red blood cells. Normally this DNA material is removed by the spleen during circulation of red blood cells. They can be seen in post-splenectomy and in patients with severe anaemia where the body is regenerating red blood cells quickly.

Question 44

What are Howell-Jolly bodies and why might they be seen?

Answer 44

Howell-Jolly bodies are individual blobs of DNA material seen inside red blood cells. Normally this DNA material is removed by the spleen during circulation of red blood cells. They can be seen in post-splenectomy and in patients with severe anaemia where the body is regenerating red blood cells quickly.

Question 45

Why might % of reticulocytes be higher than normal (aprox 1%) and what does this demonstrate?

Answer 45

Rapid turnover of RBC - rapid turnover of red blood cells, such as haemolytic anaemia. They demonstrate that the bone marrow is active in replacing lost cells.

Question 46

What are schistocytes?

Answer 46

Schistocytes are fragments of red blood cells. They indicate the red blood cells are being physically damaged by trauma during their journey through the blood vessels.

Question 47

Why might schistocytes be seen on blood film?

Answer 47

They may indicate networks of clots in small blood vessels caused by:
Haemolytic uraemic syndrome
Disseminated intravascular coagulation (DIC) or Thrombotic thrombocytopenia purpura.

They can also be present in replacement metallic heart valves and haemolytic anaemia.

Question 48

What is seen here and why might they be seen?

Answer 48

Schistocytes are fragments of red blood cells. They indicate the red blood cells are being physically damaged by trauma during their journey through the blood vessels. They may indicate networks of clots in small blood vessels caused by haemolytic uraemic syndrome, disseminated intravascular coagulation (DIC) or thrombotic thrombocytopenia purpura. They can also be present in replacement metallic heart valves and haemolytic anaemia.

Question 49

What are sideroblasts and why might they be seen on blood films?

Answer 49

Sideroblasts are immature red blood cells that contain blobs of iron. They occur when the bone marrow is unable to incorporate iron into the haemoglobin molecules. They can indicate a myelodysplasic syndrome.

Question 50

What is seen here and why might they be present?

Answer 50

Sideroblasts are immature red blood cells that contain blobs of iron. They occur when the bone marrow is unable to incorporate iron into the haemoglobin molecules. They can indicate a myelodysplasic syndrome.

Question 51

What are smudge cells and why might they be seen?

Answer 51

Smudge cells are ruptured white blood cells that occur during the process of preparing the blood film due to aged or fragile white blood cells.

They can indicate chronic lymphocytic leukaemia.

Question 52

What are seen here and why might they be present?

Answer 52

Smudge cells are ruptured white blood cells that occur during the process of preparing the blood film due to aged or fragile white blood cells.

They can indicate chronic lymphocytic leukaemia.

Question 53

What are spherocytes and why might they be seen on blood film?

Answer 53

Spherocytes are spherical red blood cells without the normal bi-concave disk space. They can indicated autoimmune haemolytic anaemia or hereditary spherocytosis.

Question 54

What are seen here and why might they be present?

Answer 54

Spherocytes are spherical red blood cells without the normal bi-concave disk space. They can indicated autoimmune haemolytic anaemia or hereditary spherocytosis.

Question 55

Causes of microcytic anaemia?

Answer 55

T – Thalassaemia

A – Anaemia of chronic disease

I – Iron deficiency anaemia

L – Lead poisoning

S – Sideroblastic anaemia

Question 56

Causes of normocytic anaemia?

Answer 56

There are 3 As and 2 Hs for normocytic anaemia:

A – Acute blood loss

A – Anaemia of Chronic Disease

A – Aplastic Anaemia

H – Haemolytic Anaemia

H – Hypothyroidism

Question 57

What are the two types of macrocytic anaemia and what is the difference??

Answer 57

Megaloblastic or normoblastic

Megaloblastic anaemia is the result of impaired DNA synthesis preventing the cell from dividing normally. Rather than dividing it keeps growing into a larger, abnormal cell. This is caused by a vitamin deficiency.

Normblastic is not related to DNA synthesis

Question 58

What are the causes of megaloblastic anaemia?

Answer 58

B12 deficiency
Folate deficiency

Question 59

What are the causes of normoblastic macrocytic anaemia?

Answer 59

Alcohol
Reticulocytosis (usually from haemolytic anaemia or blood loss)
Hypothyroidism
Liver disease
Drugs such as azathioprine

Question 60

Causes of macrocytic anaemia

Answer 60

Megaloblastic:

B12 deficiency
Folate deficiency

Normoblastic:

Alcohol
Reticulocytosis (usually from haemolytic anaemia or blood loss)
Hypothyroidism
Liver disease
Drugs such as azathioprine

Question 61

Generic SYMPTOMS of anaemia?

Answer 61

Tiredness

Shortness of breath

Headaches

Dizziness

Palpitations

Worsening of other conditions such as angina, heart failure or peripheral vascular disease

Question 62

SYMPTOMS specific to iron deficiency anemia?

Answer 62

Pica describes dietary cravings for abnormal things such as dirt and can signify iron deficiency

Hair loss can indicate iron deficiency anaemia

Question 63

Generic SIGNS of anaemia?

Answer 63

Pale skin

Conjunctival pallor

Tachycardia

Raised respiratory rate

Question 64

SIGNS specific to iron deficiency anaemia?

Answer 64

Koilonychia (spoon shaped nails)
Angular cheilitis (swollen red patches at corners of the mouth)
Atrophic glossitis ( smooth tongue due to atrophy of the papillae)
Brittle hair + nails
Post-cricoid webs

Question 65

What sign may be specific to a haemolytic anaemia?

Answer 65

Jaundice

Question 66

What specific clinical signs indicate CKD as the underlying cause of anaemia?

Answer 66

Oedema, hypertension and excoriations on the skin

Question 67

What specific clinical sign indicates thalassaemia as the underlying cause of anaemia?

Answer 67

Bone deformities

Question 68

When anaemia is found, what further initial investigations will be performed?

Answer 68

Haemoglobin
Mean Cell Volume (MCV)
B12
Folate
Ferritin
Blood film

Question 69

When anaemia is found and initial investigations (MCV, B12, Folate, Ferritin, Blood film) have been performed, what further investigations might be considered?

Answer 69

Oesophago-gastroduodenoscopy (OGD) and colonoscopy to investigate for a gastrointestinal cause of unexplained iron deficiency anaemia. This is done on an urgent cancer referral for suspected gastrointestinal cancer.

Bone marrow biopsy may be required if the cause is unclear

Question 70

The bone marrow requires iron to produce haemoglobin. There are several scenarios where iron stores can be used up and the patient can become iron deficient, such as?

Answer 70

Insufficient dietary iron
Iron requirements increase (for example in pregnancy)
Iron is being lost (for example slow bleeding from a colon cancer)
Inadequate iron absorption

Question 71

Where is iron absorbed?

Answer 71

Duodenum and jejunum

Question 72

How can PPIs cause iron deficiency?

Answer 72

Acid from the stomach to keep the iron in the soluble ferrous (Fe2+) form.

When the acid drops it changes to the insoluble ferric (Fe3+) form.

Therefore, medications that reduce the stomach acid such as proton pump inhibitors (lansoprazole and omeprazole) can interfere with iron absorption

Question 73

What is the soluble form of iron?

Answer 73

Ferrous Fe2+

Question 74

What is the insoluble form of iron?

Answer 74

Ferric - Fe3+

Question 75

What autoimmune conditions can cause iron deficiency?

Answer 75

Conditions that result in inflammation of the duodenum or jejunum such as coeliac disease or Crohn’s disease can also cause inadequate iron absorption.

Question 76

What the the main causes of iron deficiency?

Answer 76

Blood loss is the most common cause in adults (commonly menorrhagia, oesophagitis, gastritis)

Dietary Insufficiency is the most common cause in growing children

Poor iron absorption (consider Crohn’s, coeliac)

Increased requirements during pregnancy

Question 77

What should iron deficiency anaemia arise suspicion for?

Answer 77

GI tract cancer

Question 78

How does iron travel around the blood?

Answer 78

Ferric ions (insoluble) bound to transferrin (carrier protein)

Question 79

What is TIBC?

Answer 79

Total iron binding capacity

The total space on the transferrin molecules for the iron to bind.

Therefore, total iron binding capacity is directly related to the amount of transferrin in the blood.

Question 80

Calculating transferrin saturation?

Answer 80

Transferrin Saturation = Serum Iron / Total Iron Binding Capacity

Expressed as a percentage

Question 81

Ferritin levels in iron deficiency anemia?

Answer 81

LOW - highly suggestive of iron deficiency

NORMAL - possible, if there are reasons to have raised ferritin such as infection

HIGH - If ferritin is high then this is difficult to interpret and is likely to be related to inflammation rather than iron overload. Ferritin is released from cells in inflammation, such as infection or cancer

Question 82

Why is serum iron not a useful measure when used alone?

Answer 82

Serum iron varies significantly throughout the day with higher levels in the morning and after eating iron containing meals. On its own serum iron is not a very useful measure.

Question 83

What does transferrin saturation indicate?

Answer 83

Transferrin saturation gives a good indication of the total iron in the body. In normal adults it is around 30%, however if there is less iron in the body transferrin will be less saturated and if iron levels go up transferrin will be more saturated. It can temporarily increase after eating a meal rich in iron or taking iron supplements so a fasting sample gives the most accurate results.

Question 84

What can TIBC be used as a marker for, and when might you expect it to be hig/low?

Answer 84

Total iron binding capacity can be used as a marker for how much transferrin is in the blood.

It is an easier test to perform than measuring transferrin.

Both TIBC and transferrin levels increase in iron deficiency and decrease in iron overload.

Question 85

Supplementation with iron and acute liver damage (lots of iron is stored in the liver) can give the impression of iron overload, increasing all iron related markers in the blood - except for?

Answer 85

TIBC - which will be low

Question 86

What two things can increase the values of serum ferritin, serum iron, and transferring saturation, giving the impression of iron overload?

Answer 86

Supplementation with iron
Acute liver damage (lots of iron is stored in the liver)

TIBC will be low

Question 87

Management of iron deficiency anemia?

Answer 87

New iron deficiency in an adult without a clear underlying cause (for example heavy menstruation or pregnancy) should be investigated with suspicion. This involves doing a oesophago-gastroduodenoscopy (OGD) and a colonoscopy to look for cancer of the gastrointestinal tract.

1. Blood transfusion.
2. Iron infusion e.g. “cosmofer”
3. Oral iron e.g. ferrous sulfate 200mg three times daily

When correcting iron deficiency anaemia with iron you can expect the haemoglobin to rise by around 10 grams/litre per week.

Question 88

When correcting iron deficiency anaemia with iron you can expect the haemoglobin to rise at what rate?

Answer 88

Around 10 grams/litre per week.

Question 89

What are the options for correcting iron deficiency anaemia?

Answer 89

Blood transfusion. This will immediately correct the anaemia but not the underlying iron deficiency and also carries risks.

Iron infusion e.g. “cosmofer”. There is a very small risk of anaphylaxis but it quickly corrects the iron deficiency. It should be avoided during sepsis as iron “feeds” bacteria.

Oral iron e.g. ferrous sulfate 200mg three times daily. This slowly corrects the iron deficiency. Oral iron causes constipation and black coloured stools. It is unsuitable where malabsorption is the cause of the anaemia.

Question 90

Correcting iron deficiency: blood transfusion advantages and disadvantages?

Answer 90

Advantages:

Immediately corrects the anaemia

Disadvantages:

Does not correct the underlying iron deficiency

Risks and complications of blood transfusion:
- Blood borne infections like HIV, hepatitis are possible but rare
- Other reactions like graft- versus- host disease, delayed hemolytic reaction and acute immune hemolytic reaction are also seen
- Allergic reactions, anaphylactic reaction
- Fever

Question 91

Correcting iron deficiency: iron infusion e.g. ‘‘cosmofer’’ advantages and disadvantages?

Answer 91

Advantages:

Quickly corrects the anaemia iron deficiency

Disadvantages:

'’Feeds’’ bacteria in SEPSIS

Small risk of anaphylaxis

Question 92

Correcting iron deficiency: iron infusion e.g. ‘‘cosmofer’’ advantages and disadvantages?

Answer 92

Advantages:

Quickly corrects the anaemia iron deficiency

Disadvantages:

'’Feeds’’ bacteria in SEPSIS

Small risk of anaphylaxis

Question 93

Correcting iron deficiency: oral iron e.g. ferrous sulfate advantages and disadvantages?

Answer 93

Advantages:

Least invasive

Treats underlying iron deficiency (if not due to malabsorption)

Disadvantages:

Does not work if cause if malabsorption

Cn cause constipation and black coloured stools

Question 94

Hodgkin’s lymphoma risk factors?

Answer 94

HIV

Epstein-Barr Virus

Autoimmune conditions such as rheumatoid arthritis and sarcoidosis

Family history

Question 95

Features of lymphadenopathy in Hodgkin’s lymphoma?

Answer 95

Neck, axilla or inguinal lymph nodes typically affected

Non-tender, rubbery

May be painful when drinking alcohol

Question 96

Symptoms of lymphoma other than lymphadenopathy and B symptoms?

Answer 96

Fatigue
Itching
Cough
Shortness of breath
Abdominal pain
Recurrent infections

Question 97

How is ?lymphoma investigated?

Answer 97

Lymph node biopsy is the key diagnostic test.

LDH (often raised in HL but not specific)

CT, MRI and PET scans can be used for diagnosing and staging lymphoma and other tumours.

Question 98

What marker is often raise in Hodgkin’s lymphoma?

Answer 98

Lactate dehydrogenase (LDH)

Question 99

Key finding on lymph node biopsy in patient’s with Hodgkin’s lymphoma?

Answer 99

REED-STERNBERG CELL

They are abnormally large B cells that have multiple nuclei that have nucleoli inside them.

This can give them the appearance of the face of an owl with large eyes.

Question 100

What is seen here, and what is this characteristic of?

Answer 100

Abnormally large B cell with multiple nuclei with nucleoli inside them - REED STERNBERG CELL

The Reed-Sternberg cell is the key finding from lymph node biopsy in patients with Hodgkin’s lymphoma.

Question 101

The Ann Arbor staging system is used for both Hodgkins and non-Hodgkins lymphoma. What stages does it classify disease into?

Answer 101

Stage 1: Confined to one region of lymph nodes.

Stage 2: In more than one region but on the same side of the diaphragm (either above or below).

Stage 3: Affects lymph nodes both above and below the diaphragm.

Stage 4: Widespread involvement including non-lymphatic organs such as the lungs or liver.

Question 102

The Ann Arbor staging system is used for both Hodgkins and non-Hodgkins lymphoma. What does it put importance on?

Answer 102

The system puts importance on whether the affected nodes are above or below the diaphragm

Question 103

Management of Hodgkin’s lymphoma and the associated risks of concern?

Answer 103

The key treatments are chemotherapy and radiotherapy.

The aim of treatment is to cure the condition.

This is usually successful however there is a risk of relapse, other haematological cancers and side effects of medications.

Chemotherapy creates a risk of leukaemia and infertility.

Radiotherapy creates a risk of cancer, damage to tissues and hypothyroidism.

Question 104

Notable types of NHL?

Answer 104

Burkitt lymphoma

MALT lymphoma

Diffuse large B cell lymphoma

Question 105

What infections if Burkitt lymphoma associate with?

Answer 105

Epstein-Barr virus
Malaria
HIV

Question 106

What does MALT lymphoma affect?

Answer 106

Affects the mucosa-associated lymphoid tissue, usually around the stomach.

It is associated with H. pylori infection.

Question 107

How does diffuse large B cell lymphoma present and in what age group?

Answer 107

Diffuse large B cell lymphoma often presents as a rapidly growing painless mass in patients over 65 years.

Question 108

What type of lymphoma is associated with H.pylori infection?

Answer 108

MALT lymphoma (affects the mucosa-associated lymphoid tissue, usually around the stomach)

Question 109

Risk factors for non-Hodgkin’s lymphoma?

Answer 109

HIV

Epstein-Barr Virus

H. pylori (MALT lymphoma)

Hepatitis B or C infection

Exposure to pesticides and a specific chemical
called trichloroethylene used in several industrial processes

Family history

Question 110

What chemical exposures increase the risk of NHL?

Answer 110

Pesticides

Trichloroethylene (used in industrial processes)

Question 111

Differentiating between HL and NHL?

Answer 111

The presentation is similar, often they can only be differentiated when the lymph node is biopsied.

Question 112

Management of non-Hodgkin’s lymphoma?

Answer 112

Management involves a combination of treatments depending on the type and staging of the lymphoma:

Watchful waiting
Chemotherapy
Monoclonal antibodies such as rituximab
Radiotherapy
Stem cell transplantation

Question 113

Relationship between age and subtype of leukaemia?

Answer 113

“ALL CeLLmates have CoMmon AMbitions” to remember the progressive ages of the different leukaemia from 45-75 in steps of 10 years. Remember that ALL (the first in the mnemonic) most commonly affects children under 5 years.

Under 5 and over 45 – acute lymphoblastic leukaemia (ALL)

Over 55 – chronic lymphocytic leukaemia (CeLLmates)

Over 65 – chronic myeloid leukaemia (CoMmon)

Over 75 – acute myeloid leukaemia (AMbitions)

Question 114

What type of leukaemia is most common in children under 5?

Answer 114

Acute Lymphoblastic Leukaemia (ALL)

Question 115

What ages are typically affected by Acute Lymphoblastic Leukaemia (ALL)?

Answer 115

Under 5s, over 45s

Question 116

What ages are typically affected by Acute Myeloid Leukaemia (AML)?

Answer 116

Over 75s

Question 117

What ages are typically affected by Chronic Myeloid Leukaemia (CML)?

Answer 117

Over 65s

Question 118

What ages are typically affected by Chronic Lymphocytic Leukaemia?

Answer 118

Over 55s

Question 119

Differentials for a presentation of bruising and petechiae?

Answer 119

Leukaemia
Meningococcal septicaemia
Vasculitis
Henoch-Schonlein Purpura (HSP)
Idiopathic Thrombocytopenia Purpura (ITP)
Non-accidental injury

Question 120

Diagnostic tests in leukaemia (and their reasoning)

Answer 120

Full blood count is the initial investigation. NICE recommend a full blood count within 48 hours for patients with suspected leukaemia.

Children or young adults with ptechiae or hepatosplenomegaly should be referred immediately to the hospital.

Blood film can be used to look for abnormal cells and inclusions.

Lactate dehydrogenase (LDH) is a blood test that is often raised in leukaemia but is not specific to leukaemia. It can be raised in other cancers and many non-cancerous diseases.

Bone marrow biopsy can be used to analyse the cells in the bone marrow. This is the main investigation for establishing a definitive diagnosis of leukaemia.

Chest xray may show infection or mediastinal lymphadenopathy.

Lymph node biopsy can be used to assess lymph node involvement or investigate for lymphoma.

Lumbar puncture may be used if there is central nervous system involvement.

CT, MRI and PET scans can be used for staging and assessing for lymphoma and other tumours.

Question 121

What is the main investigation for establishing a definitive diagnosis of leukaemia?

Answer 121

Bone marrow biopsy

Question 122

NICE recommend a full blood count within what time period for patients with suspected leukaemia?

Answer 122

48hrs

Question 123

Under what circumstances should suspected leukaemia be referred immediately to hospital?

Answer 123

Children or young adults with ptechiae or hepatosplenomegaly should be referred immediately to the hospital.

Question 124

What are the various techniques used to obtain bone marrow biopsy?

Answer 124

Bone marrow aspiration: involves taking a liquid sample full of cells from within the bone marrow.

Bone marrow trephine: involves taking a solid core sample of the bone marrow and provides a better assessment of the cells and structure.

Samples from bone marrow aspiration can be examined straight away however a trephine sample requires a few days of preparation.

Bone marrow biopsy is usually taken from the iliac crest. It involves a local anaesthetic and a specialist needle.

Question 125

What happens in Acute Lymphoblastic Leukaemia?

Answer 125

Acute lymphoblastic leukaemia is where there is malignant change in one of the lymphocyte precursor cells. It causes acute proliferation of a single type of lymphocyte, usually B-lymphocytes. Excessive proliferation of these cells causes them to replace the other cell types being created in the bone marrow, leading to a pancytopenia.

Question 126

Around what ages does ALL peak

Answer 126

2-4 years

Question 127

What conditions is ALL associated with?

Answer 127

Downs Syndrome

Philadelphia chromosome (t(9:22) translocation) - in 30% of adults and 3-5% of children with ALL.

Question 128

What is seen on blood film of ALL

Answer 128

Blast cells

• a partially differentiated cell, usually referred to as a unipotent cell that has lost most of its stem cell properties

Question 129

What happens in CLL?

Answer 129

Chronic lymphocytic leukaemia is where there is chronic proliferation of a single type of well differentiated lymphocyte, usually B-lymphocytes.

Question 130

How might CLL present?

Answer 130

Often it is asymptomatic but it can present with infections, anaemia, bleeding and weight loss.

It can cause warm autoimmune haemolytic anaemia.

Question 131

What type of leukaemia can cause warm autoimmune haemolytic anaemia?

Answer 131

Chronic Lymphocytic Leukaemia

• lymphoma
• chronic lymphocytic leukaemia

Question 132

What can CLL transform into?

Answer 132

high-grade lymphoma.

This is called Richter’s transformation.

Question 133

What is seen in blood film in CLL?

Answer 133

Smear or smudge cells

Question 134

What happens in CML?

Answer 134

Chronic myeloid leukaemia has three typical phases: the chronic phase, the accelerated phase and the blast phase. The chronic phase can last around 5 years, is often asymptomatic and patients are diagnosed incidentally with a raised white cell count.

Question 135

How is CML often diagnosed?

Answer 135

Incidentally, with raised WCC

Question 136

What are the phases of CML?

Answer 136

CHRONIC

Can last around 5 years, asymptomatic

ACCELERATED

abnormal clast cell take up a high proportion of the cells in the bone marrow and blood (up to 20%), patients become more symptomatic, develop anaemia and thrombocytopenia and become immunocompromised.

BLAST PHASE

An even high proportion of blast cells and blood (>30%). This phase has severe symptoms and pancytopenia. It is often fatal.

Question 137

What cytogenetic change is characteristic of CML?

Answer 137

The Philadelphia chromosome, which is a translocation of genes between chromosome 9 and 22: it is a t(9:22) translocation.

Question 138

What is the most common acute leukaemia in adults?

Answer 138

Acute Myeloid Leukaemia

It can present at any age but normally presents from middle age onwards.

Question 139

AML blood film

Answer 139

A blood film will show a high proportion of blast cells.

These blast cells can have rods inside their cytoplasm that are named Auer rods.

Question 140

What might AML be the result of?

Answer 140

It can be the result of a transformation from a myeloproliferative disorder such as polycythaemia ruby vera or myelofibrosis.

Question 141

Most common leukaemia in children. Associated with Down syndrome.

Answer 141

Acute lymphoblastic leukaemia

Question 142

Most common leukaemia in adults overall. Associated with warm haemolytic anaemia, Richter’s transformation into lymphoma and smudge / smear cells.

Answer 142

Chronic lymphocytic leukaemia

Question 143

Leukaemia which has three phases including a 5 year “asymptomatic chronic phase”. Associated with the Philadelphia chromosome.

Answer 143

Chronic myeloid leukaemia

Question 144

What type of leukaemia can be the result of a transformation from a myeloproliferative disorder, associated with Auer rods?

Answer 144

Acute myeloid leukaemia

Question 145

What is seen here and what is this characteristic of?

Answer 145

Auer rods, associated with acute myeloid leukaemia

Question 146

Management of leukaemia?

Answer 146

Treatment will be coordinated by an oncology multi-disciplinary team. Leukaemia is primarily treated with chemotherapy and steroids.

Other therapies include:

Radiotherapy
Bone marrow transplant
Surgery

Question 147

Potential complications of chemotherapy management in leukaemia?

Answer 147

Failure

Stunted growth and development in children

Infections due to immunodeficiency

Neurotoxicity

Infertility

Secondary malignancy

Cardiotoxicity

Tumour lysis syndrome

Question 148

What is released in tumour lysis syndrome?

Answer 148

Uric acid

Potassium, phosphate (can lead to hypocalcemia)

Question 149

What can be are to reduce the high uric acid levels in tumour lysis syndrome?

Answer 149

Allopurinol or rasburicase

Question 150

What is myeloma?

Answer 150

Myeloma is a cancer of the plasma cells. These are a type of B lymphocyte that produce antibodies. Cancer in a specific type of plasma cell results in large quantities of a single type of antibody being produced. Myeloma accounts for around 1% of all cancers.

Question 151

What are plasma cells and what happens to them in myeloma?

Answer 151

These are a type of B lymphocyte that produce antibodies.

Cancer in a specific type of plasma cell results in large quantities of a single type of antibody being produced.

Question 152

What are the premalignant conditions that may progress to myeloma?

Answer 152

Monoclonal gammopathy

Smouldering myeloma

Question 153

What is multiple myeloma

Answer 153

Multiple myeloma is where the myeloma (multiple myeloma is where the myeloma affects multiple areas of the body) affects multiple areas of the body.

Question 154

What is monoclonal gammopathy of undetermined significance?

Answer 154

Where there is an excess of a single type of antibody or antibody components without other features of myeloma or cancer.

This is often an incidental finding in an otherwise healthy person and as the name suggests the significance is unclear.

It may progress to myeloma and patients are often followed up routinely to monitor for progression.

Question 155

What is smouldering myeloma?

Answer 155

Smouldering myeloma is where there is progression of MGUS with higher levels of antibodies or antibody components.

It is premalignant and more likely to progress to myeloma than MGUS.

Waldenstrom’s macroglobulinemia is a type of smouldering myeloma where there is excessive IgM specifically.

Question 156

In what type of smouldering myeloma where there is excessive IgM specifically?

Answer 156

Waldenstrom’s macroglobulinemia

Question 157

Pathophysiology of myeloma?

Answer 157

Genetic mutation of plasma cells (B lymphocytes that have become activated to produce a certain antibody) causing it to rapidly and uncontrollably multiply.

These plasma cells produce one type of antibody (also called immunoglobulins. They are complex molecules made up of two heavy chains and two light chains arranged in a Y shape. They help the immune system recognise and fight infections by targeting specific proteins on the pathogen. They come in 5 main types: A, G, M, D and E)

This single type of antibody that is produced by all the identical cancerous plasma cells can be called a monoclonal paraprotein. This means a single type of abnormal protein.

The “Bence Jones protein” that can be found in the urine of many patients with myeloma is actually a part (subunit) of the antibody called the light chains.

Question 158

What are the 5 main types of antibodies?

Answer 158

A

G

M

D
and
E

Question 159

Immunoglobulins in myeloma?

Answer 159

When you measure the immunoglobulins in a patient with myeloma, one of those types will be significantly abundant.

More than 50% of the time this is immunoglobulin type G (IgG).

This single type of antibody that is produced by all the identical cancerous plasma cells can be called a monoclonal paraprotein. This means a single type of abnormal protein.

Question 160

What is the most common immunoglobulin excess in myeloma?

Answer 160

IgG

Question 161

What can be found in the urine of many patients with myeloma?

Answer 161

“Bence Jones protein”

Question 162

What is the Bence Jones protein that can be found in the urine of many patients with myeloma?

Answer 162

A part (subunit) of the antibody called the light chains

Question 163

What is low in myeloma and why?

Answer 163

The cancerous plasma cells invade the bone marrow. This is described as bone marrow infiltration.

This causes suppression of the development of other blood cell lines leading to anaemia (low red cells), neutropenia (low neutrophils) and thrombocytopenia (low platelets).

Question 164

What happens in myeloma bone disease?

Answer 164

Myeloma bone disease is a result of increased osteoclast activity and suppressed osteoblast activity.

Osteoclasts absorb bone and osteoblasts deposit bone.

This results in the metabolism of bone becoming imbalanced as more bone is being reabsorbed than constructed.

This is caused by cytokines released from the plasma cells and the stromal cells (other bone cells) when they are in contact with the plasma cells.

Question 165

Common sites off myeloma bone disaese?

Answer 165

Skull
Spine
Long bones
Ribs

Question 166

Myeloma bone disease - osteolytic lesions

Answer 166

The abnormal bone metabolism is patchy, meaning that in some areas the bone becomes very thin whereas others remain relatively normal.

These patches of thin bone can be described as osteolytic lesions.

Question 167

How can myeloma cause pathological fractures?

Answer 167

Myeloma bone disease is a result of increased osteoclast activity and suppressed osteoblast activity.

This results in the metabolism of bone becoming imbalanced as more bone is being reabsorbed than constructed

The abnormal bone metabolism is patchy, meaning that in some areas the bone becomes very thin (osteolytic lesions) whereas others remain relatively normal.

These weak points in bone lead to pathological fractures.

For example, a vertebral body in the spine may collapse (vertebral fracture) or a long bone such as the femur may break under minimal force.

Question 168

What electrolyte disturbance may be seen in myeloma and why?

Answer 168

Increase in osteoclast activity caused by cytokines released from the plasma cells and the stromal cells (other bone cells) when they are in contact with the plasma cells.

Calcium is reabsorbed from the bone into the blood. This results in hypercalcaemia (high blood calcium).

Question 169

What are plasmacytomas and where can they occur?

Answer 169

People with myeloma can also develop plasmacytomas.

These are individual tumours made up of the cancerous plasma cells.

They can occur in the bones, replacing normal bone tissue or can occur outside bones in the soft tissue of the body.

Question 170

Why might patients with myeloma develop renal impairment (Myeloma Renal Disease)

Answer 170

High levels of immunoglobulins (antibodies) can block the flow through the tubules

Hypercalcaemia impairs renal function (increase osteoclast activity)

Dehydration

Medications used to treat the conditions such as bisphosphonates can be harmful to the kidneys

Question 171

What issues can plasma viscosity cause?

Answer 171

Easy bruising

Easy bleeding

Reduced or loss of sight due to vascular disease in the eye

Purple discolouration to the extremities (purplish palmar erythema)

Heart failure

Question 172

Why is there hypeviscosity in myeloma?

Answer 172

Plasma viscosity increases when there are more proteins in the blood.

These are proteins like immunoglobulins and fibrinogen, both of which increase with inflammation.

In myeloma there are large amounts of immunoglobulins in the blood causing the plasma viscosity to be significantly higher.

Question 173

Four key features of myeloma?

Answer 173

C – Calcium (elevated)
R – Renal failure
A – Anaemia (normocytic, normochromic) from replacement of bone marrow.
B – Bone lesions/pain

Question 174

What type of anemia occurs in myeloma?

Answer 174

Normocytic, normochromic - from replacement of bone marrow

Question 175

Risk factors for myeloma?

Answer 175

Older age

Male

Black African ethnicity

Family history

Obesity

Question 176

In what patients do NICE suggest considering myeloma in?

Answer 176

Over 60s with persistent bone pain (particularly back pain) or unexplained fractures

Question 177

Myeloma - initial investigations

Answer 177

FBC (low white blood cell count in myeloma)
Calcium (raised in myeloma)
ESR (raised in myeloma)
Plasma viscosity (raised in myeloma)

If any of these are positive or myeloma is still suspected:

B – Bence–Jones protein (request urine electrophoresis)
L – Serum‑free Light‑chain assay
I – Serum Immunoglobulins
P – Serum Protein electrophoresis

Question 178

FBC in myeloma

Answer 178

Anaemia (normocytic + normochromic)

Low white blood cell count

Question 179

What is used to confirm the diagnosis of myeloma?

Answer 179

Bone marrow biopsy

Question 180

Imaging in myeloma?

Answer 180

Imaging is required to assess for bone lesions. The order of preference to establish this is:

1. Whole body MRI
2. Whole body CT
3. Skeletal survey (xray images of the full skeleton)

Patients only require one investigation but may not tolerate or be suitable for MRI or CT.

Question 181

Myeloma X ray signs?

Answer 181

Punched out lesions

Lytic lesions

“Raindrop skull” caused by many punched out (lytic) lesions throughout the skull that give the appearance of raindrops splashing on a surface

Question 182

Aim of treatment in myeloma/disease course?

Answer 182

The aim of treatment is to control disease. It usually takes a relapsing-remitting course and treatment aims to improve quality and quantity of life.

Management will be undertaken by the haematology and oncology specialist multidisciplinary team.

Question 183

What is the first line treatment of myeloma?

Answer 183

First line treatment usually involves a combination of chemotherapy with:

Bortezomid
Thalidomide
Dexamethasone

Question 184

Management of myeloma?

Answer 184

Chemotherapy is first line: bortezomid, thalidomide, dexamethasone

Stem cell transplantation (as part of a clinical trial, where patients are suitable)

VTE with aspirin or LMWH whilst on certain chemotherapy regimes (e.g. thialidomide) as there is a higher risk of developing a thrombus

Myeloma bone disease can be improved using bisphosphonates.

Radiotherapy to bone lesions can improve bone pain

Orthopaedic surgery can stabilise bones or treat fractures.

Cement augmentation can improve spine stability and pain

Question 185

Specific management of myeloma bone disease

Answer 185

Myeloma bone disease can be improved using bisphosphonates. These suppress osteoclast activity.

Radiotherapy to bone lesions can improve bone pain.

Orthopaedic surgery can stabilise bones (e.g. by inserting a prophylactic intramedullary rod) or treat fractures.

Cement augmentation involves injecting cement into vertebral fractures or lesions and can improve spine stability and pain

Question 186

What are the complications of myeloma itself and the treatments?

Answer 186

Infection

Pain

Renal failure

Anaemia

Hypercalcaemia

Peripheral neuropathy

Spinal cord compression

Hyperviscocity

Question 187

What are the three main myeloproliferative disorders?

Answer 187

Primary myelofibrosis

Polycythaemia vera

Essential thrombocythemia

Question 188

What are myeloproliferative disorders?

Answer 188

Conditions occurring due to uncontrolled proliferation of a single type of stem cells consider a type of bone marrow cancer

Question 189

Primary myelofibrosis is the result of proliferation of what?

Answer 189

Hematopoietic stem cells

Question 190

Polycythaemia vera is the result of proliferation of what?

Answer 190

The erythroid cell line

Question 191

Essential thrombocythaemia is the result of proliferation of what?

Answer 191

The megakaryocytic cell line

Question 192

What disease is the result of proliferation of the megakaryocytic cell line?

Answer 192

Essential thrombocythaemia

Question 193

What disease is the result of proliferation of the erythroid cell line?

Answer 193

Polycythaemia vera

Question 194

What disease is the result of proliferation of the hematopoietic stem cells?

Answer 194

Primary myelofibrosis

Question 195

Mutations in which genes are associated with myeloproliferative disorders?

Answer 195

JAK2
MPL
CALR

Question 196

Myeloproliferative disorders have the potential to progress and transform into what?

Answer 196

acute myeloid leukaemia

Question 197

What drug is used to target the JAK2 mutation?

Answer 197

ruxolitinib

JAK2 inhibitor

Question 198

What can myelofibrosis be the result of?

Answer 198

Myeloproliferative disorders: primary myelofibrosis, polycythaemia vera or essential thrombocythemia

Question 199

What happens in myelofibrosis and what can this lead to?

Answer 199

Myelofibrosis is where the proliferation of the cell line leads to fibrosis of the bone marrow.

The bone marrow is replaced by scar tissue in response to cytokines that are released from the proliferating cells.

One particular cytokine is fibroblast growth factor.

This fibrosis affects the production of blood cells and can lead to anaemia and low white blood cells (leukopenia).

When the bone marrow is replaced with scar tissue the production of blood cells (haematopoiesis) starts to happen in other areas such as the liver and spleen.

This is known as extramedullary haematopoiesis and can lead to hepatomegaly and splenomegaly.

This can lead to portal hypertension.

If it occurs around the spine it can lead to spinal cord compression.

Question 200

Presentation of myeloproliferative disorders?

Answer 200

Initially, myeloproliferative disorders can be asymptomatic.

They can present systemic symptoms:

Fatigue
Weight loss
Night sweats
Fever

There may be signs and symptoms of underlying complications:

Anaemia (except in polycythaemia)
Splenomegaly (abdominal pain)
Portal hypertension (ascites, varices and abdominal pain)
Low platelets (bleeding and petechiae)
Thrombosis is common in polycythaemia and thrombocythaemia
Raised red blood cells (thrombosis and red face)
Low white blood cells (infections)

Question 201

What three signs are key O/E for polycythaemia vera?

Answer 201

Conjunctival plethora (excessive redness to the conjunctiva in the eyes)
A “ruddy” complexion
Splenomegaly

Question 202

Myeloproliferative disorder various FBC findings?

Answer 202

Polycythaemia Vera:

Raised haemoglobin (more than 185g/l in men or 165g/l in women)

Primary Thrombocythaemia:

Raised platelet count (more than 600 x 109/l)

Myelofibrosis (due to primary MF or secondary to PV or ET) can give variable findings:

• Anaemia
• Leukocytosis or leukopenia (high or low white cell counts)
• Thrombocytosis or thrombocytopenia (high or low platelet counts)

Question 203

What might be seen on a blood film in myelofibrosis?

Answer 203

Teardrop-shaped RBCs,

Varying sizes of red blood cells (poikilocytosis)

Immature red and white cells (blasts).

Question 204

Diagnosis of myeloproliferative disorders?

Answer 204

Bone marrow biopsy is the test of choice to establish a diagnosis. Bone marrow aspiration is usually “dry” as the bone marrow has turned to scar tissue.

Testing for the JAK2, MPL and CALR genes can help guide management.

Question 205

Management of Primary Myelofibrosis

Answer 205

Patients with mild disease with minimal symptoms might be monitored and not actively treated.

Allogeneic stem cell transplantation is potentially curative but carries risks.

Chemotherapy can help control the disease, improve symptoms and slow progression but is not curative on its own.

Supportive management of the anaemia, splenomegaly and portal hypertension.

Question 206

Management of Polycythaemia Vera

Answer 206

Venesection can be used to keep the haemoglobin in the normal range. This is the first line treatment.

Aspirin can be used to reduce the risk of developing blood clots (thrombus formation).

Chemotherapy can be used to control the disease.

Question 207

Management of Essential Thrombocythaemia

Answer 207

Aspirin can be used to reduce the risk of developing blood clots (thrombus formation).

Chemotherapy can be used to control the disease.

Question 208

What is myelodysplastic syndrome?

Answer 208

Myelodysplastic syndrome is caused by the myeloid bone marrow cells not maturing properly and therefore not producing healthy blood cells.

There are a number of specific types of myelodysplastic syndrome.

Question 209

Myelodysplastic syndrome causes low levels of blood components that originate from the myeloid cell line, including?

Answer 209

Anaemia
Neutropenia (low neutrophil count)
Thrombocytopenia (low platelets)

Question 210

In which patients is myelodysplastic syndrome more common?

Answer 210

It is more common in patients above 60 years of age and in patients that have previously had treatment with chemotherapy or radiotherapy.

Question 211

What does myelodysplastic syndrome have a risk of transforming into?

Answer 211

There is an increased risk of transforming into acute myeloid leukaemia.

Question 212

?Presentation of myelodysplastic syndrome

Answer 212

Patients may be asymptomatic and incidentally diagnosed based on a full blood count.

They may present with symptoms of anaemia (fatigue, pallor or shortness of breath), neutropenia (frequent or severe infections) or thrombocytopenia (purpura or bleeding).

Question 213

How might myelodysplastic syndrome be diagnosed?

Answer 213

Full blood count will be abnormal. There may be blasts on the blood film.

The diagnosis is confirmed by bone marrow aspiration and biopsy.

Question 214

Blood film in myelodysplastic syndrome

Answer 214

Blasts

Question 215

Management of myelodysplastic syndrome?

Answer 215

Depending on the symptoms, risk of progression and overall prognosis the treatment options are:

Watchful waiting
Supportive treatment with blood transfusions if severely anaemic
Chemotherapy
Stem cell transplantation

Question 216

How might blood product transfusion complications be broadly classified?

Answer 216

immunological: acute haemolytic, non-haemolytic febrile, allergic/anaphylaxis

infective

transfusion-related acute lung injury (TRALI)

transfusion-associated circulatory overload (TACO)

other: hyperkalaemia, iron overload, clotting

Question 217

Why might non-haemolytic febrile reaction occur in blood product transfusion?

Answer 217

Thought to be caused by antibodies reacting with white cell fragments in the blood product and cytokines that have leaked from the blood cell during storage

due to white blood cell HLA antibodies

often the result of sensitization by previous pregnancies or transfusions

Question 218

Features of non-haemolytic febrile reaction?

Answer 218

Fever, chills

Red cell transfusion (1-2%)
Platelet transfusion (10-30%)

Question 219

Management of non-haemolytic febrile reaction?

Answer 219

Slow or stop the transfusion

Paracetamol

Monitor

Question 220

Why might minor allergic reaction occur in blood product transfusion?

Answer 220

Causes by foreign plasma proteins

Question 221

Why might anaphylaxis occur in blood product transfusion?

Answer 221

Can be caused by patients with IgA deficiency who have anti-IgA antibodies

Question 222

Management of minor allergic reaction in blood product transfusion?

Answer 222

Temporarily stop the transfusion
Antihistamine
Monitor

Question 223

Management of anaphylaxis in blood product transfusion?

Answer 223

Stop the transfusion

IM adrenaline

ABC support
oxygen
fluids

Question 224

During blood product transfusion, what might suggest anaphylaxis?

Answer 224

Hypotension, dyspnoea, wheezing, angioedema.

Question 225

Features of minor allergic reaction in blood product transfusion?

Answer 225

Pruritus, urticaria

Question 226

Why might acute haemolytic reaction occur in blood product transfusion?

Answer 226

ABO-incompatible blood e.g. secondary to human error

Question 227

Features of acute haemolytic reaction

Answer 227

Fever, abdominal pain, hypotension

Question 228

Management of acute haemolytic reaction

Answer 228

Stop transfusion

Confirm diagnosis
check the identity of patient/name on blood product
send blood for direct Coombs test, repeat typing and cross-matching

Supportive care
fluid resuscitation

Question 229

Why might transfusion-associated circulatory overload (TACO) occur?

Answer 229

Excessive rate of transfusion, pre-exisiting heart failure

Question 230

Transfusion-associated circulatory overload (TACO) features

Answer 230

Pulmonary oedema, hypertension

Question 231

Transfusion-associated circulatory overload (TACO) management

Answer 231

Slow or stop transfusion

Consider intravenous loop diuretic (e.g. furosemide) and oxygen

Question 232

Why does Transfusion-related acute lung injury (TRALI) occur?

Answer 232

Non-cardiogenic pulmonary oedema thought to be secondary to increased vascular permeability caused by host neutrophils that become activated by substances in donated blood

Question 233

Features of Transfusion-related acute lung injury (TRALI)

Answer 233

Hypoxia, pulmonary infiltrates on chest x-ray, fever, hypotension, acute respiratory sidress syndrome

Question 234

Transfusion-related acute lung injury (TRALI) management

Answer 234

Stop the transfusion

Oxygen and supportive care

Question 235

What happens in acute hemolytic transfusion reaction?

Answer 235

Acute haemolytic transfusion reaction results from a mismatch of blood group (ABO) which causes massive intravascular haemolysis.

This is usually the result of red blood cell destruction by IgM-type antibodies.

Question 236

When do the symptoms occur in acute haemolytic transfusion reaction?

Answer 236

Symptoms begin minutes after the transfusion is started and include a fever, abdominal and chest pain, agitation and hypotension.

Question 237

Complications of acute haemolytic transfusion reaction?

Answer 237

Disseminated intravascular coagulation, and renal failure

Question 238

When do allergic/anaphylaxis reactions occur in blood transfusion?

Answer 238

Symptoms typically arise within minutes of starting the transfusion and severity can range from urticaria to anaphylaxis with hypotension, dyspnoea, wheezing, and stridor, or angioedema.

Question 239

Management of simple urticaria in blood transfusion?

Answer 239

Simple urticaria should be treated by discontinuing the transfusion and with an antihistamine. Once the symptoms resolve, the transfusion may be continued with no need for further workup.

Question 240

Within how long does TRALI occur?

Answer 240

within 6 hours of transfusion

Question 241

Key differences between TRALI and TACO

Answer 241

TRALI - HYPOTENSION
TACO - HYPERTENSION

Question 242

Concerns with vCJD transmission in blood transfusion?

Answer 242

although the absolute risk is very small, vCJD may be transmitted via blood transfusion
a number of steps have been taken to minimise this risk, including:

from late 1999 onward, all donations have undergone removal of white cells (leucodepletion) in order to reduce any vCJD infectivity present

from 1999, plasma derivatives have been fractionated from imported plasma rather than being sourced from UK donors. Fresh Frozen Plasma (FFP) used for children and certain groups of adults needing frequent transfusions is also imported

from 2004 onward, recipients of blood components have been excluded from donating blood

Question 243

Blood products: whole blood fractions?

Answer 243

Packed red cells
Platelet rich plasma
Platelet concentrate
Fresh frozen plasma
Cryoprecipitate
SAG-MAnnitol Blood

Question 244

What is SAG-Mannitol blood, and how much can be used?

Answer 244

Removal of all plasma from a blood unit and substitution with:

Sodium chloride
Adenine
Anhydrous glucose
Mannitol

Up to 4 units of SAG M Blood may be administered. Thereafter whole blood is preferred. After 8 units, clotting factors and platelets should be considered.

Question 245

Blood transfusuion: What is cryoprecipitate and what does it allow for?

Answer 245

Formed from supernatant of FFP.
Rich source of Factor VIII and fibrinogen.

Allows large concentration of factor VIII to be administered in small volume.

Question 246

What is FFP prepared from?

Answer 246

Single units of blood

Question 247

FRESH FROZEN PLASMA

Answer 247

Prepared from single units of blood.

Contains clotting factors, albumin and immunoglobulin.

Unit is usually 200 to 250ml.

Usually used in correcting clotting deficiencies in patients with hepatic synthetic failure who are due to undergo surgery.

Usual dose is 12-15ml/Kg-1.

It should not be used as first line therapy for hypovolaemia.

Question 248

How is platelet concentrate prepared and used?

Answer 248

Prepared by high speed centrifugation and administered to patients with thrombocytopaenia.

Question 249

Which patients are administered platelet rich plasma?

Answer 249

Usually administered to patients who are thrombocytopaenic and are bleeding or require surgery.

Question 250

How is platelet rich plasma obtained?

Answer 250

It is obtained by low speed centrifugation.

Question 251

When are packed red cells used?

Answer 251

Used for transfusion in chronic anaemia and cases where infusion of large volumes of fluid may result in cardiovascular compromise.

Question 252

How are packed red cells obtained?

Answer 252

Product obtained by centrifugation of whole blood.

Question 253

What whole blood fractions MUST be cross matched?

Answer 253

Packed red cells

Fresh frozen plasma

Cryoprecipitate

Whole blood

Question 254

What whole blood fraction can be ABO incompatible in adults?

Answer 254

Platelets

Question 255

What are cell saver devices?

Answer 255

These collect patients own blood lost during surgery and then re-infuse it. There are two main types:

Those which wash the blood cells prior to re-infusion. These are more expensive to purchase and more complicated to operate. However, they reduce the risk of re-infusing contaminated blood back into the patient.

Those which do not wash the blood prior to re-infusion.

Question 256

Advantage of cell saver devices?

Answer 256

Their main advantage is that they avoid the use of infusion of blood from donors into patients and this may reduce risk of blood borne infection.

It may be acceptable to Jehovah’s witnesses.

Question 257

When are cell saver devices contraindicated?

Answer 257

It is contraindicated in malignant disease for risk of facilitating disease dissemination.

Question 258

Stepwise management when immediate or urgent surgery is required in patients taking warfarin?

Answer 258

1. Stop warfarin
2. Vitamin K (reversal within 4-24 hours)
   IV takes 4-6h to work (at least 5mg)
   Oral can take 24 hours to be clinically effective
3. Fresh frozen plasma
   Used less commonly now as 1st line warfarin reversal
   30ml/kg-1
   Need to give at least 1L fluid in 70kg person (therefore not appropriate in fluid overload)
   Need blood group
   Only use if human prothrombin complex is not available
4. Human Prothrombin Complex (reversal within 1 hour)
   Bereplex 50 u/kg
   Rapid action but factor 6 short half life, therefore give with vitamin K

Question 259

What are the two causes of B12 deficiency?

Answer 259

insufficient dietary intake of vitamin B12 or pernicious anaemia.

Question 260

What is pernicious anaemia?

Answer 260

Pernicious anaemia is a cause of B12 deficiency anaemia. B12 deficiency can be caused by

Autoimmune condition - antibodies form against the parietal cells or intrinsic factor

A lack of intrinsic factor prevents the absorption of vitamin B12 and the patient becomes vitamin B12 deficient.

Question 261

What is intrinsic factor and where is it produced?

Answer 261

Parietal cells of the stomach produce a protein called INTRINSIC FACTOR - essential for the absorption of vitamin B12 in the ileum

Question 262

What neurological symptoms can B12 deficiency cause?

Answer 262

PERIPHERAL NEUROPATHY WITH NUMBNESS OR PARAESTHESIA (PINS AND NEEDLES)

Loss of vibration sense or proprioception

Visual changes

Mood or cognitive changes

Question 263

What can be tested for to diagnose pernicious anemia?

Answer 263

Autoantibodies -

INTRINSIC FACTOR ANTIBODY - first line investigation

Gastric parietal cell antibody can also be tested but is less helpful

Question 264

Management of B12 deficiency

Answer 264

DIETARY DEFICIENCY (if not severe): oral replacement with cyanocobalamin

PERNICIOUS ANEMIA - IM hydroxocobalamin
They can be treated with 1mg of intramuscular hydroxocobalamin 3 times weekly for 2 weeks, then every 3 months.
(Oral replacement is inadequate because the problem is with absorption rather than intake)

More intense regimens are used where there are neurological symptoms (e.g. 1mg every other day until the symptoms improve).

Question 265

What is important in management of folate deficiency and why?

Answer 265

If there is also folate deficiency it is important to check and treat B12 deficiency first before correcting the folate deficiency.

Treating patients with folic acid when they have a B12 deficiency can lead to subacute combined degeneration of the cord.

Question 266

If there is also folate deficiency it is important to check and treat B12 deficiency first before correcting the folate deficiency - why?

Answer 266

Treating patients with folic acid when they have a B12 deficiency can lead to subacute combined degeneration of the cord.

Must correct B12 deficiency quickly

Question 267

What is haemolytic anaemia and what are the two general reasons it occurs?

Answer 267

Haemolytic anaemia is where there is destruction of red blood cells (haemolysis) leading to anaemia.

There are a number of inherited conditions that cause the red blood cells to be more fragile and break down faster than normal leading to chronic haemolytic anaemia.

There are also a number of acquired conditions that lead to increased breakdown of red blood cells and haemolytic anaemia.

Question 268

Inherited causes of haemolytic anaemia?

Answer 268

Hereditary Spherocytosis

Hereditary Elliptocytosis

Thalassaemia

Sickle Cell Anaemia

G6PD Deficiency

Question 269

Acquired causes of haemolytic anaemia?

Answer 269

Autoimmune haemolytic anaemia

Alloimmune haemolytic anaemia (transfusions
reactions and haemolytic disease of newborn)

Paroxysmal nocturnal haemoglobinuria

Microangiopathic haemolytic anaemia

Prosthetic valve related haemolysis

Question 270

What are the features that might be seen in a patient with a haemolytic anaemia due to the destruction of RBC - and why?

Answer 270

(prehepatic) jaundice (unconjugated bilirubin released in breakdown of RBC)

Anaemia (reduction in circulating RBC)

Splenomegaly (spleen becomes filled with destroyed red blood cells)

Question 271

Investigations + findings haemolytic anaemia?

Answer 271

FULL BLOOD COUNT

Full blood count shows a normocytic anaemia

BLOOD FILM

Blood film shows schistocytes (fragments of red blood cells)

DIRECT COOMBS TEST

Direct Coombs test is positive in autoimmune haemolytic anaemia

Question 272

What is the most common inherited haemolytic anaemia in northern Europeans?

Answer 272

Hereditary spherocytosis

Question 273

What is hereditary spherocytosis and how is it inherited?

Answer 273

It is an autosomal dominant condition.

It causes sphere shaped red blood cells that are fragile and easily break down when passing through the spleen.

• most common hereditary haemolytic anaemia in people of northern European descent
• autosomal dominant defect of red blood cell cytoskeleton
• the normal biconcave disc shape is replaced by a sphere-shaped red blood cell
• red blood cell survival reduced as destroyed by the spleen

Question 274

What is seen here?

Answer 274

Spherocytosis (fragments of RBC) seen in haemolytic anaemia

Question 275

How might hereditary spehrocytosis present?

Answer 275

It presents with jaundice, gallstones, splenomegaly, failure to thrive, MCHC elevated, and notably aplastic crisis in the presence of the parvovirus.

Question 276

What infection does hereditary spherocytosis notably present with in aplastic crisis?

Answer 276

Parovirus

Question 277

How is hereditary spherocytosis diagnosed?

Answer 277

It is diagnosed by family history and clinical features with spherocytes on the blood film.

The mean corpuscular haemoglobin concentration (MCHC) is raised on a full blood count.

Reticulocytes will be raised due to rapid turnover of red blood cells.

the British Journal of Haematology (BJH) guidelines state that ‘patients with a family history of HS, typical clinical features and laboratory investigations (spherocytes, raised mean corpuscular haemoglobin concentration [MCHC], increase in reticulocytes) do not require any additional tests
if the diagnosis is equivocal the BJH recommend the EMA binding test and the cryohaemolysis test
for atypical presentations electrophoresis analysis of erythrocyte membranes is the method of choice

Question 278

Investigation findings - hereditary spherocytosis?

Answer 278

Spherocytes on the blood film.

The mean corpuscular haemoglobin concentration (MCHC) is raised on a full blood count.

Reticulocytes will be raised due to rapid turnover of red blood cells.

Question 279

What is hereditary elliptocytosis and how does it compare to hereditary spherocytosis?

Answer 279

Hereditary elliptocytosis is very similar to hereditary spherocytosis except that the red blood cells are ellipse shaped.

It is also autosomal dominant.

Presentation and management are the same:

• It presents with jaundice, gallstones, splenomegaly and notably aplastic crisis in the presence of the parvovirus. elliptocytosis on the blood film.
• The mean corpuscular haemoglobin concentration (MCHC) is raised on a full blood count. Reticulocytes will be raised due to rapid turnover of red blood cells.
• Treatment is with folate supplementation and splenectomy. Removal of the gallbladder (cholecystectomy) may be required if gallstones are a problem.

Question 280

What is G6PD deficiency and how is it inherited?

Answer 280

G6PD deficiency is a condition where there is a defect in the red blood cell enzyme G6PD.

It is more common in Mediterranean and African patients and is X LINKED RECESSIVE

It causes crises that are triggered by infections, medications or fava beans (broad beans).

Question 281

Presentation of G6PD deficiency?

Answer 281

It presents with jaundice (usually in the neonatal period), gallstones, anaemia, splenomegaly and Heinz bodies on blood film. May also see bite and blister cells.

Question 282

How is G6PD enzyme deficiency diagnosed?

Answer 282

G6PD enzyme assay

levels should be checked around 3 months after an acute episode of hemolysis, RBCs with the most severely reduced G6PD activity will have hemolysed → reduced G6PD activity → not be measured in the assay → false negative results

Question 283

What might trigger a crisis (sudden onset of jaundice and haemolytic anaemia) in a patient with G6PD deficiency?

Answer 283

Infections

Fava beans (broad beans)

Medications

Medications that trigger haemolysis include:
- Primaquine (an antimalarial)
- Ciprofloxacin
- Sulfonylureas
- Sulfasalazine and other sulphonamide drugs.

Question 284

What is Autoimmune haemolytic anaemia and what are the two ‘types’?

Answer 284

Autoimmune haemolytic anaemia occurs when antibodies are created against the patient’s red blood cells.

These antibodies lead to destruction of the red blood cells.

There are two types based on the temperature at which the auto-antibodies function to cause the destruction of red blood cells:

• Warm Type Autoimmune Haemolytic Anaemia
• Cold Type Autoimmune Haemolytic Anaemia

Question 285

Warm vs cold AIHA - which is more common?

Answer 285

Warm

Question 286

What is meant by warm autoimmune haemolytic anaemia and why does it occur?

Answer 286

Autoimmune haemolytic anaemia occurs when antibodies are created against the patient’s red blood cells.

These antibodies lead to destruction of the red blood cells.

Haemolysis occurs at normal or above normal temperatures.

In warm AIHA the antibody (usually IgG) causes haemolysis best at body temperature and haemolysis tends to occur in extravascular sites, for example the spleen.

It is usually idiopathic, meaning that it arises without a clear cause.

Other causes:

autoimmune disease: e.g. systemic lupus

erythematosus*

neoplasia

lymphoma

chronic lymphocytic leukaemia

drugs: e.g. methyldopa

Question 287

What is cold agglutinin disease and what occurs?

Answer 287

Also known as cold autoimmune haemolytic anemia.

At lower temperatures (e.g. less than 10ºC) the antibodies against red blood cells attach themselves to the red blood cells and cause them to clump together.

This is called agglutination.

This agglutination results in the destruction of the red blood cells as the immune system is activated against them and they get filtered and destroyed in the spleen.

The antibody in cold AIHA is usually IgM and causes haemolysis best at 4 deg C. Haemolysis is mediated by complement and is more commonly intravascular. Features may include symptoms of Raynaud’s and acrocynaosis. Patients respond less well to steroids

Question 288

What might cold AIHA/cold agglutinin disease occur secondary to?

Answer 288

Conditions such as:

• Lymphoma
• Leukaemia
• Systemic lupus erythematosus

Infections such as:

-Mycoplasma
- EBV
- CMV
- HIV

Question 289

Management of AIHA?

Answer 289

Blood transfusions

Prednisolone (steroids)

Rituximab (a monoclonal antibody against B cells)

Splenectomy

Question 290

What is Alloimmune Haemolytic Anaemia and in what senarios does it occur?

Answer 290

Alloimmune haemolytic anaemia occurs where an there is either foreign red blood cells circulating in the patients blood causing an immune reaction that destroys those red blood cells or there is a foreign antibody circulating in their blood that acts against their own red blood cells and causes haemolysis.

The two scenarios where this occurs are transfusion reactions and haemolytic disease of the newborn.

In hemolytic transfusion reactions red blood cells are transfused into the patient. The immune system produces antibodies against antigens on those foreign red blood cells. This creates an immune response that leads to the destruction of those red blood cells.

In haemolytic disease of the newborn there are antibodies that cross the placenta from the mother to the fetus. These maternal antibodies target antigens on the red blood cells of the fetus. This causes destruction of the red blood cells in the fetus and neonate.

Question 291

What is the abnormality in paroxysmal nocturnal haemoglobinuria and what occurs subsequently?

Answer 291

Paroxysmal nocturnal haemoglobinuria is a rare condition that occurs when a specific genetic mutation in the haematopoietic stem cells in the bone marrow occurs during the patients lifetime.

The specific mutation results in a loss of the proteins on the surface of red blood cells that inhibit the complement cascade.

The loss of protection against the complement system results in activation of the complement cascade on the surface of red blood cells and destruction of the red blood cells.

Question 292

Presentation of paroxysmal nocturnal haemoglobinuria?

Answer 292

The characteristic presentation is red urine in the morning containing haemoglobin and haemosiderin.

The patient becomes anaemic due to the haemolysis.

They are also predisposed to thrombosis (e.g. DVT, PE and hepatic vein thrombosis) and smooth muscle dystonia (e.g. oesophageal spasm and erectile dysfunction).

Question 293

Management of paroxysmal nocturnal haemoglobinuria?

Answer 293

Management is with ECULIZUMAB or BONE MARROW TRANSPLANTATION

Eculizumab is a monoclonal antibody that targets complement component 5 (C5) causing suppression of the complement system.

Bone marrow transplantation can be curative.

Question 294

What is MAHA?

Answer 294

Microangiopathic haemolytic anaemia (MAHA) is where the small blood vessels have structural abnormalities that cause haemolysis of the blood cells travelling through them.

Question 295

What might microangiopathic haemolytic anaemia occur secondary to?

Answer 295

This is usually secondary to an underlying condition:

• Haemolytic Uraemic Syndrome (HUS)
• Disseminated Intravascular Coagulation (DIC)
• Thrombotic Thrombocytopenia Purpura (TTP)
• Systemic Lupus Erythematosus (SLE)
• Cancer

Question 296

What is Prosthetic Valve Haemolysis and why does it occur?

Answer 296

Haemolytic anaemia is a key complication of prosthetic heart valves.

It occurs in both bioprosthetic and metallic valve replacement.

It is caused by turbulence around the valve and collision of red blood cells with the implanted valve (the valve churns up the cells and they break down)

Question 297

What is the management Prosthetic Valve Haemolysis?

Answer 297

Monitoring

Oral iron

Blood transfusion if severe

Revision surgery may be required in severe cases

Question 298

What is thalassaemia and what occurs?

Answer 298

Thalassaemia is related to a genetic defect in the protein chains that make up haemoglobin.

Normal haemoglobin consists of 2 alpha and 2 beta-globin chains.

Defects in alpha-globin chains leads to alpha thalassaemia. Defects in the beta-globin chains leads to beta thalassaemia. Both conditions are autosomal recessive. The overall effect is varying degrees of anaemia depends on the type and mutation.

In thalassaemia, the red blood cells are more fragile and break down more easily. The spleen acts as a sieve to filter the blood and remove older blood cells.

The bone marrow expands to produce extra red blood cells to compensate for the chronic anaemia.

Question 299

Thalassemia - signs and symptoms

Answer 299

Microcytic anaemia (low mean corpuscular volume)
Fatigue
Pallor
Jaundice
Gallstones
Splenomegaly
Poor growth and development
Pronounced forehead and malar eminences

Question 300

Physical features seen in thalassemia?

Answer 300

Susceptibility to fractures and prominent features such as a pronounced forehead and malar eminences (cheekbones) due to bone marrow expansion (to compensate for the chronic anaemia)

Splenomegaly - in thalassaemia the spleen collects all the destroyed red blood cells and swells, resulting in

Pallor

Jaundice

Question 301

Thalassaemia - investigations and results?

Answer 301

Full blood count shows a microcytic anaemia.

Haemoglobin electrophoresis is used to diagnose globin abnormalities.

DNA testing can be used to look for the genetic abnormality

Pregnant women in the UK are offered a screening test for thalasseamia at booking.

Question 302

Iron abnormalities in thalassaemia?

Answer 302

Iron overload occurs in thalassaemia as a result of faulty creation of red blood cells, recurrent transfusions and increased absorption of iron in response to the anaemia.

Patients with thalassaemia have serum ferritin levels monitored to check for iron overload. Management involves limiting transfusions and iron chelation.

Question 303

Iron overload in thalassaemia causes effects similar to haemochromatosis - such as?

Answer 303

Fatigue

Liver cirrhosis

Infertility and impotence

Heart failure

Arthritis

Diabetes

Osteoporosis and joint pain

Question 304

What is the defect in alpha-thalassemia?

Answer 304

Alpha-thalassaemia is caused by defects in alpha-globin chains. The gene coding for this protein is on chromosome 16.

Question 305

Management of alpha-thalassemia?

Answer 305

Monitoring the full blood count
Monitoring for complications
Blood transfusions
Splenectomy may be performed
Bone marrow transplant can be curative

Question 306

What is the defect in Beta-thalassaemia?

Answer 306

Beta-thalassaemia is caused by defects in beta-globin chains. The gene coding for this protein is on chromosome 11.

Question 307

What are the three types of beta-thalassaemia and how do they differ?

Answer 307

1. Thalassaemia minor - carriers of an abnormally functioning beta globin gene, they have one abnormal and one normal gene, mild microcytic anaemia
2. Thalassaemia intermedia - two abnormal copies of the beta-globin gene (x2 defective genes or x1 defective gene + x1 deletion gene), causes a more significant microcytic anaemia
3. Thalassaemia major - patients are homozygous for the deletion genes & have no functioning beta-globin genes at all.
   This is the most severe form and usually presents with severe anaemia and failure to thrive in early childhood.

Question 308

Beta-thalassemia management?

Answer 308

1. Thalassaemia minor - usually patients only require monitoring and no active treatment
2. Thalassaemia intermedia - patients require monitoring and occasional blood transfusions.
   If they need more transfusions they may require iron chelation to prevent iron overload.
3. Thalassaemia major regular transfusions, iron chelation and splenectomy. Bone marrow transplant can potentially be curative.

Question 309

What does thalassaemia major cause?

Answer 309

1. Severe microcytic anaemia
2. Splenomegaly
3. Bone deformities

Likely to present with failure to thrive in childhood

Question 310

What is sickle cell anaemia and what is the underlying abnormaliy?

Answer 310

Sickle cell anaemia is a genetic condition that causes sickle (crescent) shaped red blood cells. This makes the red blood cells fragile and more easily destroyed leading to an haemolytic anaemia. Patients with sickle cell anaemia are prone to various types of sickle cell crises.

Patients with sickle-cell disease have an abnormal variant called haemoglobin S (HbS). HbS causes red blood cells to be an abnormal “sickle” shape.

Sickle cell anaemia is an autosomal recessive condition where there is an abnormal gene for beta-globin on chromosome 11.

One copy of the gene results in sickle-cell trait.

Patients with sickle-cell trait are usually asymptomatic.

Two abnormal copies are required for sickle-cell disease.

Question 311

Why is sickle cell disease more common in patients from areas traditionally affected by malaria such as Africa, India, the Middle East and the Caribbean?

Answer 311

Having one copy of the gene (sickle-cell trait) reduces the severity of malaria.

As a result, patients with sickle-cell trait are more likely to survive malaria and pass on their genes.

Therefore, there is a selective advantage to having the sickle cell gene in areas of malaria.

This leads to a high proportion of the population in these areas having the gene.

Question 312

Diagnosis of sickle cell anaemia/sickle cell trait?

Answer 312

Pregnant women at risk of being carriers of the sickle cell gene are offered testing during pregnancy.

Sickle cell disease is also tested for on the on the newborn screening heel prick test at 5 days of age.

Question 313

Complications of sickle cell anaemia?

Answer 313

Anaemia

Increased risk of infection

Stroke

Avascular necrosis in large joints such as the hip

Pulmonary hypertension

Painful and persistent penile erection (priapism)

Chronic kidney disease

Sickle cell crises

Acute chest syndrome

Question 314

General management of sickle cell anaemia?

Answer 314

Avoid dehydration and other triggers of crises

Ensure vaccines are up to date

Antibiotic prophylaxis to protect against infection with penicillin V (phenoxymethypenicillin)

Hydroxycarbamide can be used to stimulate production of fetal haemoglobin (HbF).

Fetal haemoglobin does not lead to sickling of red blood cells.

This has a protective effect against sickle cell crises and acute chest syndrome.

Blood transfusion for severe anaemia

Bone marrow transplant can be curative

Question 315

What are sickle cell crises and why might they occur?

Answer 315

Sickle cell crisis is an umbrella term for a spectrum of acute crises related to the condition.

These range from mild to life threatening.

They can occur spontaneously or be triggered by stresses such as infection, dehydration, cold or significant life events.

Question 316

Management of sickle cell crisis?

Answer 316

There is no specific treatment for sickle cell crises and they are managed supportively:

Have a low threshold for admission to hospital
Treat any infection
Keep warm
Keep well hydrated (IV fluids may be required)
Simple analgesia such as paracetamol and ibuprofen
Penile aspiration in priapism

NSAIDs such as ibuprofen should be avoided where there is renal impairment.

Question 317

Specific types of sickle cell crisis?

Answer 317

Vaso-occlusive Crisis (AKA painful crisis)
Splenic sequestration crisis
Aplastic crisis
Acute chest syndrome

Question 318

Why does vaso-occlusive crisis occur?

Answer 318

Vaso-occlusive crisis is caused by the sickle shaped blood cells clogging capillaries causing distal ischaemia. It is associated with dehydration and raised haematocrit.

Question 319

Vaso-occlusive crisis - symptoms and management

Answer 319

Symptoms are typically pain, fever and those of the triggering infection.

It can cause priapism in men by trapping blood in the penis causing a painful and persistent erection.
This is a urological emergency and is treated with aspiration of blood from the penis.

Supportive management:

Have a low threshold for admission to hospital
Treat any infection
Keep warm
Keep well hydrated (IV fluids may be required)

Question 320

Why does splenic sequestration crisis occur + what are the potential consequences?

Answer 320

Splenic sequestration crisis is caused by red blood cells blocking blood flow within the spleen.

This causes an acutely enlarged and painful spleen.

The pooling of blood in the spleen can lead to a severe anaemia and circulatory collapse (hypovolaemic shock).

Recurrent crises can lead to splenic infarction and therefore susceptibility to infections.

Question 321

Splenic sequestration crisis - management?

Answer 321

Splenic sequestration crisis is considered an emergency.

Management is supportive with blood transfusions and fluid resuscitation to treat anaemia and shock.

Splenectomy prevents sequestration crisis and is often used in cases of recurrent crises.

Question 322

Management of aplastic crisis in sickle cell anaemia?

Answer 322

It leads to significant anaemia.

Management is supportive with blood transfusions if necessary. It usually resolves spontaneously within a week.

Question 323

What is aplastic crisis in sickle cell anaemia and what is it commonly triggered by?

Answer 323

Aplastic crisis describes a situation where there is a temporary loss of the creation of new blood cells. This is most commonly triggered by infection with parvovirus B19.

Question 324

Management of sickle cell crisis: ACS

Answer 324

Is a medical emergency with a high mortality and requires prompt supportive management and treatment of the underlying cause:

Antibiotics or antivirals for infections
Blood transfusions for anaemia
Incentive spirometry using a machine that encourages effective and deep breathing
Artificial ventilation with NIV or intubation may be required

Question 325

Sickle cell crisis: why might ACS occur?

Answer 325

Infection (e.g. pneumonia or bronchiolitis)
Non-infective causes (e.g. pulmonary vaso-occlusion or fat emboli).

Question 326

Sickle cell crisis: what does a diagnosis of ACS require?

Answer 326

Fever or respiratory symptoms with

New infiltrates seen on a chest xray

Question 327

What is thrombocytopenia and what are the two general causes?

Answer 327

Thrombocytopenia describes a low platelet count.

The normal platelet count is between 150 to 450 x 109/L.

Problems with production or destruction.

Question 328

Thrombocytopenia - causes related to problems with production?

Answer 328

Sepsis

B12 or folic acid deficiency

Liver failure causing reduced thrombopoietin production in the liver

Leukaemia

Myelodysplastic syndrome

Question 329

Thrombocytopenia - causes related to problems with destruction?

Answer 329

Medications (sodium valproate, methotrexate, isotretinoin, antihistamines, proton pump inhibitors)

Alcohol

Immune thrombocytopenic purpura

Thrombotic thrombocytopenic purpura

Heparin-induced thrombocytopenia

Haemolytic-uraemic syndrome

Question 330

What medications can causes thromocytopenia?

Answer 330

Sodium valproate
Methotrexate
Isotretinoin
Antihistamines
Proton pump inhibitors

Heparin-induced thrombocytopenia

Question 331

How might thrombocytopenia present?

Answer 331

Mild thrombocytopenia - may be asymptomatic and found incidentally on a full blood count.

Platelet counts below 50 x 109/L will result in easy or spontaneous bruising and prolonged bleeding times:
- Nosebleeds
- Bleeding gums
- Heavy periods
- Easy bruising or blood in the urine or stools.

Platelet counts below 10 x 109/L are high risk for spontaneous bleeding:
- Spontaneous intracranial haemorrhage
- GI bleeds are particularly concerning

Question 332

Platelet counts below what will result in easy or spontaneous bruising and prolonged bleeding times - i.e.
- Nosebleeds
- Bleeding gums
- Heavy periods
- Easy bruising or blood in the urine or stools.

Answer 332

50 x 109/L

Question 333

Platelet counts below what are high risk for spontaneous bleeding, making haemorrhage or GI bleeds particularly concerning?

Answer 333

10 x 109/L

Question 334

Key differentials for prolonged bleeding?

Answer 334

Thrombocytopenia (low platelets)

Haemophilia A and haemophilia B

Von Willebrand Disease

Disseminated intravascular coagulation (usually secondary to sepsis)

Question 335

What is ITP (immune thrombocytopenic purpura) and what is it also known as?

Answer 335

autoimmune thrombocytopenic purpura
idiopathic thrombocytopenic purpura
primary thrombocytopenic purpura

ITP is a condition where antibodies are created against platelets.

This causes an immune response against platelets, resulting in the destruction of platelets and a low platelet count.

Question 336

Management + patient advice for IPT

Answer 336

Management options include:

Prednisolone (steroids)
IV immunoglobulins
Rituximab (a monoclonal antibody against B cells)
Splenectomy

The platelet count needs to be monitored and the patient needs education about concerning signs of bleeding such as persistent headaches and melaena and when to seek help.

Additional measures such as carefully controlling blood pressure and suppressing menstrual periods are also important.

Question 337

What is Thrombotic Thrombocytopenic Purpura?

Answer 337

This is a condition where tiny blood clots develop throughout the small vessels of the body using up platelets and causing thrombocytopenia, bleeding under the skin and other systemic issues. It affect the small vessels so it is described as a microangiopathy.

Question 338

Why happens in Thrombotic Thrombocytopenic Purpura and why does this occur?

Answer 338

Tiny blood clots develop throughout the small vessels clots develop due to a problem with a specific protein called ADAMTS13

This protein normally inactivates von Willebrand factor and reduces platelet adhesion to vessel walls and clot formation.

A shortage in this protein leads to von Willebrand factor overactivity and the formation of blood clots in small vessels

This causes platelets to be used up leading to thrombocytopenia.

The blood clots in the small vessels break up red blood cells, leading to haemolytic anaemia.

Deficiency in the ADAMTS13 protein can be due to an inherited genetic mutation or due to autoimmune disease where antibodies are created against the protein.

Question 339

Management of thrombotic thrombocytopenic purpura?

Answer 339

Treatment is guided by a haematologist and may involve plasma exchange, steroids and rituximab (a monoclonal antibody against B cells).

Question 340

Basic pathophysiology of heparin induced thrombocytopenia?

Answer 340

Heparin induced thrombocytopenia (HIT) involves the development of antibodies against platelets in response to exposure to heparin.

These heparin induced antibodies specifically target a protein on the platelets called platelet factor 4 (PF4).

These are anti-PF4/heparin antibodies.

The HIT antibodies bind to platelets and activate clotting mechanisms.

This causes a hypercoagulable state and leads to thrombosis.

They also break down platelets and cause thrombocytopenia.

Therefore there is an unintuitive situation where a patient on heparin with low platelets forms unexpected blood clots.

Question 341

How is heparin induced thrombopenia diagnosed?

Answer 341

Diagnosis is by testing for the HIT antibodies in the patients blood.

Question 342

How is heparin induced thrombopenia managed?

Answer 342

Management is by stopping heparin and using an alternative anticoagulant guided by a specialist.

Question 343

What is the role of ADAMTS13 and why might it be deficient?

Answer 343

This protein normally inactivates von Willebrand factor and reduces platelet adhesion to vessel walls and clot formation (shortage in this protein leads to von Willebrand factor overactivity and the formation of blood clots in small vessels)

Deficiency in the ADAMTS13 protein can be due to an inherited genetic mutation or due to autoimmune disease where antibodies are created against the protein.

Question 344

What is the most common inherited cause of abnormal bleeding (haemophilia)?

Answer 344

Von Willebrand disease

Question 345

Underlying causes of Von Willebrand disease?

Answer 345

Most causes are autosomal dominant.

The causes involve:

• a deficiency
• absence
• malfunctioning

of a glycoprotein called von Willebrand factor (VWF).

There are three types based on the underlying cause and ranging from type 1 to type 3. Type 3 is the most severe.

Question 346

Von Willebrand Disease - presentation?

Answer 346

Patients present with a history of unusually easy, prolonged or heavy bleeding:

Bleeding gums with brushing

Nose bleeds (epistaxis)

Heavy menstrual bleeding (menorrhagia)

Heavy bleeding during surgical operations

Family history of heavy bleeding or von Willebrand disease is very relevant.

Question 347

Diagnosis of Von Willebrand Disease

Answer 347

History of abnormal bleeding, family history

Bleeding assessment tools and laboratory investigations

Due to all the underlying causes there is no easy von Willebrand disease test. This can make diagnosis challenging

Question 348

Management of Von Willebrand Disease

Answer 348

Von Willebrand disease does not require day to day treatment.

Management is required either in response to major bleeding or trauma (to stop bleeding) or in preparation for operations (to prevent bleeding):
- Desmopressin can be used to stimulates the release of VWF
- VWF can be infused
- Factor VIII is often infused along with plasma-derived VWF

Women with VWD that suffer from heavy periods can be managed by a combination of:

Tranexamic acid
Mefanamic acid
Norethisterone
Combined oral contraceptive pill
Mirena coil

Hysterectomy may be required in severe cases.

Question 349

What is the deficiency in Haemophilia A?

Answer 349

Haemophilia A is caused by a deficiency in factor VIII.

Question 350

What is the deficiency in Haemophilia B?

Answer 350

Haemophilia B (also known as Christmas disease) is caused by a deficiency in factor IX.

Question 351

Inheritance pattern of Haemophilias A and B?

Answer 351

Both haemophilia A and B are X linked recessive.

This means in order to have the condition all of the X chromosomes need to have the abnormal gene.

Men only require one abnormal copy as they only have one X chromosome.

Women require abnormal copies on both their X chromosomes, and if only one copy is affected they are a carrier of the condition.

Therefore haemophilia A and B almost exclusively affect males.

For a female to be affected they would require an affected father and a mother that is either a carrier or also affected.

Question 352

How and when might haemophilia A and B present?

Answer 352

Both haemophilia A and B are severe bleeding disorders. Patients can bleed excessively in response to minor trauma and are also at risk of spontaneous haemorrhage without any trauma.

Most cases present in neonates or early childhood. It can present with intracranial haemorrhage, haematomas and cord bleeding in neonates.

Spontaneous bleeding into joints (haemoathrosis) and muscles are a classic feature of severe haemophilia. If untreated this can lead to joint damage and deformity.

Abnormal bleeding can occur in other areas:

Gums
Gastrointestinal tract
Urinary tract causing haematuria
Retroperitoneal space
Intracranial
Following procedures

Question 353

Management of haemophillia

Answer 353

Management should be coordinated by a specialist.

The affected clotting factors (VIII or IX) can be replaced by intravenous infusions. This can be either prophylactically or in response to bleeding. A complication of this treatment is formation of antibodies against the clotting factor resulting in the treatment becoming ineffective.

Acute episodes of bleeding or prevention of excessive bleeding during surgical procedures involve:

Infusions of the affected factor (VIII or IX)

Desmopressin to stimulate the release of von Willebrand Factor

Antifibrinolytics such as tranexamic acid

Question 354

What is diagnosis of haemophilia based on?

Answer 354

Bleeding scores
Coagulation factor assays
Genetic testing

Question 355

Acute episodes of bleeding or prevention of excessive bleeding during surgical procedures in patients with haemophilia involve what?

Answer 355

• Infusions of the affected factor (VIII or IX)
• Desmopressin to stimulate the release of von Willebrand Factor
• Antifibrinolytics such as tranexamic acid

Question 356

Deficiency in factor IX

Answer 356

haemophilia b

Question 357

Deficiency in factor VIII

Answer 357

haemophilia A

Question 358

What is VTE and what might it progress to?

Answer 358

Venous thromboembolism (VTE) is a common and potentially fatal condition. It involves blood clots (thrombi) developing in the circulation. This usually occurs secondary to stagnation of blood and hyper-coagulable states. When a thrombus develops in the venous circulation, it is called a deep vein thrombosis (DVT).

Once a thrombus has developed, it can travel (embolise) from the deep veins, through the right side of the heart and into the lungs, where it becomes lodged in the pulmonary arteries. This blocks blood flow to areas of the lungs and is called a pulmonary embolism (PE).

If the patient has a hole in their heart (for example, an atrial septal defect), the blood clot can pass through to the left side of the heart and into the systemic circulation. If it travels to the brain, it can cause a large stroke.

Question 359

Risk factors for VTE/PE

Answer 359

Immobility
Recent surgery
Long haul travel
Pregnancy
Hormone therapy with oestrogen (combined oral contraceptive pill and hormone replacement therapy)
Malignancy
Polycythaemia
Systemic lupus erythematosus
Thrombophilia

Question 360

Thrombophilias are conditions that predispose patients to develop blood clots. There are a large number of these, such as?

Answer 360

Antiphospholipid syndrome
Factor V Leiden
Antithrombin deficiency
Protein C or S deficiency
Hyperhomocysteinaemia
Prothombin gene variant
Activated protein C resistance

Question 361

What thrombophillia might you suspect in a patient with recurrent VTE + miscarriage

Answer 361

Antiphospholipid syndrome, diagnosed by testing for antiphospholipid antibodies

Question 362

VTE prophylaxis

Answer 362

Every patient admitted to hospital should be assessed for their risk of venous thromboembolism (VTE). If they are at increased risk of VTE, they should receive prophylaxis unless contraindicated.

Prophylaxis is usually with low molecular weight heparin, such as enoxaparin. Contraindications include active bleeding or existing anticoagulation with warfarin or a DOAC.

Anti-embolic compression stockings are also used, unless contraindicated. The main contraindication for compression stockings is significant peripheral arterial disease.

Question 363

DVT presentation

Answer 363

DVTs are almost always unilateral. Bilateral DVT is rare and bilateral symptoms are more likely due to an alternative diagnosis such as chronic venous insufficiency or heart failure. DVTs can present with:

Calf or leg swelling
Dilated superficial veins
Tenderness to the calf (particularly over the site of the deep veins)
Oedema
Colour changes to the leg

Question 364

Diagnosing DVT/PE

Answer 364

Wells Score

The Wells score predicts the risk of a patient presenting with symptoms having a DVT or PE. It includes risk factors such as recent surgery and clinical findings such as unilateral calf swelling 3cm greater than the other leg.

Diagnosis

D-dimer is a sensitive (95%), but not specific, blood test for VTE. This makes it helpful in excluding VTE where there is a low suspicion. It is almost always raised if there is a DVT; however other conditions can also cause a raised d-dimer:

Pneumonia
Malignancy
Heart failure
Surgery
Pregnancy

Doppler ultrasound of the leg is required to diagnose deep vein thrombosis. NICE recommends repeating negative ultrasound scans after 6-8 days if a positive D-dimer and the Wells score suggest a DVT is likely.

Pulmonary embolism can be diagnosed with a CT pulmonary angiogram (CTPA) or ventilation-perfusion (VQ) scan. CTPA is usually preferred, unless the patient has significant kidney impairment or a contrast allergy.

Question 365

Measuring legs in ?DVT

Answer 365

To examine for leg swelling, measure the circumference of the calf 10cm below the tibial tuberosity.

More than 3cm difference between calves is significant.

Question 366

DVT: initial management

Answer 366

The initial management for a suspected or confirmed DVT or PE is with anticoagulation. In most patients, NICE (2020) recommend treatment dose apixaban or rivaroxaban. It should be started immediately in patients where DVT or PE is suspected, and there is a delay in getting the scan.

The NICE guidelines (2020) recommend considering catheter-directed thrombolysis in patients with a symptomatic iliofemoral DVT and symptoms lasting less than 14 days. This involves inserting a catheter under x-ray guidance through the venous system to apply thrombolysis directly into the clot.

Question 367

LONG TERM ANTI COAGULATION - VTE

Answer 367

The options for long term anticoagulation in VTE are a DOAC, warfarin, or LMWH.

DOACs are oral anticoagulants that do not require monitoring. They were called “novel oral anticoagulants” (NOACs), but this has been changed to “direct-acting oral anticoagulants” (DOACs). Options are apixaban, rivaroxaban, edoxaban and dabigatran. They are suitable for most patients, including patients with cancer.

Warfarin is a vitamin K antagonist. The target INR for warfarin is between 2 and 3 when treating DVTs and PEs. It is the first-line in patients with antiphospholipid syndrome (who also require initial concurrent treatment with LMWH).

Low molecular weight heparin (LMWH) is the first-line anticoagulant in pregnancy.

Question 368

Duration of long term anticoagulation following VTE?

Answer 368

3 months if there is a reversible cause (then review)

Beyond 3 months if the cause is unclear, there is recurrent VTE, or there is an irreversible underlying cause such as thrombophilia (often 6 months in practice)

3-6 months in active cancer (then review)

Question 369

What is an inferior vena cava filter, and when might it be used?

Answer 369

Inferior vena cava filters are devices inserted into the inferior vena cava, designed to filter the blood and catch any blood clots travelling from the venous system, towards the heart and lungs.

They act as a sieve, allowing blood to flow through whilst stopping larger blood clots.

They are used in unusual cases of patients with recurrent PEs or those that are unsuitable for anticoagulation.

Question 370

Investigating unprovoked DVT?

Answer 370

When patients have their first VTE without a clear cause, the NICE guidelines from 2020 recommend reviewing the medical history, baseline blood results and physical examination for evidence of cancer.

In patients with an unprovoked DVT or PE that are not going to continue anticoagulation (they have finished 3-6 months of treatment and are due to stop), NICE recommends considering testing for:

• Antiphospholipid syndrome (check antiphospholipid antibodies)
• Hereditary thrombophilias (only if they have a first-degree relative also affected by a DVT or PE)

Question 371

What is Budd-Chiari syndrome?

Answer 371

Budd-Chiari syndrome is where a blood clot (thrombosis) develops in the hepatic vein, blocking the outflow of blood. It is associated with hyper-coagulable states. It causes acute hepatitis.

Question 372

Triad of symptoms in Budd-Chiari syndrome?

Answer 372

Abdominal pain
Hepatomegaly
Ascites

Question 373

Management of Budd-Chiari syndrome?

Answer 373

Management involves anticoagulation (heparin or warfarin), investigating for the underlying cause of hyper-coagulation and treating hepatitis.

Question 374

Cytomegalovirus (CMV) is transmitted in leucocytes. As most blood products (except granulocyte transfusions) are now leucocyte depleted CMV negative products are rarely required - in which cases are they indicated?

Answer 374

Granulocyte transfusions
Intra-uterine transfusions
Neonates up to 28 days posts expected date of delivery
Pregnancy: elective transfusion during pregnancy (not labour or delivery)

Question 375

Irradiated blood products are depleted of T-lymphocytes and used to avoid transfusion-associated graft versus host disease (TA-GVHD) caused by engraftment of viable donor T lymphocytes. When are they indicated?

Answer 375

Granulocyte transfusion
Intra-uterine transfusions
Neonates up to 28 days post expected date of delivery
Bone marrow/stem cell transplants
Immunocompromised
Patients with/previous Hodgkin lymphoma

Question 376

When is FFP used, and how does it differ from red cells?

Answer 376

most suited for ‘clinically significant’ but without ‘major haemorrhage’ in patients with a prothrombin time (PT) ratio or activated partial thromboplastin time (APTT) ratio > 1.5

typically 150-220 mL

can be used prophylactically in patients undergoing invasive surgery where there is a risk of significant bleeding

In contrast to red cells, the universal donor of FFP is AB blood because it lacks any anti-A or anti-B antibodies

Question 377

What does cryoprecipitate contain?

Answer 377

contains concentrated Factor VIII:C, von Willebrand factor, fibrinogen, Factor XIII and fibronectin, produced by further processing of Fresh Frozen Plasma (FFP).

much smaller volume than FFP, typically 15-20mL

Question 378

When is cryoprecipitate used?

Answer 378

Clinically it is most commonly used to replace fibrinogen

most suited for patients for ‘clinically significant’ but without ‘major haemorrhage’ who have a fibrinogen concentration < 1.5 g/L

example use cases include disseminated intravascular coagulation, liver failure and hypofibrinogenaemia secondary to massive transfusion.

It may also be used in an emergency situation for haemophiliacs (when specific factors not available) and in von Willebrand disease

can be used prophylactically in patients undergoing invasive surgery where there is a risk of significant bleeding where the fibrinogen concentration < 1.0 g/L

Question 379

When is prothrombin complex concentrate used?

Answer 379

used for the emergency reversal of anticoagulation in patients with either severe bleeding or a head injury with suspected intracerebral haemorrhage

can be used prophylactically in patients undergoing emergency surgery depending on the particular circumstance

Question 380

Transfusion thresholds for adults?

Answer 380

Patients without ACS - 70 g/L

Patients with ACS - 80 g/L

Question 381

Transfusion targets for adults?

Answer 381

Patients without ACS - 70-90 g/L

Patients with ACS - 80-100 g/L

ie. up to 20 above the transfusion threshold

Question 382

Red blood cells should be stored at what temperature prior to infusion?

Answer 382

red blood cells should be stored at 4°C

Question 383

In a non-urgent scenario, a unit of RBC is usually transfused over what time period?

Answer 383

90-120 minutes

Question 384

What is Graft Versus host disease and why does it occur?

Answer 384

Graft versus host disease (GVHD) is a multi-system complication of allogeneic bone marrow transplantation.

Less frequently, it may also occur following solid organ transplantation or transfusion in immunocompromised patients.

The disease occurs when T cells in the donor tissue (the graft) mount an immune response toward recipient (host) cells.

It is not to be confused with transplant rejection (in which recipient immune cells activate an immune response toward the donor tissue).

Prognosis is generally poor.

Question 385

What criteria is used to diagnose graft versus host disease?

Answer 385

Three conditions required for diagnosis of GVHD, known as the Billingham criteria 1:

The transplanted tissue contains immunologically functioning cells

The recipient and donor are immunologically different

The recipient is immunocompromised

Question 386

GVHD - risk factors

Answer 386

Poorly matched donor and recipient (particularly HLA)

Type of conditioning used prior to transplantation

Gender disparity between donor and recipient

Graft source (bone marrow or peripheral blood source associated with higher risk than umbilical cord blood)

Question 387

Within what timeframe does acute GVDH occur?

Answer 387

100 days

Question 388

Within what timeframe does chronic GVDH occur?

Answer 388

Classically 100 days following transplantation

May occur following acute disease, or can arise de novo

Question 389

Clinical features of chronic GVHD

Answer 389

Has a more varied clinical picture: often lung and eye involvement in addition to skin and GI, although any organ system may be involved

Skin: Many manifestations including poikiloderma, scleroderma, vitiligo, lichen planus

Eye: Often keratoconjunctivitis sicca, also corneal ulcers, scleritis

GI: Dysphagia, odynophagia, oral ulceration, ileus.

Oral lichenous changes are a characteristic early sign (2)

Lung: my present as obstructive or restrictive pattern lung disease

Question 390

Clinical features of acute GVDH

Answer 390

Usually affects the skin (>80%), liver (50%), and gastrointestinal tract (50%)
Multi-organ involvement carries a worse prognosis**

Painful maculopapular rash (often neck, palms and soles), which may progress to erythroderma or a toxic epidermal necrolysis-like syndrome

Jaundice

Watery or bloody diarrhoea

Persistent nausea and vomiting

Can also present as a culture-negative fever

Question 391

Investigating GVHD?

Answer 391

Investigations (largely dependent on which organs are involved):

LFTs may demonstrate cholestatic jaundice. Hepatitis screen/ultrasound may be useful to exclude other causes

Abdominal imaging may reveal air-fluid levels and small bowel thickening (‘ribbon sign’)

Lung function testing

Biopsy of affected tissue may aid in diagnosis if there is uncertainty

Question 392

Management of GVHD

Answer 392

Management consists of immunosuppression and supportive measures.

Intravenous steroids are the mainstay of immunosuppressive treatment in severe cases of acute GVHD.

Extended courses of steroid therapy are often needed in chronic GVHD and dose tapering is vital.

Second-line therapies include anti-TNF, mTOR inhibitors and extracorporeal photopheresis.

Excessive immunosuppression may predispose patients to infection, and also limit the beneficial graft-versus-tumour effect of the transplant.

Topical steroid therapy may be sufficient in mild disease with limited cutaneous involvement.

Question 393

Features of aplastic anaemia?

Answer 393

Characterised by pancytopenia and a hypoplastic bone marrow

Peak incidence of acquired = 30 years old

Features:

normochromic, normocytic anaemia

leukopenia, with lymphocytes relatively spared
thrombocytopenia

may be the presenting feature acute lymphoblastic or myeloid leukaemia

a minority of patients later develop paroxysmal nocturnal haemoglobinuria or myelodysplasia

Question 394

What electrolyte abnormalities may be present in tumour lysis syndrome?

Answer 394

hyperkalaemia, hyperphosphataemia, hyperuricaemia and hypocalcaemia.

Question 395

What is the mainstay of treatment for those with beta-thalassaemia major?

Answer 395

Fortnightly blood transfusions

Question 396

First line recommendation from NICE for neutropenic sepsis

Answer 396

Piperacillin with tazobactam is recommended as the first-line antibiotic by NICE,

Question 397

What is the roles of hydroxycarbamide in sickle cell anaemia?

Answer 397

Hydroxycarbamide (previously known as hydroxyurea) is a ribonucleotide reductase inhibitor that increases the levels of foetal haemoglobin (Hb F) in the blood, which has been shown to reduce the frequency of sickle cell crises, reduce hospitalisation and decrease mortality.

Question 398

What clotting factors do heparins affect and how?

Answer 398

Prevents activation factors 2,9,10,11

Question 399

What clotting factors does warfarin affect and how?

Answer 399

Affects synthesis of factors 2,7,9,10

Question 400

What clotting factors are involved in DIC?

Answer 400

Factors 1,2,5,8,11

Question 401

What clotting factors are affected by liver disease?

Answer 401

Factors 1,2,5,7,9,10,11

Question 402

Interpretation blood clotting test results:

APTT INCREASED

PT INCREAED

BLEEDING TIME NORMAL

Answer 402

VITAMIN K DEF

Question 403

Interpretation blood clotting test results:

APTT INCREASED

PT NORMAL

BLEEDING TIME NORMAL

Answer 403

Haemophilia

Question 404

Interpretation blood clotting test results:

APTT INCREASED

PT NORMAL

BLEEDING TIME INCREASED

Answer 404

von Willebrand’s disease

Question 405

What is acute intermittent porphyria + what is the abnormality + in which patients does it present?

Answer 405

Acute intermittent porphyria (AIP) is a rare autosomal dominant condition caused by a defect in porphobilinogen deaminase, an enzyme involved in the biosynthesis of haem.

The results in the toxic accumulation of delta aminolaevulinic acid and porphobilinogen.

It characteristically presents with abdominal and neuropsychiatric symptoms in 20-40-year-olds.

AIP is more common in females (5:1)

Question 406

Presentation of acute intermittent porphyria?

Answer 406

abdominal: abdominal pain, vomiting

neurological: motor neuropathy

psychiatric: e.g. depression

hypertension and tachycardia common

Question 407

Acute intermittent porphyria:: diagnosis and management

Answer 407

Diagnosis

classically urine turns deep red on standing

raised urinary porphobilinogen (elevated between

attacks and to a greater extent during acute attacks)

assay of red cells for porphobilinogen deaminase

raised serum levels of delta aminolaevulinic acid and porphobilinogen

Management

avoiding triggers

acute attacks

IV haematin/haem arginate

IV glucose should be used if haematin/haem arginate is not immediately available

Question 408

Features of AML?

Answer 408

Features are largely related to bone marrow failure:

anaemia: pallor, lethargy, weakness

neutropenia: whilst white cell counts may be very
high, functioning neutrophil levels may be low leading to frequent infections etc

thrombocytopenia: bleeding

splenomegaly

bone pain

Question 409

AML - poor prognostic factors

Answer 409

> 60 years
20% blasts after first course of chemo
cytogenetics: deletions of chromosome 5 or 7

Question 410

Acute promyelocytic leukaemia M3

Answer 410

associated with t(15;17)

fusion of PML and RAR-alpha genes

presents younger than other types of AML (average = 25 years old)
Auer rods (seen with myeloperoxidase stain)
DIC or thrombocytopenia often at presentation
good prognosis

The importance of identifying APML lies in both the presentation (classically disseminated intravascular coagulation) and management

Question 411

AML CLASSIFICATION

Answer 411

Classification - French-American-British (FAB)

MO - undifferentiated
M1 - without maturation
M2 - with granulocytic maturation
M3 - acute promyelocytic
M4 - granulocytic and monocytic maturation
M5 - monocytic
M6 - erythroleukaemia
M7 - megakaryoblastic

Question 412

Antiphospholipid syndrome is an acquired disorder characterised by a predisposition to both venous and arterial thromboses, recurrent fetal loss and thrombocytopenia. It may occur as a primary disorder or secondary to other conditions, most commonly systemic lupus erythematosus (SLE).

What complications may occur during pregnancy?

Answer 412

recurrent miscarriage
IUGR
pre-eclampsia
placental abruption
pre-term delivery
venous thromboembolism

Question 413

Management of antiphospholipid syndrome?

Answer 413

low-dose aspirin should be commenced once the pregnancy is confirmed on urine testing

low molecular weight heparin once a fetal heart is seen on ultrasound. This is usually discontinued at 34 weeks gestation

these interventions increase the live birth rate seven-fold

Question 414

Causes of aplastic anaemia?

Answer 414

idiopathic
congenital: Fanconi anaemia, dyskeratosis congenita
drugs: cytotoxics, chloramphenicol, sulphonamides, phenytoin, gold
toxins: benzene
infections: parvovirus, hepatitis
radiation

Question 415

What is aplastic anaemia and what are the features?
What might it be a presenting feature of?

Answer 415

Characterised by pancytopenia and a hypoplastic bone marrow

Peak incidence of acquired = 30 years old

Features

• normochromic, normocytic anaemia
• leukopenia, with lymphocytes relatively spared
  thrombocytopenia

may be the presenting feature acute lymphoblastic or myeloid leukaemia

a minority of patients later develop paroxysmal nocturnal haemoglobinuria or myelodysplasia

Question 416

Mgx of warm AIHA?

Answer 416

treatment of any underlying disorder
steroids (+/- rituximab) are generally used first-line

Question 417

Investigations: AIHA

Answer 417

general features of haemolytic anaemia
anaemia
reticulocytosis
low haptoglobin
raised lactate dehydrogenase (LDH) and indirect bilirubin
blood film: spherocytes and reticulocytes
specific features of autoimmune haemolytic anaemia
positive direct antiglobulin test (Coombs’ test).

Question 418

Features of Beta-thallasemia major?

Answer 418

presents in the first year of life with failure to thrive and hepatosplenomegaly

microcytic anaemia

HbA2 & HbF raised

HbA absent

Question 419

HOW is Beta-Thalasemia major managed and how can this cause complications?

Answer 419

repeated transfusion

this leads to iron overload → organ failure
iron chelation therapy is therefore important (e.g. desferrioxamine)

Question 420

Blood abnormalities in thalassemia?

Answer 420

mild hypochromic, microcytic anaemia - microcytosis is characteristically disproportionate to the anaemia

HbA2 raised (> 3.5%)

Question 421

BLOOD FILM: ABNORMALITY AND ASSOCIATED CONDITION

Answer 421

TARGET CELLS

Sickle-cell/thalassaemia
Iron-deficiency anaemia
Hyposplenism
Liver disease

Question 422

BLOOD FILM: ABNORMALITY AND ASSOCIATED CONDITION

Answer 422

POIKILOCYTES ‘Tear-drop’

Myelofibrosis

Question 423

BLOOD FILM: ABNORMALITY AND ASSOCIATED CONDITION

Answer 423

SPHEROCYTES

Hereditary spherocytosis
Autoimmune hemolytic anaemia

Question 424

BLOOD FILM: ABNORMALITY AND ASSOCIATED CONDITION

Answer 424

BASOPHILLIC STRIPPING

Lead poisoning
Thalassaemia
Sideroblastic anaemia
Myelodysplasia

Question 425

BLOOD FILM: ABNORMALITY AND ASSOCIATED CONDITION

Answer 425

Howell Jolly bodies

Hyposplenism

Question 426

BLOOD FILM: ABNORMALITY AND ASSOCIATED CONDITION

Answer 426

HEINZ BODIES

G6PD deficiency Alpha-thalassaemia

Question 427

BLOOD FILM: ABNORMALITY AND ASSOCIATED CONDITION

Answer 427

Schistocytes (‘helmet cells’)

Intravascular haemolysis
Mechanical heart valve
Disseminated intravascular coagulation

Question 428

BLOOD FILM: ABNORMALITY AND ASSOCIATED CONDITION

Answer 428

‘Pencil’ poikilocytes

Iron deficency anaemia

Question 429

BLOOD FILM: ABNORMALITY AND ASSOCIATED CONDITION

Answer 429

Burr cells (echinocytes)

Uraemia
Pyruvate kinase deficiency

Question 430

BLOOD FILM: ABNORMALITY AND ASSOCIATED CONDITION

Answer 430

Acanthocytes

Abetalipoproteinemia

Question 431

When might hypersegmented neutrophils be seen?

Answer 431

megaloblastic anaemia

Question 432

What might be seen on a typical blood film in hyposlenism?

Answer 432

target cells
Howell-Jolly bodies
Pappenheimer bodies
siderotic granules
acanthocytes

Question 433

What might be seen on a typical blood film in iron def anemia?

Answer 433

target cells
‘pencil’ poikilocytes
if combined with B12/folate deficiency a ‘dimorphic’ film occurs with mixed microcytic and macrocytic cells

Question 434

What type of lymphoma is Burkitts Lymphoma?

Answer 434

high-grade B-cell neoplasm

Question 435

What are the two main types of Burkitts Lymphoma?

Answer 435

endemic (African) form: typically involves maxilla or mandible

sporadic form: abdominal (e.g. ileo-caecal) tumours are the most common form. More common in patients with HIV

Question 436

Two specific risk factors for Burkitts lymphoma?

Answer 436

Burkitt’s lymphoma is associated with the c-myc gene translocation, usually t(8:14).

The Epstein-Barr virus (EBV) is strongly implicated in the development of the African form of Burkitt’s lymphoma and to a lesser extent the sporadic form

Question 437

Microscopic findings In Burkitt’s lymphoma?

Answer 437

‘starry sky’ appearance: lymphocyte sheets interspersed with macrophages containing dead apoptotic tumour cells

Question 438

What emergency complication may occur as a result of Burkitt’s lymphoma?

Answer 438

Management is with chemotherapy. This tends to produce a rapid response which may cause ‘tumour lysis syndrome’.

Rasburicase (a recombinant version of urate oxidase, an enzyme which catalyses the conversion of uric acid to allantoin*) is often given before the chemotherapy to reduce the risk of this occurring.

Complications of tumour lysis syndrome include:

hyperkalaemia
hyperphosphataemia
hypocalcaemia
hyperuricaemia
acute renal failure

*allantoin is 5-10 times more soluble than uric acid, so renal excretion is more effective

Question 439

Potential complications of CLL?

Answer 439

anaemia
hypogammaglobulinaemia leading to recurrent infections
warm autoimmune haemolytic anaemia in 10-15% of patients
transformation to high-grade lymphoma (Richter’s transformation)

Question 440

What is Richter’s transformation?

Answer 440

Ritcher’s transformation occurs when leukaemia cells enter the lymph node and change into a high-grade, fast-growing non-Hodgkin’s lymphoma. Patients often become unwell very suddenly.

Ritcher’s transformation is indicated by one of the following symptoms:
lymph node swelling
fever without infection
weight loss
night sweats
nausea
abdominal pain

Question 441

Features of CLL?

Answer 441

often none: may be picked up by an incidental finding of lymphocytosis
constitutional: anorexia, weight loss
bleeding, infections
lymphadenopathy more marked than chronic myeloid leukaemia

Question 442

What proliferates in CLL?

Answer 442

monoclonal proliferation of well-differentiated lymphocytes which are almost always B-cells (99%)

Question 443

CLL investigations + findings

Answer 443

full blood count:

• lymphocytosis
• anaemia: may occur either due to bone marrow replacement on autoimmune hemolytic anaemia (AIHA)
• thrombocytopenia: may occur either due to bone marrow replacement on immune thrombocytopenia (AIHA)

blood film: smudge cells (also known as smear cells)

immunophenotyping is the key investigation:
most cases can be identified using a panel of antibodies specific for CD5, CD19, CD20 and CD23

Question 444

CML: genetic abnormalities

Answer 444

The Philadelphia chromosome is present in more than 95% of patients with chronic myeloid leukaemia (CML).

It is due to a translocation between the long arm of chromosome 9 and 22 - t(9:22)(q34; q11).

This results in part of the ABL proto-oncogene from chromosome 9 being fused with the BCR gene from chromosome 22.

The resulting BCR-ABL gene codes for a fusion protein that has tyrosine kinase activity in excess of normal.

Question 445

CML: presentation

Answer 445

Presentation (60-70 years)

anaemia: lethargy

weight loss and sweating are common

splenomegaly may be marked → abdo discomfort

an increase in granulocytes at different stages of
maturation +/- thrombocytosis

decreased leukocyte alkaline phosphatase

may undergo blast transformation (AML in 80%, ALL in 20%)

Question 446

Management of CML?

Answer 446

imatinib is now considered first-line treatment
inhibitor of the tyrosine kinase associated with the BCR-ABL defect
very high response rate in chronic phase CML

hydroxyurea

interferon-alpha

allogenic bone marrow transplant

Question 447

What is Cryoglobulinaemia and what types exist?

Answer 447

Immunoglobulins which undergo reversible precipitation at 4 deg C, dissolve when warmed to 37 deg C. One-third of cases are idiopathic

Three types

• type I (25%):
  monoclonal - IgG or IgM
  associations: multiple myeloma, Waldenstrom macroglobulinaemia

type II (25%)
mixed monoclonal and polyclonal: usually with rheumatoid factor
associations: hepatitis C, rheumatoid arthritis, Sjogren’s, lymphoma

type III (50%)
polyclonal: usually with rheumatoid factor
associations: rheumatoid arthritis, Sjogren’s

Question 448

Cryoglobulinaemia features

Answer 448

• Raynaud’s only seen in type I
• cutaneous
  vascular purpura
  distal ulceration
  ulceration

arthralgia

renal involvement
- diffuse glomerulonephritis

Question 449

Cryoglobulinemia - investigations and management?

Answer 449

Investigations

low complement (esp. C4)
high ESR

Management

treatment of underlying condition e.g. hepatitis C
immunosuppression
plasmapheresis

Question 450

Dabigatran - mechanism of action, excretion, reversal

Answer 450

Direct thrombin inhibitor

Majority Renal

Idarucizumab

Question 451

Rivaroxaban - mechanism of action, excretion, reversal

Answer 451

Direct factor Xa inhibtor

Majority liver

Andexanet alfa

Question 452

Apixiban - mechanism of action, excretion, reversal

Answer 452

Direct factor Xa inhibitor

Majority feacal

Andexanet alfa*

Question 453

Apixiban - mechanism of action, excretion, reversal

Answer 453

Direct factor Xa inhibitor

Majority feacal

Andexanet alfa*

Question 454

Edoxaban - mechanism of action, excretion, reversal

Answer 454

Direct factor Xa inhibitor

Majority feacal

None

Question 455

Prothrombin time - prolonged
APTT - normal
Bleeding time - normal
Platelet count - normal

Answer 455

Warfarin administration

Question 456

Prothrombin time - Normal
APTT - Normal
Bleeding time - Prolonged
Platelet count - Normal

Answer 456

Aspirin administration?-

Question 457

Prothrombin time Normal (/prolonged)
APTT Prolonged
Bleeding time Normal
Platelet count Normal

Answer 457

Heparin

Question 458

Prothrombin time Prolonged
APTT Prolonged
Bleeding time Prolonged
Platelet count Normal

Answer 458

DIC

Question 459

Typical blood picture in DIC

Answer 459

↓ platelets

↓ fibrinogen

↑ PT & APTT

↑ fibrinogen degradation products

schistocytes due to microangiopathic haemolytic anaemia

Question 460

Causes of DIC

Answer 460

sepsis

trauma

obstetric complications e.g. aminiotic fluid embolism or hemolysis, elevated liver function tests, and low platelets (HELLP syndrome)

malignancy

Question 461

How does the process of coagulation and fibrinolysis differ from homeostatic conditions in DIC?

Answer 461

Under homeostatic conditions:

• Coagulation and fibrinolysis are coupled.
• The activation of the coagulation cascade yields thrombin that converts fibrinogen to fibrin; the stable fibrin clot being the final product of hemostasis.
• The fibrinolytic system breaks down fibrinogen and fibrin. Activation of the fibrinolytic system generates plasmin (in the presence of thrombin), which is responsible for the lysis of fibrin clots.
• The breakdown of fibrinogen and fibrin results in - polypeptides (fibrin degradation products).
• In a state of homeostasis, the presence of plasmin is critical, as it is the central proteolytic enzyme of coagulation and is also necessary for fibrinolysis.

In DIC:

• processes of coagulation and fibrinolysis are dysregulated, and the result is widespread clotting with resultant bleeding.
• Regardless of the triggering event of DIC, once initiated, the pathophysiology of DIC is similar in all conditions.
• One critical mediator of DIC is the release of a transmembrane glycoprotein (tissue factor =TF).
• TF is present on the surface of many cell types (including endothelial cells, macrophages, and monocytes) and is not normally in contact with the general circulation, but is exposed to the circulation after vascular damage.
  For example, TF is released in response to exposure to cytokines (particularly interleukin 1), tumour necrosis factor, and endotoxin.
• This plays a major role in the development of DIC in septic conditions.
• TF is also abundant in tissues of the lungs, brain, and placenta. This helps to explain why DIC readily develops in patients with extensive trauma.
• Upon activation, TF binds with coagulation factors that then triggers the extrinsic pathway (via Factor VII) which subsequently triggers the intrinsic pathway (XII to XI to IX) of coagulation.

Question 462

What is the most common inherited thrombophilia?

Answer 462

Factor V Leiden (activated protein C resistance) is the most common inherited thrombophilia, being present in around 5% of the UK population.

Question 463

What is the abnormality in factor V Leiden (activated protein C resistance)

Answer 463

It is due to a gain of function mutation in the Factor V Leiden protein.

The result of the mis-sense mutation is that activated factor V (a clotting factor) is inactivated 10 times more slowly by activated protein C than normal.

Factor V Leiden heterozygous is more common than homozygous, whereas homzygous carries a bigger risk of VTE

Question 464

What inherited thrombophilia carries the highest risk of VTE?

Answer 464

Antithrombin III deficiency

Question 465

What is Fanconi anemia?

Answer 465

Autosomal recessive inherited anemia.

Features

haematological:
aplastic anaemia
increased risk of acute myeloid leukaemia
neurological

skeletal abnormalities:
short stature
thumb/radius abnormalities
cafe au lait spots

Question 466

G6PD DEFICIENCEY PATHOPHYSIOLOGY

Answer 466

G6PD is the first step in the pentose phosphate pathway, which converts glucose-6-phosphate→ 6-phosphogluconolactone

this reaction also results in nicotinamide adenine dinucleotide phosphate (NADP) → NADPH
i.e. glucose-6-phosphate + NADP → 6-phosphogluconolactone + NADPH

NADPH is important for converting oxidizied glutathine back to it’s reduced form

reduced glutathine protects red blood cells from oxidative damage by oxidants such as superoxide anion (O2-) and hydrogen peroxide
↓ G6PD → ↓ reduced NADPH → ↓ reduced glutathione → increased red cell susceptibility to oxidative stress

Question 467

G6PD DEFICIENCY VS HEREDITARY SPHEROCYTOSIS

Answer 467

Question 468

What are granulocyte-colony stimulating factors?

Answer 468

Recombinant human granulocyte-colony stimulating factors are used to increase neutrophil counts in patients who are neutropenic secondary to chemotherapy or other factors.

Examples include:
filgrastim
perfilgrastim

Question 469

Common translocations associated with haematological malignancies

Answer 469

t(9;22) - Philadelphia chromosome

t(15;17)

t(8;14)

t(11;14)

t(14;18)

Question 470

t(9;22) - Philadelphia chromosome - haematological malignancy associations

Answer 470

present in > 95% of patients with CML
this results in part of the Abelson proto-oncogene being moved to the BCR gene on chromosome 22
the resulting BCR-ABL gene codes for a fusion protein which has tyrosine kinase activity in excess of normal
poor prognostic indicator in ALL

Question 471

t(15,17) - haematological malignancy associations

Answer 471

seen in acute promyelocytic leukaemia (M3)
fusion of PML and RAR-alpha genes

Question 472

t(18,14) - haematological malignancy associations

Answer 472

seen in Burkitt’s lymphoma
MYC oncogene is translocated to an immunoglobulin gene

Question 473

t(11,14) - haematological malignancy associations

Answer 473

Mantle cell lymphoma
deregulation of the cyclin D1 (BCL-1) gene

Question 474

t(14,18) - Philadelphia chromosome - haematological malignancy associations

Answer 474

follicular lymphoma
increased BCL-2 transcription

Question 475

What infections are associated with haematological mallignancies?

Answer 475

Viruses
EBV: Hodgkin’s and Burkitt’s lymphoma, nasopharyngeal carcinoma
HTLV-1: Adult T-cell leukaemia/lymphoma
HIV-1: High-grade B-cell lymphoma

Bacteria
Helicobacter pylori: gastric lymphoma (MALT)

Protozoa
malaria: Burkitt’s lymphoma

Question 476

Indications of intravascular haemolysis (as opposed for extra-vascular)?

Answer 476

In intravascular haemolysis, free haemoglobin is released which then binds to haptoglobin.

As haptoglobin becomes saturated haemoglobin binds to albumin forming methaemalbumin (detected by Schumm’s test).

Free haemoglobin is excreted in the urine as haemoglobinuria, haemosiderinuria

Question 477

Causes of intravascular haemolysis?

Answer 477

mismatched blood transfusion
G6PD deficiency*
red cell fragmentation: heart valves, TTP, DIC, HUS
paroxysmal nocturnal haemoglobinuria
cold autoimmune haemolytic anaemia

Question 478

Causes of extravascular haemolysis?

Answer 478

haemoglobinopathies: sickle cell, thalassaemia
hereditary spherocytosis
haemolytic disease of newborn
warm autoimmune haemolytic anaemia

Question 479

What is hereditary angiodema and what is the abnormality?

Answer 479

Hereditary angioedema (HAE) is an autosomal dominant condition associated with low plasma levels of the C1 inhibitor (C1-INH, C1 esterase inhibitor) protein.

C1-INH is a multifunctional serine protease inhibitor - the probable mechanism behind attacks is uncontrolled release of bradykinin resulting in oedema of tissues.

Question 480

Features of hereditary angiodema?

Answer 480

Investigation
C1-INH level is low during an attack
low C2 and C4 levels are seen, even between attacks. Serum C4 is the most reliable and widely used screening tool

Symptoms
attacks may be proceeded by painful macular rash
painless, non-pruritic swelling of subcutaneous/submucosal tissues
may affect upper airways, skin or abdominal organs (can occasionally present as abdominal pain due to visceral oedema)
urticaria is not usually a feature

Question 481

How is hereditary angioedema managed?

Answer 481

acute
HAE does not respond to adrenaline, antihistamines, or glucocorticoids

IV C1-inhibitor concentrate, fresh frozen plasma (FFP) if this is not available
prophylaxis: anabolic steroid Danazol may help

Question 482

Management of hereditary spherocytosis?

Answer 482

acute haemolytic crisis:

treatment is generally supportive
transfusion if necessary

longer term treatment:

folate replacement
splenectomy

Question 483

What are the subtypes of HL?

Answer 483

Nodular sclerosing
Mixed cellularity
Lymphocyte predominant
Lymphocyte depleted

Question 484

What is the most common type of HL?

Answer 484

Nodular sclerosing

Question 485

Which type of HL has the best prognosis?

Answer 485

Lymphocyte predominant

Question 486

Which type of HL has the worst prognosis?

Answer 486

Lymphocyte depleted

Question 487

Which type of HL is more common in women and associated with lacunar cells?

Answer 487

Nodular sclerosing

Question 488

Indicators of poor prognosis in HL?

Answer 488

Lymphocyte depleted subtype

‘B’ symptoms also imply a poor prognosis
weight loss > 10% in last 6 months
fever > 38ºC
night sweats

age > 45 years
stage IV disease
haemoglobin < 10.5 g/dl
lymphocyte count < 600/µl or < 8%
male
albumin < 40 g/l
white blood count > 15,000/µl

Question 489

Most common lymphadenopathy in HL?

Answer 489

most commonly in the neck (cervical/supraclavicular) > axillary > inguinal

Question 490

What is alcohol-induced lymph node pain characteristic of?

Answer 490

alcohol-induced lymph node pain is characteristic of Hodgkin’s lymphoma but is seen in less than 10% of patients

Question 491

What might you expect to see on investigations for HL?

Answer 491

normocytic anaemia
- may be multifactorial e.g. hypersplenism, bone marrow replacement by HL, Coombs-positive haemolytic anaemia etc

eosinophilia
- caused by the production of cytokines e.g. IL-5

LDH raised

lymph node biopsy:
Reed-Sternberg cells are diagnostic: these are large cells that are either multinucleated or have a bilobed nucleus with prominent eosinophilic inclusion-like nucleoli (thus giving an ‘owl’s eye’ appearance)

Question 492

How is lymphoma staging subdivided?

Answer 492

A = no systemic symptoms other than pruritus
B = weight loss > 10% in last 6 months, fever > 38c, night sweats (poor prognosis)

Question 493

Management of HL?

Answer 493

chemotherapy is the mainstay of treatment. Two combinations may be used:

1. ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine): considered the standard regime
2. BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone): alternative regime with better remission rates but higher toxicity

radiotherapy

combined modality therapy (CMT)

chemotherapy followed by radiotherapy

hematopoietic cell transplantation
- may be used for relapsed or refractory classic Hodgkin lymphoma

Question 494

Potnetial complications of HL treatment?

Answer 494

most patients now achieve long-term survival free of Hodgkin’s lymphoma with modern therapy
complications of treatment are therefore more of an issue for these patients:

• secondary malignancies are a risk, in particular - solid tumours: breast and lung

Question 495

Causes and features of hyposplenism?

Answer 495

Causes
splenectomy
sickle-cell
coeliac disease, dermatitis herpetiformis
Graves’ disease
systemic lupus erythematosus
amyloid

Features
Howell-Jolly bodies
siderocytes

Question 496

What is ITP, and how does it differ in adults compared to in children?

Answer 496

Immune (or idiopathic) thrombocytopenic purpura (ITP) is an immune-mediated reduction in the platelet count. Antibodies are directed against the glycoprotein IIb/IIIa or Ib-V-IX complex.

Children with ITP usually have an acute thrombocytopenia that may follow infection or vaccination. In contrast, adults tend to have a more chronic condition.

Question 497

Features of ITP in adults

Answer 497

Presentation
may be detected incidentally following routine bloods
symptomatic patients may present with
petechiae, purpura
bleeding (e.g. epistaxis)
catastrophic bleeding (e.g. intracranial) is not a common presentation

Investigations

full blood count: isolated thrombocytopenia
blood film

a bone marrow examination is no longer used routinely, shows megakaryocytes in the marrow. This should be carried out prior to the commencement of steroids in order to rule out leukaemia

antiplatelet antibody testing has poor sensitivity and doesn’t affect clinical management so is not commonly done, but will usually show IgG antibodies

Question 498

What is Evan’s syndrome?

Answer 498

ITP in association with autoimmune haemolytic anaemia (AIHA)

Question 499

ITP management?

Answer 499

first-line treatment for ITP is oral prednisolone

pooled normal human immunoglobulin (IVIG) may also be used
- it raises the platelet count quicker than steroids, therefore may be used if active bleeding or an urgent invasive procedure is required

splenectomy is now less commonly used, indicated when if platelets < 30 after 3 months of steroid therapy

immunosuppressive drugs e.g. cyclophosphamide

Question 500

What type of anemia iron deficiency

Answer 500

hypochromic microcytic anaemia

Question 501

Blood film in iron def. anemia?

Answer 501

Blood film anisopoikilocytosis (red blood cells of different sizes and shapes) , target cells, ‘pencil’ poikilocytes

Question 502

Haematinics in iron def. anaemia?

Answer 502

Serum ferritin this will likely be low, as serum ferritin correlates with iron stores. However, it is important to recognise that ferritin can be raised during states of inflammation; so a raised ferritin does not necessarily rule out iron deficiency anaemia if the is co-occurring inflammation. For patients with co-occurring inflammatory disease, other iron studies can be performed.
Total iron-binding capacity (TIBC)/transferrin this will be high. A high TIBC reflects low iron stores. . Note that the transferrin saturation will however be low

Question 503

What Hb warrants a 2ww referral to gastrwoenterologist?

Answer 503

Post-menopausal women with a haemoglobin level ≤10 and men with a haemoglobin level ≤11 should be referred to a gastroenterologist within 2 weeks.

Question 504

Iron deficiency anaemia vs. AOCD haematemics?

Answer 504

Question 505

Haemolysis bloods?

Answer 505

LDH (initial + monitoring)
Bilirubin (intiial +monitoring)
Reticulocytes (initial +monitoring)
Blood film (not req. for monitoring)
Haptoglobin (not req. for monitoring)
Direct antiglobulin test (direct coombes) (not req. for monitoring)

Question 506

What is indicated for platelets <100

Answer 506

Platelet infusion

Question 507

What is indicated for INR >2.5

Answer 507

Vit K + prothrombin complex concentrate

Question 508

What is indicated for fibrinogen <1.0g/l

Answer 508

Cryoprecipitate