Establishing a therapeutic range for heparin therapy

Ann Intern Med. 1993 Jul 15;119(2):104-9. doi: 10.7326/0003-4819-119-2-199307150-00002.


Objective: To compare two methods of determining a therapeutic range of activated partial thromboplastin time (aPTT) results.

Design: Cohort studies.

Setting: Referral teaching hospital.

Patients: Inpatients who received unfractionated heparin intravenously for venous thromboembolic disease.

Measurements: A therapeutic range determined by aPTT ratios of 1.5 to 2.5 times the control value as compared with a therapeutic range determined by protamine titration heparin levels of 0.2 to 0.4 U/mL.

Results: For all aPTT reagents studied, a ratio of 1.5 times the control value is much less than a minimum protamine titration heparin level of 0.2 U/mL. Various manufacturers' aPTT reagents and reagent lots from the same manufacturer show considerable variation in response to heparin and therefore have different therapeutic ranges.

Conclusions: A different dose of heparin would be required to produce an aPTT ratio of 1.5 times the control value, depending on the reagent used. Establishing a therapeutic range for aPTT results using protamine titration heparin levels of 0.2 to 0.4 U/mL as a reference standard is practical and compensates for the variable response of aPTT reagents to heparin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Heparin / administration & dosage*
  • Heparin / blood
  • Humans
  • Indicators and Reagents
  • Partial Thromboplastin Time*
  • Reference Values
  • Regression Analysis
  • Thromboembolism / blood
  • Thromboembolism / drug therapy
  • Titrimetry


  • Indicators and Reagents
  • Heparin