Haemolytic anaemia: diagnostic approach: Case

Case discussion

Diagnosis and immediate assessment

This boy presents chronic compensated haemolysis with the classic clues to hereditary spherocytosis: intermittent jaundice worse with illness, splenomegaly, a father with a splenectomy and gallstones, spherocytes on the film, a raised mean corpuscular haemoglobin concentration, and a negative direct antiglobulin test that excludes autoimmune haemolytic anaemia. The first step is to confirm the diagnosis with the recommended flow cytometric screen rather than relying on the film alone, because spherocytes also appear in warm autoimmune haemolytic anaemia and the distinction rests on the direct antiglobulin test and the confirmatory assay. [1]

Confirmatory testing

The International Council for Standardization in Haematology recommends eosin-5-maleimide binding flow cytometry as the preferred screening test for the hereditary red cell membrane disorders, because it binds band 3 and the Rh-related proteins whose reduced density is the common endpoint of the different molecular defects. The test is more sensitive and specific than the older osmotic fragility test, which is also raised after any recent transfusion. If the screen is positive, sodium dodecyl sulfate polyacrylamide gel electrophoresis of the red cell membrane proteins confirms the diagnosis and identifies the defective protein, which has implications for family counselling. [2]

Pathophysiology

Hereditary spherocytosis destabilises the vertical interactions between the membrane skeleton and the lipid bilayer, through defects in ankyrin, spectrin, band 3 or protein 4.2. The red cell loses surface area relative to its volume and becomes a small, dense, rigid spherocyte that cannot deform in the splenic microcirculation. The spleen traps and destroys the spherocytes, producing the chronic haemolysis, splenomegaly, raised reticulocyte count, low haptoglobin and raised unconjugated bilirubin. The raised mean corpuscular haemoglobin concentration reflects the dehydration and surface-area loss of the spherocyte. [1]

Management

The immediate management is supportive: folic acid supplementation to support the brisk erythropoiesis of chronic haemolysis, surveillance for pigment gallstones, and a clear plan for haemolysis crises triggered by infection. Most children with hereditary spherocytosis run a stable, compensated course and do not need splenectomy. Splenectomy is curative and is reserved for severe transfusion-dependent disease or recurrent crises; when undertaken, it must be preceded by pneumococcal, meningococcal and Haemophilus vaccination, with lifelong penicillin prophylaxis planning and education about the risk of overwhelming post-splenectomy infection. [1]

Family and genetic counselling

The inheritance is autosomal dominant in about three-quarters of families, which fits the father's history here, but recessive forms and new mutations exist, so a negative family history does not exclude the diagnosis. The family should be counselled that first-degree relatives warrant screening with a full blood count, film and confirmatory test, because mild disease is easily missed until a crisis. Counselling should address the natural history, the role of splenectomy and asplenic safety, and the importance of presenting early with febrile illness. [3]

Disposition and follow-up

The boy needs haematology referral for confirmatory testing and a long-term management plan, with folic acid supplementation, an abdominal ultrasound for gallstones, and structured follow-up to monitor his haemoglobin and splenic size. Family screening should be arranged, and the family given written safety-net advice about haemolysis crises and severe infection. The prognosis is excellent with modern supportive care, and most children lead full, active lives with surveillance and education rather than intervention. [1]