The platelet-refractory bone marrow transplant patient: prophylaxis and treatment of bleeding

Refractoriness to platelet transfusions remains a significant problem for oncology patients, occurring in 30% to 70% of multiply transfused recipients with bone marrow failure. Nonimmune causes are often present and include disseminated intravascular coagulation, concurrent use of amphotericin B, infection, presence of palpable spleen, use of antibacterial antibiotics, bleeding, veno-occlusive disease, and fever. Immune causes are also commonly responsible for refractoriness, with HLA alloimmunization dominating the list of immune factors. HLA antibodies can be identified in 25% to 30% of transfused leukemia patients and can be present in as many as 80% of aplastic anemia patients. Developing a consistent approach to managing these refractory patients is essential to preventing and treating bleeding manifestations. An HLA type should be obtained for all patients anticipated to have chronic transfusion requirements. Screening for lymphocytotoxic antibodies can confirm suspected HLA alloimmunization. Histocompatible platelets (cross-match compatible and HLA matched) should be provided for all patients with HLA antibodies. A number of other therapeutic modalities have been used in an effort to manage the alloimmunized patient; most of these methods have had little or no proven benefit. When bleeding develops in the alloimmunized patient, there are few therapeutic choices. If histocompatible platelets are unavailable or unsuccessful, massive platelet transfusions of pooled platelet concentrates are commonly used, although this practice is of no proven benefit. While antifibrinolytic agents have been available for over 30 years, they are only recently being applied to control bleeding in chronic thrombocytopenia. We have successfully managed bleeding episodes in thrombocytopenic bone marrow transplant recipients with the use of epsilon aminocaproic acid. A number of these patients were platelet refractory with demonstrable platelet antibodies. Platelet refractoriness continues to plague multiply transfused oncology patients. While preventative measures may ultimately benefit some patients, this problem will continue to manifest itself. A consistent approach to transfusion support needs to be implemented to best manage this challenging patient population.