Posttransfusion purpura following bone marrow transplantation

Abstract

Thrombocytopenia is a major cause of morbidity and hospital expense following bone marrow transplantation. Platelet transfusions in these patients are frequently complicated by the recipient's development of antibodies to HLA class I antigens. When these patients become refractory to the transfusion of HLA-matched platelets, the recipient's platelet antigen phenotype must be determined, to ensure that donor platelets will be phenotypically compatible. Cases of alloimmunization to HPA-1a and HPA-1b resulting in refractoriness to transfused platelets and the subsequent development of a posttransfusion purpura-like syndrome are reported. In the first case, a 43-year-old woman with Stage IV infiltrating ductal breast cancer presented to the hospital for a transplant of autologous peripheral blood stem cells. After the transplant, her platelet count remained less than 10 x 10(9) per L, despite daily platelet transfusions, including HLA-matched platelets. Fourteen days following the transplant, her serum was found to contain anti-HPA-1a. Initially, the patient was refractory to the transfusion of HPA-1a-negative platelets, but after treatment with intravenous immunoglobulin, she had transient increases in posttransfusion platelet counts. She was also treated with a staphylococcal protein A immunoadsorption column and has not had any such subsequent refractoriness. Her genotype has been found, by use of allele-specific oligonucleotide hybridization with white cell DNA, to be HPA-1b/1b. The second case involved a 32-year-old woman with chronic myelogenous leukemia who received an unrelated-donor marrow transplant. Three years later, her CML recurred, and she was treated with interferon-alpha. Four months afterward, she experienced interferon-alpha-induced thrombocytopenia and the interferon therapy was discontinued. She received 12 platelet transfusions in 20 days, but none was effective. Antibodies specific for HLA antigens and HPA-1b were detected, and three HLA-matched, HPA-1b-negative apheresis platelet components were given, but without effect. Two days after treatment with methylprednisolone (1 g intravenously) and prednisone (2 mg/kg/day orally), her platelet count was 26 x 10(9) per L, and after 8 more days, it was 102 x 10(9) per L, without further transfusions. She was found to be homozygous for HPA-1a (HPA-1a/1a). Anti-HPA-1a and anti-HPA-1b can cause refractoriness to platelet transfusions in bone marrow transplant patients. Testing for platelet-specific antibodies should be considered in all patients who are refractory to HLA-matched platelets.