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


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


METHODS
Search of PubMed database from 1984 to 2001.


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


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


RESULTS
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.
Raschke
Robert
R
Good Samaritan Regional Medical Center, 1111 East McDowell Road, Phoenix, Arizona 85006, USA. robertraschke@bannerhealth.com
Hirsh
Jack
J
Guidry
James R
JR
D000925:Anticoagulants / Q000008:administration & dosage*; D016903:Drug Monitoring / Q000379:methods / Q000592:standards*; D006493:Heparin / Q000008:administration & dosage*; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage*; D006801:Humans; D008485:Medical Audit; D010314:Partial Thromboplastin Time; D011655:Pulmonary Embolism / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D020246:Venous Thrombosis / Q000188:drug therapy*
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D006493:Heparin