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Ecarin clotting time but not aPTT correlates with PEG-hirudin plasma activity.

AbstractBACKGROUND:
Novel antithrombotic agents such as hirudin have shown promise in the therapy of acute coronary syndromes. PEG-hirudin (polyethyleneglycol conjugated hirudin) has been developed to provide a longer plasma half-life and more stable antithrombotic plasma levels. Privious trials indicated a narrow therapeutic window for hirudin and a number of aPTT (activated partial thromboplastin time)-monitored trials investigating hirudin in acute coronary syndromes had to be stopped because of intracranial bleeding complications.
OBJECTIVES:
The present study evaluates the ecarin clotting time (ECT), a parameter based on the conversion of prothrombin by the snake venom enzyme ecarin, for the monitoring of PEG-hirudin therapy.
METHODS:
Plasma from either healthy volunteers (n=20) or from patients (n=10) suffering from unstable angina pectoris (UAP) was spiked with increasing PEG-hirudin concentrations. In a prospective randomized clinical trial patients with UAP were treated with intravenous PEG-hirudin or heparin over 72 hours. Patients were randomized to the following treatment groups: (1) heparin control group, n=15; (2) PEG-hirudin low dose (0.1 mg/kg bolus, 0.01 mg/kg/h infusion), n=19; (3) intermediate dose (0.15 mg/kg and 0.015 mg/kg/h), n=17; 4) high-dose (0.2 mg/kg and 0.02 mg/kg/h), n=16. Spiked plasma samples and plasma from UAP patients treated with i.v. PEG-hirudin were analyzed for aPTT, ECT, and PEG-hirudin levels.
RESULTS:
A linear correlation up to the highest therapeutic concentrations could be observed between PEG-hirudin plasma concentrations and the ECT. This was true for both plasma samples spiked with PEG-hirudin in vitro as well as for samples taken from patients treated with i.v. PEG-hirudin (correlation coefficient 0.9, respect.) In contrast the aPTT did not show a reliable linear correlation to PEG-hirudin concentrations.
CONCLUSION:
Monitoring of PEG-hirudin therapy by ECT may help to avoid inadequate anticoagulation or overdosing. Thus, the safety and efficacy profile of PEG-hirudin therapy is likely to be enhanced by ECT monitoring.
AuthorsM Moser, J Ruef, K Peter, B Kohler, D C Gulba, N Paterna, T Nordt, W Kübler, C Bode
JournalJournal of thrombosis and thrombolysis (J Thromb Thrombolysis) Vol. 12 Issue 2 Pg. 165-9 (Oct 2001) ISSN: 0929-5305 [Print] Netherlands
PMID11729368 (Publication Type: Clinical Trial, Evaluation Study, Journal Article, Randomized Controlled Trial)
Chemical References
  • Antithrombins
  • Fibrinolytic Agents
  • Hirudins
  • polyethyleneglycol-hirudin
  • Endopeptidases
  • ecarin
Topics
  • Angina, Unstable (blood, drug therapy)
  • Antithrombins (analysis, pharmacokinetics, therapeutic use)
  • Blood Coagulation Tests (methods, standards)
  • Drug Monitoring (methods, standards)
  • Endopeptidases
  • Fibrinolytic Agents
  • Hirudin Therapy
  • Hirudins (analogs & derivatives, blood, pharmacokinetics)
  • Humans
  • Partial Thromboplastin Time
  • Regression Analysis

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