Suboptimal monitoring and dosing of unfractionated heparin in comparative studies with low-molecular-weight heparin

Ann Intern Med. 2003 May 6;138(9):720-3. doi: 10.7326/0003-4819-138-9-200305060-00008.


Background: Site-specific validation of the activated partial thromboplastin time (aPTT) therapeutic range is required to ensure administration of the optimal dose of unfractionated heparin. Therapeutic ranges of 1.5 to 2.5 times the control value are subtherapeutic for most modern aPTT reagents.

Purpose: To audit the appropriateness of aPTT monitoring in clinical trials comparing unfractionated heparin and low-molecular-weight heparin in patients with venous thromboembolism.

Data sources: Search of PubMed database from 1984 to 2001.

Study selection: Randomized, controlled trials that compared unfractionated and low-molecular-weight heparin for the treatment of venous thromboembolism.

Data extraction: Use of unvalidated and potentially suboptimal therapeutic ranges for aPTT in patients assigned to receive unfractionated heparin.

Data synthesis: Fifteen studies met inclusion criteria. Only 3 studies used a validated aPTT therapeutic range, and 11 studies used a range that included aPTT values 1.5 times the control value. Ten studies reported unfractionated heparin doses, and 7 of these documented a reduction to less than 30 000 U/d in response to aPTT results.

Conclusions: Most studies monitored unfractionated heparin inappropriately. This shortcoming could be responsible for the reduced efficacy of unfractionated heparin in clinical trials.

Publication types

  • Meta-Analysis

MeSH terms

  • Anticoagulants / administration & dosage*
  • Drug Monitoring / methods
  • Drug Monitoring / standards*
  • Heparin / administration & dosage*
  • Heparin, Low-Molecular-Weight / administration & dosage*
  • Humans
  • Medical Audit
  • Partial Thromboplastin Time*
  • Pulmonary Embolism / drug therapy*
  • Randomized Controlled Trials as Topic
  • Venous Thrombosis / drug therapy*


  • Anticoagulants
  • Heparin, Low-Molecular-Weight
  • Heparin