Thrombosis research
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Thrombosis research · May 2001
Superiority of enoxaparin over heparin in combination with a GPIIb/IIIa receptor antagonist during coronary thrombolysis in dogs.
It is known that a low-molecular-weight heparin (LMWH) is more effective than unfractionated heparin in unstable angina/non-Q-wave myocardial infarction (UA/NQMI) and the platelet GPIIb/IIIa receptors play an important role in acute myocardial infarction (AMI). Therefore, enoxaparin might have a similar advantage over heparin when used with a GPIIb/IIIa antagonist (RPR109891) in coronary thrombolysis. After induction of coronary thrombosis in anesthetized dogs, infusion of saline, enoxaparin, heparin, RPR109891, enoxaparin+RPR109891, or heparin+RPR109891 was initiated followed 15 min later by recombinant tissue plasminogen activator (rt-PA). ⋯ Enoxaparin+RPR109891 maintained flow for a significantly longer time compared to saline, enoxaparin, heparin, and heparin+RPR109891. Enoxaparin+RPR109891 and heparin+RPR109891 increased the template bleeding time by 2- and 3-fold and activated partial thromboplastin time (APTT) by 1.3- and 3-fold, respectively. These data suggest that enoxaparin is more effective and potentially safer than heparin when combined with a GPIIb/IIIa receptor antagonist during rt-PA-induced coronary thrombolysis.
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Thrombosis research · Feb 2001
Effects of agents, used to treat bleeding disorders, on bleeding time prolonged by a very high dose of a direct thrombin inhibitor in anesthesized rats and rabbits.
Melagatran is the active form of the oral, direct thrombin inhibitor, H 376/95, that is under evaluation in clinical trials for the prevention and treatment of thromboembolism. In this study, a single dose, calculated on body weight basis, of antifibrinolytic treatment, factor VIIa, factor VIII with and without von Willebrand factor (vWF), factor IX, activated (APCC) or nonactivated (PCC) prothrombin complex concentrates was given intravenously to rats and rabbits, in an attempt to reverse the prolonged bleeding time during intensive anticoagulation with melagatran (2 micromol/kg/h). The doses used were at or above human therapeutic doses. ⋯ In conclusion, APCCs were found to be the most effective agents for reversing bleeding time induced by a very high plasma concentration of melagatran. APCC and recombinant activated factor FVII (rF VIIa) effectively shortened the prolonged WBCT. Thus, stimulating thrombin generation with the use of APCC may counteract the anticoagulant effect observed with a very high dose of a thrombin inhibitor.
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Thrombosis research · Feb 2001
Effect of activated prothrombin complex concentrate or recombinant factor VIIa on the bleeding time and thrombus formation during anticoagulation with a direct thrombin inhibitor.
Melagatran is the active form of the oral, direct thrombin inhibitor H 376/95. In several animal models of thrombosis, the antithrombotic properties of melagatran have been demonstrated, without any increase in experimental bleeding. However, as with all anticoagulants, in emergency situations, reversal of the anticoagulation may be necessary. In this study, increasing doses of activated prothrombin complex concentrate (APCC, Feiba) or recombinant factor VIIa (r-F VIIa, NovoSeven) were superimposed on high doses of melagatran, or saline, in anaesthetised rats. The haemostatic effect was evaluated in two bleeding time models and a potential prothrombotic effect was evaluated in an arterial thrombosis model. Compared with melagatran alone (0.5 micromol/kg/h), Feiba in doses of > or =25 U/kg significantly shortened the prolonged bleeding time and reduced blood loss. In addition, Feiba > or =50 U/kg when added to melagatran (2 micromol/kg/h), significantly reduced bleeding time. No potentiation of thrombus formation was observed when Feiba was added to melagatran, compared with controls. NovoSeven at high doses (2-10 mg/kg) produced a nonsignificant trend in reduction of blood loss and with the highest dose (10 mg/kg) producing only a mild nonsignificant reduction in bleeding time. The prolonged prothrombin time (PT) and the ecarin clotting time (ECT) were more effectively shortened by Feiba than by NovoSeven. In contrast, whole blood clotting time (WBCT) was more effectively shortened by NovoSeven than by Feiba. Activated partial thromboplastin time (APTT) was shortened by NovoSeven but was prolonged by Feiba. Thrombin-antithrombin (TAT) complex formation was increased in a dose-dependent fashion more effectively by Feiba than by NovoSeven. ⋯ Feiba (APCC) reversed prolonged bleeding time and blood loss in rats treated with high doses of melagatran and compared with the control group thrombus formation was not potentiated. NovoSeven (r-F VIIa) at high doses had less pronounced effects on blood loss and bleeding times compared with Feiba.
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Thrombosis research · Jan 2001
Post-thrombotic syndrome after primary event of deep venous thrombosis 10 to 20 years ago.
We investigated the impact of the extent of primary deep venous thrombosis (DVT) and recurrent thrombotic events in accordance to other presumed prognostic factors for long-term clinical outcome after first DVT. ⋯ Our results show that primary four-level DVT, calf vein thrombosis, recurrence of ipsilateral DVT and a non-sufficient oral anticoagulation are of prognostic significance for developing clinically relevant PTS within 10 to 20 years after first DVT.
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Spinal and epidural anesthesia/analgesia provide several advantages over systemic opioids, including superior analgesia, reduced blood loss and need for transfusion, and decreased incidence of thromboembolic complications. However, patients hospitalized for major surgery often receive an anticoagulant and/or antiplatelet medication perioperatively to prevent venous thrombosis and pulmonary embolism, although the pharmacologic agent, degree of anticoagulation desired, and duration of therapy remain controversial. These patients are often not considered candidates for spinal or epidural anesthesia/analgesia because of a theoretically greater risk of spinal hematoma. ⋯ The incidence of neurologic dysfunction resulting from hemorrhagic complications associated with central neural blockade is estimated to be less than 1 in 150,000 epidural and less than 1 in 220,000 spinal anesthetics. The decision to perform neuraxial blockade on these patients must be made on an individual basis, weighing the risk of spinal hematoma from needle or catheter placement against the theoretical benefits gained. Familiarity with the pharmacology of hemostasis-altering drugs, as well as case reports and clinical studies involving patients undergoing neuraxial blockade while receiving these medications will guide the clinician faced with this difficult decision.