Haemolytic anaemia

Question 1

What is HA?

Answer 1

RBC breakdown before normal lifespan of 120d

Question 2

Extravascular HA

Answer 2

RBCs destroyed by RE system (phagocytes in LNs, spleen, Kupffer cells of liver)
- Most allo-immune, hereditary spherocytosis

Question 3

Intravascular HA

Answer 3

RBCs destroyed in circulation

- Malaria, G6PD deficiency, MAHA, Drugs, PNH

Question 4

Raised MCV
Polychromasia on blood film
Erythroid hyperplasia in BM

Answer 4

Reticulocytosis

Question 5

Reticulocytosis
Unconjugated bilirubinaemia
Raised LDH
Gallstones

Answer 5

Haemolytic anaemia

Question 6

Free plasma Hb
Reduced haptoglobin
Haemoglobinuria (coca cola / port wine)
Methaemaglobinuria

Answer 6

Intravascular HA

Question 7

Splenomegaly

Answer 7

Extravascular HA

Question 8

As an erythroid hyperplasia state, HA increases the risk of…

Answer 8

• Parvovirus B19
• Iron overload
• Osteoporosis

Question 9

Vertical interaction proteins
Band 3, Protein 4.2, Ankyrin, B-spectrin
Weak membrane = haemolysis
Osmotic fragility test

Answer 9

Hereditary spherocytosis

H is closer to E, and V is closer to S

Question 10

Horizontal interaction proteins
A-spectrin, B-spectrin, Protein 4.1
Weak membrane = haemolysis

Answer 10

Hereditary elliptocytosis

H is closer to E, and V is closer to S

Question 11

2 Membrane defect HAs

Answer 11

Hereditary spherocytosis

Hereditary elliptocytosis

Question 12

Abnormal sensitivity of RBCs to heat

Answer 12

Hereditary pyropoikilocytosis

Question 13

Heinz bodies + bite cells
Irregularly contracted cells
Hemi-ghosts
Mediterranean, Africa, Middle East (malaria endemic areas)
Neonatal jaundice
Precipitant - moth balls, primaquine anti-malarial, fava beans, Abx (sulphonamides, ciprofloxacin, nitrofurantoin)

Answer 13

G6PD deficiency
(Enzyme in glycolysis pathway that produces NADPH - needed to form glutathione to protect RBCs against oxidative stress)

Question 14

Drug precipitants of haemolysis in G6PD

Answer 14

Oxidative stress from:
Anti-malarials (primaquine)
Abx (sulphonamides, ciprofloxacin, nitrofurantoin)
Vitamin K, dapsone
Fava broad beans
Moth balls

Question 15

Kinocytic cells
Lack of ATP production to maintain Na/K ATPase pump = cell lysis
Hypoxia precipitates
Most haemolysis occurs in splenic vessels as hypoxic

Answer 15

Pyruvate kinase deficiency

Question 16

2 key Enzyme defect HAs

Answer 16

G6PD deficiency

Pyruvate kinase deficiency

Question 17

Basophilic stippling of RBCs

Pyrimidines toxic to RBCs

Answer 17

Pyrimidine 5’nucleotidase deficiency

Question 18

DAT / Coombs’ positive

Answer 18

Auto-immune HA

Can be warm, cold or PCH

Question 19

Classification of acquired HA

Answer 19

Immune or non-immune
Immune: Auto-immune (warm, cold or PCH) or allo-immune (transfusion reaction or HDFN)
Non-immune: PNH, MAHA, malaria, drugs

Question 20

Positive DAT / Coomb’s
IgG mediated
Lymphoproliferative disease, penicillin, SLE

Answer 20

Warm AIHA

Question 21

Positive DAT / Coomb’s
IgM + C3 mediated
EBV + mycoplasma infections

Answer 21

Cold AIHA

Question 22

Positive DAT / Coomb’s

Donath-Landsteiner antibodies stick to RBCs when cold then complement-mediated haemolysis on re-warming

Answer 22

Paroxysmal cold haemoglobinuria

Question 23

Schistocytes

Answer 23

MAHA

Fibrin deposition in small damaged vessels = mechanical RBC destruction

Question 24

Ham’s test
Morning haemoglobinuria
Loss of protective GPI markers = night-time complement mediated lysis

Answer 24

PNH

Question 25

What are the main types of MAHA?

Answer 25

TTP
HUS
DIC
HELLP

Question 26

Pentad of MAHA, fever, neuro signs, thrombocytopenia + renal impairment
VWF multimers due to ADAMST13 inhibition

Answer 26

TTP

Question 27

E coli 0157

MAHA + diarrhoea

Answer 27

HUS

Question 28

Widespread clotting with subsequent bleeding

Sepsis / trauma / cancer

Answer 28

DIC