title: Ecarin clotting time but not aPTT correlates with PEG-hirudin plasma activity.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Dept. of Internal Medicine III (Cardiology), University of Heidelberg, Bergheimer Strasse 58, D-69115 Heidelberg, Germany. johannes_ruef@med.uni-heidelberg.de
authors.forename: M
authors.initials: M
authors.lastname: Moser
authors.forename: J
authors.initials: J
authors.lastname: Ruef
authors.forename: K
authors.initials: K
authors.lastname: Peter
authors.forename: B
authors.initials: B
authors.lastname: Kohler
authors.forename: D C
authors.initials: DC
authors.lastname: Gulba
authors.forename: N
authors.initials: N
authors.lastname: Paterna
authors.forename: T
authors.initials: T
authors.lastname: Nordt
authors.forename: W
authors.initials: W
authors.lastname: Kübler
authors.forename: C
authors.initials: C
authors.lastname: Bode
mesh_terms: D000789:Angina, Unstable / Q000097:blood / Q000188:drug therapy; D000991:Antithrombins / Q000032:analysis / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001780:Blood Coagulation Tests / Q000379:methods / Q000592:standards; D016903:Drug Monitoring / Q000379:methods* / Q000592:standards; D010450:Endopeptidases; D005343:Fibrinolytic Agents; D024764:Hirudin Therapy; D006629:Hirudins / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D010314:Partial Thromboplastin Time; D012044:Regression Analysis
chemical_list: D000991:Antithrombins; D005343:Fibrinolytic Agents; D006629:Hirudins; C104614:polyethyleneglycol-hirudin; D010450:Endopeptidases; C020097:ecarin