Rapid dissociation of platelet-rich fibrin clots in vitro by a combination of plasminogen activators and antiplatelet agents.
Thrombin promotes the formation of arterial thrombi by converting fibrinogen to fibrin and by causing platelets to aggregate. We have examined the combined effects of plasminogen activators and inhibitors of platelet aggregation on the lysis of platelet-rich fibrin clots formed by alpha-thrombin in citrated platelet-rich plasma. The extent of platelet aggregation and clot formation were measured by recording light transmission in an aggregometer. Immediately after the formation of platelet-rich fibrin clots, addition of 2,000 U/ml streptokinase or 50 micrograms/ml recombinant tissue-type plasminogen activator alone resulted in the degradation of polymerized fibrin and the release of trapped platelet aggregates without causing significant platelet deaggregation. Preincubation of the platelet-rich plasma with 20 microM indomethacin for 1 min before thrombin stimulation or simultaneous addition of prostaglandin E1 (10 microM) with the plasminogen activators after thrombin stimulation resulted in spontaneous platelet deaggregation. Because platelet aggregation is, in part, mediated by the binding of Arg-Gly-Asp-containing adhesive proteins to activated platelets, the effect of Arg-Gly-Asp peptides on platelet deaggregation was examined. By itself, Gly-Arg-Gly-Asp-Ser-Pro specifically caused dose- and time-dependent deaggregation of platelet aggregates formed by ADP or by thrombin in the presence of 1 mM Gly-Pro-Arg-Pro, but had no effect on the dissociation of thrombin-induced platelet-rich fibrin clots. In combination with streptokinase or recombinant tissue-type plasminogen activator, Gly-Arg-Gly-Asp-Ser-Pro enhanced the rate of lysis of platelet-rich fibrin clots. The control Gly-Arg-Gly-Glu-Ser-Pro peptide was completely ineffective.(ABSTRACT TRUNCATED AT 250 WORDS)
Lam
S C
SC
Department of Pharmacology, University of Illinois, Chicago.
Dieter
J P
JP
Strebel
L C
LC
Taylor
T M
TM
Muscolino
G
G
Feinberg
H
H
Le Breton
G C
GC
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000527:Alprostadil / Q000494:pharmacology; D000595:Amino Acid Sequence; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D005337:Fibrin / Q000187:drug effects / Q000502:physiology*; D005342:Fibrinolysis / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008969:Molecular Sequence Data; D010960:Plasminogen Activators / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013300:Streptokinase / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; D000244:Adenosine Diphosphate; D005337:Fibrin; D011451:Prostaglandin-Endoperoxide Synthases; D013300:Streptokinase; D010960:Plasminogen Activators; D013917:Thrombin; D010959:Tissue Plasminogen Activator; D000527:Alprostadil; D007213:Indomethacin