A Transfusion Reaction due to Anti-ER5 in a Hyposplenic β0 Thalassemia Major Patient

Abstract

A 6-year-old boy of Libyan ethnic origin was referred to pediatric hematology 3 months after entering the United Kingdom as a refugee. The child was known to have thalassemia major. His parents were first cousins. He had previously been transfused every 4 weeks, received chelation therapy and had been splenectomized. More recently, transfusion requirement had increased to every 2 weeks and he had developed post-transfusion hemoglobinuria, which was not ameliorated by corticosteroids. He had not been transfused since arriving in the United Kingdom and his hemoglobin concentration (Hb) was 72 g/L. Anti-c and anti-E were present together with a panagglutinating antibody directed at the high frequency antigen, ER5. It was not possible to source ER5-negative blood and he was therefore transfused with Rh-typed red cells under cover of intravenous immunoglobulin, methylprednisolone, and eculizumab. Transfusion led to an initial rise of Hb to 96 g/L but, despite the precautions taken, by 3 days the Hb had fallen to 65 g/L. His mother reported that following the transfusion his urine had again become red.

Post-transfusion his blood film (both images, ×100 objective) showed hypochromic red cells, target cells, Howell–Jolly bodies, Pappenheimer bodies, schistocytes, alpha chain inclusions within hypochromic erythrocytes (upper image), and nucleated red blood cells. In addition to the evidence of thalassemia and hyposplenism, there were also considerable numbers of spherocytes, indicating a transfusion reaction. The direct antiglobulin test was positive for immunoglobulin G (+). Molecular analysis showed homozygosity for β⁰ thalassemia, specifically NM_000518.4: c93-22_95del p.? In addition, there was homozygosity for the Xmn1 (−158) polymorphism of the HBG2 gene, which leads to some increase in hemoglobin F synthesis.

ER5 is a recently recognized, high incidence antigen, antibodies to which can cause hemolytic disease of the fetus and newborn [1]. Future management of the child will be fraught with problems.