Haematology

Question 1

Describe the pathophysiology of G6PD deficiency.

Answer 1

X-linked mutation in G6PDH gene - 1st enzyme in pentose phosphate pathway.

Decreased G6PDH in RBCs… decreased NADPH… oxidised glutathione (GSSH) not reduced to GSH… increased susceptibility to oxidative stress (e.g. lipid peroxidation and protein damage).

Various precipitants (cause increased NADPH requirements) can cause haemolytic crisis as haemoglobin aggregates (Heinz bodies) bind RBC membrane… altered RBCs destroyed by spleen… haemolytic anaemia and increased bilirubin… jaundice.

Question 2

Describe the common presentation of G6PD deficiency and possible precipitants

Answer 2

Depends on severity of enzyme deficiency, most are asymptomatic.

Presentation:

• Hx of neonatal jaundice (may be severe enough to require transfusion)
• Hx of intravascular haemolysis after precipitant
• gallstones are common
• +/- splenomegaly

Precipitants:

• severe infection
• drugs, e.g. primaquine, sulfonamides, ciprofloxacin and nitrofurantoin
• DKA
• AKI
• broad beans

Question 3

how would you manage a pt with G6PD deficiency?

Answer 3

1. avoid precipitants
2. folic acid supplements (required for erythropoiesis)
3. splenectomy if severe

Question 4

describe the pathophysiology of hereditary spherocytosis

Answer 4

Autosomal dominant (some cases autosomal recessive) mutation in gene coding for RBC membrane protein (e.g. ankyrin, a-/B-spectrin, band 3, protein 4.2)… membrane loss through release of microvesicles… decreased surface:volume ratio (round) rather than biconcave)… loss of deformability… trapped in microvasculature esp. in spleen sinusoids… extravascular haemolysis… splenomegaly, anaemia and jaundice.

Question 5

describe the possible complications of hereditary spherocytosis

Answer 5

1. haemolytic crisis (secondary to viral infection): accelerated erythrocyte haemolysis… more pronounced anaemia and jaundice
2. aplastic crisis (secondary to viral infection): temporary erythrocyte maturation arrest… dramatic decrease in Hb level and reticulocyte count… more pronounced anaemia.
3. folate deficiency: due to increased BM requirements… megaloblastic anaemia (cellular division requires folate)
4. gallstones: composed of calcium bilirubinate (bilirubin increased in bile during RBC haemolysis)

Question 6

describe pathophysiology of haemophilia A. what are the symptoms and diagnostic tests? what is treatment?

Answer 6

• deficiency of Factor VIII, X-linked recessive inheritance
• symptoms: easy bruising, ‘spontaneous’ haemorrhage after minor trauma e.g. haemarthrosis, massive haemorrhage after trauma
• tests: prolonged APTT and low factor VIII assay
• treatment: infusion of recombinant factor VIII

Question 7

describe pathophysiology of haemophilia B. what are the symptoms and diagnostic tests? what is treatment?

Answer 7

• deficiency of factor IX, X-linked recessive inheritance
• symptoms: easy bruising, ‘spontaneous’ haemorrhage after minor trauma e.g. haemarthrosis, massive haemorrhage after trauma
• tests: prolonged APTT and low factor IX assay
• treatment: infusion of recombinant factor IX

Question 8

what is von Willebrand disease? what are the diagnostic tests?

Answer 8

• most common inherited bleeding disorder, deficiency/abnormality in vWF
• symptoms vary from asymptomatic to severe bleeding disorder
• tests: raised bleeding time and APTT (as vWF acts to form platelet plug and stabilise F8)