Plasmin-induced platelet aggregation and platelet release reaction. Effects on hemostasis.
Trypsin-activated pig plasmin and human plasmin activated by streptokinase (SK) caused aggregation of a suspension of washed platelets from human, rabbit, or pig blood. The platelet aggregation was reversible, but it was accompanied by a significant release of adenine nucleotides, serotonin, and platelet fibrinogen. Platelet fibrinogen was eventually digested. The effect of plasmin on platelets was inhibited by soybean trypsin inhibitor, epsilon aminocaproic acid, Persantin, prostaglandin E(1), and phenylbutazone. Short treatment of platelets with plasmin enhanced their sensitivity to ADP; however, this sensitivity was lost during longer incubation with plasmin. This enzyme also made platelets less sensitive to collagen and thrombin. Injecting SK into rabbits (10,000 U/kg body weight) caused a transitory drop of platelet count. These platelets lost part of their serotonin and fibrinogen. The administration of Persantin or of epsilon aminocaproic acid to rabbits before the injection of SK protected platelets from the loss of serotonin. Pretreatment with Persantin also resulted in partial protection of platelet fibrinogen in rabbits injected with SK. Platelets obtained from rabbits that had received both Persantin and SK were much more reactive with collagen than platelets obtained from rabbits injected with SK alone. Rabbits pretreated with Persantin did not show prolongation of the primary bleeding time that occurred after SK injection to control rabbits. It is suggested that plasmin generated after SK injection causes platelet release reaction in vivo. This may contribute to the hemostatic defect occurring during thrombolytic therapy or during systemic activation of fibrinolysis due to the other factors.
D000227:Adenine Nucleotides / Q000378:metabolism; D000614:Aminocaproates / Q000494:pharmacology; D000818:Animals; D000933:Antifibrinolytic Agents / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects*; D003094:Collagen / Q000494:pharmacology; D004176:Dipyridamole / Q000494:pharmacology; D005340:Fibrinogen / Q000378:metabolism; D005341:Fibrinolysin / Q000494:pharmacology*; D006487:Hemostasis; D006801:Humans; D010653:Phenylbutazone / Q000494:pharmacology; D010973:Platelet Adhesiveness / Q000187:drug effects; D011453:Prostaglandins / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000378:metabolism; D013300:Streptokinase / Q000494:pharmacology; D013552:Swine; D013917:Thrombin / Q000494:pharmacology; D014361:Trypsin Inhibitors / Q000494:pharmacology
D000227:Adenine Nucleotides; D000614:Aminocaproates; D000933:Antifibrinolytic Agents; D011453:Prostaglandins; D014361:Trypsin Inhibitors; D012701:Serotonin; D004176:Dipyridamole; D005340:Fibrinogen; D003094:Collagen; D013300:Streptokinase; D013917:Thrombin; D005341:Fibrinolysin; D010653:Phenylbutazone