Are activated clotting times helpful in the management of anticoagulation with subcutaneous low-molecular-weight heparin?
BACKGROUND
Enoxaparin has recently been shown to be superior to unfractionated heparin in patients with unstable angina/non-ST-elevation myocardial infarction. Theoretical advantages of low-molecular-weight heparin versus unfractionated heparin include a higher ratio of anti-Xa to anti-IIa activity (3:1 for enoxaparin), a more predictable dose response that precludes the need for frequent monitoring, and the convenience of subcutaneous administration. Both activated partial thromboplastin time and activated clotting time (ACT) are used to monitor anticoagulation with heparin, and ACTs are now standard during percutaneous coronary intervention (PCI) with heparin. At doses of up to 90 mg, subcutaneous enoxaparin leads to a modest dose-related increase in activated partial thromboplastin time, but the effect on ACT is unknown.


METHODS
Thrombolysis In Myocardial Infarction (TIMI) 11A was a multicenter, dose-ranging trial to evaluate the safety and tolerability of subcutaneous enoxaparin in patients with unstable angina/non-ST-elevation myocardial infarction. We obtained peak (mean 4.3 hours after enoxaparin) and trough (mean 11.5 hours after enoxaparin) anti-Xa levels and ACTs for 26 patients in the TIMI 11A trial.


RESULTS
Despite doses of enoxaparin in the range of 89 +/- 19 mg every 12 hours and significant increases in anti-Xa levels even at trough, there was no change in the ACT measured by HemoTec and only a small increase with Hemachron. The correlation of peak Hemachron ACT with peak anti-Xa levels was poor (R = 0.5, P =.08).


CONCLUSIONS
In contrast to heparin, ACTs are not useful for assessment of anticoagulation with subcutaneous enoxaparin and should not be relied on in patients receiving enoxaparin who require acute PCI. Studies to determine the optimal dose, safety, and efficacy of enoxaparin in patients undergoing PCI are underway.
Henry
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TD
Hennepin County Medical Center, Minneapolis, MN, USA. henry003@tc.umn.edu
Satran
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D
Knox
L L
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Iacarella
C L
CL
Laxson
D D
DD
Antman
E M
EM
D000787:Angina Pectoris / Q000097:blood / Q000188:drug therapy*; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects*; D006328:Cardiac Catheterization; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D017984:Enoxaparin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007279:Injections, Subcutaneous; D019476:Insect Proteins; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy*; D012471:Salivary Proteins and Peptides / Q000097:blood; D014914:Whole Blood Coagulation Time
D000925:Anticoagulants; D017984:Enoxaparin; D019476:Insect Proteins; D012471:Salivary Proteins and Peptides; C114100:anticoagulant factor Xa protein, Aedes aegypti