Weight-based argatroban dosing nomogram for treatment of heparin-induced thrombocytopenia.
BACKGROUND
Manufacturer recommendations for argatroban use in the setting of heparin-induced thrombocytopenia (HIT) state that the dosage should be titrated to a goal activated partial thromboplastin time (aPTT) of 1.5-3 times the baseline aPTT. The lack of a clear dosing strategy with argatroban may result in delayed stabilization of aPTT. There are no published nomograms to guide the dosing of argatroban.


OBJECTIVE
To study the anticoagulant effect and incidence of bleeding and thrombotic events in patients receiving argatroban, with doses determined using a weight-based nomogram.


METHODS
Patients with suspected or documented HIT at an 800-bed teaching community hospital were prospectively treated, in a nonrandomized, nonblinded manner, with argatroban; dosage adjustments were made according to 1 of 2 variations of a dosing nomogram: standard or hepatic/critically ill. The primary outcomes were time to aPTT stabilization and percentage of patients whose aPTTs were within the therapeutic range of 45-90 seconds at 6, 12, 24, 48, 72, and 96 hours. Secondary outcomes were the percentage of patients whose aPTTs were subtherapeutic, supratherapeutic, or above the therapeutic threshold of 45 seconds at each time interval; incidence of thrombotic events; number of dosage adjustments to achieve stabilization; and number of major bleeding events.


RESULTS
Fifty-one patients were prospectively treated using the standard (n = 34) and hepatic/critically ill (n = 17) nomograms. Mean time to aPTT stabilization was 16.25 hours with the standard nomogram and 27.05 hours with the hepatic/critically ill nomogram. The percentages of patients with aPTTs within the therapeutic range at each time interval were 82.4%, 82.4%, 88.2%, 96.4%, 100%, and 100% with the standard nomogram and 58.8%, 82.4%, 76.5%, 93.3%, 100%, and 90.9% with the hepatic/critically ill nomogram. There were no thrombotic events after the initiation of argatroban. Three cases of major bleeding occurred.


CONCLUSIONS
The nomogram is an effective dosing tool for achieving and maintaining therapeutic levels of anticoagulation.
Ansara
Alexander J
AJ
Internal Medicine, Department of Pharmacy, Methodist Hospital (Clarian Health), Indianapolis, IN 46202, USA. aansara@clarian.org
Arif
Sally
S
Warhurst
Robert D
RD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage*; D001120:Arginine / Q000031:analogs & derivatives; D001835:Body Weight / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D049451:Nomograms; D010875:Pipecolic Acids / Q000008:administration & dosage*; D011446:Prospective Studies; D013449:Sulfonamides; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000188:drug therapy*; D016896:Treatment Outcome
D000925:Anticoagulants; D010875:Pipecolic Acids; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; C031942:argatroban