1s: Haemolytic Anaemia

Question 1

How long do red cells survive for, what happens after?

Answer 1

120 days, undergoes haemolytic

Question 2

Examples of Intravascular and Extravascular (removal in reticuloendothelial system) haemolysis

Answer 2

Extravascular

• Autoimmune
• Alloimmune = an immune response to nonself antigens from members of the same species (all of us)
• Hereditary spherocytosis (AD inheritance)

Intravascular

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

Question 3

Hereditary haemolytic anaemias are disorders of the (3)

Answer 3

Membrane (cytoskeletal proteins, cation permeability)

Haemoglobin

Red cell metabolism (thalassaemia, SSD, unstable Hb variants)

Question 4

What are 4 consequences of haemolysis?

Answer 4

Anaemia (may not be present if output from bone marrow is high enough)

Erythroid hyperplasia (increased RBC production and reticulocyte circulation)

Increased folate demand

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 (iron overload in liver)

Question 5

Clinical and laboratory features of the with a. haemolytic disorder

Answer 5

Clinical = pallor, jaundice, splenomegaly, pigmenturia, FHx

Laboratory = anaemia, reticulocytosis, polychromatic, UP BR/LDH, LOW haptoglobin, haemoglobinuria, haemsiderinuria

Question 6

Name two defects in the RBC membrane

Answer 6

• Hereditary spherocytosis (vertical interaction; band 3, protein 4.2, ankyrin, b Spectrin)
• Hereditary elliptocytosis (horizontal interaction; b Spectrin, a Spectrin, protein 4.1)

Question 7

Name two defects in the RBC membrane

Answer 7

• Hereditary spherocytosis (vertical interaction; band 3, protein 4.2, ankyrin, b Spectrin)
• Hereditary elliptocytosis (horizontal interaction; b Spectrin, a Spectrin, protein 4.1)

Question 8

What is hereditary spherocytosis?

Answer 8

AD

Spectrin or ankyrin deficiency  problems in RBC cytoskeleton

• B19 susceptibility + propensity to develop gallstones
• 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
• On a pathology slide = lack of central pallor
• Extravascular haemolysis

Question 9

What is hereditary elliptocytosis?

Answer 9

• Spectrin mutation
• Homozygous state = hereditary pyropoikilocytosis (dangerous) IMAGE
• Heterozygous state = hereditary elliptocytosis (not very dangerous)

Question 10

RBC Metabolism examples

Answer 10

G6PD deficiency

PK deficiency

Pyrimidine 5 nucleotidase deficiency (basophilic inclusions on slide)

Question 11

G6PD deficiency

genetics and physiology

clinical effects and pathology

Answer 11

• G6PD Deficiency
  
  • 400m affected, X-linked (clinical effects in males or homozygous females)
  • G6P catalyses 1^st step in pentose phosphate pathway (to generate NADPH)
  • Clinical effects:
    
    • 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)
  • Clinical pathology slides:
    
    • Bite cells, hemi-ghosts, nucleated RBCs, Heinz bodies (methyl violet stain)

Question 12

Other metabolic RBC disorders

Answer 12

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

Question 13

First line investigations for haemolytic anaemias

Answer 13

Question 13

First line investigations for haemolytic anaemias

Answer 13

Question 14

Management of haemolytic anaemias

Answer 14

• Folic acid supplementation
• Avoidance of precipitating factors (oxidants in G6PD deficiency)
• Red cell transfusion/exchange
• Immunisation (hepatitis A and B)
• Monitor for chronic complications
• Cholecystectomy for symptomatic gallstones

Splenectomy if indicated (i.e. thalassaemia syndromes, severe pyropoikilocytosis, etc.)

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

Question 15

Warm vs Cold AIHA on DAT test (Coombs positive)

Answer 15

Question 16

Paroxysmal cold haemoglobinuria (also a type of AIHA)

Answer 16

Haemoglobin in urine usually causes by viral infection e.g. measles, syphilis, VZV

Donath-Landsteiner antibodies → stick to RBCs in cold → Complement-mediated haemolysis on rewarming (self-limiting as IgG so dissociate at higher temperature than IgM)

Question 17

2 examples of Non-Immune (Coombs Negative Acquired Haemolytic Anaemia)

Answer 17

Paroxysmal Nocturnal Haemoglobinuria

Microangiopathic haemolytic anaemia (MAHA)

Question 18

Paroxysmal Nocturnal haemoglobinuria

Answer 18

Question 19

Microangiopathic Haemolytic Anaemia (MAHA)

Answer 19

Question 20

What is TTP?

Answer 20