Abstract

This investigation is aimed at identification and characterization of HLA, platelet-specific and drug dependent antibodies in RPT. The investigators plan to establish the potential biological significance of these antibodies, determine the frequency of occurrence, and determine which types of antibodies are most likely to induce platelet destruction. This will be accomplished by both laboratory and clinical investigation. Detection, identification and characterization of platelet antigens and antibodies in patients refractory to platelet transfusion will be investigated using several immunologic assays, including immunofluorescence, lymphocytotoxicity, protein A rosette formation, a sensitive new monoclonal antibody-specific antigen capture ELISA (MAIPA), immunoblotting and immunoprecipitation. Platelet and complement activating properties of antibodies in patients with RPT will be investigated by aggregometry, ATP release, and the cytotoxic 51-Cr release assay. Correlation of laboratory findings with clinical outcome will be investigated by transfusing platelets that lack antigens for the corresponding platelet antibodies to patients refractory to platelet transfusion and then monitoring the patients' platelet counts, bleeding symptoms, and platelet usage.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL044917-02
Application #
3363726
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1990-07-01
Project End
1993-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
2
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
University of Minnesota Twin Cities
Department
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455

  Publications

Christie, D J; Howe, R B; Lennon, S S et al. (1993) Treatment of refractoriness to platelet transfusion by protein A column therapy. Transfusion 33:234-42
Christie, D J; Sauro, S C; Cavanaugh, A L et al. (1993) Severe thrombocytopenia in an acquired immunodeficiency syndrome patient associated with pentamidine-dependent antibodies specific for glycoprotein IIb/IIIa. Blood 82:3075-80
Christie, D J (1993) Specificity of drug-induced immune cytopenias. Transfus Med Rev 7:230-41
Christie, D J; Leja, D N; Carlson, D L et al. (1993) Characterization of platelet activation induced by HLA antibodies associated with alloimmune thrombocytopenia. J Lab Clin Med 121:437-43
Christie, D J; Sauro, S C; Fairbanks, K D et al. (1993) Detection of clonal platelet antibodies in immunologically-mediated thrombocytopenias: association with circulating clonal/oligoclonal B cells. Br J Haematol 85:277-84
Stroncek, D F; Vercellotti, G M; Hammerschmidt, D E et al. (1992) Characterization of multiple quinine-dependent antibodies in a patient with episodic hemolytic uremic syndrome and immune agranulocytosis. Blood 80:241-8
Christie, D J; Swinehart, C D (1992) Human platelet activating antibodies. Semin Thromb Hemost 18:186-92
Christie, D J; Pulkrabek, S; Putnam, J L et al. (1991) Posttransfusion purpura due to an alloantibody reactive with glycoprotein Ia/IIa (anti-HPA-5b). Blood 77:2785-9