Haemolytic anaemia Flashcards
Define haemolytic anaemia.
Haemolytic anaemia encompasses a number of conditions that result in the premature destruction of RBCs (<120 days) and anaemia.
Define haemolysis and state the different types.
Shortened RBC survival
- Intravascular or extravascular (in reticuloendothelial)
- Inherited or acquired
What are the acquired and hereditary causes of haemolytic anaemia?
Hereditary - membrane related, red cell metabolism related or due to haemoglobin defect.
What are the causes of intravascular vs extravascular haemolysis?
Intravascular:
- Malaria (common)
- G6PD
- ABO mismatch
- Drugs
- MAHA
- PNH
Extravascular:
- Autoimmune
- Alloimmune
- Hereditary spherocytosis
What are the main types of haemolytic anaemia associated with membrane defects?
Spherocytosis = Vertical interaction
Elliptocytosis = Horizontal interaction
What is G6PD deficiency?
X linked condition - prevalent where malaria is endemic as it offers some protection against falciparum malaria.
G6PD is important in maintaining glutathione in reduced state.
G6PD role
Enzyme catalyses first step in pentose phosphate(hexose monophosphate) pathway - generates NADPH required to maintain intracellular glutathione(GSH) which is needed to protect the cell against oxidative stress
So G6PD deficiency causes haemolytic anaemia in response to oxidative stress.
What is meant by “warm” and “cold” antibodies?
“Warm” antibodies (IgG) agglutinate erythrocytes at 37oC.
- Associated with SLE
- Lymphomas
- Methyldopa.
“Cold” antibodies (IgM) agglutinate erythrocytes at room temperature or colder.
- Associated with infections (e.g. Mycoplasma, EBV)
- OR lymphomas.
- Donath-Landsteiner antibody is present in cold-immune disease.
What is the most common inherited haemolytic anaemia? How common is haemolytic anaemia?
- Common
- Hereditary spherocytosis is the most common inherited haemolytic anaemia in northern Europe.
What are the signs and symptoms of haemolytic anaemia?
- Pallor
- Jaundice
- Hepatosplenomegaly
- Haematuria
- Hx of anaemia
Ask systemic illness, FH, drug and travel history.
What are the common presentations of G6PD deficiency?
- Neonatal jaundice - probably most common cause of kernicterus worldwide
- Acute haemolysis(triggered by oxidants/infection)
- Chronic haemolytic anaemia(rare)
How do you diagnose haemolytic anaemia?
- Anaemia
- Increased reticulocytes
- Polychromasia
- Hyperbilirubinaemia
- LDH high - cell content released
- Haptoglobins absent
- Haemoglobinuria
- Haemosiderinuria
Bloods -
- FBC - low Hb, high reticulocytes(>1.5%) , high MCV
- MCHC - increased (may indicate presence of spherocytes/reticulocytes)
- Bilirubin - elevated, but not >70 to 85 micromol/L (5 mg/dL) unless liver function is impaired
- Haptoglobin - decreased; suggestive of increased free Hb.
- LDH - high
- U&E
- Folate
Blood film -
- Leucoerythroblastic picture
- Macrocytosis
- Nucleated erythrocytes or reticulocytes
- Polychromasia
- Abnormal forms such as schistocytes, spherocytes, elliptocytes, spur cells, blister cells, bite cells, tear drops, erythrocyte Heinz bodies (denatured Hb, stained with methyl violet seen in G6PD deficiency)
- RBC inclusions may occur with malaria, babesiosis, and Bartonella infections
What other investigations should you do for haemolytic anaemia?
Blood film
Direct antiglobulin test (DAT)/Coombs’ - detect Ig on RBCs in AI disease
Urinalysis - in intravascular haemolysis there is haemoglobinuria and haemosiderinuria
Osmotic fragility - identifies membrane abnormalities
G6PD +/- PK activity - metabolic causes of haemolysis.
Ham’s test/flow cytometry of GPI linked proteins - lysis of erythrocytes in acidified serum in paroxysmal nocturnal haemoglobinuria.
Hb electrophoresis or enzyme assays - when other causes excluded. HbS in sickle cell, HbA2/HbF raised in thalassaemia.
Thick and thin blood film - malaria
Heinz body stain - G6PD for oxidative haemolysis
Other:
Donath-Landsteiner antibody - present in cold-immune disease
BM biopsy - erythroid hyperplasia
ANA - in SLE, assoc with HA in 10% of cases.
What are the general consequences of RBC haemolysis?
- Anaemia
- Erythroid hyperplasia
- Folate demand increased
- Parvovirus B19
- Gallstones
- Risk of iron overload
- Risk of osteoporosis
What are the triggers of haemolysis in G6PD?
- Anti-malarials - primaquine
- Antibiotics - sulphonamides, cipro, nitro
- Dapsone
- Vitamin K
- Infection
- Fava beans
- Moth balls
What are the principles of management of haemolytic anaemia?
Conservative:
- Avoidance of precipitating factors e.g. oxidants in G6PD deficiency
- Immunisation against blood borne viruses e.g. hepatitis A and B
- Monitor for chronic complications
Medical:
- Folic acid supplementation
- Red cell transfusion/exchange
- Corticosteroids or immunosuppressant - if immune cause
Surgical:
- Cholecystectomy for symptomatic gallstones
- Splenectomy if indicated
What type of jaundice is caused by haemolytic anaemia?
Pre-hepatic, unconjugated
