Haemolytic anaemia: diagnostic approach: SAQ

Part A (10 marks)

a) What is the most likely diagnosis, and which three features of the laboratory panel confirm that this is haemolytic anaemia? (3 marks) [1]

The most likely diagnosis is warm autoimmune haemolytic anaemia, suggested by the post-infectious onset, pallor, jaundice, splenomegaly, spherocytes, and a direct antiglobulin test positive for immunoglobulin G. The three features confirming haemolysis are a raised reticulocyte count of 9 per cent, an undetectable haptoglobin, and a raised lactate dehydrogenase, with the raised unconjugated bilirubin and the falling haemoglobin completing the picture of red cell destruction outstripping marrow production. [1]

b) Why is the direct antiglobulin test pattern (positive for immunoglobulin G) consistent with a warm rather than a cold antibody process? (3 marks) [2]

Warm autoimmune haemolytic anaemia is mediated by immunoglobulin G with a thermal optimum near 37 degrees Celsius, which coats the red cell and produces spherocytes with extravascular destruction in the spleen, giving a direct antiglobulin test positive for immunoglobulin G. Cold agglutinin disease, by contrast, is mediated by immunoglobulin M that fixes complement in cool peripheral vessels and then detaches, leaving the direct antiglobulin test positive for complement (C3d) only and producing red cell agglutination rather than spherocytes. The immunoglobulin G coating and spherocytes here therefore point to a warm process. [2]

c) Outline the immediate management priorities while awaiting definitive treatment. (3 marks) [3]

The immediate priority is cardiovascular stability. Because the haemoglobin is 62 g per litre and she has symptoms, she needs monitoring and likely red cell support while corticosteroids are started. The blood bank should be alerted early because the autoantibody reacts with all donor cells, so the least incompatible unit is released and transfused under close observation. Corticosteroids are the first-line definitive therapy, and folic acid and hydration are supportive measures. A search for an underlying autoimmune or immunodeficiency driver should begin in parallel. [3]

d) What is the expected haemoglobin response after transfusion, and why must you recheck it? (1 mark) [1]

The expected rise may be blunted because the autoantibody continues to destroy transfused cells, so a delayed haemolytic reaction can deepen the anaemia days later. The haemoglobin must be rechecked after the unit to detect ongoing destruction. [1]

Part B (10 marks)

A separate 4-year-old boy of Mediterranean background presents with sudden pallor and cola-coloured urine two days after eating fava beans. His haemoglobin is 58 g per litre with bite cells and Heinz bodies on the film, and the direct antiglobulin test is negative. [2]

e) What is the most likely diagnosis, and what is the inheritance pattern? (2 marks) [2]

The most likely diagnosis is glucose-6-phosphate dehydrogenase deficiency triggered by fava beans, suggested by the Mediterranean background, the acute intravascular haemolysis with cola-coloured urine, bite cells and Heinz bodies, and the negative direct antiglobulin test. The inheritance is X-linked recessive, so males are affected and females are carriers or mosaic. [2]

f) What confirmatory test should be sent, and why must the timing be handled with care? (3 marks) [2]

The glucose-6-phosphate dehydrogenase enzyme assay, or Beutler fluorescent spot test, confirms the diagnosis, but the assay must be interpreted with care during the acute attack. The most severely enzyme-deficient cells are preferentially destroyed first, leaving relatively normal cells to be sampled, so the assay can return falsely normal during the crisis. The test must be repeated two to three months later in remission before the family is reassured. [2]

g) How does the direct antiglobulin test help distinguish this boy's anaemia from the girl's in Part A? (3 marks) [2]

The direct antiglobulin test is the master branch point of the haemolysis algorithm. In the girl's warm autoimmune haemolytic anaemia it is positive, proving an antibody-mediated immune process, whereas in this boy's glucose-6-phosphate dehydrogenase deficiency it is negative, confirming a non-immune intrinsic red cell defect. The test therefore immediately directs the girl toward immunosuppression and the boy toward trigger avoidance and supportive care. [2]

h) Name two long-term management priorities for this boy and his family. (2 marks) [2]

Two long-term priorities are strict avoidance of known oxidative triggers (fava beans, sulphonamides, primaquine, rasburicase, naphthalene) and education of the family and the child about recognising a crisis and presenting early. Parental and school education is the single most important intervention for long-term safety. [2]