title: Optimal therapeutic level of heparin therapy in patients with venous thrombosis.
abstract: BACKGROUND
  Audits of heparin sodium therapy suggest that heparin administration is fraught with difficulty. The literature indicates that the current clinical practice of intuitive ordering of heparin results in inadequate therapy because of fear of bleeding. The importance of exceeding the lower limit of the therapeutic range has been strongly supported by findings of prospective clinical trials. Firm evidence indicates that failure to exceed the lower limit is associated with unacceptably high rates of recurrent venous thromboembolism. By comparison, evidence supporting the risk of exceeding the upper limit of the therapeutic range is weak.
  
  
  OBJECTIVE
  The purposes of this study were (1) to validate prospectively an approach designed to minimize the proportion of patients receiving subtherapeutic doses of heparin and (2) to determine the effectiveness and safety of decreasing the heparin dosage infused on the basis of activated partial thromboplastin time (APTT) prolongation reflecting both heparin and warfarin sodium effects.
  
  
  METHODS
  We performed a randomized double-blind study evaluating a prescriptive approach to heparin administration in patients receiving heparin or heparin with warfarin. Thromboembolic and bleeding complications were objectively documented.
  
  
  RESULTS
  Only 1% and 2% of patients had subtherapeutic heparin levels for 24 hours or more in the heparin and combined groups, respectively. Recurrent venous thromboembolism occurred infrequently in both groups (7%). Sixty-nine (69%) of 99 patients receiving combined therapy had supratherapeutic values, compared with 24 (24%) of 100 receiving heparin; bleeding complications occurred in 9% and 12%, respectively.
  
  
  CONCLUSIONS
  Our findings demonstrate that no association exists between supratherapeutic APTT responses and bleeding, which is in direct contrast to the observed association between subtherapeutic APTT responses and recurrent venous thromboembolism.
authors.affiliation: Clinical Trials Unit, University of Calgary, Alberta, Canada.
authors.forename: R D
authors.initials: RD
authors.lastname: Hull
authors.forename: G E
authors.initials: GE
authors.lastname: Raskob
authors.forename: D
authors.initials: D
authors.lastname: Rosenbloom
authors.forename: J
authors.initials: J
authors.lastname: Lemaire
authors.forename: G F
authors.initials: GF
authors.lastname: Pineo
authors.forename: B
authors.initials: B
authors.lastname: Baylis
authors.forename: J S
authors.initials: JS
authors.lastname: Ginsberg
authors.forename: A A
authors.initials: AA
authors.lastname: Panju
authors.forename: P
authors.initials: P
authors.lastname: Brill-Edwards
authors.forename: R
authors.initials: R
authors.lastname: Brant
mesh_terms: D004311:Double-Blind Method; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006493:Heparin / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D010314:Partial Thromboplastin Time; D012008:Recurrence; D013924:Thrombophlebitis / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D014859:Warfarin; D006493:Heparin