TY - JOUR
T1 - Reactive coagulation induced by plasmin in patients treated with recombinant tissue-type plasminogen activator
AU - Gram, J.
AU - Munkvad, S.
AU - Leebeek, F. W.G.
AU - Kluft, C.
AU - Jespersen, J.
N1 - © Lippincott-Raven Publishers.
PY - 1993/4
Y1 - 1993/4
N2 - Background: We and others have demonstrated that administration of thrombolytic agents causes the generation of thrombosis-promoting agents. At present, we have studied whether formation in vivo of excessive amounts of plasmin is responsible for the activation of coagulation in patients treated with recombinant tissue-type plasminogen activator. Methods: Modified crossed immunoelectrophoresis was used for determination of the plasminogen-binding form of α2-antiplasmin. Enzyme-linked immunosorbent assay methods were used for determination of hemostatic reaction products. Results: The association between the generation of hemostatic reaction products and the exhaustion of the plasminogen-binding form of α2-antiplasmin (PBα2AP) was studied in 21 patients with acute myocardial infarction and 11 patients with unstable angina pectoris who were given a 3-hour, 100-mg intravenous infusion of recombinant tissue-type plasminogen activator (rt-PA). We observed in all patients a fall in blood concentrations of PBα2AP (P < 0.01) after 2.25 hours of treatment and, simultaneously, a significant increase in fibrin degradation products (P < 0.01), D-dimer (P < 0.01), fibrinogen degradation products (P < 0.01), prothrombin fragment 1+2 (P < 0.01), and thrombin-antithrombin III complexes (P < 0.01). When we evaluated individual data, we observed high concentrations of the reaction products when the PBα2AP concentration after 2.25 hours of treatment was lower than 25% of the pretreatment values. Also, we observed highly significant associations between the increase in the plasma concentrations of fibrin degradation products and thrombin-antithrombin III complexes (r(s) = 0.72; P < 0.01), the increase in plasma concentrations of fibrin degradation products and prothrombin fragment 1+2 (r(s) = 0.63; P < 0.01), the increase in plasma concentrations of D-dimer and thrombin-antithrombin III complexes (r(s) = 0.78; P < 0.01), and the increase in plasma concentrations of D-dimer and prothrombin fragment 1+2 (r(s) = 0.79; P < 0.01). Conclusions: Generation of excessive amounts of plasmin is the main factor in producing the procoagulant response in patients who receive thrombolytic therapy with rt-PA, and intravenous heparin does not abolish this response. Plasmin inhibitors might be used in relation to thrombolytic therapy as indirect 'antithrombotics.'
AB - Background: We and others have demonstrated that administration of thrombolytic agents causes the generation of thrombosis-promoting agents. At present, we have studied whether formation in vivo of excessive amounts of plasmin is responsible for the activation of coagulation in patients treated with recombinant tissue-type plasminogen activator. Methods: Modified crossed immunoelectrophoresis was used for determination of the plasminogen-binding form of α2-antiplasmin. Enzyme-linked immunosorbent assay methods were used for determination of hemostatic reaction products. Results: The association between the generation of hemostatic reaction products and the exhaustion of the plasminogen-binding form of α2-antiplasmin (PBα2AP) was studied in 21 patients with acute myocardial infarction and 11 patients with unstable angina pectoris who were given a 3-hour, 100-mg intravenous infusion of recombinant tissue-type plasminogen activator (rt-PA). We observed in all patients a fall in blood concentrations of PBα2AP (P < 0.01) after 2.25 hours of treatment and, simultaneously, a significant increase in fibrin degradation products (P < 0.01), D-dimer (P < 0.01), fibrinogen degradation products (P < 0.01), prothrombin fragment 1+2 (P < 0.01), and thrombin-antithrombin III complexes (P < 0.01). When we evaluated individual data, we observed high concentrations of the reaction products when the PBα2AP concentration after 2.25 hours of treatment was lower than 25% of the pretreatment values. Also, we observed highly significant associations between the increase in the plasma concentrations of fibrin degradation products and thrombin-antithrombin III complexes (r(s) = 0.72; P < 0.01), the increase in plasma concentrations of fibrin degradation products and prothrombin fragment 1+2 (r(s) = 0.63; P < 0.01), the increase in plasma concentrations of D-dimer and thrombin-antithrombin III complexes (r(s) = 0.78; P < 0.01), and the increase in plasma concentrations of D-dimer and prothrombin fragment 1+2 (r(s) = 0.79; P < 0.01). Conclusions: Generation of excessive amounts of plasmin is the main factor in producing the procoagulant response in patients who receive thrombolytic therapy with rt-PA, and intravenous heparin does not abolish this response. Plasmin inhibitors might be used in relation to thrombolytic therapy as indirect 'antithrombotics.'
UR - http://www.scopus.com/inward/record.url?scp=0027253582&partnerID=8YFLogxK
U2 - 10.1097/00019501-199304000-00009
DO - 10.1097/00019501-199304000-00009
M3 - Article
C2 - 8261210
AN - SCOPUS:0027253582
SN - 0954-6928
VL - 4
SP - 371
EP - 378
JO - Coronary Artery Disease
JF - Coronary Artery Disease
IS - 4
ER -