Haemolytic anaemias

Question 1

What is the life of red cells?

Answer 1

120 days

Question 2

What are the types of haemolysis?

Answer 2

Intravascular/ Extravascular
Inherited/ Acquired

Question 3

What are the types of extravascular haemolysis?

Answer 3

Autoimmune
Alloimmune
Hereditary spherocytosis (AD inheritance)

Question 4

What are the types of intravascular haemolysis?

Answer 4

Malaria`
G6PD and PK deficiencies
Mismatched ABO blood transfusion
Cold anti-body haemolytic syndromes
Drugs
Microangiopathic HA’s (i.e. TTP)
Paroxysmal nocturnal haemoglobinuria

Question 5

What are the causes of hereditary haemolytic anaemias?

Answer 5

Disorders of:
RBC membrane
Metabolism
Hb

Question 6

What are the consequences of haemolysis?

Answer 6

o Anaemia (may not be present if output from bone marrow is high enough)
o Erythroid hyperplasia (increased RBC production and reticulocyte circulation)
o Increased folate demand
o Susceptibility to:
 Parvovirus B19 (DNA virus)
 Gallstones (inc. risk in those with Gilbert’s syndrome – UGT 1A1 TA7/TA7 genotype)
 Iron overload
 Osteoporosis
 Hepatic siderosis

Question 7

What are the clinical features of a haemolytic disorder?

Answer 7

o Clinically – pallor, jaundice, splenomegaly, pigmenturia, FHx
o Laboratory – anaemia, reticulocytosis, polychromasia, inc. BR, inc. LDH, dec. haptoglobins, haemoglobinuria, haemosiderinuria

Question 8

What are the defects in the RBC membranes?

Answer 8

o Hereditary spherocytosis (vertical interaction; band 3, protein 4.2, ankyrin, beta Spectrin) See diagram above
o Hereditary elliptocytosis (horizontal interaction; beta Spectrin, alpha Spectrin, protein 4.1)

Question 9

What is hereditary spherocytosis?

Answer 9

• Hereditary spherocytosis (AD):
o Spectrin or ankyrin deficiency -> problems in RBC cytoskeleton
 B19 susceptibility + propensity to develop gallstones
o Hallmark = increased sensitivity to lysis in hypotonic saline (osmotic fragility test)
 Di-binding test (eosin-5-maleimide / EMA) is more often used to the OFT
o On a pathology slide = lack of central pallor
o Extravascular haemolysis

Question 10

What is hereditary elliptocytosis?

Answer 10

AD
o Spectrin mutation
o Homozygous state = hereditary pyropoikilocytosis (dangerous)
o Heterozygous state = hereditary elliptocytosis (not very dangerous)

Question 11

What is G6PD deficiency?

Answer 11

o 400m affected, X-linked (clinical effects in males or homozygous females)
o G6P catalyses 1st step in pentose phosphate pathway (to generate NADPH)

Question 12

What are the clinical effects of G6PD deficiency?

Answer 12

 Neonatal jaundice (but otherwise asymptomatic)
 Acute haemolysis (triggered by oxidants (drugs, fava beans) or infection)
• Anti-malarials (Primaquine)
• Antibiotics (sulphonamides, ciprofloxacin, nitrofurantoin)
• Other (Dapsone, Vitamin K)
• Fava beans and mothballs
 Chronic haemolytic anaemia (rare)

Question 13

What do these slides show?

Answer 13

Bite cells, hemi-ghosts, nucleated RBCs, Heinz bodies (methyl violet stain)

Question 14

What are the other metabolic RBC disorders?

Answer 14

o Pyruvate kinase deficiency (echinocytes and spherocytes on slide)
 Echinocytes = ‘hedgehog-like’ -> see picture
o Pyrimidine 5’-nucleotidase deficiency (basophilic inclusions on slide)

Question 15

What are the first line investigations of haemolytic anaemia?

Answer 15

Question 16

What is the management of haemolytic anaemia?

Answer 16

o Folic acid supplementation
o Avoidance of precipitating factors (oxidants in G6PD deficiency)
o Red cell transfusion/exchange
o Immunisation (hepatitis A and B)
o Monitor for chronic complications
o Cholecystectomy for symptomatic gallstones
o Splenectomy if indicated (i.e. thalassaemia syndromes, severe pyropoikilocytosis, etc.)

Question 17

What is the criteria for splenectomy?

Answer 17

• Transfusion dependence Growth delay
• Physical limitation (Hb≤8g/dL) Hypersplenism
• Age not <3yo (but before 10)

Question 18

What are the features of warm and cold autoimmune disease?

Answer 18

Question 19

What is paroxysmal cold haemoglobinuria?

Answer 19

Haemoglobin in the urine cause by viral infections (like measloes, syphilis, VZV)

Donath-Landsteiner antibodies (Stick to RBCs in cold- complement mediated haemolysis on rewarming- self limiting as IgG so dissociated at higher temp than IgM)

Question 20

What is paroxysmal nocturnal haemoglobinuria?

Answer 20

Question 21

What is MAHA?

Answer 21

Question 22

What is TTP?

Answer 22

Question 23

What is HUS?

Answer 23