Heparin-induced thrombocytopenia: further studies of the effects of heparin-dependent antibodies on platelets.
Studies were performed with the sera of five patients with heparin-induced thrombocytopenia. Each patient serum was found to cause heparin-dependent aggregation of normal and Bernard-Soulier syndrome platelets but not Glanzmann's thrombasthenia or fixed normal platelets. This antibody effect was blocked by inhibition of both aerobic and anaerobic metabolism and an increase in intraplatelet c-AMP with prostaglandin E1. These findings suggest that the antibody-induced platelet aggregation was not a passive agglutination of cells but an active process requiring metabolic energy and membrane glycoproteins IIb/IIIa but not glycoprotein Ib. In addition, platelet aggregation by four patient sera was inhibited by aspirin or apyrase indicating a prostaglandin synthesis and ADP-dependent mechanism and the reaction could be suppressed by dipyridamole alone. However, platelet aggregation induced by the serum of one patient was only inhibited partially by the combination of aspirin and apyrase suggesting mediation of the antibody effect in part by a pathway independent of extracellular ADP and prostaglandin synthesis and this antibody reaction could only be completely suppressed by a combination of aspirin and dipyridamole. Heterogeneity exhibited by these antibodies may influence the choice and effectiveness of antiplatelet therapy in heparin-induced thrombocytopenia.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000906:Antibodies / Q000276:immunology*; D001241:Aspirin / Q000494:pharmacology; D001606:Bernard-Soulier Syndrome / Q000188:drug therapy; D004176:Dipyridamole / Q000494:pharmacology; D006493:Heparin / Q000009:adverse effects* / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D010974:Platelet Aggregation / Q000187:drug effects; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D013915:Thrombasthenia / Q000188:drug therapy; D013921:Thrombocytopenia / Q000139:chemically induced*
D000906:Antibodies; D011448:Prostaglandin Antagonists; D011458:Prostaglandins E; D000244:Adenosine Diphosphate; D004176:Dipyridamole; D006493:Heparin; D001241:Aspirin