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Sharon's Phase 2a Medicine Revision > Haematology > Flashcards

Haematology Flashcards

1
Q

Define anaemia

A

Anaemia is a lower-than-normal concentration of haemoglobin or red blood cells (Hb <130g/L in men, <120 g/L women)

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2
Q

What is aplastic anaemia?

A

A form of pancytopenia - deficiency of all three cellular components of the blood including red cells, white cells, and platelets

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3
Q

What is haemolytic anaemia?

A

A form of anaemia characterised by an increased breakdown of red blood cells

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4
Q

What is microcytic anaemia?

A

A form of anaemia characterised by a reduced mean corpuscular volume (MCV) i.e. the average size of your red blood cells.

MCV = <80 femtolitres [fL]

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5
Q

What are some examples of microcytic anaemia?

A
  • Iron deficiency
  • Lead poisoning
  • Anaemia of chronic disease
  • Thalassaemia
  • Sideroblastic anaemia
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6
Q

What is macrocytic anaemia?

A

A form of anaemia characterised by an increased mean corpuscular volume (MCV) i.e. the average size of your red blood cells.

MCV >100 femtolitres [fL]

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7
Q

What is macrocytic anaemia?

A

A form of anaemia characterised by an increased mean corpuscular volume (MCV) i.e. the average size of your red blood cells.

MCV >100 femtolitres [fL]

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8
Q

What is normocytic anaemia?

A

A form of anaemia with normal MCV of 80-100 femtolitres [fL]

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9
Q

What are some examples of normocytic anaemia?

A
  • Sickle cell
  • Hereditary spherocytosis,
  • G6PDH deficiency
  • Malaria
  • Autoimmune Haemolytic
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10
Q

What are some examples of macrocytic anaemia?

A

Megaloblastic:
Folate deficiency: e.g. dietary insufficiency

B12 deficiency: e.g. pernicious anaemia

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11
Q

What general symptoms might a patient with anaemia present with?

A

Fatigue, headache, dizziness, dyspnoea (especially on exertion)

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12
Q

What general signs might a patient with anaemia present with?

A

Tachycardia, skin pallor, conjunctiva pallor, intermittent claudication

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13
Q

What symptoms and signs might a patient with iron deficiency anaemia present with?

A

Symtoms

  • Fatigue
  • Dyspnoea on exertion
  • Pica
  • Restless legs syndrome

Signs:

  • Nail changes - thinning, flattening, and then spooning of the nails (rare)
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14
Q

What is the aetiology of iron deficiency anaemia?

A
  • Inadequate dietary iron intake
  • Impaired iron absorption (e.g. gastric surgery, or coeliac disease)
  • Increased iron loss because of bleeding, usually in the GI tract (e.g. peptic ulcer disease)
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15
Q

What are 4 main risk factors of iron deficiency anaemia?

A

Pregnancy
Vegetarian and vegan diet
Menorrhagia (heavy periods)
Hookworm infestation

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16
Q

What tests/investigations would you carry out on a patient with suspected iron deficiency anaemia?

A
  • Haemoglobin and haematocrit (% of blood occupied by RBCs) (low)
  • Platelet count (low, normal or elevated)
  • MCV (mean corpuscular volume) - < 80 fL
  • MCH (mean corpuscular haemoglobin - average conc of haemoglobin inside one RBC) (low)
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17
Q

What is the management/treatment for iron deficiency anaemia?

A

First line: oral iron replacement
Second line: IV iron replacement

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18
Q

How is iron deficiency anaemia monitored?

A

Haemoglobin concentration and red cell indices (measures shape, size and quality of RBCs) measured every 3 months for a year, again after one further year, and thereafter when symptomatic

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19
Q

Define alpha thalassaemia

A

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.

Deletions in alpha-globin chains leads to alpha thalassaemia

Autosomal recessive

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20
Q

What is the epidemiology of alpha thialassaemia?

A

Most likely in people from Mediterranean, South-east Asia, India, Middle East and Sub-Saharan Africa as they are the malarial regions of the world

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21
Q

What is the aetiology of alpha thialassaemia?

A

Alpha-thalassaemia is a group of disorders of haemoglobin synthesis, caused by deletions in at least 1 of the 4 alpha-globin genes (on chromosome 16).

The severity of the anaemia depends on the number of genes mutated.

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22
Q

What is the pathophysiology of alpha thialassaemia?

A
  • Silent carrier - one gene deletion is asymptomatic
  • Alpha thalassemia trait - 2 gene deletion > mildly anaemic
  • HbH: 3 gene deletions mean patient is unable to form alpha chains, beta chains form tetramers (HbH), which damage erythrocytes causing moderate to severe disease
  • Hb Bart’s (alpha thalassemia major) - 4 gene deletions, death in utero as gamma chains form tetramers which cannot carry oxygen efficiently.
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23
Q

What signs and symptoms might a patient with alpha-thialassaemia present with?

A

Common:
Anaemia (fatigue, pallor)
Splenomegaly

Uncommon:
Pronounced forehead and malar eminences

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24
Q

What investigations/tests would you carry out for a patient with suspected alpha-thialassemia?

A

1) FBC - microcytic anaemia with reticulocytosis as bone marrow increase production of erythrocytes to compensate

2) Haemoglobin electrophoresis (diagnostic)

  • Silent carrier: normal electrophoresis
  • Alpha thalassaemia trait: near-normal haemoglobin electrophoresis
  • HbH: HbH (beta chain tetramers) present on electrophoresis

3) Peripheral smear (blood film) - microcytic, hypochromic erythrocytes (lack of pigment), as well as target cells and nucleated RBCs (Howell-Jolly bodies)

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25
Q

What are the differential diagnosis for alpha-thialassemia?

A
  • Iron deficiency anaemia
  • Beta-thalassaemia
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26
Q

What is the treatment/management for alpha-thialassaemia?

A
  • Alpha thialassaemia trait - mild anaemia no treatment needed

HbH:

  • Monitoring the full blood count
  • Monitoring for complications
  • Regular blood transfusions if symptomatic or Hb < 70g/L
  • Iron chelation- to treat iron overload
  • Splenectomy
  • Bone marrow transplant can be curative
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27
Q

Define beta-thialassemia

A

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

Beta thalassaemia occurs due to impaired synthesis of β-globin. 2 alleles (on chromosome 11) are responsible for chain synthesis. Mutations (not deletions like in alpha thalassaemia) can cause reduced or absent beta chain synthesis, resulting in 3 possible phenotypes, with thalassaemia major being the most severe

Autosomal recessive

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28
Q

What is the epidemiology of beta-thialassemia?

A

Most likely in people from Mediterranean, South-east Asia, India, Middle East and Sub-Saharan Africa as they are the malarial regions of the world

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29
Q

What is the aetiology of beta-thialassemia?

A

Beta-thalassaemia is an inherited microcytic anaemia caused by mutation(s) of the beta-globin gene, 2 alleles on chromosome 11 > decreased or absent synthesis of beta-globin, resulting in ineffective erythropoiesis (RBC production)

Range from beta-thialassaemia trait (asymptomatic), beta-thialassaemia intermedia and beta-thialassaemia major (severe anaemia and skeletal changes).

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30
Q

What are the risk factors for beta-thialassaemia and alpha-thiassaemia?

A
  • Mediterranean, South-east Asia, India, Middle East and Sub-Saharan Africa background
  • Positive family history
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31
Q

What are the three different types of beta-thialassemia?

A
  • Beta-thalassaemia trait (minor) = B/B+
  • Beta-thalassaemia intermedia = B+/B+ or B+/B0
  • Beta-thalassaemia major = B0/B0

B = normal beta-chain
B+ = reduced beta-chain
B0 = absent beta-chain

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32
Q

Describe beta-thlassaemia minor

A
  • Patients with beta thalassaemia minor are carriers of an abnormally functioning beta globin gene. They have one abnormal and one normal allele (B/B+)
  • Thalassaemia minor causes a mild microcytic anaemia and present with anaemia symptoms such as fatigue.
  • Usually only require monitoring and no active treatment.
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33
Q

Describe beta-thialassaemia intermedia

A

Patients have two abnormal copies of the beta-globin gene - defective gene and/or beta-zero mutation gene (resulting in absent beta-chain)

  • Either two defective genes (B+/B+) or
  • One defective gene and B0 gene (B+/B0)
  • Causes more significant microcytic anaemia
  • Require monitoring and occasional blood transfusions.
  • If patients need more transfusions they may require iron chelation to prevent iron overload.
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34
Q

Describe beta-thialassaemia major

A

Patients are homozygous for the beta-zero mutation in the beta-globin genes (B0/B0)

  • No functioning beta-globin genes = absent beta chain production
  • Most severe form and usually presents in children < 2 with:
  • Severe microcytic anaemia
  • Failure to thrive
  • Splenomegaly
  • Bone deformities
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35
Q

What are the tests/investigations you would carry out for a patient with suspected beta-thialassaemia?

A

1) FBC (microcytic anaemia)

2) Peripheral smear (microcytic red cells, tear drops, target cells, nucleated RBCs)

3) Reticulocyte count (elevated)

4) Haemoglobin electrophoresis (diagnostic) - reduced HbA (normal Hb unit 2 alpha and 2 beta chains)

5) DNA testing can be used to look for the genetic abnormality

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36
Q

What are some DDx for beta-thialassaemia?

A
  • Congenital dyserythropoietic anaemia (CDA)
  • Pyruvate kinase (PK) deficiency
  • Mild iron deficiency anaemia
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37
Q

What is the treatment/management for beta-thialassaemia?

A

1) Minor- genetic counselling and iron advice

2) Intermedia: non-transfusion-dependent

  • 1st line – transfusions at times of symptomatic anaemia or if Hb < 70 g/L
  • Consider iron monitoring + chelation therapy to prevent iron overload

3) Intermedia: transfusion-dependent & Major

1st line –

  • Regular transfusion
  • Iron monitoring + chelation
  • Genetic counselling

Consider

  • Splenectomy
  • Stem cell/bone marrow transplantation might be curative
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38
Q

Name one complication of beta-thialassaemia

A

Iron overload

It causes effects similar to haemochromatosis:

Fatigue
Liver cirrhosis
Infertility and impotence
Heart failure
Arthritis
Diabetes
Osteoporosis and joint pain

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39
Q

What is iron overload?

A

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.

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40
Q

How is iron overload managed?

A

Management involves montioring serum ferritin levels for iron overload, limiting transfusions and iron chelation.

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41
Q

What follow-up monitoring is carried for patients with beta-thialassaemia?

A
  • Iron load
  • Cardiovascular function
  • Hepatobiliary function
  • Renal function
  • Endocrine function
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42
Q

Define normocytic anaemia

A

Anaemia with normal MVC ( 80-100 femtolitres [fL]) but low number of RBCs

E.g. haemolytic anaemia

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43
Q

What is haemolytic anaemia?

A

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

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44
Q

What are some causes of haemolytic anaemia?

A
  • Sickle cell
  • Thialassaemia
  • Autoimmune haemolytic anaemia
  • Sepsis / disseminated intravascular
    coagulopathy (DIC)
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45
Q

Define sickle cell anaemia

A

Sickle cell anaemia is an autosomal recessive mutation in the beta chain of haemoglobin, resulting in sickling of red blood cells (RBCs) and haemolysis.

The point mutation results in a hydrophilic glutamic acid amino acid being substituted for a hydrophobic valine, changing the structure of the beta chain.

If only one gene is mutated, this is called sickle cell trait. If both are mutated, this is known as sickle cell disease.

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46
Q

What is the epidemiology of sickle cell anaemia?

A
  • More common in patients from areas traditionally affected by malaria, such as Africa, India, the Middle East and the Caribbean.
  • 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.
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47
Q

What is the aetiology of sickle cell anaemia?

A

Normal haemoglobin consists of 2 alpha-globin and 2 beta-globin subunits

  • Sickle cell disease is due to a single nucleotide polymorphism (SNP) in the beta gene (HBB) , the mutation causes the GAG codon to be changed to GTG.
  • Glutamic acid is substituted for valine at position 6 on one or both beta hemoglobin subunits, giving rise to haemoglobin S (HbS).
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48
Q

What is the pathophysiology of sickle cell anaemia?

A

HbS is more prone to sickling and haemolysis.

When exposed to low oxygen levels (e.g. in the smaller capillaries on the leg) haemoglobin S (HbS) precipitates, causing the RBC to be distorted into a sickle/crescent shape, which are fragile and stiff.

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49
Q

What signs and symptoms might a patient with sickle cell anaemia present with?

A

General anaemia symptoms:

Symptoms: fatigue, headache, dizziness, dyspnoea (especially on exertion)

Signs: tachycardia, skin pallor, conjunctiva pallor, intermittent claudication

Haemolytic anaemia (e.g. sickle cell): jaundice, dark urine, gallstones

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50
Q

What tests/investigations are used to diagnose sickle cell anaemia?

A

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

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

3) FBC - normocytic anaemia with reticulocytosis

4) Blood film - sickled RBCs, target cells, Howell-Jolly bodies

5) Hb electrophoresis and solubility - diagnostic - increased HbS and reduced/absent HbA

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51
Q

What is the general management for sickle cell anaemia?

A

Long-term/general:

  • Pain management with meds
  • Avoid dehydration and other triggers of crises
  • Ensure vaccines are up to date
  • Antibiotic prophylaxis (penicillin first choice, erythromycin if allergic)
  • Hydroxycarbamide to stimulate production of fetal haemoglobin (HbF).
  • Blood transfusion for severe anaemia
  • Folic acid supplement - raises Hb levels
  • Bone marrow transplant can be curative
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52
Q

What is sickle-cell crisis?

A

Umbrella term for a spectrum of acute crises related to sickle cell anaemia.

Spontaneously or be triggered by stresses such as infection, dehydration, cold or significant life events.

Can be life-threatening

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53
Q

What are some acute symptoms of sickle-cell disease (caused sickle cell crisis)?

A

1) Sequestration crisis - presents with abdominal pain

  • RBCs sickle in the spleen, causing pooling of blood and a rapid drop in Hb and platelets

2) Aplastic crisis

  • Infection with parvovirus B19 causes bone marrow suppression
  • Sudden onset pallor, fatigue, and anaemia

3) Vaso-occlusive (thrombotic) crisis: painful, vaso-occlusive episodes occur as RBCs sickle in various organs such as bones, lungs, kidneys, and genitalia.

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54
Q

What is the treatment/management for an episode of sickle-cell crisis?

A
  • Have a low threshold for admission to hospital
  • Oxygen - if hypoxic or to prevent sickling
  • Treat any infection
  • Keep warm
  • Keep well hydrated (IV fluids may be required)
  • Simple analgesia such as paracetamol and ibuprofen
  • Penile aspiration in priapism (persistent erection)
  • Exchange transfusion - removal of HbW in exchange for normal Hb in severe crises
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55
Q

What are the complications of sickle cell anaemia?

A

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

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56
Q

Name 4 possible causes of B12 deficiency

A
  • Pernicious anaemia
  • Malabsorption (coeliac, IBD, bowel resection, ileostomy)
  • Decreased dietary intake e.g. vegan, found in meat, fish, eggs, milk
  • Chronic nitrous oxide use
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57
Q

Define pernicious anaemia

A

Lack of intrinsic factor, usually produced by parietal cells in the stomach. Allows B12 absorption in the terminal ileum

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58
Q

What signs and symptoms might a patient with B12 deficiency present with?

A

General anaemia presentation & lemon yellow skin

A range of neurological signs and symptoms:

  • Peripheral neuropathy with numbness or paraesthesia (pins and needles)
  • Loss of vibration sense or proprioception
  • Visual changes
  • Mood or cognitive changes
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59
Q

What tests/investigations would you carry out for a patient with suspected B12 deficiency?

A

Blood tests: raised MCV, Low haematocrit, low B12

Blood film: ‘Megaloblastic’ anaemia – segmented nucleated neutrophils 6+ lobes

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60
Q

What is the treatment for B12 deficiency?

A

Dietary deficiency: oral replacement with cyanocobalamin

Pernicious anaemia: problem is absorption not intake so parenteral hydroxycobalamin given instead

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61
Q

Name 4 causes of folate (vitamin B9) deficiency

A
  • Inadequate dietary intake
  • Increased demand, eg pregnancy
  • Malabsorption, eg coeliac disease, excess alcohol.
  • Drugs: anti-epileptics (phenytoin, valproate), methotrexate, trimethoprim
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62
Q

What tests/investigations would you carry out for a patient with suspected folate (B9) deficiency?

A

Similar to B12 deficiency

Blood tests: raised MCV, Low Hb, low serum folate, low red cell folate (better indicator of folate status)

Blood film: ‘Megaloblastic’ anaemia – segmented nucleated neutrophils 6+ lobes

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63
Q

What is the treatment for folate deficiency?

A

Folate helps to form healthy red blood cells.

  • Dietary changes: leafy greens, brown rice
  • Treat underlying cause
  • Oral folic acid supplement
  • Make sure to correct B12 levels before treating folate deficiency as treating folate before B12 deficiency will worsen subacute combined degeneration of the (spinal) cord.
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64
Q

Define acute myeloid leukaemia (AML)

A

Acute myeloid leukaemia (AML) is a life-threatening haematological malignancy, it involves the proliferation of myeloblasts and is the most common acute leukaemia in adults.

A myeloblast = immature WBC

Physiologically, myeloblasts become mature WBCs called granulocytes (neutrophils, eosinophils and basophils).

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65
Q

What are the risk factors for AML?

A
  • Increasing age: mostly affects the elderly (average diagnosis age 68-year-olds)
  • Myelodysplastic syndromes (cancer)
  • Myeloproliferative neoplasms (BM makes too many RBCs, WBCs or platelets)
  • Previous chemotherapy or radiation exposure
  • Benzene: painters, petroleum and rubber manufacturers
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66
Q

What is the pathophysiology of acute myeloid leukaemia (AML)?

A
  • t(15:17) chromosomal translocation
  • The rapid proliferation of immature myeloblasts.
  • Results in replacement of normal bone marrow with leukemia cells and a drop in other cell lineages, including red blood cells, platelets and normal white blood cells. This eventually results in bone marrow failure.
  • Present mostly in the elderly
  • Only 15% 5-year survival
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67
Q

What tests and investigations are used to diagnose AML?

A
  • FBC -> leukocytosis, anaemia, thrombocytopenia with low reticulocyte count
  • Blood film - Auer rods
  • Bone marrow biopsy - ≥20% myeloblasts is diagnostic
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68
Q

What signs and symptoms might a patient with AML present with?

A

Symptoms

  • Fatigue
  • Bleeding/bruising
  • Infection
  • Anorexia (loss of appetite)
  • Weight loss

Signs

  • Pallor
  • Lymphadenopathy
  • Hepatosplenomegaly
  • Gum hypertrophy
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69
Q

What is the treatment/management for AML?

A
  • Chemotherapy (cytarabine and an antracycline)
  • Antibiotics for neutropenia
  • Stem cell/bone marrow transplant - last resort
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70
Q

Define chronic myeloid leukaemia (CML)

A

Chronic myeloid leukaemia (CML) involves the neoplastic proliferation of myeloblast cells (haematopoietic stem cells) in the bone marrow

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71
Q

What is the pathophysiology of CML?

A

Chromosomes 9 and 22 translocation > abnormal chromosome 22 (Philadelphia chromosome).

  • BCR gene on chromosome 22 fused to ABL gene on chromosome 9 > BCR-ABL fusion oncogene > resulting p210 BCR-ABL protein, hallmark of CML
  • Tyrosine kinase irreversibly activated > uncontrolled cellular division> disrupting normal haematopoiesis
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72
Q

What signs and symptoms might a patient with CML present with?

A

Symptoms

  • Fatigue
  • Easy bleeding/bruising
  • Recurrent infections
  • Shortness of breath
  • Weight loss and night sweats

Signs

  • Pyrexia
  • Pallor (anaemia sign)
  • Abdominal tenderness
  • MASSIVE splenomegaly :(
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73
Q

What tests and investigations are used to diagnose CML?

A
  • FBC -> anaemia, thrombocytopenia, leukocytosis
  • Bone marrow biopsy - myeloblast infiltration in bone marrow
  • Blood film - increase in all stages of maturing granulocytes
  • Molecular testing - for Philadelphia chromosome
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74
Q

What is the treatment/management for CML?

A

First line: Tyrosine kinase inhibitors (Imatinib)
Chemotherapy
Stem cell/bone marrow transplant

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75
Q

What are some possible complications of CML?

A

Possible progression to AML if untreated/ late Dx

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76
Q

Define Acute lymphoblastic leukaemia (ALL)

A

Acute lymphoblastic leukaemia (ALL) is a malignant clonal disease that involves the proliferation of lymphoblasts, most commonly of the B cell lineage.

t(12;21) is the most common cytogenetic abnormality in children.

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77
Q

What is the pathophysiology of ALL?

A

In adults, like in CML, the Philadelphia chromosome is the most common cytogenetic abnormality > constitutively active tyrosine kinase. However it is more associated with CML.

These genetic aberration results in excessive proliferative of lymphoblasts which accumulates in the bone marrow > bone marrow failure > anaemia and thrombocytopenia

Lymphoblasts leak into the blood and can invade tissues such as testicles, meninges and kidneys.

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78
Q

Who is most at risk for developing ALL?

A
  • Children less than 5 years of age (75% cases in children under 6 years old)
  • Associated with trisomy 21 (Down’s syndrome)
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79
Q

What chromosome abnormality is ALL associated with?

A

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

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80
Q

What tests and investigations are used to diagnose ALL?

A
  • FBC - anaemia, thrombocytopenia, lymphocytosis, normocytic anaemia with low reticulocyte count
  • Blood film - shows lymphoblast cells
  • Bone marrow biopsy - = or more than 20% lymphoblasts is diagnostic
  • Imaging (CXR/CT) -> lymphadenopathy
  • Cytogenetic/molecular studies - identify t(12;21) or t(9;22)
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81
Q

What signs and symptoms might a patient with ALL present with?

A

Symptoms:

  • Fatigue
  • Fever
  • Loss of appetite
  • Easy bleeding/bruising
  • Recurrent infections
  • Bone pain - BM infiltration
  • Weight loss

Signs

  • Hepatosplenomegaly
  • Lymphadenopathy
  • CNS infiltration > headaches, CN palsies
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82
Q

What is the treatment/management for a patient with ALL?

A
  • Blood and platelet transfusions
  • Chemotherapy (methotrexate)
  • Steroids
  • Stem cell/bone marrow transplant
  • Antibiotics
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83
Q

Define chronic lymphocytic leukaemia (CLL)

A

Chronic lymphocytic leukaemia is where there is chronic and neoplastic proliferation of mature B lymphocytes > they collect in blood and can be seen on blood film.

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84
Q

Who is most at risk of developing CLL?

A

CLL usually affects adults over 55 years of age.

Most common type of leukaemia in adults

Men twice as likely as women

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85
Q

What signs and symptoms might a patient with CLL present with?

A

Symptoms:

  • Fatigue
  • Easy bruising: prolonged bleeding and mucosal bleeding due to thrombocytopaenia
  • Loss of appetite
  • Weight loss
  • Fever
  • Recurrent infections
  • Night sweats, weight loss

Signs

  • Hepatosplenomegaly: neoplastic cells invade the liver and spleen
  • Signs of anaemia e.g. pallor
  • Lymphadenopathy
86
Q

What tests/investigations are used in diagnosing CLL?

A
  • FBC -> anaemia, thrombocytopenia, leukocytosis
  • Blood film -> increased mature lymphocytes, smudge/smear cells due to fragile WBC that rupture on film
  • Immunophenotype: CD5, CD19, CD20, CD 23
  • Low immunoglobulins levels (hypogammaglobulinemia)
  • Genetic analysis: identify chromosomal deletions, e.g. del 17p, which helps guide treatment
87
Q

What is the treatment/management for CLL?

A
  • Watch and wait in early stages
  • Chemotherapy (rituximab)
  • Stem cell/bone marrow transplant
88
Q

What complications can CLL lead to?

A

CLL can transform into high-grade lymphoma becasue B-cells can massively accumulate in the lymph nodes > massive lymphadenopathy > aggressive lymphoma

This is called Richter’s transformation.

89
Q

Define Hodgkin’s lymphoma (HL)

A

A type of lymphoma caused by neoplastic proliferation of lymphocytes in the lymphatic system.

HL = Reed-Sternberg cells, large B cells with prominent ‘owl’s eye nuclei’ which secrete inflammatory cytokines and attract reactive inflammatory cells, resulting in ‘B symptoms’.

Bimodal age distribution with peaks around 15 - 35 and > 65

90
Q

What would you see histologically in nodular lymphocyte predominant HL?

A
  • Popcorn cells
  • Reed-Sternberg cells are rarely seen
91
Q

What are the risk factors for HL?

A
  • HIV
  • Epstein-Barr Virus (causes glandular fever)
  • Autoimmune conditions such as rheumatoid arthritis and sarcoidosis
  • Family history
92
Q

What signs and symptoms might a patient with HL present with?

A
  • Lymphadenopathy - enlarged lymph nodes might be in the neck, axilla (armpit) or inguinal (groin) region.
  • Non-tender and feel “rubbery”
  • Lymph nodes painful upon drinking alcohol
  • B-symptoms - fever, night sweats, weight loss
93
Q

What tests/investigations are used to diagnose HL?

A
  • FBC: leukocytosis with pancytopaenia if bone marrow involved
  • Lactate Dehydrogenase: elevated
  • Ultrasound of lymph nodes: indicate malignancy features
  • Lymph node biopsy > Reed Sternberg cells ( large, abnormal lymphocytes that contain >1 nucleus)
  • Erythrocyte sedimentation rate test (ESR) - increased which indicates inflammation
  • Imaging (CXR/CT) for staging
94
Q

What is the Ann Arbor Staging for HL and NHL?

A

The Ann Arbor Staging system puts importance on whether affected nodes are above or below the diaphragm.

Stage 1: Confined to one region of lymph nodes.
Stage 2: In more than one region but on the same side of the diaphragm
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.

And
A: no B symptoms
B: B symptoms present

95
Q

What is the treatment/management for HL?

A
  • ABVD chemotherapy
  • Doxorubicin (brand name adriamycin), bleomycin, vinblastine, dacarbazine
  • Radiotherapy
  • Steroids
  • Stem cell/bone marrow transplant
96
Q

What is a complication that can develop with recent/high dose chemotherapy?

A

Febrile neutropenia

Px = Fever (38c+), tachycardia, rigors, tachypnoea (rapid breathing)

Tx = broad spectrum antibiotics (e.g. amoxicillin)

97
Q

Define Non-Hodgkin’s Lymphoma

A

NHL is a group of lymphomas

Burkitt lymphoma: associated with EBV, malaria, and HIV.

MALT lymphoma affects the mucosa-associated lymphoid tissue, usually around the stomach. It is associated with H. pylori infection.

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

98
Q

What age group is most at risk of developing NHL?

A

Predominantly affects adults over the age of 40

99
Q

What signs/symptoms might a patient with NHL present with?

A
  • Painless lymphadenopathy
  • B symptoms > weight loss, night sweats, fever
  • Can get hepatosplenomegaly
100
Q

What tests/investigations are used to diagnose NHL?

A
  • Imaging (CXR/CT) for staging (Ann Arbor)
  • Lymph node biopsy > no Reed Sternberg cells - the only way to differentiate from HL
101
Q

What is the treatment/management for NHL?

A
  • Watchful waiting
  • RCHOP chemotherapy (Rituximab (mAb), Cyclophosphamide, Hydroxy-daunorubicin
    Vincristine (brand name Oncovin)
  • Prednisolone
  • Radiotherapy
  • Stem cell transplantation
102
Q

Define multiple myeloma (MM)

A

Neoplastic monoclonal proliferation of a plasma cell (B-cells that produce antibodies) that affect MULTIPLE areas of the body

103
Q

Whcih age group is most at risk for MM?

A

Predominantly occurs in those over the age of 40

104
Q

Which disease is MM closely associated with?

A

Monoclonal gammopathy of undetermined significance (MGUS)

  • Abnormally high levels of an immunoglobulin released by abnormal plasma cells
  • 1% develop into myeloma
105
Q

What symptoms/signs might a patient with MM present with?

A

Old CRAB

Old -70+

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

106
Q

What tests/investigations are used to diagnose MM?

A
  • FBC > anaemia
  • ESR > raised
  • Blood film > Rouleaux formation
  • Serum and urine electrophoresis -> Bence Jones protein in urine (part of antibody subunit) + hypercalcemia
  • Imaging (x-ray/CT) -> bone lesions
  • Diagnostic bone marrow biopsy 10% plasma cells
107
Q

What is the pathophysiology of MM?

A

Immunoglobin: A, G, M, D and E (GAMED)

Patient with MM - one of them raised in blood

50% cases = IgG

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

108
Q

What is treatment/management for MM?

A

First-line treatment combination of chemotherapy with:

Bortezomid
Thalidomide
Dexamethasone

Stem cell transplantation can be used as part of a clinical trial where patients are suitable.

109
Q

What is the DDx for MM?

A

MGUS - Monoclonal gammopathy of undetermined significance

  • BM biopsy < 10% plasma cells
  • No or little paraprotein spike
  • Asymptomatic
110
Q

Define polycythaemia

A

A high concentration of erythrocytes in the blood

111
Q

What are the different types of polycythaemia?

A
  • Absolute > split into primary and secondary
  • Relative
112
Q

Define relative polycythaemia

A

There are a normal number of erythrocytes, but there is a reduction in plasma

113
Q

What are the causes of relative polycythaemia?

A

Obesity, dehydration, and excessive alcohol consumption

114
Q

Define absolute polycythaemia and state the difference between primary and secondary polycythaemia

A

There is an increased number of erythrocytes:

  • Primary polycythaemia
    Abnormality in the bone marrow - known as polycythaemia vera
  • Secondary polycythaemia
    A disease outside the bone marrow causing overstimulation of the bone marrow
115
Q

What are some causes of secondary polycythaemia?

A

COPD, sleep apnoea, PKD, renal artery stenosis, kidney cancer

116
Q

What is the aetiology of polycythaemia vera (primary polycythaemia)?

A

95% of cases are due to JAK2 mutation (gene that encodes for a protein that promotes the proliferation of cells).

117
Q

What signs and symptoms might a patient with polycythaemia vera present with?

A

General polycythaemia symptoms:

  • Headaches
  • Dizziness
  • Fatigue
  • Blurred vision
  • Red skin (hands, face, and feet)
  • Hypertension

Specific to polycythaemia vera:

  • Itching, especially after contact with warm water (e.g., a bath)
  • Hepatosplenomegaly
118
Q

What investigations/tests might you carry out to diagnose polycythaemia vera?

A

FBC:
- Raised haemoglobin (> 185g/l in men or 165g/l in women)
- Raised haematocrit, white cell count, and platelet count
- Genetic testing for JAK2 mutation
- Serum erythropoietin > decreased (can be normal or increased in other types of polycythaemia)

119
Q

What is the treatment/management for polycythaemia vera?

A

First line: venesection (removing blood) to keep the haemoglobin in the normal range.

Aspirin can be used to reduce thrombus formation

Chemotherapy for patients at high risk of thrombosis

120
Q

Define HIV (Human Immunodeficiency Virus)

A

HIV is a (single-stranded) RNA retrovirus. HIV-1 is the most common type, and HIV-2 is rare outside West Africa. The virus enters and destroys the CD4 T-helper cells of the immune system.

121
Q

What are the risk factors for HIV?

A
  • Unprotected anal, vaginal or oral sexual activity
  • Mother to child at any stage of pregnancy, birth or breastfeeding (called vertical transmission)
    –Sharing needles, needle-stick injuries, or blood splashed in an eye
122
Q

What is the pathophysiology of HIV?

A
  • HIV attaches to CD4 receptors and co-receptor on T-helper cells, dendritic cells, and macrophages via the GP120 protein
  • HIV enters the target cell by injecting its single strand of RNA into target cell
  • Reverse transcriptase enters nucleus and transcribes complementary proviral DNA (ready to be integrated into host genome)
  • During infections, when the host immune cell mounts an response, new HIV viruses are transcribed and translated at the same time
  • New viruses leave by exocytosis from cell membrane to infect more cells
123
Q

Describe the stages of HIV infection.

A
  1. Seroconversion (primary infection): flu-like symptoms 2 - 6 weeks after exposure
  2. Asymptomatic infection - immune system mounts a response to initial infection
  3. Chronic phase - viral load increases, T-cell numbers decrease (~500 cells/mm2 and patients can still fight infections)
  4. AIDS-related complex (ARC) - T cell count < 200 cells/mm2. Fever, night sweats, diarrhea, weight loss, minor opportunistic infections, e.g., oral candida, oral hairy leucoplakia
  5. Acquired immunodeficiency syndrome (AIDS) - sharp spike in HIV viral load - end-stage HIV.
124
Q

What conditions are considered “AIDS-defining illnesses”?

A

“AIDS-defining illnesses” -

  • Kaposi’s sarcoma
  • Pneumocystis pneumonia
  • Cytomegalovirus infection
  • Candidiasis (oesophageal or bronchial)
  • Lymphomas
  • Tuberculosis
125
Q

What investigations and tests are used to diagnose HIV?

A

Antibody testing - anti HIV IgG

Testing for the p24 antigen- specific HIV antigen in the blood - earlier detection

PCR testing for the HIV RNA levels tests directly for the number of viral copies in the blood, giving a viral load.

126
Q

What is the treatment/management for HIV?

A

HAART (Highly Active Anti-Retroviral Treatment):

A combination of antiretroviral therapy (ART) medications offered to everyone with a diagnosis of HIV irrespective of viral load or CD4 count.

  • Starting regime = two NRTIs (nucleoside/nucleotide reverse transcriptase inhibitors) e.g. tenofovir and emtricitabine and 3rd agent.

Treatment aims to achieve a normal CD4 count and undetectable viral load.

If the patient has a normal CD4 and an undetectable viral load on ART, treat their physical health problems as you would an HIV-negative patient.

127
Q

HIV: what is post-exposure prophylaxis (PEP)?

A

Post-exposure prophylaxis (PEP) used after exposure to HIV to reduce the risk of transmission.

PEP is not 100% effective and must be commenced in less than 72 hours after exposure.
PEP involves a combination of ART therapy. The current regime is Truvada (emtricitabine and tenofovir) and raltegravir for 28 days.

128
Q

What monitoring is carried out for a patient with HIV?

A

1) CD4 Count:

  • 500-1200 cells/mm3 = normal
  • Under 200 cells/mm3 = end-stage HIV (AIDS) and increased risk of opportunistic infections

2) Viral Load (VL)- number of copies of HIV RNA per ml of blood.

“Undetectable” = viral load below the lab’s recordable range (usually 50 – 100 copies/ml). vs 100,000s in untreated HIV

129
Q

Define Glucose-6-phosphate dehydrogenase deficiency

A

Unlikely to come up in exams, but good to know so can eliminate in SBA

G6P has a role in pentose sugar metabolism, also protects RBCs from damage.
In G6PD, RBC’s are exposed to more oxidative stress = haemolysis

130
Q

What are the risk factors for G6PD?

A

X-linked (men), from West Africa, Middle-east, Asia

131
Q

What signs and symptoms might a patient with G6PD present with?

A

Neonates: jaundice

Adults:

-Dark urine: haemaglobinuria
- Jaundice
- Splenomegaly
- Symptoms of anaemia: pallor and dyspnoea
- Backpain

132
Q

What investigations and tests are used to diagnose G6PD?

A

Bloods: anaemia, increased LDH (Lactate dehydrogenase - used to detect tissue damage), increased reticulocytes,
Blood smear: Heinz bodies (requires special prep)

133
Q

Define Von Willebrand Disease

A

The most common inherited cause of abnormal bleeding (haemophilia). Caused by a deficiency, absence or malfunctioning of a glycoprotein called von Willebrand factor (VWF).

Type 1 to type 3 depending on cause

134
Q

How would a patient with VWD present in clinic?

A
  • 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
  • A family history of heavy bleeding or von Willebrand disease
135
Q

What is the management for VWD?

A

VWD is non-curable and does not need day to day tretment. Only in response to major bleeds or before operations:

  • Desmopressin can be used to stimulate the release of VWF
  • VWF can be infused
  • Factor VIII is often infused along with plasma-derived VWF
  • Women with VWD and heavy periods managed with oral contraceptive pill and coil.
136
Q

Define haemophilia

A

Inherited severe bleeding disorders.

Haemophilia A is most common, caused by a deficiency in factor VIII.

Haemophilia B (also known as Christmas disease) is caused by a deficiency in factor IX. Behaves clinically like haemophilia A.

137
Q

What is the aetiology of haemophilia?

A

X linked recessive disorders > affects men more than women

offspring need to inherit both X chromosomes with abnormal gene

Women are normally carriers - one X chromosome with abnormal gene

138
Q

What signs and symptom might a patient with haemophilia present with?

A
  • Excessive bleeding in response to minor trauma and spontaneous haemorrhage
  • Often presents early in childhood with intracranial haemorrhage, haematomas and cord bleeding in neonates.
  • Spontaneous bleeding into joints (haemoathrosis) and muscles are classic features of severe haemophilia (remember for exam!)

Abnormal bleeding can occur in:
- Gums
- Gastrointestinal tract
- Urinary tract causing haematuria
- Retroperitoneal space

139
Q

What investigations/tests are used to diagnose haemophilia?

A
  • Increased APTT (time taken for blood to clot) and decreased factor VIII in coagulation factor assays
  • Genetic testing
  • Bleeding scores

Haemophilia DOES NOT affect bleeding time.

140
Q

What is the treatment/management for haemophilia

A

Management should be coordinated by a specialist, avoid NSAIDS and IM injections

IV infusion of factor VIII (8) or IX (9) prophylactically or in response to bleeding. However, the body may form antibodies against the clotting factors > ineffective

During surgery to prevent or stop bleeding:

  • Infusions of the affected factor (VIII or IX)
  • Desmopressin to stimulate the release of von Willebrand Factor
  • Antifibrinolytics
141
Q

Define malaria

A

An infectious disease caused by members of the Plasmodium family of protozoan parasites

142
Q

How is malaria spread?

A

Bites from the female Anopheles mosquitoes > bites and sucks up blood of infected human > injects parasite to next human they bite

143
Q

What are the 4 types of malaria?

A
  • Plasmodium falciparum
  • Plasmodium vivax
  • Plasmodium ovale
  • Plasmodium malariae
144
Q

Which form of malaria is most severe and dangerous?

A

Plasmodium falciparum, accounts for 75% of cases in UK

145
Q

Which form of malaria is most severe and dangerous?

A

Plasmodium falciparum, accounts for 75% of cases in UK

146
Q

Pathophysiology of malaria: Describe how sporozoites enter and infect a human

A

A female anopheles mosquito sucks up infected blood, the malaria in the blood reproduces in the mosquito gut producing thousands of sporozoites

Mosquito bites another human > sporozoites injected > sporozoites travel to liver of newly infected person

147
Q

Pathophysiology of malaria: What happens after sporozoites enter the liver of the newly infected person?

A

They mature into merozoites which enter the blood and infect RBCs > reproduce over 48 hours > RBCs rupture > release more merozoites into blood > haemolytic anaemia

So people infected with malaria have high fever spikes every 48 hours

148
Q

What signs and symptoms might a patient with malaria present with?

A

Consider malaria in patients with fever and who recently returned from an endemic area (mainly African countries).

Non-specific Symptoms
- Fever, sweats and rigors
- Malaise
- Myalgia
- Headache
- Vomiting

Signs
- Pallor due to the anaemia
- Hepatosplenomegaly
- Jaundice as bilirubin is released during the rupture of red blood cells

149
Q

What investigations/tests are used to diagnose malaria?

A

Malaria blood film - shows the parasites, concentration and type

3 samples over 3 days due to 48-hour cycle of malaria release into the blood.

150
Q

What is the treatment/management for malaria?

A

Uncomplicated: quinine sulphate and doxycycline
Complicated: IV artesunate and quinine dihydrochloride

151
Q

Define hereditary spherocytosis

A
  • A condition where the red blood cells are sphere-shaped, making them fragile and easily destroyed when passing through the spleen.
  • Most common inherited haemolytic anaemia in northern Europeans.
  • Autosomal dominant condition.
152
Q

What signs and symptoms might a patient with hereditary spherocytosis present with?

A

General anaemia symptoms:
- Jaundice
- Anaemia
- Gallstones
- Splenomegaly

Haemolytic crisis - triggered by infection, haemolysis, anaemia and jaundice is more significant.

Aplastic crisis - increased haemolysis, anaemia and jaundice but no increased extra reticulocyte production from bone marrow to account for loss like in normal blood > often triggered by parvovirus

153
Q

What investigations and tests are used to diagnose hereditary spherocytosis?

A
  • Family history
  • Blood film - spherocytes present
  • Mean corpuscular haemoglobin conc (MCHC) increased on FBC
  • Reticulocytes increased due to rapid turnover of RBCs
154
Q

What is the treatment/management for patients with hereditary spherocytosis?

A
  • Folate supplement (erythropoiesis)
  • Splenectomy
  • Cholecystectomy if gallstones
  • Blood transfusions during acute crises
155
Q

Define autoimmune haemolytic anaemia (AIHA)

A

A condition where antibodies are created against the patient’s red blood cells. These antibodies lead to the destruction of the red blood cells.

2 types: warm and cold depending on the optimal temperature at which the autoantibodies cause destruction of RBCs

156
Q

Define warm-type AIHA

A

IgG-mediated, autoantibodies bind at body temperature of 37°C.

157
Q

Define cold-type AIHA

A

IgM-mediated, autoantibodies bind at temperatures <4c (some say <10c).

Causes a chronic anaemia made worse by the cold, often associated with Raynaud’s or acrocyanosis (blueish colour to extremities)

158
Q

What are the causes of warm-type AIHA?

A

Most are idiopathic;

Secondary causes: lymphoproliferative disease (CLL, lymphoma), drugs, autoimmune disease, eg SLE (systemic lupus erythematosus)

159
Q

What are the causes of cold-type AIHA?

A

Often secondary to conditions

  • Lymphoma, leukaemia, systemic lupus erythematosus
  • Infections such as mycoplasma, EBV, CMV and HIV.
160
Q

What is the treatment/management for AIHA?

A
  • Prednisolone (steroids)
  • Rituximab (a monoclonal antibody against B cells)
  • Splenectomy
  • Cold type AIHA - keep warm as well
161
Q

Define thrombocytopenia

A

Low platelet count

Normal platelet count = 150 to 450 x 10^9/L

Causes can be split into problems with production or destruction

162
Q

What is Immune Thrombocytopenic Purpura (ITP)?

A

Problem with destruction
Antibodies are created against platelets = immune response against platelets, resulting in the destruction of platelets and a low platelet count

163
Q

What are purpura and what do they look like?

A

Small, flat spots caused by blood leaking and pooling under the skin’s surface

Dark brown/black spots on darker skin
Purple spots on lighter skin

164
Q

What signs and symptoms might a patient with ITP present with?

A

Mild thrombocytopenia asymptomatic and found incidentally on FBC

  • Platelet count below 50 x 10^9/L

Symptoms:
- nosebleeds
- bleeding gums
- easy bruising
- Blood in urine or stools

SIgns
Prolonged bleeding times.

Platelet counts below 10 x 10^9/L = high risk for spontaneous bleeding e.g., intracranial haemorrhage or GI bleeds

165
Q

What are the DDx for prolonged or abnormal bleeding?

A
  • Thrombocytopenia (low platelets)
  • Haemophilia A and haemophilia B
  • Von Willebrand Disease
  • Disseminated intravascular coagulation (usually secondary to sepsis)
166
Q

What is the treatment/management for ITP?

A
  • Prednisolone (steroids)
  • IV immunoglobulins
  • Rituximab (a monoclonal antibody against B cells)
  • Splenectomy
  • Controlling BP
  • Suppressing menstrual periods
167
Q

What monitoring is carried out for patients with ITP?

A

Monitoring platelet count
Educating patient about concerning signs of bleeding e.g., persistent headache and melaena (black, smelly stool indictive of upper GI bleed) and when to seek help

168
Q

Define Thrombotic Thrombocytopenic Purpura (TTP)

A

A condition where tiny blood clots develop throughout the small vessels of the body using up platelets and causing thrombocytopenia and bleeding under the skin

169
Q

What is the pathophysiology of TTP?

A

TTP is caused by a genetic or acquired deficiency of a protease (ADAMTS13) that normally cleaves multimers of von Willebrand factor (VWF).

Large VWF multimers form, causing platelet aggregation and fibrin deposition in small vessels, leading to microthrombi.

170
Q

What are some illnesses that can trigger TTP?

A
  • Idiopathic (40%)
  • Autoimmunity (eg SLE)
  • Cancer
  • Pregnancy
  • Drug associated (eg quinine)
  • Haematopoietic stem cell transplant
171
Q

What tests/investigations are used to diagnose TTP?

A
  • Haematuria/proteinuria (blood/protein in urine)
  • Blood film: fragmented RBC, decreased platelets, decreased Hb. Clotting tests are normal
172
Q

What is the treatment/management for TTP?

A

Treatment is guided by a haematologist and may involve:
- Plasma exchange - urgent life-saving
- Steroids (prednisolone)
- Rituximab (a monoclonal antibody against B cells).

173
Q

Cancer treatment complication: define tumour lysis syndrome (TLS)

A

An oncological emergency resulting from cancer treatment (usually chemotherapy) caused by a rapid breakdown of large numbers of cancer cells and subsequent release of large amounts of intracellular content into the bloodstream which overwhelms normal homeostatic mechanisms.

174
Q

Cancer treatment complication: what are the different types of TLS?

A

Laboratory TLS: presence of two or more of the following metabolic abnormalities: hyperuricaemia, hyperphosphataemia, hyperkalaemia, or hypocalcaemia

Clinical TLS: laboratory TLS with one or more of the following clinical manifestations: acute kidney injury, cardiac arrhythmia, seizure, or sudden death.

175
Q

What types of cancer is TLS most associated with?

A

Highly proliferative, bulky, chemosensitive haematological malignancies, particularly high-grade non-Hodgkin’s lymphoma (e.g., Burkitt’s lymphoma) and acute lymphoblastic leukaemia

176
Q

What signs and symptoms might a patient with TLS present with?

A

Take history and note the following:
Haematological malignancy
Pre-existing renal impairment

Symptoms:
- Syncope/chest pain/dyspnoea
- Seizures
- Nausea and vomiting
- Anorexia
- Diarrhoea
- Muscle weakness

177
Q

What investigations/tests would you carry out for a patient with suspected TLS?

A
  • serum uric acid (≥476 mmol/L or 25% increase from baseline)
  • serum phosphate (children: ≥2.1 mmol/L, adults ≥1.45 mmol/L or 25% increase)
  • serum potassium (≥6.0 mmol/L or 25% increase)
  • serum calcium (≤1.75 mmol/L or 25% decrease)
178
Q

What is the treatment/management for TLS?

A

Focused on prevention

  • Low-risk patients: regular monitoring and assessment
  • Intermediate/high-risk patients: IV hydration and regular monitoring & assessment

Acute laboratory/clinical TLS:

  • Urgent treatment of cardiac arrhythmia and seizures
  • Fluid resuscitation with/without loop diuretics
179
Q

What complications can TLS lead to?

A
  • Acute kidney injury
  • Cardiac arrhythmias
  • Seizures
  • Neuromuscular dysfunction

All can cause considerable morbidity and in some cases death.

180
Q

What is neutropenia?

A

Neutropenia is a low neutrophil count.

Normal: >1.5 x 10⁹/L
Mild: 1 to 1.5 x 10⁹/L
Moderate: 0.5 to 0.99 x 10⁹/L
Severe: 0.2 to 0.49 x 10⁹/L
Very severe: <0.2 x 10⁹/L.

181
Q

What is neutrophilia?

A

Elevated neutrophil count with or without leukocytosis (elevated WBC count)

Neutrophilia with leukocytosis =

  • Neutrophil count >7.7×10⁹/L
  • WBC count > 11×10⁹/L

Neutrophilia without leukocytosis

  • Neutrophil count >7.7×10⁹/L
  • WBC count <11×10⁹/L
182
Q

What is lymphopenia?

A

Lymphocyte count on FBC in an adult patient that is below the lower limit of the normal range

Usually lower in elderly patients (> 0.5 x 10^9/L)

In healthy adults <1 x 10^9/L

183
Q

What is lymphophilia (lymphocytosis)?

A

Increased lymphocyte count or proportion of lymphocytes in the blood above normal range

184
Q

What is thrombocytopenia?

A

Thrombocytopenia is a low circulating platelet count (<150,000 per microlitre).

185
Q

What is thrombophilia?

A

Increased tendency of the blood to form clots - increases risk of DVT and PE

186
Q

What is PT/INR?

A

PT/INR is coagulation time via the extrinsic clotting pathway.

PT = prothrombin time
INR = international normalised ratio

normal PT/INR = 10 - 13.5 seconds

Norma INR = 0.8 - 1.2

INR = patient PT/ref PT

Used to monitor patients on warfarin

187
Q

What is PT/INR used to monitor?

A

Used to monitor patients on warfarin

188
Q

What conditions might increase INR?

A
  • Anticoagulants
  • Liver disease
  • Vitamin K deficiency
  • Disseminated intravascular coagulopathy
189
Q

How might warfarin affect INR?

A

Increases INR (between 2 -3)

Normal INR = 0.8 - 1.2

190
Q

What is APTT?

A

Activated Partial Thromboplastin Time - another test that measures blood coagulation time via the intrinsic pathway (factors 8, 9, 11, 12)

Normal APTT = 35 - 45s

191
Q

What is APTT used to monitor?

A

Patients on heparin therapy

192
Q

How might heparin affect APTT?

A

Increases APTT to 60 -80 s

193
Q

What conditions might prolong APTT?

A
  • Haemophilia A (factor 8)
  • Haemophilia B (factor 9)
  • VWF disease

PT normal, APTT prolonged in the above conditions

194
Q

What are some examples of normocytic anaemia?

A
  • Sickle cell
  • Hereditary spherocytosis,
  • G6PDH deficiency
  • Malaria
195
Q

What is the pathophysiology of Polycythaemia vera (PCV)?

A

A myeloproliferative disorder characterised by neoplasia of mature myeloid cells, in particular those involved in the red cell lineage, within the bone marrow.

It is a primary polycythaemia that results in increased red blood cells (polycythaemia), as well as increased neutrophils (neutrophilia) and platelets (thrombocytosis)

196
Q

Define disseminated intravascular coagulation

A

Simultaneous coagulation and haemorrhage caused by the initial formation of thrombi which consume clotting factors (factors 5,8) and platelets, ultimately leading to bleeding.

197
Q

What are the causes of DIC ?

A
  • Infection e.g. sepsis
  • Malignancy
  • Trauma e.g. major surgery, burns
  • Liver disease
198
Q

What are signs and symptoms of DIC?

A

Clinically bleeding is usually a dominant feature, bruising, ischaemia and organ failure

199
Q

What tests/investigations are used to diagnose DIC?

A

Blood tests: prolonged clotting times, thrombocytopenia, decreased fibrinogen, increased fibrinogen degradation products

200
Q

What is the treatment/management plan for DIC?

A

Treat the underlying cause and supportive management

201
Q

DDx iron-deficency anaemia

A
  • Anaemia of chronic disease
  • Thalassemia
202
Q

DDx pernicious anaemia (B12)

A
  • Folic acid (B9) deficiency
  • Alcoholic liver disease
203
Q

DDx sickle cell anaemia

A
  • Gout - swelling, severe pain and redness of affected joint
  • Septic arthritis - fever and swelling of affected joint

Mimicks sickle cell crisis

204
Q

DDx Von Willebrand disease

A
  • Mild haemophilia A
205
Q

DDx haemophilia

A
  • Von Willebrand disease
  • Platelet dysfunction
206
Q

DDx acute lymphoblastic leukaemia

A

Acute myeloid leukaemia (DDx swap)

207
Q

DDx chronic lymphocytic leukaemia

A

Leukemic phase of lymphoma

208
Q

DDx Hodgkin’s and non-Hodgkin’s lymphoma

A

Each other

209
Q

DDx HIV

A
  • Infectious mononucleosis
  • Cytomegalovirus infection
210
Q

DDx Malaria

A
  • Meningitis or encephalitis.
  • COVID-19.
211
Q

DDx for polycythemia

A
  • Secondary polycythemia due to hypoxia
  • Essential thrombocytopenia
  • Chronic myeloid leukaemia

Sharon's Phase 2a Medicine Revision (10 decks)

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