Alloimmunization is one of the major causes of refractoriness associated with platelet transfusion therapy. This can lead to significant morbidity and morality. Management of platelet refractoriness often is not effective; thus, prevention of platelet refractoriness is preferable. Several approaches have been attempted to reduce alloimmunization to platelet transfusion including use of: HLA matched platelets, single donor platelets, leukocyte-poor platelets, and immunosuppressive therapies, such as treatment of recipients with cyclosporine or transfusion of platelets treated with ultraviolet irradiation. Although HLA class I antibodies are frequently implicated as a cause of platelet refractoriness, they do not account for poor platelet responses in all alloimmunized patients. Only a relatively minor role has been ascribed to platelet-specific and/or drug-dependent antibodies in platelet refractoriness and no systematic study has investigated their potential role in this problem. The discovery in 1988 of new platelet alloantigens, such as Br a and Bak b, and the recent association of amphotericin B and vancomycin, with platelet refractoriness strongly suggest the need for a comprehensive test to analyze serum from refractory patients for all possible anti-platelet antibodies. Therefore, an investigation is proposed to reduce the incidence of alloimmunization and subsequent platelet refractoriness by reducing the number of donor exposures through use of single donor platelets and red cells that have been depleted of leukocytes. Twenty- four patients with newly diagnosed ANLL will be entered yearly in the randomized trial. It is further proposed to develop a sensitive and specific laboratory test to detect platelet refractoriness due to alloimmunization. The assays to be used include monoclonal antibody- specific antigen capture ELISA, immunofluorescence, protein A rosette formation, 51 Cr release and lymphocytotoxicity.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HL042802-02
Application #
3553338
Study Section
Special Emphasis Panel (SRC (GK))
Project Start
1989-08-01
Project End
1994-05-31
Budget Start
1990-06-01
Budget End
1991-05-31
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Type
Schools of Veterinary Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455