title: Recurrent venous thrombosis and heparin therapy: an evaluation of the importance of early activated partial thromboplastin times.
abstract: BACKGROUND
  The presence of an association between early subtherapeutic activated partial thromboplastin times (aPTTs) and recurrent venous thromboembolism (VTE) remains controversial.
  
  
  OBJECTIVE
  To determine the relation between early subtherapeutic aPTTs and recurrent VTE in patients who were treated with intravenous (i.v.) unfractionated heparin (UFH).
  
  
  METHODS
  We studied 961 patients with acute VTE who received i.v. UFH in 3 randomized trials that compared the use of i.v. UFH (loading dose: 5000 U i.v.; initial infusion, 1250-1280 U/h) with that of subcutaneous low-molecular-weight heparin. According to aPTT criteria, patients were classified as being in a subtherapeutic or a therapeutic state during the first 24 and 48 hours of treatment. All episodes of possible recurrent VTE were adjudicated by an independent committee that was unaware of the aPTTs.
  
  
  RESULTS
  At 24 hours, in 886 patients who were eligible for the analysis, the rate of recurrent VTE in the subtherapeutic group was 6.7% (11/163) compared with 5.3% (38/723) in the therapeutic group. The odds ratio for recurrence in patients in the subtherapeutic vs the therapeutic group at 24 hours was 1.30 (95% confidence interval: 0.64-2.63; P = .46). At 48 hours, in 917 patients who were eligible for the analysis, the rate of recurrent VTE in the subtherapeutic group was 7.8% (5/64) compared with 5.7% (49/853) in the therapeutic group. The odds ratio for recurrence in patients in the subtherapeutic vs the therapeutic group at 48 hours was 1.32 (95% confidence interval: 0.51-3.44; P = .56).
  
  
  CONCLUSIONS
  In patients with acute VTE who receive an i.v. bolus of 5000 U, followed by a starting dose of at least 1250 U/h of UFH, a subtherapeutic aPTT response during the first 48 hours of treatment is not associated with a large increase in the risk of recurrent VTE.
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada. anands@fhs.mcmaster.ca
authors.forename: S S
authors.initials: SS
authors.lastname: Anand
authors.forename: S
authors.initials: S
authors.lastname: Bates
authors.forename: J S
authors.initials: JS
authors.lastname: Ginsberg
authors.forename: M
authors.initials: M
authors.lastname: Levine
authors.forename: H
authors.initials: H
authors.lastname: Buller
authors.forename: M
authors.initials: M
authors.lastname: Prins
authors.forename: S
authors.initials: S
authors.lastname: Haley
authors.forename: C
authors.initials: C
authors.lastname: Kearon
authors.forename: J
authors.initials: J
authors.lastname: Hirsh
authors.forename: M
authors.initials: M
authors.lastname: Gent
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010314:Partial Thromboplastin Time; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D013997:Time Factors; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000097:blood / Q000188:drug therapy* / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D006493:Heparin