(496) Evaluation of Antithrombin Administration During Heparin Anticoagulation in Critically Ill Patients

Introduction: Antithrombin has been well-validated to mitigate heparin resistance and reduce fresh frozen plasma requirements in cardiopulmonary bypass. However, there is a paucity of data for antithrombin’s safety and efficacy outside of cardiac surgery. The purpose of this study was to evaluate the efficacy and safety of antithrombin in critically ill patients receiving intravenous heparin for anticoagulation outside of the operating room.

Methods: This was a multi-center, retrospective case series of patients admitted to an intensive care unit within the Emory Healthcare system who received heparin for therapeutic anticoagulation and antithrombin from July 2017 to June 2023. The primary outcome was the incidence of patients with therapeutic anti-Xa levels within 24 hours of antithrombin administration. Secondary outcomes included total time in therapeutic range, heparin infusion rates, and antithrombin activity assay levels before and after administration. Safety outcomes included incidence of new hemorrhage and thrombosis.

Results: A total of 63 patients with similar baseline characteristics were included in the study. Antithrombin was administered after a median duration of 4 days of intravenous heparin therapy. Mean antithrombin levels were 49.9% and 79.9% prior to and after administration of antithrombin, respectively. The incidence of therapeutic anti-Xa within 24 hours occurred in 47 out of 63 patients (74.6%). Patients remained in therapeutic range 50% of the time seven days after antithrombin administration, with 26 patients (41.3%) experiencing at least one supratherapeutic anti-Xa level. Forty-two patients (66.7%) were able to maintain their current heparin infusion rate or had it decreased after antithrombin administration. Rates of new thrombosis or hemorrhage within seven days were 6.3% and 4.8%, respectively.

Conclusions: Antithrombin appears to be safe and effective for mitigating heparin resistance and achieving therapeutic anticoagulation in critically ill patients outside of the operating room. Lower body weight and BMI and augmented renal function may be associated with decreased heparin response to antithrombin administration. Adequately powered randomized controlled trials are required to further evaluate the efficacy and safety of antithrombin.