Evaluation of initial heparin infusion rates for a high-dose protocol

Abstract

Unfractionated heparin is widely used as anticoagulant therapy for thrombotic disease. However, determining appropriate dosing by intravenous infusion is highly variable in practice. Multiple standardized protocols have been adopted, including a weight-based nomogram entailing a loading dose of 80 U/kg, followed by an initial infusion rate of 18 U/kg/h. In some instances, 18 U/kg/h has resulted in supratherapeutic activated partial thromboplastin time (aPTT). This study aimed to determine if an initial heparin infusion rate of 14 U/kg/h per a high-dose protocol achieved therapeutic anticoagulation more rapidly than 18 U/kg/h. A retrospective chart review performed at a Veterans Health Administration facility located in the southwestern U.S. identified 129 patients hospitalized from January 2009 to August 2011 receiving a high-dose protocol for heparin with an initial infusion rate of 14 or 18 U/kg/h. The proportion of patients achieving subtherapeutic, at goal, or supratherapeutic aPTT on two subsequent mornings was determined. Time to reach therapeutic aPTT was assessed with a multivariable generalized linear model. Patients provided 18 U/kg/h for heparin anticoagulation therapy experienced elevated aPTT values initially. Also, these patients generally took 1.41 times longer to reach therapeutic aPTT than patients receiving 14 U/kg/h [estimate = 0.34, 95% CI 0.11, 0.57; p < 0.01]. Larger body mass index led to increased time to reach therapeutic anticoagulation. This study's results suggest that patients may benefit from receiving an initial heparin infusion rate of 14 U/kg/h over 18 U/kg/h. Decreasing the time to therapeutic aPTT may further help reduce workload from monitoring and dose titrations.