Haemolytic anaemias Flashcards
What is the life of red cells?
120 days
What are the types of haemolysis?
Intravascular/ Extravascular
Inherited/ Acquired
What are the types of extravascular haemolysis?
Autoimmune
Alloimmune
Hereditary spherocytosis (AD inheritance)
What are the types of intravascular haemolysis?
Malaria`
G6PD and PK deficiencies
Mismatched ABO blood transfusion
Cold anti-body haemolytic syndromes
Drugs
Microangiopathic HA’s (i.e. TTP)
Paroxysmal nocturnal haemoglobinuria
What are the causes of hereditary haemolytic anaemias?
Disorders of:
RBC membrane
Metabolism
Hb
What are the consequences of haemolysis?
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
What are the clinical features of a haemolytic disorder?
o Clinically – pallor, jaundice, splenomegaly, pigmenturia, FHx
o Laboratory – anaemia, reticulocytosis, polychromasia, inc. BR, inc. LDH, dec. haptoglobins, haemoglobinuria, haemosiderinuria
What are the defects in the RBC membranes?
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)
What is hereditary spherocytosis?
• 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
What is hereditary elliptocytosis?
AD
o Spectrin mutation
o Homozygous state = hereditary pyropoikilocytosis (dangerous)
o Heterozygous state = hereditary elliptocytosis (not very dangerous)
What is G6PD deficiency?
o 400m affected, X-linked (clinical effects in males or homozygous females)
o G6P catalyses 1st step in pentose phosphate pathway (to generate NADPH)
What are the clinical effects of G6PD deficiency?
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)
What do these slides show?
Bite cells, hemi-ghosts, nucleated RBCs, Heinz bodies (methyl violet stain)
What are the other metabolic RBC disorders?
o Pyruvate kinase deficiency (echinocytes and spherocytes on slide)
Echinocytes = ‘hedgehog-like’ -> see picture
o Pyrimidine 5’-nucleotidase deficiency (basophilic inclusions on slide)
What are the first line investigations of haemolytic anaemia?
What is the management of haemolytic anaemia?
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.)
What is the criteria for splenectomy?
- Transfusion dependence Growth delay
- Physical limitation (Hb≤8g/dL) Hypersplenism
- Age not <3yo (but before 10)
What are the features of warm and cold autoimmune disease?
What is paroxysmal cold haemoglobinuria?
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)
What is paroxysmal nocturnal haemoglobinuria?
What is MAHA?
What is TTP?
What is HUS?
