Quinine- and quinidine-dependent antiplatelet antibodies. Requirement of factor VIII-related antigen for platelet damage and for in vitro transformation of lymphocytes from patients with drug-induced thrombocytopenia.

The requirement of Factor VIII-related antigen (VIIIR:Ag) for platelet damage by quinine-and quinidine-dependent antibodies was studied in platelet-rich plasma (PRP) of four patients with severe von Willebrand's disease (vWd) (Factor VIII deficiency). Platelet factor 3 availability, platelet aggregation, and release of [(14)C]serotonin from labeled vWd-PRP by drug-dependent antibodies were significantly reduced in comparison with PRP from normal controls. Addition of purified VIIIR:Ag restored levels of platelet damage to that of normal PRP. In vWd-PRP, platelet damage by two human antiplatelet sera, not dependent on drugs, and by a rabbit antiplatelet serum did not differ from that in normal PRP. PRP from patients deficient in Factor VIII coagulant activity, Factor IX, or Factors II, VII, IX, and X behaved like normal PRP. The role of VIIIR:Ag in forming antigen able to transform lymphocytes of patients who had recovered from drug-induced thrombocytopenia was investigated by measuring incorporation of [methyl-(3)H]thymidine into DNA. When lymphocytes were cultured for 7 d, significantly less transformation occurred in response to platelets and the drug in the presence of vWd sera than in normal sera or sera deficient only in Factor VIII coagulant activity or Factor IX. Addition of purified VIIIR:Ag to vWd sera restored transformation to that obtained in normal sera. Nonspecific lymphocyte transformation by pokeweed mitogen was not affected by VIIIR:Ag. Thus VIIIR:Ag is involved both in platelet damage by drug-dependent antibodies and in the interaction between platelet and drug which produces an antigen able to transform sensitized lymphocytes.