HAEMOLYTIC ANAEMIA

Haemolytic Anaemia



Haemolytic Anaemia

This first known case of concurrent congenital dyserythropoietic anaemia (CDA) and autoimmune haemolytic anaemia (AIHA) which occurred in a hispanic male and spanned 6 years from the age of 2. Light and electron microscopy of bone marrow erythroblasts and immunophenotyping confirmed CDA; serum/eluate warm autoantibodies and positive direct antiglobulin tests (DAT) associated with severe, episodic anaemias established AIHA. Cytogenetic analysis of bone marrow cells and peripheral blood lymphocytes ascertained sex chromosome aneuploidy (48 XY,+ Y,+ Y). Recurrent, life-threatening episodes of transfusion-dependent anaemia refractory to steroids and intravenous immune globulin, were put into stable remission at age 8 years when splenectomy successfully managed both disorders.

Congenital dyserythropoietic anaemia (CDA) is a group of rare hereditary anaemias (types I-IV) which are characterized on the basis of distinct histology, electron microscopy, biochemistry, serology and genetic inheritance patterns. Of these, the most commonly encountered is CDA type II which is inherited in an autosomal recessive manner and is also referred to as hereditary erythroblastic multinuclearity with positive acidified serum (HEMPAS). CDA type IV may be morphologically indistinguishable from CDA type II by light and electron microscopy; however, CDA type IV has a negative acidified serum test and no increased expression of I and i antigens on the red cell (RBC) membrane (Beutler & Valentine, 1994; Miller, 1995). Autoimmune haemolytic anaemia (AIHA) is also a rare cause of anaemia in children (estimated annual incidence 0.2 in 100 000 children in the United States) (Sokol et al, 1981). Chronic AIHA, more common in older children, especially females, can be the presenting feature of a more serious underlying disorder, such as systemic lupus erythematosis, Hodgkin's or non-Hodgkin's lymphoma. It is characterized by a lack of complete resolution and an often relapsing course.

Case Report

Clinical History

A 2-year-old hispanic male presented to a local children's hospital with fever, lethargy and pallor. His physical examination revealed diffuse adenopathy, moderate splenomegaly and severe anaemia with a haemoglobin of 4.7 g/dl, an absolute reticulocyte count of 51.6 x 10/l and a positive direct antiglobulin test (DAT). A bone marrow aspirate sample revealed erythroid cell precursors with dyserythropoietic features. The patient was treated with i.v. methyl-prednisolone, gamma globulin and a transfusion with incompatible RBCs, necessitated by a serum IgG autoantibody of broad specificity. The patient was discharged with no medication; he had a haemoglobin of 12.4g/dl and diagnosis of DAT-positive autoimmune haemolytic anaemia and dyserythropoiesis. Of note, his birth history was significant for neonatal hyperbilirubinaemia requiring phototherapy and a blood transfusion. His family history was non-contributory. The patient's prolonged clinical course and key events are shown in Fig 1.

From age 2 to 8 years the patient had intermittently severe transfusion-dependent haemolytic anaemia. The patient concurrently carried the diagnosis of AIHA and CDA after an extensive evaluation of the RBC precursors, repeat bone marrow examination and serologic testing. Due to recurrent episodes of severe transfusion-dependent anaemia, the patient underwent a splenectomy at age 8. At surgery, an enlarged spleen was resected and a repeat bone marrow aspirate ...