Haemolytic anaemia: diagnostic approach: Viva

Opening question

What is your diagnostic approach to this child, and what single test do you most need next? [2]

This child has haemolytic anaemia: the falling haemoglobin with a reticulocyte count of 11 per cent, undetectable haptoglobin, raised lactate dehydrogenase and raised unconjugated bilirubin confirm red cell destruction outstripping marrow production. The spherocytes on the film narrow the differential to warm autoimmune haemolytic anaemia or hereditary spherocytosis. The single test I most need is the direct antiglobulin test, because it is the master branch point: a positive result proves an immune process and points to warm autoimmune haemolytic anaemia, while a negative result redirects me to the inherited membrane disorders. [2]

Branch 1: Confirming haemolysis

Explain how you would confirm haemolysis from the laboratory panel alone. [1]

The confirmatory panel is the reticulocyte count, lactate dehydrogenase, haptoglobin and unconjugated bilirubin. The reticulocyte count of 11 per cent shows the marrow is responding, lactate dehydrogenase rises as cells lyse, haptoglobin falls or disappears because it binds and clears free haemoglobin, and unconjugated bilirubin rises from haemoglobin breakdown. The combination, with a falling haemoglobin, establishes haemolysis before any test for the cause. [1]

Branch 2: The direct antiglobulin test

The direct antiglobulin test returns positive for immunoglobulin G. What does this tell you, and what are the implications for transfusion? [1]

A direct antiglobulin test positive for immunoglobulin G, with spherocytes and a thermal optimum near body temperature, confirms warm autoimmune haemolytic anaemia. The autoantibody reacts with all donor red cells, so the blood bank may be unable to find a fully compatible unit; the least incompatible unit is released and transfused under close observation. I would alert the blood bank early, send a group-and-save before any transfusion, and recheck the haemoglobin after the unit because ongoing destruction can blunt the expected rise. [1]

Branch 3: The negative-test pathway

Suppose instead the direct antiglobulin test was negative. How would your approach change? [3]

A negative direct antiglobulin test redirects the workup to the non-immune causes, and the blood film becomes the guide. Spherocytes with a family history would point to hereditary spherocytosis, confirmed by eosin-5-maleimide binding flow cytometry. Bite cells or Heinz bodies would point to glucose-6-phosphate dehydrogenase deficiency, with the enzyme assay repeated in remission. Sickle or target cells would point to a haemoglobinopathy, and schistocytes would point to a microangiopathic cause. I would also keep paroxysmal nocturnal haemoglobinuria on the list if there was pancytopenia or thrombosis. [3]

Branch 4: Definitive management

Outline the definitive management of warm autoimmune haemolytic anaemia and the principles of follow-up. [1]

Corticosteroids are first-line for warm autoimmune haemolytic anaemia, reducing both antibody production and macrophage clearance of coated cells, and most children respond within the first week. The dose is tapered slowly over months to reduce relapse. Relapsing or steroid-dependent disease is treated with rituximab or splenectomy in selected cases, and intravenous immunoglobulin has a role in severe or refractory disease. Because a substantial minority are secondary to autoimmune disease or immunodeficiency, every child needs a search for the underlying driver, and I would involve haematology and screen for systemic lupus erythematosus and immunodeficiency. [1]

Closing question

Summarise the three diagnostic tiers of haemolysis in a way you could teach a junior colleague. [2]

The first tier confirms haemolysis with reticulocytes, lactate dehydrogenase, haptoglobin and unconjugated bilirubin. The second tier splits immune from non-immune with the direct antiglobulin test. The third tier uses the blood film to guide a single confirmatory assay, whether eosin-5-maleimide binding for hereditary spherocytosis, the enzyme assay in remission for glucose-6-phosphate dehydrogenase deficiency, or electrophoresis and high-performance liquid chromatography for the haemoglobinopathies. Moving through these tiers in order prevents the scattergun battery of tests and delivers the diagnosis efficiently. [2]

Examiner notes

This viva assesses the candidate's ability to confirm haemolysis, use the direct antiglobulin test as the master branch point, and select confirmatory tests guided by the film. Key teaching points are the three diagnostic tiers, the warm-versus-cold distinction on antibody class and direct antiglobulin test pattern, the difficulty and principles of transfusion in autoimmune haemolytic anaemia, and the importance of an underlying-cause search. Strong candidates name the eosin-5-maleimide binding test for hereditary spherocytosis and the need to repeat the glucose-6-phosphate dehydrogenase assay in remission. [3]