Paediatrics: Haemolytic anaemias

Haemolytic anaemias

Haemolysis causes reduction in the normal mean RBC survival of 120 days. Causes can be intrinsic (RBC membrane defects, enzyme defects, or haemoglobinopathies) or extrinsic (immune mediated or mechanical RBC fragmentation).

Diagnosis

History

·  Symptoms: e.g. headache, dizziness, fever, chills, dark urine, back or abdominal pain (intravascular haemolysis).

·  Possible precipitating factors: e.g. infection, medications, foods such as fava beans in G6PD deficiency.

·  Ancestry: e.g. African, Mediterranean, or Arabic ancestry is suggestive of G6PD deficiency in boys.

·  Family history: e.g. gallstones in spherocytosis.

Examination 

Specific examination should include temperature, pallor, jaundice, splenomegaly. Look for leg ulcers.

Investigations

FBC and blood film

·  Increased reticulocyte count suggests increased RBC production in response to haemolysis or blood loss.

·  Platelet count: thrombocytopenia with normal clotting suggests HUS, thrombotic thrombocytopenic purpura (TTP); with abnormal clotting suggests DIC.

·  Pancytopenia: consider viral infection, malignancy, hypersplenism.

·  Abnormal blood film: e.g. spherocytes or other RBC abnormalities, malaria parasites, features of RBC fragmentation (schistocytes, burr cells).

Specific tests include the following:

·  Unconjugated bilirubin: raised level = increased RBC destruction.

·  Lactate dehydrogenase: raised activity = increased RBC production.

·  Free plasma Hb, haemoglobinuria, haemosiderin in urine (all increased in intravascular haemolysis).

·  Coombs antiglobulin test to establish if there is immune or non-immune haemolysis. Positive direct Coombs test (DCT) = antibodies on RBC surface. Positive indirect Coombs test = antibodies in serum.

·  If DCT +ve, screen serum for red cell isoimmune antibodies, e.g. neonatal rhesus or ABO haemolytic disease.

·  If DCT +ve, IgG- and C3- specific reagents suggest warm and cold antibody autoimmune haemolysis respectively.

·  IgM for mycoplasma; CMV; EBV; rubella; for cold antibody autoimmune haemolysis.

·  Hb electrophoresis for sickle cell anaemia, thalassaemias, unstable Hbs, e.g. Hb Koln.

·  Flow cytometry for hereditary spherocytosis.

·  RBC enzyme assays for RBC enzyme defects, e.g G6PD.

If history suggestive, immunophenotyping (CD55 + CD59) for paroxysmal nocturnal haemoglobinuria (PNH).