title: Heparin inhibits spontaneous thrombolysis and the thrombolytic effect of both streptokinase and tissue-type plasminogen activator. An in vitro study of the dislodgement of platelet-rich thrombi formed from native blood.
abstract: Two in vitro models of coronary thrombolysis in man, i.e. dislodgement of thrombi formed from non-anticoagulated human blood, either by (i) shear-stress or (ii) interaction of platelets with type I collagen fibre, were studied. Heparinization (1 U/ml) of blood prior to thrombus formation by (i) strongly inhibited spontaneous dislodgement (P less than 0.0001). Heparin (1 U/ml), when added with streptokinase (SK) or tissue-type plasminogen activator (rt-PA) prior to thrombus formation, considerably delayed thrombolysis. Furthermore, thrombolysis occurred much earlier when thrombi were perfused with SK or rt-PA in native than in heparinized blood. Heparin inhibited binding of 125I-rt-PA (17%, P less than 0.02) and plasminogen (88%, P less than 0.0005) to platelets activated by ADP in citrated platelet-rich plasma. We conclude that heparin interferes with the fibrinolytic system at the surface of activated platelets. Our findings suggest that heparin administration prior to thrombolytic therapy for acute myocardial infarction should be questioned.
authors.affiliation: Department of Haematology, St. Bartholomew's Hospital, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Görög
authors.forename: C D
authors.initials: CD
authors.lastname: Ridler
authors.forename: I B
authors.initials: IB
authors.lastname: Kovacs
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000378:metabolism; D006487:Hemostasis / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D010958:Plasminogen / Q000378:metabolism; D013300:Streptokinase / Q000037:antagonists & inhibitors*; D013927:Thrombosis / Q000097:blood*; D010959:Tissue Plasminogen Activator / Q000037:antagonists & inhibitors* / Q000097:blood
chemical_list: D010958:Plasminogen; D006493:Heparin; D013300:Streptokinase; D010959:Tissue Plasminogen Activator