Evans Syndrome Associated with En ^a Antibody Leading to Fatal Immune Hemolytic Anemia.

Abstract 3148

Poster Board III-85

A 40 year old man presented with epistaxis. The patient presented to another institution with Stage 2A lymphocyte-predominant Hodgkin's lymphoma (HL) at the age of 28, thirteen years prior to the current admission. The patient received mantle irradiation without chemotherapy. One year later he developed thrombocytopenia. Workup was negative for relapse of his HL. He was HIV-seronegative. Idiopathic thrombocytopenic purpura (ITP) was diagnosed; his platelet count recovered on prednisone therapy, which was then tapered. One year later, the patient presented with a platelet count of 2,000/μl in association with CT evidence of disseminated lymphadenopathy and bone marrow involvement with relapsed HL for which he received salvage chemotherapy. In Sept 2000, he had high dose therapy and underwent autologous stem cell transplantation. The HL remained in remission over the next 9 years, but the patient reported multiple episodes of thrombocytopenia treated with several courses of steroids and intravenous immunoglobulin (IVIG) and splenectomy in 2001. The patient presented to our hospital in May 2009 with flu-like symptoms, epistaxis of one day's duration, and a platelet count of 6,000/μL. The WBC was 18,000/μL, hemoglobin 10.5 g/dl, and MCV 86 fl. The peripheral smear showed markedly reduced platelets, Howell Jolly bodies, mild anisocytosis, many nucleated rbcs, and microspherocytes, but no schistocytes. The reticulocyte count was 4.6%, ferritin 13,495 ng/ml, iron 216 μg/dl, TIBC 255 μg/dl, folate, B12, PT, and PTT normal, haptoglobin < 8 mg/dl, LDH 376 IU/l, and indirect bilirubin 2.9 mg/dl. Cultures of blood and urine were negative. The patient's antibody studies were done at a local Immunohematology Reference Laboratory. The direct and indirect antiglobulin tests were positive. The patient's red cells were coated with IgG (strong) and C3 (weak). An acid eluate from the red cells reacted strongly by the indirect antiglobulin test with all panel cells tested but was non-reactive with red cells of the rare M^kM^k phenotype (null phenotype of the MNS blood group system). The patient's serum by saline indirect antiglobulin test showed the same reactivity as the eluate and also an autoanti-I. These results were consistent with the presence of a warm autoantibody with anti-En^a specificity, defined as an antibody directed at the epitopes on glycophorin A. No alloantibodies were detected. Anti-I is a common cold autoagglutinin found in human sera and is not clinically significant. Evans syndrome (autoimmune hemolytic anemia and immune thrombocytopenic purpura) was diagnosed. The patient began prednisone 1 mg/kg daily, with improvement in his platelet count to 70,000/μl in three days. However, his hemoglobin fell from 10.5 to 4.0 g/dl within 24 hours, with an increase in leukocytes to 44,600/μL. IVIG (2 g/kg in divided doses) was added. Due to the presence of anti-En^a antibodies, no cross-match-compatible blood was available from the regional blood center. One day later, the patient became somnolent, hypoxemic and acidotic requiring intubation and mechanical ventilation. Due to his deteriorating clinical status, blood incompatible with the autoantibody was transfused. Immediately after the transfusion began, the patient became pulse-less. Cardiopulmonary resuscitation was begun, but the patient succumbed to cardiovascular collapse. His serum was noted to be amber (in contrast to yellow in a pre-transfusion sample), suggesting hemolysis. The direct antiglobulin test was strongly positive on the pre and post transfusion specimens and En^a autoantibody was again detected. Anti- En^a is an immune antibody that reacts with high incidence antigens on glycophorin A (GPA), the MN antigen-carrying molecule. This antibody reacts against all or part of GPA and may cause hemolytic transfusion reactions. As illustrated in our fatal case, it is difficult, if not impossible, to find compatible donor blood for patients with anti- En^a autoantibody. This is the first patient, to our knowledge, to be reported with anti-En^a associated with Evans syndrome.