Monoclonal antibodies against platelet membrane glycoproteins IIb/IIIa andIb alpha inhibit platelet dependent thrombin generation by different mechanisms

The antithrombotic effect of antiplatelet agents is principally due to thei r anti-aggregatory action, but these agents may also interfere with coagula tion. We have Investigated the effect of monoclonal antibodies (MAb) to pla telet membrane glycoproteins (GP) IIb/IIIa and Ib alpha on thrombin generat ion. Antibodies to platelet membrana glycoprotein IIb/IIIa (RFGP56 and c7E3) wer e shown to inhibit platelet-mediated thrombin generation stimulated hv both intrinsic and extrinsic methods. An antibody to GP Ib alpha (RFGP37) also Inhibited thrombin generation in these systems. FITC-annexin V was used to determine the effect of these antibodies on the exposure of procoagulant phospholipids on the platelet membrane, and it was found that the anti-IIb/IIIa antibodies reduced this. whereas the anti-Ib alpha antibody caused an increase. We conclude that our monoclonal antibodies against platelet membrane glycop roteins IIb/IIIa and Ib alpha inhibit platelet dependent thrombin generatio n by different mechanisms.