Haematology

Question 1

What is the lifespan of a normal RBC?

Answer 1

120 days

Question 2

What is the definition of haemolysis?

Answer 2

Haemolysis can be defined as shortened red cell survival.

Question 3

What are the broad ways of categorising haemolytic anaemias?

Answer 3

o Intravascular (within circulation) vs extravascular (removal by reticuloendothelial system)
o Inherited or Acquired

Question 4

List the causes of extravascular haemolysis

Answer 4

Autoimmune (Warm antibody haematolytic anaemia) can be primary (idiopathic), or secondary (associated with lymphoma, SLE etc).

Alloimune (Haemolytic tranfusion reactions and heamolytic disease of the newborn).

Hereditary spherocytosis

Question 5

List the causes of intravascular haemolysis

Answer 5

Malaria (mainly plasmodium falciparum can be depicted as black water fever)

G6PD deficiency (one of the most common genetic conditions worldwide, as confers a protection against malaria?)

Mismatched blood transfusion: ABO

Cold antibody haemolytic syndromes

Drugs

Microangiopathic haemolytic anaemia, e.g. haemolytic uraemic syndrome (HUS), thrombotic thrombocytopaenic purpura (TTP) (characterised by damage to the endothelium).

Paroxysmal nocturnal haemoglobinuria

Question 6

List the causes of inherited haemolysis

Answer 6

Hereditary spherocytosis

Hereditary elliptocytosis

G6PD deficiency

Pyruvate kinase deficiency

Sickle cell disease

Thalassaemias

Question 7

List the causes of acquired haemolysis

Answer 7

Autoimmune – warm or cold

Alloimmune – haemolytic transfusion reactions

Mechanical, e.g. metal valves, trauma

PNH, MAHA

Infections, e.g. malaria

Drugs

Question 8

What is the sequelae of haemolysis?

Answer 8

o May or may not have anaemia
o Patients often develop erythroid hyperplasia with increased red cell production and circulating reticulocytes (immature red cells)
o Increased folate demand (in developed world, doesn’t tend to lead to deficiency)
o Susceptibility to effect of Parvovirus B19 - infects developing reticulocytes and arrests development. In patients with shortened red cell survival, can lead to a dangerous levels of haemoglobin levels. Self-limiting, as virus is cleared by immune system, but patients with haemolytic anaemias experience an aplastic crisis, requiring treatment.
o Propensity to gallstones due to increased generation of bilirubin
§ Co-inheritance of Gilbert syndrome further increases risk of cholelithiasis in chronic haemolytic anaemia: UGT1A1 TA7/TA7 genotype
o Iron overload (irrespective of whether they receive transfusions)–> hepatic siderosis (Perl’s stain)
o Osteoporosis

Question 9

What are the clinical features of heamolysis?

Answer 9

o Pallor (anaemia)
o Jaundice (due to increased production of bilirubin)
o Splenomegaly (greater in extravascular haemolysis, or extramedullary haematopoiesis)
o Pigmenturia
o Family History

Question 10

Describe the types of membrane defects that can lead to haemolysis

Answer 10

o Hereditary spherocytosis
§ Most common genetic defect of red cell cytoskeleton.
§ Family history in 75% (typically autosomal dominantt)
§ In vitro red cells shows increased sensitivity to lysis in hypotonic saline (osmotic fragility test).
§ The dye binding test is a flow cytometry test most commonly used to diagnose spherocytosis.

o Hereditary elliptocytosis
§Tends to be autosomal dominant, except hereditary pyropikilocytosis (autosomal recessive)

Question 11

Describe the demographical features of G6PD Deficiency

Answer 11

The commonest RBC enzyme defect (400 million worldwide). Prevalent in areas of malarial endemicity - African, Mediterranean & Middle Eastern populations. X-linked - clinical effects seen predominantly in hemizygous males and homozygous females; heterozygous females get a milder condition.

Question 12

What is the pathophysiology of G6PD Deficiency?

Answer 12

G6P catalyses first step in pentose phosphate (hexose monophosphate) pathway - generates NADPH required to maintain intracellular glutathione (GSH), which protects RBC from oxidant damage.

Question 13

What are the clinical features of G6PD Deficiency?

Answer 13

Red cells vulnerable to oxidative stress results in a number of clinical effects:
o Attacks of rapid anaemia & jaundice due to acute intravascular haemolysis triggered by oxidants (drugs)/infection
o Neonatal jaundice
o Chronic haemolytic anaemia (rare)
Most people with G6PD are healthy and asymptomatic most of the time.

Question 14

What are the precipitants of intravascular haemolysis in G6PD Deficiency?

Answer 14

o Antimalarials - primaquine
o Antibiotics - sulphonamides, ciprofloxacin, nitrofurantoin
o Other drugs - dapsone, vit K
o Fava beans
o Mothballs
List is not comprehensive - always check before prescribing.

Question 15

What is the most common defect in the glycolytic pathway?

Answer 15

Pyruvate Kinase deficiency (autosomally recessive)

Question 16

What are the clinical features of Pyruvate Kinase deficiency?

Answer 16

Clinical features:
o Severe neonatal jaundice
o Splenomegaly
o Haemolytic anaemia (chronic haemolytic anaemia)

Question 17

What are the first-line investigations for those with unexplained haemolysis?

Answer 17

o Direct antiglobulin test (autoimmune haemolysis)
o Urinary haemosiderin/haemoglobin
o Osmotic fragility 
o G6PD +/- PK activity 
o Haemoglobin separation (A and F%)
o Heinz body stain
o Ham’s test (for paroxysmal nocturnal haemoglobinuria)/flow cytometry of GPI-linked proteins
o Thick and thin blood film (malaria)

Question 18

What are the general principles of management for haemolysis?

Answer 18

o Folic acid supplementation
o Avoidance of precipitating factors, e.g. oxidants in G6PD deficiency
o Red cell transfusion/exchange
o Immunisation against blood borne viruses, e.g. hep A and B - as patients require red cell transfusions.
o Monitor for chronic complications
o Cholecystectomy for symptomatic gallstones
o Splenectomy

Question 19

What are the indications for a splenectomy?

Answer 19

PK deficiency and some other enzymopathies

Hereditary spherocytosis

Severe elliptocytosis/pyropoikilocytosis

Thalassaemia syndromes

Immune haemolytic anaemia