Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coagulation activation markers were studied in 148 patients undergoing total hip replacement under recombinant-hirudin (Desirudin, Revasc) prophylaxis with the aim of investigating the efficacy and safety of this anticoagulant compared with heparin in terms of biological effects on coagulation variables and bleeding. Hirudin (10, 15 or 20 mg s.c. b.i.d.) or unfractionated heparin (5000 IU s.c. t.i.d.) was administered immediately before surgery and continued for 8-12 days. Activated partial thromboplastin time (aPTT), prothrombin activation fragment F1 + 2 (F1 + 2), thrombin-antithrombin III complexes (TAT) and D-dimer were measured at baseline and on postoperative days 1,3 and 6, immediately before the morning injection. In comparison with baseline values, heparin had little effect on aPTT whereas the three hirudin doses prolonged aPTT significantly with no differences among the three doses. Moreover, there were no group differences in perioperative or cumulative blood loss or transfusion requirements. F1 + 2 fragment, TAT and D-dimer plasma levels were higher than at baseline during the entire postoperative period, with different trends (F1 + 2 increasing, TAT decreasing, D-dimer increasing, decreasing and then increasing again), but without significant differences among the four treatment groups. Our findings suggest that specific inhibition of thrombin seems a safe and efficacious mode of blocking thrombin activity after hip surgery although it does not prevent thrombin generation.
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PMID:Markers of hemostatic system activation during thromboprophylaxis with recombinant hirudin in total hip replacement. 870 98

Desirudin is a renally eliminated direct thrombin inhibitor approved to prevent venous thromboembolism. Empiric dosage adjustment and activated partial thromboplastin time (aPTT) monitoring in patients with moderate renal impairment are recommended, but supportive data are lacking. The objective of this study was to evaluate appropriate desirudin dosing in moderate renal impairment and the effect of desirudin on aPTT in moderate renal impairment. Desirudin plasma concentration and aPTT data were extracted from 6 studies. Participants with normal renal function or moderate renal impairment (creatinine clearance [ClCr] 31-60 mL/min) were included. Pharmacokinetic and Monte Carlo simulations were done. After administration of desirudin 15 mg every 12 hours subcutaneously (SC) to steady state, peak desirudin concentrations were 35 and 47 nmol/L in the normal and moderate renal function groups, respectively. Monte Carlo simulations found median 2-hour C(max) concentrations of 51.7 nmol/L in normal renal function and 52.4 nmol/L in moderate renal impairment. Desirudin exhibits a linear relationship when the square root of desirudin concentration is plotted versus the aPTT ratio (r(2) = 0.76). These analyses support the dosing of desirudin at 15 mg every 12 hours SC without aPTT monitoring in patients with moderate renal impairment.
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PMID:Desirudin dosing and monitoring in moderate renal impairment. 1991 80

Because of an extreme risk for thromboemboli, patients with suspected heparin-induced thrombocytopenia (HIT) require immediate initiation of an alternative anticoagulant. The only therapies approved by the Food and Drug Administration require intravenous infusion of expensive direct thrombin inhibitors. This prospective, randomized, open-label, exploratory study compared the clinical and economic utility of subcutaneous desirudin vs argatroban, the most frequently used agent for suspected or immunologically confirmed HIT, with or without thrombosis. Sixteen patients were randomized to treatment with fixed-dose desirudin (15 or 30 mg) every 12 hours or activated partial thromboplastin time-adjusted argatroban by intravenous infusion. Arm A included 8 patients naive to direct thrombin inhibitor therapy, whereas Arm B included 8 patients on argatroban for at least 24 hours before randomization. The primary efficacy measure was the composite of new or worsening thrombosis (objectively documented), amputation, or death. Other end points included major and minor bleeding while on drug therapy, time to platelet count recovery, and pharmacoeconomics. No amputations or deaths occurred. One patient randomized to argatroban had worsening of an existing thrombosis. Major bleeding occurred in 2 patients on argatroban and in none during desirudin treatment. There was 1 minor bleed in each treatment group. The average medication cost per course of treatment was $1688 for desirudin and $8250 for argatroban. Desirudin warrants further study as a potentially cost-effective alternative to argatroban in patients with suspected HIT.
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PMID:A randomized, open-label pilot study comparing desirudin and argatroban in patients with suspected heparin-induced thrombocytopenia with or without thrombosis: PREVENT-HIT Study. 2107 12