Haemolytic anaemia Flashcards
What is HA?
RBC breakdown before normal lifespan of 120d
Extravascular HA
RBCs destroyed by RE system (phagocytes in LNs, spleen, Kupffer cells of liver)
- Most allo-immune, hereditary spherocytosis
Intravascular HA
RBCs destroyed in circulation
- Malaria, G6PD deficiency, MAHA, Drugs, PNH
Raised MCV
Polychromasia on blood film
Erythroid hyperplasia in BM
Reticulocytosis
Reticulocytosis
Unconjugated bilirubinaemia
Raised LDH
Gallstones
Haemolytic anaemia
Free plasma Hb
Reduced haptoglobin
Haemoglobinuria (coca cola / port wine)
Methaemaglobinuria
Intravascular HA
Splenomegaly
Extravascular HA
As an erythroid hyperplasia state, HA increases the risk of…
- Parvovirus B19
- Iron overload
- Osteoporosis
Vertical interaction proteins
Band 3, Protein 4.2, Ankyrin, B-spectrin
Weak membrane = haemolysis
Osmotic fragility test
Hereditary spherocytosis
H is closer to E, and V is closer to S
Horizontal interaction proteins
A-spectrin, B-spectrin, Protein 4.1
Weak membrane = haemolysis
Hereditary elliptocytosis
H is closer to E, and V is closer to S
2 Membrane defect HAs
Hereditary spherocytosis
Hereditary elliptocytosis
Abnormal sensitivity of RBCs to heat
Hereditary pyropoikilocytosis
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)
G6PD deficiency (Enzyme in glycolysis pathway that produces NADPH - needed to form glutathione to protect RBCs against oxidative stress)
Drug precipitants of haemolysis in G6PD
Oxidative stress from: Anti-malarials (primaquine) Abx (sulphonamides, ciprofloxacin, nitrofurantoin) Vitamin K, dapsone Fava broad beans Moth balls
Kinocytic cells
Lack of ATP production to maintain Na/K ATPase pump = cell lysis
Hypoxia precipitates
Most haemolysis occurs in splenic vessels as hypoxic
Pyruvate kinase deficiency
2 key Enzyme defect HAs
G6PD deficiency
Pyruvate kinase deficiency
Basophilic stippling of RBCs
Pyrimidines toxic to RBCs
Pyrimidine 5’nucleotidase deficiency
DAT / Coombs’ positive
Auto-immune HA
Can be warm, cold or PCH
Classification of acquired HA
Immune or non-immune
Immune: Auto-immune (warm, cold or PCH) or allo-immune (transfusion reaction or HDFN)
Non-immune: PNH, MAHA, malaria, drugs
Positive DAT / Coomb’s
IgG mediated
Lymphoproliferative disease, penicillin, SLE
Warm AIHA
Positive DAT / Coomb’s
IgM + C3 mediated
EBV + mycoplasma infections
Cold AIHA
Positive DAT / Coomb’s
Donath-Landsteiner antibodies stick to RBCs when cold then complement-mediated haemolysis on re-warming
Paroxysmal cold haemoglobinuria
Schistocytes
MAHA
Fibrin deposition in small damaged vessels = mechanical RBC destruction
Ham’s test
Morning haemoglobinuria
Loss of protective GPI markers = night-time complement mediated lysis
PNH
What are the main types of MAHA?
TTP
HUS
DIC
HELLP
Pentad of MAHA, fever, neuro signs, thrombocytopenia + renal impairment
VWF multimers due to ADAMST13 inhibition
TTP
E coli 0157
MAHA + diarrhoea
HUS
Widespread clotting with subsequent bleeding
Sepsis / trauma / cancer
DIC
