Haematology (Meded)

Question 1

An 82 year old woman is admitted with a reduced GCS following a fall in her bathtub at home. She has a past medical history of hypertension, hypercholesterolaemia, atrial fibrillation and hypothyroidism. She takes Amlodipine, Simvastatin, Warfarin and Levothyroxine. CT head on admission demonstrates a subdural haemorrhage and INR is 8.2

What is the most appropriate management?
A. Administer Vit K and omit warfarin
B. Administer prothrombin complex & omit warfarin
C. Omit warfarin
D. Administer platelets & vitamin K
E. Administer prothrombin complex, vitamin K & omit warfarin

Answer 1

E. Administer prothrombin complex, vitamin K & omit warfarin

Question 2

Symptoms of DIC:

Answer 2

e.g. epistaxis, gingival bleeding, haematuria, bleeding from cannula sites. Patients may also present with fever, confusion, or coma.

Question 3

A 32-year-old man presents to his general practitioner with a 2-month history of a lump in his neck. He thinks this lump is slowly getting bigger. He feels well, is otherwise asymptomatic and has had no recent infections or illnesses. On examination, a 3-cm lymph node is felt in the left anterior chain. It is rubbery, with no tethering to the surrounding skin and no overlying skin changes.

Which of the following investigations is most likely to confirm the diagnosis?

A. Positron emission tomography–computed tomography (PET-CT) scan

B. Monospot test

C. Excisional lymph node biopsy

D. Acid-fast bacilli culture

E. Fine needle aspiration (FNA) of the affected lymph node

Answer 3

C. Excisional lymph node biopsy

This patient is presenting with a history typical of lymphoma: persistent, gradually enlarging, painless, rubbery lymphadenopathy. This patient is within the typical age-range for Hodgkin’s lymphoma and Non-Hodgkin’s lymphoma can occur at any age. Although this patient lacks any other symptoms, a significant proportion of patients with lymphoma do not have any B symptoms (especially in early disease). The gold standard diagnostic test is an excisional lymph node biopsy. Excising the whole lymph node allows the lymph node architecture to be examined, which is useful to determine the type and grade of lymphoma.

Not E. Fine needle aspiration (FNA) of the affected lymph node

Although this may confirm a diagnosis of lymphoma, FNA will not allow examination of the lymph node architecture, which is important to determine the subtype and grade of lymphoma. In Hodgkin’s lymphoma specifically, the relative paucity of Reed–Sternberg cells makes confirming the diagnosis more challenging with an FNA when compared with an excisional lymph node biopsy.

Question 4

what drug can exacerbate hodgkin’s lymphoma?

Answer 4

Alcohol
- In some people, the affected lymph nodes can become painful after drinking alcohol

Question 5

what investigations are done in Hodgkin’s lymphoma?

Answer 5

1. Lactate dehydrogenase (LDH) is a blood test that is often raised in Hodgkin’s lymphoma but is not specific and can be raised in other cancers and many non-cancerous diseases.
2. (excisional) Lymph node biopsy is the key diagnostic test.
3. The Reed-Sternberg cell is the key finding from lymph node biopsy in patients with Hodgkin’s lymphoma. 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. The Reed-Sternberg cell is a popular feature in medical exams.
4. CT, MRI and PET scans can be used for diagnosing and staging lymphoma and other tumours.

Question 6

A 36 year old female presents to the general practitioner complaining of a six week history of fatigue, pallor and shortness of breath on exertion. She has no past medical history of note. On examination she has jaundice of the sclera and conjunctival pallor. Blood test results are shown below. A blood film shows spherocytes and direct Coombs test is positive.

Investigation Result Normal Range
Haemoglobin 66 g/l 115-160 g/l
Mean Corpuscular Volume 98 fl 82-100 fl
Bilirubin 28 umol/l 3-17 umol/l
Lactate dehydrogenase 580 iu/l 200-450 iu/l
Which of the following is the next best step in management?

A. Hydroxocobalamin

B. Splenectomy

C. Plasmapheresis

D. Ferrous fumarate

E. Prednisolone

Answer 6

E. Prednisolone

Warm autoimmune haemolytic anaemia is the most common type of autoimmune haemolytic anaemia. It most often occurs idiopathically but can also occur secondary to lymphoproliferative malignancies, inflammatory conditions and certain medications including ciprofloxacin, cephalosporin, methyldopa and non-steroidal anti-inflammatories. Features in this case study confirming a diagnosis of warm autoimmune haemolytic anaemia include the significant normocytic anaemia with raised bilirubin and lactate dehydrogenase with a positive Coombs test which confirms an autoimmune cause of the haemolytic anaemia. The first line treatment for warm autoimmune haemolytic anaemia is steroids. Blood transfusions may also be necessary depending on the patient’s clinical symptoms and the severity of the anaemia. Second-line options include Immunosuppressives and splenectomy

Not B. Splenectomy

Splenectomy may be considered in refractory cases of warm autoimmune haemolytic anaemia to reduce the degree of phagocytosis of erythrocytes by macrophages, but it would not be a first line option

Question 7

Ann arbor staging:

Answer 7

Stage 1 – one LN region (LN region can include spleen)
Stage 2 – two or more LN regions on the same side of the diaphragm
Stage 3 – two or more LN regions on opposite sides of the diaphragm Stage 4 – extranodal sites (liver, BM)

B added if B symptoms present

(A) if the patient is asymptomatic or (B) if the patient presents with B symptoms (fever, night sweats, or weight loss).
X if there is bulky nodal disease (>10 cm or >1/3 of the intra-thoracic diameter).
(S) if there is splenic involvement.
(E) if there is extra-nodal disease.

Question 8

A 5 year old boy presents to the Paediatric Emergency Department with his father. He has recently been treated for a urinary tract infection with nitrofurantoin. Although his urinary symptoms have improved, his father has now noticed yellowing of the patient’s eyes and increased fatigue. The family have recently moved to the United Kingdom from Greece and his father reports the patient’s only past medical history is an episode of neonatal jaundice. On examination the patient has jaundiced sclera and appears lethargic. Blood test results are shown below.

Investigation Result Normal Range
Haemoglobin 62 g/l 135-180 g/l
White Cell Count 7.8 10^9^/l 4.0-11.0 10^9^/l
Platelets 265 10^9^/l 150-400 10^9^/l
Mean Corpuscular Volume 86 fl 82-100 fl
Bilirubin 29 umol/l 3-17 umol/l
Which of the following findings on blood film is consistent with the most likely diagnosis?

A. Howell-Jolly bodies

B. Pappenheimer bodies

C. Target cells

D. Burr cells (echinocytes)

E. Heinz bodies and bite cells

Answer 8

E. Heinz bodies and bite cells

This patient is presenting with haemolytic anaemia caused by underlying glucose-6-phosphate dehydrogenase deficiency (G6PD). G6PD is an X-linked recessive genetic disorder in which a deficiency of the glucose-6-phosphate enzyme results in free radicals destroying erythrocytes in response to oxidative stress. It occurs more commonly in patients of Mediterranean and African ethnicities. Triggers for haemolysis include intercurrent illnesses and infections, fava beans, henna and certain medications including nitrofurantoin, ciprofloxacin, sulfa-drugs and anti-malarials such as primaquine. The classic finding on blood film is Heinz bodies (denatured haemoglobin secondary to oxidative damage) and bite cells (erythrocytes with an irregular membrane caused by splenic macrophages attempting to remove Heinz bodies)

Question 9

A 45 year old female is diagnosed with essential thrombocythaemia following a hospital admission with a pulmonary embolism. She has a past medical history of asthma and deemed unsuitable to take regular aspirin for this reason.

Which would be the most appropriate treatment for this patient?

A. Platelet transfusion

B. Prednisolone

C. Hydroxyurea

D. Allogenic stem cell transplant

E. Recombinant factor IX

Answer 9

C. Hydroxyurea

This is correct. Hydroxyurea (hydroxycarbamide) may be used in high risk patients for essential thrombocythaemia. Essential thrombocythaemia occurs due to the clonal proliferation of megakaryocytes leading to persistently elevated platelet levels. Hydroxyurea suppresses the bone production of platelets in the bone marrow. This should reduce her risk of further venous thromboses

Question 10

what is essential thrombocytopenia associated with?

Answer 10

50% associated with JAK2
Also associated with MPL mutation and CALR

Question 11

blood film of essential thrombocytopenia:

Answer 11

An MPD where megakaryocytes dominate the BM

Question 12

A 75 year old asymptomatic man is found to be mildly anaemic on routine blood tests. He past medical history includes hypertension, and atrial fibrillation secondary to valvular heart disease (he received a metallic aortic valve replacement 6 years earlier). He currently takes amlodipine, lisinopril, bisoprolol, simvastatin and warfarin.

On examination there is an irregular pulse with a loud second heart sound, but nil else of note.

First line blood tests demonstrate: normocytic anaemia (106 g/L); normal white cell and platelet counts; normal urea and electrolytes; unconjugated hyperbilirubinaemia (60 mmol/L), but otherwise normal liver function; normal C-reactive protein.

Second line blood tests reveal that iron studies and haematinics are normal, but The LDH level is raised. A few reticulocytes are noted on the peripheral blood film.

What is the single most likely causes of this patient’s anaemia?

A. Acute blood loss

B. Haemolytic anaemia

C. Iron deficiency

D. Drug-induced anaemia

E. Chronic myeloid leukaemia

Answer 12

B. Haemolytic anaemia

Metallic aortic valves are known to cause non-immune haemolytic anaemia in some cases (probably due to shear stress against the foreign material of the valve)

Question 13

An 8 year old male child of African descent presents to the general practitioner with a swelling in the right lower jaw. His mother reports he has recently not been himself, has felt feverish, and has lost 2kg of weight in the last 4 weeks.

On physical examination the child appears thin and pale. There was a solitary diffuse firm swelling at the right mandible.

Which of the following blood film findings is consistent with the most likely diagnosis?

A. Reed-Sternberg cells

B. Leukaemic lymphoblastic cells

C. Mature myeloid cells

D. Nucleated red cells, left shift, and basophilic vacuolated lymphoma cells

E. Auer rods

Answer 13

D. Nucleated red cells, left shift, and basophilic vacuolated lymphoma cells

This is the correct answer. The presentation is consistent with Burkitt’s lymphoma, a high grade B cell lymphoma, the endemic form of which is common in tropical Africa. The nucleated red cells and left shift (increase in white cell precursors) occurs due to marrow involvement. Basophilic vacuolated cells are a feature of Burkitt’s lymphoma

“Starry sky” appearance

Question 14

what is the most common type of autoimmune haemolytic anaemia.

Answer 14

Warm autoimmune haemolytic anaemia >cold

Question 15

A 78-year-old woman presents to her general practitioner with a rash that has come on gradually over the past few weeks. On examination, small areas of pinpoint red and purple spots are noted on her arms and legs. She is otherwise well, with no significant past medical history.

Her blood results are shown below:

Haemoglobin (Hb) 141 g/L (115–155 g/L)
White cell count 5.3 × 109/L (3.0–10.0 × 109/L)
Platelets 54 × 109/L (150–400 × 109/L)
Activated partial thromboplastin time (APTT) 33 seconds (22–41 seconds)
Prothrombin time (PT) 10 seconds (10–12 seconds)
Which of the following is the most likely diagnosis?

A. Immune thrombocytopenic purpura (ITP)

B. Thrombotic thrombocytopenic purpura (TTP)

C. Meningococcal septicaemia

D. Haemophilia A

E. Warfarin use

Answer 15

A. ITP

ITP is an autoimmune condition of unknown cause. It leads to platelet destruction and increased risk of bleeding. This can manifest clinically as purpura, haemorrhagic bullae and (rarely) severe life-threatening bleeds (particularly in the context of trauma). Patients with ITP do not have features of other haematological diseases (eg. anaemia, leukopenia/leukocytosis, organomegaly or lymphadenopathy). Although this condition is often self-limiting in children, in adults it often has a more chronic course. The history of petechiae, thrombocytopenia and a normal APTT and PT in this case are typical of ITP.

Not TTP

Although TTP can present with thrombocytopenia, these patients are typically more unwell, presenting with neurological symptoms, abdominal symptoms, fever and anaemia. The absence of these features makes a diagnosis of TTP very unlikely.

Question 16

Non Hodgkin Lymphoma vs HL

Answer 16

Question 17

A 60-year-old man is referred urgently to haematology due to a one month history of an enlarging lump in his neck which is associated with fevers, night sweats and weight loss. He undergoes a series of investigations and is subsequently diagnosed with high-grade non-Hodgkin lymphoma. Which of the following is an example of a high-grade non-Hodgkin lymphoma (NHL)?

A. Mantle cell lymphoma

B. Diffuse large B cell lymphoma

C. Follicular lymphoma

D. Small lymphocytic lymphoma

E. Marginal zone lymphoma

Answer 17

B.
Diffuse large B cell lymphoma is a high-grade NHL. NHL can be classified into low-grade and high-grade. High-grade lymphomas grow quickly and need to be treated early and aggressively.

Mantle cell lymphoma, follicular cell lymphoma, small lymphocytic lymphoma, marginal zone lymphoma = all low grade lymphomas

Question 18

A 10 year old boy presents to a haematology clinic with weakness, fatigue and jaundice after consuming large amounts of fava beans. There is evidence of intravascular haemolysis caused by glucose-6-phosphate dehydrogenase deficiency.

Which of the following modes of inheritance is likely to cause this form of haemolytic anaemia?

A. X-linked dominant

B. Codominance

C. Autosomal dominant

D. Autosomal recessive

E. X-linked recessive

Answer 18

E. X-linked recessive

This is the correct answer. Glucose-6-phosphate dehydrogenase is a necessary enzyme required for the generation of reduced glutathione, which protects the red cell from oxidative stress. Lack of this crucial enzyme can lead to haemolytic anaemia. The inheritance of glucose-6-phosphate dehydrogenase deficiency is X-linked recessive and manifests mainly in males

Question 19

Burkitt cell lymphoma mnemonic

Answer 19

Question 20

Mantle cell lymphoma mnemonic

Answer 20

Question 21

Follicular cell lymphoma mnemonic

Answer 21

Question 22

3 main forms of Burkitt’s lymphoma:

Answer 22

1. endemic (African) form: typically involves maxilla or mandible
2. sporadic form: abdominal (e.g. ileo-caecal) tumours are the most common form. More common in patients with HIV
3. Immunodeficiency non-EBV associate/ post-transplant patients

Question 23

what is the commonest cause of isolated thrombocytopenia? Treatment?

Answer 23

ITP–> oral prednisolone

Question 24

A 58 year old man presents in extremis with reduced GCS, seizures and respiratory distress. His partner describes a 5-7 day history of fever, headache and myalgias managed as influenza by the GP, which has since evolved into his current state. He is resuscitated and admitted to the intensive care unit.

There is no social or family history of note. He has two grown-up children (both well) and a pet dog. Five weeks ago, he returned from a two-month trip to Zambia, as a civil engineering consultant.

His blood tests show Haemoglobin 98, unconjugated bilirubin 120, raised serum LDH, methaemalbuminaemia and haemoglobinuria. His Urea and Electrolytes show evidence of an acute kidney injury. His blood count and clotting screen are otherwise normal. Coombs’ test is negative.

What is the single most appropriate treatment for this disorder?

A. Artesunate

B. Eculizumab

C. Transfusion or plasma exchange

D. Prednisolone

E. Rituximab

Answer 24

A. Artesunate

This is the correct answer. This patient is presenting with acute and severe falciparum malaria. IV artesunate is the treatment of choice

Eculizumab is a monoclonal antibody inhibitor of complement-mediated cell lysis (membrane attack complex formation). It is used in atypical haemolytic uraemic syndrome and paroxysmal nocturnal haemoglobinuria. Given that the most likely diagnosis is severe malaria, these would not be the first line choice of treatment in this patient

Prednisolone may be used in the treatment of immune causes of haemolytic anaemia. Given that Coombs’ test is negative, it is unlikely to be of benefit in this case

Rituximab may be used in the treatment of immune causes of haemolytic anaemia (especially cold autoimmune haemolytic anaemia). Given that Coombs’ test is negative, it is unlikely to be of benefit in this case

Question 25

treatment for hereditary spherocytosis:

Answer 25

folic acid, may need splenectomy

Question 26

A 74 year old male presents to the emergency department with gradual onset fatigue and shortness of breath on exertion. His past medical history includes metallic aortic valve replacement due to a congenital bicuspid aortic valve. On examination he has jaundiced sclera with pale conjunctiva and splenomegaly. A venous blood gas shows haemoglobin 86 g/L (normal value for men 135-180 g/l) and the blood film is reported as showing schistocytes. Which of the following investigation findings is most likely? A. Decreased lactic dehydrogenase (LDH) B. Raised haptoglobin C. Raised mean corpuscular volume D. Raised unconjugated bilirubin E. Decreased reticulocyte count

Answer 26

D. Raised unconjugated bilirubin. The features in this case suggestive of haemolytic anaemia include symptoms of anaemia, examination finding of jaundice with splenomegaly and blood film showing schistocytes, which are fragmented red blood cells. Prosthetic heart valves, especially mechanical valves, can cause intravascular haemolysis as the turbulent blood flow around the mechanical valve causes mechanical damage to the erythrocyte. Haemolytic anaemia results in raised unconjugated bilirubin levels as haemoglobin from destroyed erythrocytes is broken down in to globin (which is recycled) and haem. Haem is further broken down into iron and unconjugated bilirubin. If the liver cannot fully compensate by conjugating and excreting the bilirubin a mild unconjugated hyperbilirubinemia is seen Not raised haptoglobin: Haptoglobin is a glycoprotein which binds to free haemoglobin in the serum to transport it to the reticuloendothelial system to be broken down. Haptoglobin levels are therefore decreased in intravascular haemolysis as the free haemoglobin rapidly binds to the haptoglobin and is the haptoglobin-haemoglobin complex is cleared by the reticuloendothelial system

Question 27

risk factors for warm autoimmune haemlolytic anaemia:

Answer 27

lymphoma, SLE, CLL, methyldopa, IgG

Question 28

RFs for cold autoimmune haemolytic anaemia & which Ig? (mnemonic):

Answer 28

Infections; EBV, mycoplasma (mir is kalt), IGM, lymphoma

Question 29

causes of microcytic anaemia (mnemonic)

Answer 29

Question 30

what are causes of macrocytic anaemia (mnemonic):

Answer 30

FATRBC -fetus (pregnancy) -antifolates (phenytoin) -thyroid (hypo) -Reticulocytosis (eg with haemolysis) -B12 ofr folate deficiency -Cirrhosis (alcohol excess or liver excess) Other: myelodysplastic syndromes/aplastic anaemia/myeloprofilerative disorders/myeloma

Question 31

A 50-year-old Caucasian male presents to his GP with headaches and dizziness. He has noted redness pain and swelling of his hands and legs. His wife complains that he is always itching after taking a bath. On examination he shows facial plethora and a mass in the left upper quadrant. Given the likely diagnosis what is the best diagnostic test? A. Serum Erythropoietin level B. Arterial oxygen saturation C. JAK2 mutation screen D. Skin biopsy E. Abdominal ultrasound

Answer 31

C. JAK2 mutation screen The patient has the signs and symptoms of polycythaemia rubra vera including facial plethora, itching after hot baths, leg swelling and splenomegaly (left upper quadrant mass). A JAK2 mutation is present in >90% of cases of polycythaemia rubra vera. Therefore finding a positive JAK2 mutation helps confirm the diagnosis Not A: Serum EPO High EPO could cause polycythaemia by stimulating erythropoiesis. However, in this case the most likely diagnosis if PCV which would in turn lead to a supressed EPO level. This is not of diagnostic value in PCV

Question 32

Blood test results in polycythaemia:

Answer 32

an increase in haematocrit, red cell count and haemoglobin concentration.

Question 33

Causes of polycythaemia:

Answer 33

Relative polycythaemia definition -Relative polycythaemia (or pseudo-polycythaemia) is where there is a falsely elevated haemoglobin secondary to a low plasma volume (remember that haemoglobin is measured as a concentration). This can be seen in dehydration or excess diuretic use. Gaisbock's syndrome -Gaisbock's syndrome can cause a pseudo-polycythaemia a disorder that is more common in young male adults, particularly smokers, and is associated with hypertension, which reduces plasma volume, hence resulting in the raised haemoglobin. Absolute polycythaemia definition -If the plasma volume is normal, the polycythaemia is an absolute polycythaemia (red cell mass will be raised). Absolute polycythaemia is classified into primary and secondary causes. Primary polycythaemia definition In primary polycythaemia there is excess erythrocytosis independent of erythropoetin (EPO). Secondary polycythaemia causes In secondary polycythaemia the excess red blood cell production is driven by excess EPO. This can be secondary to an appropriate rise in EPO, as seen in conditions of chronic hypoxia (such as COPD or high altitude). This can also be secondary to an inappropriate secretion of EPO, which may be seen as a para-neoplastic effect in renal neoplasms.

Question 34

features of primary polycythaemia:

Answer 34

Primary: Fatigue Headache Visual disturbances (secondary to hyperviscosity) Pruritus (typically after a hot bath Erythromelalgia (a painful burning sensation in the fingers and toes Arterial thrombosis (such as MI or stroke) Venous thrombosis (such as PE or DVT) Haemorrhage (intracranial or gastrointestinal) Paradoxical increased bleeding risk (due to impaired platelet function) Increased risk of gout (caused by hyperuricaemia secondary to increased cell turnover). Facial redness on examination Splenomegaly.

Question 35

PRV (Polycythaemia rubra vera) features:

Answer 35

-Polycythaemia -Hyperviscosity symptoms: Chest pain, myalgia, weakness, headache, blurred vision, loss of -concentration -'Ruddy complexion' -Splenomegaly -Raised haematocrit -Low EPO -JAK-2 mutation

Question 36

A 65-year-old woman presents to the haematology clinic after being referred by her general practitioner. She has a 3-month history of splenomegaly, fatigue and weight loss. Her blood results are shown below: Haemoglobin (Hb) 91 g/L (115-155 g/L) Mean cell volume (MCV) 92 fL (80-96 fL) White cell count 121 × 109/L (3.0-10.0 × 109/L) Platelets 600 × 109/L (150-400 × 109/L) Neutrophils 20 × 109/L (2.0-7.5 × 109/L) Lymphocytes 3.0 × 109/L (1.5-4.0 × 109/L) Monocytes 2.0 × 109/L (0.2-1.0 × 109/L) Eosinophils 3.5 × 109/L (0-0.4 × 109/L) Basophils 2.7 × 109/L (0-0.1 × 109/L) Her blood film shows a large number of mature myeloid cells Which of the following translocations is associated with the most likely diagnosis? A. t(8;14) B. t(11;22) C. t(9;22) D. t(21;21) E. t(11;14)

Answer 36

C. t(9;22) Chronic myeloid leukaemia (CML) is a haematological malignancy characterised by proliferation of myeloid cells. There are three phases: the chronic phase, the accelerated phase and the blast phase. The blast phase is characterised by an increased production of blast cells, with rapid progression and a poor prognosis. Blood results will show a massively elevated white cell count with neutrophilia, monocytosis, eosinophilia and basophilia. Some patients may have anaemia, thrombocytopenia or thrombocytosis. A bone marrow biopsy will confirm the diagnosis, with histology performed to identify a t(9;22) translocation; >95% of cases of CML are associated with the BCR-ABL t(9;22) gene translocation (also known as the Philadelphia chromosome). The first-line treatment of CML is a tyrosine kinase inhibitor (eg. imatinib), with 87% of patients responding completely to therapy. Note: acute lymphoblastic leukaemia is also associated with the Philadelphia chromosome, where it is a poor prognostic marker. A. This translocation t(8;14) is associated with Burkitt lymphoma, not CML. B. t(11;22) is associated with Ewing sarcoma D. t(21;21) is associated with Down's syndrome E. t(11;14) is associated with mantle cell lymphoma

Question 37

what's the most common acute leukaemia in adults?

Answer 37

AML is the most common acute leukaemia in adults. It is associated with myelodysplastic syndromes.

Question 38

symptoms of AML:

Answer 38

It typically presents with symptoms of bone marrow failure (anaemia, bleeding, infections) and signs of infiltration, including: hepatomegaly, splenomegaly, and gum hypertrophy.

Question 39

Diagnosis of AML:

Answer 39

Blood tests commonly show leucocytosis, but white cells can sometimes be normal or low. For this reason, diagnosis is dependent on bone marrow biopsy, as well as other molecular analyses. Characteristic biopsy findings include Auer rods.

Question 40

Management of AML:

Answer 40

AML is commonly treated with chemotherapy regimens or bone marrow transplant.

Question 41

Most common cancer in childhood:

Answer 41

ALL

Question 42

most common brain tumour in children:

Answer 42

pilocytic astrocytoma

Question 43

clinical features of ALL

Answer 43

Common presentations include symptoms caused by marrow failure (symptoms of anaemia including fatigue, abnormal bleeding/bruising caused by low platelets, and infections caused by low white cells). Symptoms may also be caused by organ infiltration, such as bone pain. Signs include painless lymphadenopathy, hepatosplenomegaly, CNS involvement (e.g. cranial nerve palsies, meningism) or testicular infiltration (resulting in painless unilateral testicular enlargement).

Question 44

diagnosis of ALL:

Answer 44

Blood results show leucocytosis and blast cells on blood film and bone marrow analysis.

Question 45

Prognosis of ALL:

Answer 45

children have a cure rate of 70-90%.

Question 46

clinical features of CML? Who is commonly affected?

Answer 46

CML is most common in middle-aged patients, with males slightly more affected. It is classically associated with the Philadelphia chromosome. CML usually presents with weight loss, tiredness, fever, and sweating. Common signs include massive splenomegaly (>75%), bleeding (due to thrombocytopenia), and gout.

Question 47

clinical features of CLL:

Answer 47

CLL typically presents asymptomatically. However, patients may present with non-tender lymphadenopathy, hepatosplenomegaly, or B symptoms (weight loss, night sweats, and fever). Features of marrow failure (infection, anaemia, and bleeding) are less common than in the acute leukaemias.

Question 48

Diagnosis of CLL:

Answer 48

The most common initial blood result is an incidental lymphocytosis. Subsequent blood film shows smudge cells, which are cells damaged as they lack a cytoskeletal protein. Flow cytometry is then used to measure particular markers expressed by the malignant cells. Other tests include bone marrow biopsy.

Question 49

Prognosis of CLL:

Answer 49

, 1/3 of cases don't progress, 1/3 of cases progress slowly, and 1/3 of cases progress actively.

Question 50

An 80 year old female complains of progressive tiredness over the past 5 months. She denies any history of anaemia, no black stools, no fresh blood per rectum. She maintained a good appetite although has lost 8 kg of weight during this time frame. Bloodwork reveals a pancytopenia, normal renal function and otherwise normal biochemistry profile. What is the next appropriate step and management? A. Urine Bence Jones protein B. Bone marrow biopsy C. Lymph node biopsy D. Thyroid function tests E. Blood film

Answer 50

E. Blood film The peripheral film can tell lots of important information regarding a pancytopenia. Nutritional deficiencies such as iron, B12 or folate will all be apparent on a film alongside rouleaux formations for multiple myeloma. Blasts and other immature cells may suggest malignancy or a primary bone marrow disorder such as myelofibrosis. The differential for pancytopenia can be wide but the film can help pinpoint the aetiology and the next stage of tests Not B: bone marrow biopsy A bone marrow biopsy will likely be needed if true pancytopenia is found and can reveal information about the proliferative state of the marrow however is not the most appropriate next step in management

Question 51

A 63 year old alcoholic with acute upper GI bleeding and shock is brought to the emergency department by ambulance. On examination abdomen is soft, the liver is not palpable but the spleen is moderately enlarged, and there are no rashes. He is resuscitated with IV fluids. Urgent full blood count reveals a Hb of 68 g/L, low grade leukocytosis and thrombocytopenia. What is the likely cause of this patient’s presentation? A. Erosion of the splenic artery B. Oesophageal varices C. Hereditary haemorrhagic telangiectasia D. Deranged clotting E. Mallory Weiss syndrome

Answer 51

B. Oesophageal varices This is the correct answer. Variceal bleeding is a good fit here for two key reasons: 1. History of alcoholism 2. Splenomegaly and thrombocytopenia. Platelet count is a good indirect measure of portal pressure, often used to help differentiate between variceal and non-variceal bleeding (portal hypertension results in splenic enlargement and hyperfunction, and thus platelet sequestration) Not E. Mallory Weiss syndrome: This is a reasonable thought. The patient may have been vomiting, resulting eventually in a Mallory Weiss oesophageal tear. Factors making this less likely include: high volume bleeding (Mallory Weiss tears more commonly cause typically minor bleeding), thrombocytopenia (thrombocytosis is more typical of acute bleeding), and otherwise unexplained splenomegaly Not B: HHT Hereditary haemorrhagic telangiectasia (aka Osler-Weber-Rendu syndrome) This is an uncommon genetic disorder characterised by mucosal and GI telangiectasia with a tendency to bleed. There are no rashes in this patient. In addition, HHT does not explain splenomegaly or thrombocytopenia

Question 52

causes of Vitamins ADEK deficiency:

Answer 52

are fat-soluble vitamins whose absorption is impaired in fat malabsorption syndromes such as biliary obstruction, coeliac disease, cystic fibrosis and short-gut syndrome.

Question 53

bleeding disorders associated with liver disease: further investigation:

Answer 53

Liver disease affects the synthesis and activity of both procoagulant and anticoagulant components of haemostasis. For this reason, detailed assessment of clotting with thromboelastography (TEG) is often required.

Question 54

what does antithrombin 3 normally inhibit?

Answer 54

factor 2a, 10a, 9a and 11a -Antithrombin deficiency therefore increases the risk of thrombosis

Question 55

RFs for acquired cases of VTE:

Answer 55

1. Patient demographics -Age increases the risk of PE. -Pregnancy and the post-natal period increases the risk of venous thromboembolism 4-10 fold. 2. Past medical history -Active malignancy, antiphospholipid antibody syndrome, any previous venous thromboembolism (PE or deep vein thrombosis), and polycythaemia vera. -Note that any illness that has resulted in the patient being bed-bound for 5 days or more is a strong risk factor. -Dehydration 3. Past surgical history -Any recent trauma or fracture, and any surgery within the last 2 months. 4. Drug history -Whether the patient takes the oral contraceptive pill or hormone replacement therapy. 5. Social history -Smoking and any recent long-haul air travel -Obesity

Question 56

A 70-year-old African male presents to his GP with fatigue, headaches and back pain. He has noted he has been constipated, urinating more frequently and his mood has been low in the last month. Over the last few months he has several chest infections and UTIs. Given the most likely underlying diagnosis, what is the most appropriate initial investigation? A. MRI Spine B. Blood film C. Serum protein electrophoresis D. Serum ACE E. Beta2 microglobulin

Answer 56

C. Serum protein electrophoresis This patients has signs and symptoms consistent with myeloma; back pain, features of hypercalcaemia (constipation, polyuria, low mood), anaemia (tiredness) and frequent infections. Serum protein electrophoresis identifies the presence of an M protein (excess of a monoclonal antibody). The presence of an M protein along with other results such as bone lesions, hypercalaemia, anaemia, plasma cells on bone biopsy and renal impairment form the diagnostic criteria for myeloma Not D: Serum ACE Raised serum ACE would be consistent with a diagnosis of sarcoidosis, which does not fit with the history of back pain, hypercalcaemia symptoms and infections (immunoparesis) Not B: Blood film Blood film may show Roleaux formation, which is associated with a high ESR. This however is not necessarily specific to myeloma Not A: MRI MRI spine may show evidence of lytic lesions however would not confirm the diagnosis. MRIs are also expensive and difficult to obtain Not E: Beta2 microglobulin Beta2 microglobulin is a prognostic test for myeloma and is not diagnostic

Question 57

The clinical features of multiple myeloma can be remembered by the mnemonic:

Answer 57

CRAB HAI * HyperCalcaemia: this arises primarily due to increased osteoclast-mediated bone resorption. * Renal impairment: this occurs due to multiple factors e.g. light chain deposition in the kidneys and hypercalcaemia. * Anaemia: note that due to marrow infiltration by the tumour other cytopenias can occur (e.g. thrombocytopenia and leukopenia). * Bone pathology: osteolytic lesions are common. This can lead to pathological fractures and vertebral compression fractures. * Hyperviscosity: this can present with headache, visual disturbances, and thrombosis. * Amyloidosis (AL): this has multiple sequelae including e.g. cardiac failure and neuropathies. * Infection: recurrent infection occurs secondary to leukopenia and immunoparesis (there is low levels of functional IgG).

Question 58

Investigations workup for multiple myeloma:

Answer 58

Work-up investigations 1. Basic bloods: FBC may show anaemia, U&E may show renal impairment (particularly raised serum creatinine), hypercalcaemia is a common feature. Skeletal survey: this is typically done with X-ray but CT/MRI is more sensitive. Findings include osteolytic bone lesions and pathological fractures. 2. Diagnostic investigations a) Serum and/or urine electrophoresis: this will show a paraprotein spike (typically IgG). b)Serum free light chain essay (Bence Jones protein): in myeloma serum free light chain levels are high. This can be used in the 1-2% of patients with non-secretory multiple myeloma (i.e. those that are negative for serum/urine monoclonal protein on electrophoresis). c) Tissue diagnosis typically by bone marrow aspirate and biopsy: myeloma is confirmed if there are >10% of plasma cells in the bone marrow. 3. Investigations to inform prognosis a) CRP (the higher the level, the worse the prognosis) b) LDH (the higher the level, the worse the prognosis) c) Beta-2 microglobulin (a very high over very low level confers poor prognosis) d) FISH and cytogenetic analysis (this may also inform the type of treatment used) e) Note that high serum creatinine and low albumin are also poor prognostic markers.

Question 59

Treatment for multiple myeloma:

Answer 59

* Supportive for CRAB symptoms inc, bispohosphonates, analgesia, surgical stabilisation and physiotherapy for bone disease -Influenza and pneumococcal vaccination for infection prevention. -Erythropoietin (± transfusion) for anaemia. * Aim of treatment: induce remission for consideration of autologous stem cell transplant which will prolong remission * Not curable * Average survival 5-7 yrs but improving with new treatments * Options: 1. Firstline–Bortezomib+/-dexamethasone, cyclophosphamide, lenalidomide 2. When in remission=>Auto-SCT–best for younger patients as prolongs remission 3. If not suitable for SCT–multiple other new agents e.g. daratumumab(anti-CD38) carfilzomb / ixazomib (protease inhibitors) panobinostat

Question 60

A 42-year-old woman attends her general practitioner complaining of a 4-day history of dark urine in the morning. She has had episodes of this in the past, but has not seen anyone about these before. She also has a 5-month history of fatigue. Her blood results are shown below: Haemoglobin (Hb) 90 g/L (115–155 g/L) Mean cell volume (MCV) 92 fL (80–96 fL) White cell count 2.4 × 109/L (3.0–10.0 × 109/L) Platelets 122 × 109/L (150–400 × 109/L) Which of the following investigations is most likely to confirm the diagnosis? A. Flow cytometry for CD55 and CD59 B. CT of kidneys, ureters and bladder (CT KUB) C. Cystoscopy D. Urine dipstick E. Ham's test

Answer 60

A. Flow cytometry for CD55 and CD59 Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired haemolytic anaemia associated with glycosyl phosphatidylinositol deficiency, leading to dysregulation of complement pathways. -immunophenotyping can show altered GPI -Morning haemoglobinuria (causing dark urine), fatigue and dyspnoea are common features. Pancytopenia may be present. There is also an association with thromboses and erectile dysfunction. -Flow cytometry of CD55 and CD59 is the gold standard diagnostic test for PNH, with low levels being diagnostic. Not E: Ham's test Ham's test was previously used for the diagnosis of PNH, but has now been superseded by flow cytometry of CD55 and CD59.

Question 61

Management of PNH (paroxysmal nocturnal haemoglobinuria)

Answer 61

The monoclonal antibody eculizumab, which inhibits formation of the membrane attack complex of the complement cascade, has been used in some subjective success in these patients (improves quality of life, but does not appear to affect mortality rates).

Question 62

6 month old girl presents to the GP with failure to thrive. Examination reveals pallor, hepatosplenomegaly and skull bossing. Investigations reveal that the child has severe anaemia and a blood film shows hypochromic, microcytic cells, target cells, and nucleated red blood cells. The child is diagnosed with beta-thalassaemia major. What is the mainstay of treatment for those with beta-thalassaemia major? A. Oral ferrous sulphate B. Hydroxyurea C. Fortnightly blood transfusions D. Corticosteroids E. Warfarin

Answer 62

C. Fortnightly blood transfusions Those with beta-thalassaemia major should have regular (2-4 weeks) blood transfusions of packed red blood cells for the rest of their life, in order to keep their haemoglobin levels in the normal range. This may, however, cause iron overload, which may be counteracted with iron chelators Not B. Hydroxyurea (hydroxycarbamide) Hydroxyurea increases production of fetal haemoglobin and is used to treat sickle cell disease if the patient suffers from frequent crises. It may sometimes be used in the treatment of thalassaemia, but it is not the first line treatment as it is less effective and predictable

Question 63

A 72 year old man presenting to his GP with fatigue and recurrent respiratory tract infections (including a recent course of antibiotics for suspected bacterial pneumonia) is found to have nucleated red blood cells, immature neutrophils and tear drop poikilocytes on blood film. On examination he is well, but an enlarged spleen is noted extending from the left hypochondrium as far as the right iliac fossa. What is the single most likely underlying diagnosis? A. Acute infection B. Primary myelofibrosis C. Tuberculosis D. Reticulocytosis E. Gaucher’s disease

Answer 63

B. Primary myelofibrosis The blood film findings described are typical of a leukoerythroblastic film, which is seen in infiltrative disease of the marrow of which primary myelofibrosis is a good example. Massive splenomegaly is also consistent with this diagnosis Not E. Gaucher's disease Gaucher’s disease is an autosomal recessive lysosomal storage disease caused by glucocerebrosidase deficiency (GBA gene, chromosome 1). Massive splenomegaly and marrow infiltration (giving the leukoerythroblastic picture described) are typical, and Type 1 Gaucher’s may present in adulthood. However, it is a relatively rare disease (certainly less common than primary myelofibrosis), and presentation at 72 years of age would be unusual (adult-onset forms generally present earlier)

Question 64

what will molecular test of myelofibrosis show?

Answer 64

JAK2 mutation or MPL mutation

Question 65

A 6-year-old boy presents with his father to the emergency department with two days of progressive shortness of breath on exertion and new visible jaundice. He is normally fit and well and has reached all of his developmental milestones. On questioning regarding the patient's diet, his father reports he has recently developed a love for fava beans, eating them with each meal for the last week. On examination, he looks well but is visibly jaundiced. His chest is clear. He has a palpable smooth mass in his left upper quadrant, but his abdomen is soft non-tender. His bloods show: A peripheral blood film is sent, which shows polychromasia and bite cells. Which of the following is the next best investigation? A. G6PD enzyme assay B. Hepatitis panel C. Direct antiglobulin test D. Screen for red blood cell pyruvate kinase activity E. Bone marrow biopsy

Answer 65

C. Direct antiglobulin test This patient likely has acute haemolytic anaemia from glucose-6-phosphate dehydrogenase deficiency following ingestion of fava beans. Direct antiglobulin test (direct Coombs test) is used to determine whether the patient has immune-mediated haemolytic anaemia Not A. G6PD enzyme assay G6PD enzyme assay is used to diagnose glucose-6-phosphate dehydrogenase deficiency. It is checked approximately 3 months following an episode of acute haemolysis, and so it would not be the next investigation

Question 66

A 55 year old male patient presents to the general practitioner with a 1 month history of back pain and fatigue. He has no past medical history of note, but has suffered from 2 episodes of pneumonia in the last 6 months. On physical examination there is bone tenderness in the lumbar region. Blood tests reveal: haemoglobin 11.5 g/dL, white blood cells 10.5 x 10^9/L, platelets 300 x 10^9/L, creatinine 200 umol/L, sodium 142 mmol/L, potassium 3.7 mmol/L, calcium 2.9 mmol/L. Which of the following is the best diagnostic investigation for the most likely diagnosis? A. Peripheral blood film B. Fluoresence in situ hybridisation (FISH) and cytogenetic analysis C. Beta2-microglobulin level D. Skeletal survey with X-ray E. Bone marrow aspirate and biopsy

Answer 66

E. Bone marrow aspirate and biopsy The patient presents with features consistent with multiple myeloma (hypercalcaemia, renal impairment, anaemia, bone involvement, and recurrent infection). Bone marrow aspirate and biopsy is necessary to confirm the diagnosis of multiple myeloma. The bone marrow biopsy will reveal >10% plasma cells in the bone marrow, differentiating the condition from monoclonal gammopathy of unknown significance (MGUS) Not B: FISH & cytogenetics Genetic abnormalities in myeloma may inform the type of chemotherapy used, and will inform prognosis, but are not diagnostic. del13 and certain chromosomal abnormalities, for example, are associated with a poor prognosis Not C: b2-microglobulin level The beta2-microglobulin level is a prognostic test in multiple myeloma. Beta-2 microglobulin is a component of the MHC class I molecules. A very high or very low beta2-microglobulin level confers poor prognosis. It is not, however, a diagnostic test as it cannot differentiate between myeloma and MGUS

Question 67

which infection is associated with Kaposi sarcoma:

Answer 67

HHV8

Question 68

Which infection is associated with T-cell lymphomas:

Answer 68

HTLV1 is associated with T-cell lymphomas

Question 69

what cancers is hepatitis C associated with

Answer 69

-diffuse large B-cell lymphoma -splenic marginal zone lymphoma -hepatocellular carcinoma

Question 70

what cancer is helicobacter pylori infection associated with?

Answer 70

gastric mucosa-associated lymphoma tissue (MALT)

Question 71

RFs of Hodgkin's lymphoma:

Answer 71

Epstein Barr Virus HIV Immunosuppression Cigarette smoking

Question 72

clinical features of hodgkin's lymphoma (diagnosis & management):

Answer 72

1. It typically presents in young adults with cervical or supraclavicular non-tender lymphadenopathy, though the location of diseased nodes can vary. 2. Alcohol-induced pain is a suggestive symptom. 3. There may be symptoms caused by compression of surrounding structures e.g. shortness of breath or abdominal pain. B symptoms (fever, night sweats, and weight loss), occur in 30% of patients. 4. It is important to examine the patient for lymphadenopathy, and to check for hepatomegaly or splenomegaly. Diagnosis: 1. Lymph node biopsy with evidence of Reed Sternberg cells is diagnostic. 2. Blood results can predict a poor prognosis via low haemoglobin and raised LDH, as they indicate high red cell turnover. 3. Staging scans are required to elucidate the extent of disease. Management 1. Treatment is usually with chemoradiotherapy.

Question 73

What description is given to red blood cells which are typically polychromatic and stain heavily for the presence of RNA?

Answer 73

reticulocyte

Question 74

What are inclusions of denatured haemoglobin within erythrocytes commonly called when seen in a peripheral blood film?

Answer 74

Glucose-6-phosphate dehydrogenase deficiency, chronic liver disease

Question 75

What is the term given to describe spherical erythrocytes which may be congenital or due to autoimmune haemolytic anaemia?

Answer 75

-often a little smaller -Hereditary spherocytosis, Autoimmune Haemolytic Anaemia

Question 76

A medical student is unsure about what cell she is looking at under the microscope. She is looking a peripheral blood film. She describes a cell with a bilobed nucleus. The cytoplasm of the cell has stained some areas with a reddish-purple colour. She says there aren't many of these in the blood film. What cell is she describing?

Answer 76

Eosinophil -Rare. 3x larger than erythrocytes. Reddish purple (acidic) granules. Bilobed nucleus

Question 77

A medical student is unsure about what cell she is looking at under the microscope. She is looking a peripheral blood film. She describes an odd looking cell that she hasn't seen before in this patient. It has lots of dark blue speckles in the cytoplasm of the cell. It is much larger than the red blood cells. What cell is she describing?

Answer 77

Basophil Rare. 3x large than erythrocytes. Deep blue (basic) granules. Bilobed nucleus

Question 78

A medical student is unsure about what cell she is looking at under the microscope. She is looking a peripheral blood film. She describes a cell that is nearly completely dark purple, except for a thin rim of slightly blue stained cytoplasm. It's roughly the same size as red blood cells. What cell is she describing?

Answer 78

Lymphocyte About the same size as erythrocytes (so, small). Giant nucleus taking up most of the cell. No granules. Nucleus is not kidney shaped.

Question 79

What are inclusions of clusters of nuclear DNA within erythrocytes commonly called when seen in a peripheral blood film? This finding is often associated with Sickle Cell Disease in adults.

Answer 79

Howell-Jolly bodies -Post-splenectomy or hyposplenism (e.g. sickle cell disease, coeliac disease, congenital, UC/Crohn's, myeloproliferative disease, amyloid) Megaloblastic anaemia, hereditary spherocytosis

Question 80

A medical student is unsure about what cell she is looking at under the microscope. She is looking a peripheral blood film. She says she has seen a number of these cells in this sample, but that they are not too common. This cell is very large and has a bilobed nucleus. She says at least 4 red blood cells could fit inside this cell. What cell is she describing?

Answer 80

Monocyte Relatively common. >3x larger than erythrocytes. Large, kidney bean shaped nucleus.

Question 81

A peripheral blood film from a patient with advanced myeloma shows a normocytic, normochromic anaemia. What other blood film finding may be found in patients with advanced myeloma and reflects a high paraprotein concentration?

Answer 81

Rouleaux formation

Question 82

normal lifespan of platelet?

Answer 82

7-10 days

Question 83

neutrophil lifespan:

Answer 83

4 days

Question 84

von Willebrand disease (vWD) presentation:

Answer 84

vWD is an autosomal dominant condition that typically presents with mucosal bleeding: 1. Excess or prolonged bleeding from minor wounds 2. Excess or prolonged bleeding post-operatively 3. Easy bruising 4. Menorrhagia 5. Epistaxis 6. GI bleeding These patients will typically have a personal history of prolonged bleeding, with a family history of vWD/prolonged bleeding. Investigations: decreased factor 8 activity, so the PT time is normal but APTT is prolonged

Question 85

different types of vwf:

Answer 85

Type 1 VWD is caused by a partial quantitative deficiency in VWF. Type 2 VWD is caused by qualitative defects in VWF (e.g. decreased adhesion to platelets or factor VIII). Type 3 VWD is caused by almost complete deficiency of VWF (can present like haemophilia)

Question 86

A 64 year old gentleman presents to the emergency department having impaled himself through the proximal left thigh with a wooden stake while gardening. The patient is bleeding profusely from the left thigh in spite of having an appropriately applied pressure dressing and a paramedic applying direct pressure. The wound is too proximal to apply a tourniquet. The patient tells you he takes warfarin for atrial fibrillation and his INR measurement this morning was 2.8 (his target range is 2.0 - 3.0). The patient takes no other medications and has no other medical history. On examination the patient is alert and orientated, he appears pale, breath and heart sounds are normal. There is active bleeding from the leg wound, and the leg appears pale with weak distal pulses. Observations show: heart rate of 127, blood pressure of 93/54, respiratory rate of 22, oxygen saturations of 96% on 15L/min oxygen via non-rebreathe mask, and temperature of 37.1 celsius. There are two large-bore IV cannulae in situ, the major haemorrhage protocol has been activated and blood has been requested for transfusion. Which of the following is the single next most appropriate action? A. Give IV heparin B. Attempt to identify and clamp a bleeding vessel C. Give IV Vitamin K 5mg and Prothrombin Complex Concentrate D. Give IV tranexamic acid 1g E. Give an IV 0.9% saline 500ml bolus

Answer 86

Give IV Vitamin K 5mg and Prothrombin Complex Concentrate This patient is clearly having a major haemorrhage, and effective haemostasis has not been achieved. As the patient is taking warfarin and having significant bleeding, vitamin K must promptly be given to help reverse this (the IV route has a quicker onset than oral) irrespective of the INR. Prothrombin complex concentrate also must be given as it works faster to reverse warfarin than IV Vitamin K. Not B. Attempt to identify & clamp a bleeding vessel: This patient is still bleeding in spite of direct pressure and a pressure dressing, removing these measures to attempt to identify a bleeding vessel will likely only mean the bleeding worsens. Given the degree of bleeding, it is unlikely that it will be possible to see anything other than a lot of blood in the wound. Outside of an operating theatre setting, and in the absence of specialist vascular expertise, it is not appropriate to try and clamp bleeding vessels given the significant risks of attempting this Not: D Give IV tranexamic acid 1g: Tranexamic acid is an anti-fibrinolytic agent that is effective in reducing bleeding and has a good evidence-base in most cases of major bleeding. As this patient is taking an oral anticoagulant treatment should first be given to directly mitigate the anticoagulant effect before giving other treatments to stop the bleeding Not E: Give an IV 0.9% saline 500ml bolus There is compelling evidence that use of IV crystalloid in the context of major trauma/major haemorrhage can be detrimental by worsening acidosis, coagulopathy and additionally by potentially dislodging clots by increasing the blood pressure. This patient is hypotensive and tachycardic, but he remains alert and is not currently profoundly shocked. The major haemorrhage protocol has been activated and blood for transfusion has been requested, as such a more important priority is to optimise this patient’s clotting by ensuring the warfarin is reversed. If there is a delay in obtaining blood products and the patient becomes progressively more unstable, it may be necessary to sustain adequate circulation by giving IV crystalloids (first clot is your deepest (best clotting factors), a lot of fluids--> breaks up that clot --> )

Question 87

A 72-year-old man presents to the GP with 3 months of general fatigue, malaise, and night sweats. Bloods reveal the following: Serum Reference Range White cell count 16.3 (3.0 - 10.0 x 10⁹ /L) Neutrophils 3.1 (2.0 - 7.5 x 10⁹ /L) Lymphocytes 8.2 (1.5 - 4.0 x 10⁹/L) Haemoglobin 78 (13.0 - 17.0 g/dL) Peripheral blood film shows smudge cells and small mature lymphocytes with round nuclei and clumped chromatin. Given the likely diagnosis, which of the following is the next best investigation? A. Iron studies B. Lymph node biopsy C. Bone marrow biopsy D. Serum electrophoresis E. Immunophenotyping

Answer 87

E. Immunophenotyping This patient most likely has chronic lymphocytic leukaemia (CLL) Immunophenotyping detects tumour markers in peripheral blood by labelling the white blood cells with antibodies directed against cell surface proteins. This allows for differentiation of leukaemic cells to show which specific type of leukaemia the patient has and so which treatment would be most appropriate Not: B lymph node biopsy: Chronic lymphocytic leukaemia can be subcategorised using immunophenotyping and flow cytometry from peripheral blood. Evaluation of lymph node biopsy is not usually necessary unless there is diagnostic doubt from the former tests Not C: bone marrow biopsy: Chronic lymphocytic leukaemia can be subcategorised using immunophenotyping and flow cytometry from peripheral blood. Therefore, evaluation of bone marrow biopsy is not usually necessary unless there is diagnostic doubt from the former tests Not D: serum electrophoresis; Serum electrophoresis is commonly used to investigate multiple myeloma or monoclonal gammopathy of uncertain significance (MGUS). While chronic lymphocytic leukaemia may produce IgM paraproteinaemia, it is not routinely used in its diagnosis

Question 88

A 65-year-old man attends the emergency department with a 6-hour history of a severe generalised headache and blurred vision. He has had similar headaches on and off for the past few months. He reports no photophobia or neck stiffness. He has a past medical history of Waldenström macroglobulinaemia (WM). On examination, his blood pressure is 170/107 mmHg and he is apyrexial. Fundoscopy reveals bilateral papilloedema and widespread fundal haemorrhages. He has a CT head, which shows no evidence of any intracranial masses or bleeds. Which of the following is the most likely diagnosis? A. Hypertensive retinopathy B. Tension headache C. Idiopathic intracranial hypertension D. Hyperviscosity syndrome E. Subarachnoid haemorrhage

Answer 88

D. Hyperviscosity syndrome Hyperviscosity syndrome is a condition characterised by a high plasma viscosity. WM is the most common cause, although it may also be associated with polycythaemia, leukaemia, paraneoplastic syndromes and connective tissue disorders. Hyperviscosity syndrome typically presents with headache, blurred vision, hypertension, heart failure, dilutional anaemia/thrombocytopenia, ischaemic stroke and venous thromboembolism. The presence of features of hyperviscosity (headache, blurred vision, and papilloedema) with a past medical history of WM makes hyperviscosity syndrome the most likely diagnosis.

Question 89

egs of malignant paraproteinaemias:

Answer 89

1. Multiple myeloma 2. Waldenstrom's macroglobulinaemia (WM) 3. Solitary plasmacytoma

Question 90

what is Waldenstrom macroglobulinemia:

Answer 90

WM is a low-grade lymphoma where monoclonal plasmacytoid lymphocytes in the marrow and organs secrete monoclonal IgM. Clinical features are caused by IgM deposition (hyperviscosity, polyneuropathy), organ infiltration (hepatosplenomegaly, lymphadenopathy), and pancytopenia. -treatment; plasmapheresis

Question 91

A 24-year-old man is receiving a transfusion of fresh frozen plasma (FFP). After 15 minutes into the transfusion, he develops shortness of breath. Observations are as follows: heart rate 120bpm, blood pressure 80/35 mmHg, and temperature 37.2ºC. On examination, you note bilateral expiratory wheeze. He has no past medical history. What is the most likely cause? A. Acute haemolytic transfusion reaction B. Anaphylactic reaction C. Bacterial contamination D. Transfusion-associated circulatory overload (TACO) E. Transfusion-related acute lung injury (TRALI)

Answer 91

B. Anaphylactic reaction The patient has features of anaphylactic shock (acute wheeze and hypotension in the absence of fever). This reaction is more common with plasma-rich blood products such as FFP, cryoprecipitate and platelets. Not E: TRALI RALI is a serious and potentially fatal complication of blood product transfusion in which a patient develops rapid onset lung injury and non-cardiogenic pulmonary oedema due to activation of immune cells in the lung. It is often associated with plasma-rich blood components such as FFP and cryoprecipitate. Although TRALI can also present with hypotension, as seen in this vignette, the acute onset within 15 minutes makes an anaphylactoid reaction more likely. Since TRALI results in non-cardiogenic pulmonary oedema, the clinical findings would typically be bibasal coarse crepitations in contrast to the expiratory wheeze that is seen in this case.

Question 92

A 40-year-old man with beta-thalassaemia is receiving a blood transfusion in hospital. Within 10 minutes of starting the transfusion, he becomes acutely unwell, with fevers, rigors and significant abdominal pain. Observations: Pulse: 124bpm Blood pressure: 94/62 mmHg Oxygen saturations: 96% on air Respiratory rate: 24/min Temperature: 38.6ºC What is the most appropriate management? A. Stop the transfusion and give IV fluids B. Stop the transfusion, give an antihistamine and then continue the transfusion at a slower rate C. Stop the transfusion and give IV diuretics D. Slow the rate of transfusion and give oral paracetamol E. Stop the transfusion, give IM adrenaline and begin fluid resuscitation

Answer 92

A. Stop the transfusion and give IV fluids Acute haemolytic transfusion reaction should be treated with generous fluid resuscitation and termination of the transfusion. Not E: Stop the transfusion, give IM adrenaline and begin fluid Stopping the transfusion and giving adrenaline is the correct management of anaphylaxis, which would present with wheeze, stridor, shortness of breath and likely skin changes such as urticaria and angioedema. It is not the correct management for acute haemolytic reaction.

Question 93

what do heinz bodies indicate?

Answer 93

Glucose-6-phosphate dehydrogenase deficiency, chronic liver disease

Question 94

when are schistocytes seen?

Answer 94

Microangiopathic anaemia, e.g. DIC, haemolytic uraemic syndrome, thrombotic thrombocytopenic purpura, pre-eclampsia

Question 95

A 43-year-old man, currently an inpatient on a surgical ward for acute pancreatitis, develops episodic epistaxis. Blood tests are taken which demonstrate the following: Platelets 52 * 109/L (150 - 400) Prothrombin time (PT) 23 secs (10-14 secs) Activated partial thromboplastin time (APTT) 46 secs (25-35 secs) Fibrinogen 0.8 g/L (2 - 4) D-Dimer 1203 ng/mL (< 400) Given the likely diagnosis, what would be expected on blood film? A. Elliptocytes B. Heinz bodies C. Howell–Jolly bodies D. Schistocytes E. Spherocytes

Answer 95

D. Schistocytes DIC is associated with schistocytes due to microangiopathic haemolytic anaemia a procoagulant state due to the activation of coagulant pathways. It can be triggered by a number of factors - in this instance, an acutely unwell patient. The blood tests show a depletion of platelets and coagulation factors, characteristic of DIC. The condition is associated with schistocytes due to microangiopathic haemolytic anaemia. Elliptocytes would not typically be expected due to DIC. These are erythrocytes that appear rod- or pencil-shaped. These are seen in iron deficiency, thalassaemia and a number of other conditions. Heinz bodies are inclusions within red blood cells due to a number of conditions, including alpha-thalassaemia and glucose-6-phosphate dehydrogenase deficiency. They would not be expected in DIC. Howell-Jolly bodies are inclusions within red blood cells, characteristic of decreased splenic function, such as post-splenectomy. They would not be expected in DIC either. Spherocytes are erythrocytes that are sphere-shaped rather than biconcave. These would not be expected in DIC, and are seen in hereditary spherocytosis.

Question 96

A 32-year-old woman who had a positive urinary pregnancy test 5-days ago attends a direct-access antenatal clinic appointment. A fetal heart is seen on ultrasound with a heart rate of 120 beats/minute. Her past medical history includes recurrent miscarriages, pulmonary embolisms and deep vein thromboses. Previous blood tests revealed a prolonged APTT and moderately elevated anticardiolipin antibody levels on 2 separate occasions. Given her likely diagnosis, what would be the most appropriate management for this patient? A. Aspirin B. Aspirin and enoxaparin C. Enoxaparin D. Enoxaparin and warfarin E. Warfarin

Answer 96

B. Aspirin and enoxaparin Antiphospholipid syndrome in pregnancy: aspirin + LMWH Important -This patient has antiphospholipid syndrome, as suggested by her history of recurrent miscarriages, blood clots and prolonged APTT and moderately elevated anticardiolipin antibody levels. The management of pregnant women with antiphospholipid syndrome and previous thrombotic events is with aspirin, which is started upon confirmation of pregnancy with a urinary test, and unfractionated or low molecular weight heparin (e.g. enoxaparin) which is started once a fetal heart is seen on ultrasound. LMWH is usually discontinued at 34 weeks gestation.

Question 97

What autoantibodies are present in antiphospholipid (Hugh's) syndrome?

Answer 97

Antibodies against cardiolipin and β2 glycoprotein, lupus anticoagulant,

Question 98

how to differentiate between hereditary spherocytosis & AIHA (both have spherocytes):

Answer 98

hereditary sperocytosis=-ve Coombs test (due to defect in proteins that make up RBC membrane, no Abs) vs AIHA (positive Coombs test due to Abs attacking RBCs)

Question 99

Which coagulation factor falls most rapidly after starting warfarin?

Answer 99

Warfarin is an anticoagulant medication that works by inhibiting the synthesis of vitamin K-dependent clotting factors, including factors II, VII, IX, and X (2, 7, 9 & 10). Among these clotting factors, factor 7 has the shortest half-life and therefore falls most rapidly after starting warfarin.

Question 100

what is plasmapheresis?

Answer 100

a method of removing blood plasma from the body by withdrawing blood, separating it into plasma and cells, and transfusing the cells back into the bloodstream. It is performed especially to remove antibodies in treating autoimmune conditions.

Question 101

How does Kleihauer test work?

Answer 101

The Kleihauer test checks how much fetal blood has passed into the mother’s blood during a sensitisation event. This test is used after any sensitising event past 20 weeks gestation, to assess whether further doses of anti-D is required. The Kleihauer test involves adding acid to a sample of the mother’s blood. Fetal haemoglobin is naturally more resistant to acid, so that they are protected against the acidosis that occurs around childbirth. Therefore, fetal haemoglobin persists in response to the added acid, while the mothers haemoglobin is destroyed. The number of cells still containing haemoglobin (the remaining fetal cells) can then be calculated.

Question 102

how does anti-D work?

Answer 102

The anti-D medication works by attaching itself to the rhesus-D antigens on the fetal red blood cells in the mothers circulation, causing them to be destroyed (before mother's immune system developing own anti-rhesus D antibodies against the baby's RBCs) This prevents the mother’s immune system recognising the antigen and creating its own antibodies to the antigen. It acts as a prevention for the mother becoming sensitised to the rhesus-D antigen.

Question 103

How does HDN happen (haemolytic disease of newborn)?

Answer 103

During subsequent pregnancies, the mother’s anti-rhesus-D antibodies can cross the placenta into the fetus. If that fetus is rhesus-D positive, these maternal anti-rhesus antibodies (IgG) attach themselves to the red blood cells of the fetus and causes the immune system of the fetus to attack them, causing the destruction of the red blood cells (haemolysis). The red blood cell destruction caused by antibodies from the mother is called haemolytic disease of the newborn (haemolytic anaemia and jaundice)

Question 104

18) Pregnant women given misoprostol to induce labour. She suddenly has severe shivers, clammy skin, vomiting. Observations - high HR, low BP. Blood results - INR of 1.9, high APTT, low fibrinogen, high D-dimers. What is the most likely obstetric event?

Answer 104

Amniotic fluid embolism (AFE) The clinical presentation and laboratory findings described suggest that the patient may be experiencing an amniotic fluid embolism (AFE). It can present similar to sepsis, pulmonary embolism or anaphylaxis: AFE is a rare but potentially life-threatening obstetric emergency that occurs when amniotic fluid, fetal cells, hair, or other debris enter the maternal circulation and trigger an acute systemic inflammatory response. The symptoms of AFE can be sudden and severe, and may include dyspnea, cyanosis, hypotension, tachycardia, cardiac arrest, seizures, and disseminated intravascular coagulation (DIC). The laboratory findings in AFE typically show evidence of coagulopathy, such as a prolonged APTT, low fibrinogen levels, and elevated D-dimer levels. Misoprostol is a prostaglandin analogue that is commonly used for cervical ripening and induction of labor. Although misoprostol is generally considered safe and effective for this purpose, it can cause uterine hyperstimulation, which can lead to fetal distress, uterine rupture, and other complications. The use of misoprostol for labor induction may increase the risk of AFE (induction of labour: RF for AFE).

Question 105

23) Venetoclax is a BCL2 inhibitor used in CLL. What cellular process does it affect?

Answer 105

Triggers apoptosis in cells (BCL2 is an anti-apoptotic protein, therefore if venetoclax is a BCL2 inhibitor, it triggers apoptosis). BCL-2 is a member of the BCL-2 family of proteins, which play important roles in regulating apoptosis in cells. These proteins control the release of cytochrome c from mitochondria, which activates the caspase cascade and ultimately leads to apoptosis. BCL-2 itself is an anti-apoptotic protein that prevents the release of cytochrome c and blocks apoptosis. Venetoclax binds to the BH3 domain of BCL-2, displacing pro-apoptotic proteins such as BIM and allowing them to activate the caspase cascade and trigger apoptosis. This results in the death of cancer cells, including those in CLL.

Question 106

Old woman with painless lymphadenopathy. Blood results - normal Hb, normal neutrophils, normal platelets, high lymphocytes. Smear cells present. Lymphocytes are CD5+ve and CD19+ve.

Answer 106

CLL (Smear CLLs=cells)

Question 107

Man has returned from India. Whilst abroad, he has malaise and jaundice which self-resolved. He now has fatigue and easy bruising. Blood results - low Hb, normal MCV, low reticulocytes, low WCC, low neutrophils, normal lymphocytes, low platelets. What is the likely diagnosis?

Answer 107

Malaria. Given the patient's history of travel to India, his symptoms of malaise and jaundice, and his current presentation with pancytopenia (low Hb, low WCC, low platelets), the most likely diagnosis is malaria. Malaria is a parasitic infection transmitted by the bite of infected female Anopheles mosquitoes. It is endemic in many parts of India and other tropical regions.The pancytopenia in malaria is caused by several factors, including the destruction of infected and uninfected red blood cells, suppression of bone marrow function, and immune-mediated destruction of blood cells. The low reticulocyte count indicates a decreased production of new red blood cells in the bone marrow. The low neutrophil count may be due to bone marrow suppression or increased consumption of neutrophils during the infection. The normal lymphocyte count may indicate an appropriate immune response to the infection.

Question 108

which infection causes aplastic anaemia?

Answer 108

parvovirus B19 (slapped cheek syndrome, Erythema infectiosum,)

Question 109

Aplastic anaemia causes mnemonic

Answer 109

(3Cs): carbamezapine (antiepileptic), carbimazole (antithyroid), chloramphenicol (antibitoics eg eye drops)

Question 110

ITP signs/symptoms (triad):

Answer 110

ITP is an autoimmune condition characterized by a low platelet count (thrombocytopenia) resulting from the destruction of platelets by the immune system. The presenting symptoms of a widespread non-blanching erythematous rash, along with elevated WCC and severe thrombocytopenia, are consistent with ITP -can follow a recent infection (eg viral) Triad: 1. Bleeding, for example from the gums, epistaxis or menorrhagia 2. Bruising 3. Petechial or purpuric rash, caused by bleeding under the skin

Question 111

TTP symptoms (mnemonic):

Answer 111

pentad: Nasty fever ruined my tubes: -neuro symptoms eg confusion - fever -renal failure/haematuria -MAHA -thrombocytopenia (ITP no fever, isolated thrombocytopenia)

Question 112

HSP tetrad:

Answer 112

1. abdominal pain, arthralgia, glomerulonephritis, rash (usually non-blanching palpable purpuric rash is noted on the buttocks and shins: without thrombocytopenia and coagulopathy)

Question 113

HUS (haemolytic uraemic syndrome) triad:

Answer 113

ecoli 0157:h7, produces shiga-like toxin, causes dysentery (especially children), attacks glomerular vessels triad: 1. thrombocytopenia 2. acute renal impairment (uraemia) 3. microangiopathic hemolytic anemia (MAHA)

Question 114

key differentials of non-blanching rash:

Answer 114

ITP meningococcal septicaemia Henoch-Schonlein purpura ( NAI

Question 115

what is Evan's syndrome?

Answer 115

Evans syndrome is an autoimmune disorder in which antibodies attack red blood cells (RBC), which deliver oxygen to body tissues, platelets (which help blood clot), and/or neutrophils (a type of white blood cell). AIHA + ITP (isolated thrombocytopenia) -can happen in CLL

Question 116

HUS, TTP, MAHA and DIC summary (triads):

Answer 116

HUS: TRM (triad mnemonic): thrombocytopenia + renal failure (+ dysentery+children)+MAHA TTP (pentad): Nasty fever ruined my tubes (neurological symptoms, fever, renal impairment, MAHA, thrombocytopenia) DIC: increase in TF exposure (associated with sepsis and pancreatitis)--> excessive extrinsic factor activation and increased consumption of platelets (thrombocytopenia) and coagulation factors Disseminated intravascular coagulation (DIC) causes (I’M STONeD!)’ -Immunological (e.g. severe allergic reactions, haemolytic transfusion reactions, pancreatitis), -Miscellaneous (e.g. aortic aneurysm, liver disease), -Sepsis/snake bites -Trauma (including serious tissue injury, burns, extensive surgery), -Obstetric (e.g. amniotic fluid embolism, placental abruption) - Neoplastic (myeloproliferative disorders as well as solid tumours such as pancreatic cancer) - Drugs (ITP no fever, isolated thrombocytopenia: caused by autoantibodies against platelet surface antigens and is a diagnosis of exclusion)

Question 117

preclinical summary of MAHA, HUS, TTP and DIC:

Answer 117

Question 118

Important features of sickle cell disease (mnemonic):

Answer 118

SICKLED MP