Thrombosis research
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Thrombosis research · Nov 1992
Neutralization of the antithrombotic effects of heparin and Fraxiparin by protamine sulfate.
In general, the in vitro anti Xa activity of low molecular weight heparins is neutralized to a lesser degree than the anti Xa activity of unfractionated heparin. To determine whether these differences occur in vivo, a rabbit stasis thrombosis model and a rat laser-induced thrombosis model were utilized. In the laser model, a similar degree of neutralization of the antithrombotic activity of heparin and Fraxiparin was obtained. ⋯ A coefficient (r = .806) was obtained for the correlation of Heptest activity to antithrombotic effect in the stasis thrombosis model, while the coefficients obtained for the other tests ranged from .152-.570. However, after neutralization by protamine, the thrombin time exhibited the highest correlation coefficient (r = .685) between ex vivo activity and residual antithrombotic effect. Since Fraxiparin retains antithrombotic activity after protamine administration, clinical benefit may be observed for this low molecular weight heparin as compared to unfractionated heparin after neutralization.
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Thrombosis research · Apr 1992
Randomized Controlled Trial Clinical TrialEffects of long-term treatment with warfarin on fibrinogen, FPA, TAT, and D-dimer in patients with coronary artery disease.
Sixty-four patients undergoing aorto-coronary bypass surgery were randomized to receive antithrombotic treatment with acetylsalicylic acid (ASA), 300 mg/d (n = 30) or warfarin, INR = 2.5 - 4.2 (n = 34). The levels of fibrinogen, thrombin-antithrombin III complexes (TAT), fibrinopeptide A (FPA) and D-dimer were assessed before surgery and 9 months postoperatively. ⋯ In the ASA group TAT levels were increased at 9 months, whereas no significant changes in fibrinogen, FPA or D-dimer from baseline were noted. Thus, a reduced activation of the coagulation system has been demonstrated during long-term treatment with warfarin in patients with coronary artery disease.
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To clarify whether activated platelets play an important role in the occurrence and exacerbation of disseminated intravascular coagulation (DIC), we investigated the effects of 4 anti-platelet drugs, a PGI2 analog (CS-570), a thromboxane synthetase inhibitor (dazoxiben), a thromboxane receptor antagonist (BM-13177), and ticlopidine, in an experimental DIC model in rats. Experimental DIC was induced by a continuous infusion of lipopolysaccharide (LPS derived from E. coli, 055 B5, 25 mg/kg/hr) for 4 hrs. In the time-course determination of the coagulation parameters and prostanoids, an abrupt increase in TxB2 (a stable metabolite of TxA2) and 6-keto-PGF1 alpha (a stable metabolite of PGI2) was followed by a decrease in platelet count, a prolongation of blood coagulation time, and an increase in fibrinogen/fibrin degradation products (FDP). ⋯ Dazoxiben, but not BM-13177, significantly inhibited the increase in TxB2 concentration at 4 hr. These observations suggest that drugs which inhibit platelet activation by a TxA2-dependent route are effective in improving DIC induced by LPS, and that drugs which inhibit multiple platelet-activating routes improve DIC in more item parameters than drugs which inhibit only the TxA2-dependent activating route. Consequently, it is concluded that activated platelets might play an important role in the occurrence and exacerbation of DIC induced by LPS, and that one of the roles of TxA2 in DIC is to activate platelets.
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Thrombosis research · Apr 1990
Case ReportsPrevention of severe bleeding by tranexamic acid in a patient with disseminated intravascular coagulation.
Severe bleeding took place in a patient when abdominal aneurysm was removed by operation. Bleeding continued after infusion of heparin, antithrombin III (ATIII), fresh platelets and fresh blood. ⋯ Second time bleeding also stopped after the administration of tranexamic acid. Major finding of plasma parameters of fibrinolysis is that alpha 2AP which had been unable to inhibit plasmin, became able to inhibit it after the administration of tranexamic acid.
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Thrombosis research · Mar 1990
Comparative StudyLocal activation of the coagulation and fibrinolysis systems in lung disease.
Extravascular coagulation and fibrinolysis is an integral part of inflammatory reactions. Disordered expression of procoagulant and profibrinolytic factors by mononuclear phagocytes of the lung (i.e. lung alveolar macrophages (LAM) and interstitial macrophages) may have important bearings on inflammatory lung tissue destruction and repair. Based on this hypothesis we have measured the presence of trigger molecules and activation products of the coagulation and fibrinolytic system in cell-free bronchoalveolar lavage fluid and in bronchoalveolar cells. ⋯ The level of PA inhibitor (PAI-2) was not significantly higher in any patient group compared to controls. The sensitivity of the method for fibrin degradation products (FDP) analysis was not high enough to detect FDP in BAL fluid of control individuals, whereas such products could be demonstrated in 25-53% of patients in various categories. We conclude that disordered expression of procoagulant and plasminogen activator activities in bronchoalveolar lavage fluid may reflect a milieu that favours accumulation of fibrin in inflammatory lung tissue and form the basis for the development of pulmonary fibrosis.