FIBRINOGEN DEGRADATION PRODUCTS GENERATION IS THE MAJOR DETERMINANT OF PLATELET INHIBITION INDUCED BY PLASMINOGEN ACTIVATORS IN PLATELET-RICH PLASMA

The platelet function defect induced by thrombolytic agents has been r eferred either to the degradation of platelet surface receptors or to the anti-aggregatory effect of fibrinogen degradation products (FgDPs) . In the present study we have evaluated platelet aggregation induced by ADP, collagen and ristocetin after incubation of washed platelets o r platelet-rich plasma (PRP) with plasmin (1.1-3.4IU/ml), plasminogen activators (PAs) (streptokinase 250-1000 IU/ml; urokinase, 10-1000 IU/ ml; t-PA 0.5-10 mug/ml) or FgDPs (0.062-2 mg/ml). In parallel the surf ace levels of platelet GP Ib and IIb/IIIa complex were determined by f luorescence flow cytometry using specific monoclonal antibody. Washed platelets treated with plasmin (1.1IU/ml) for 10 to 90 min showed a pr ogressive reduction of ristocetin-induced platelet agglutination and a progressive reduction of surface GP lb. Surface expression of GP IIb/ IIIa complex was significantly increased after plasmin exposure. The a ddition of PAs to PRP resulted in a marked reduction of ADP-induced pl atelet aggregation. Collagen-induced platelet aggregation was only sli ghtly affected. Similar changes were observed when PRP was preincubate d with high concentrations of FgDPs. In PRP treated with PAs platelet surface levels of GP Ib and GP IIb/IIIa complex did not show any signi ficant changes. In conclusion our results show that in plasma no prote olysis of platelet adhesive receptors occurs after plasminogen activat ion. The platelet inhibition observed after incubation of PRP with PAs is likely to be caused by FgDPs generation.