Due to the pronounced hypercoagulable state in heparin-induced thrombocytopenia (HIT), alternatives to heparin that do not interact with HIT antibodies are needed for anticoagulation management. This study was designed to determine whether the oral factor Xa inhibitor apixaban could be used. Functional platelet activation with apixaban in the presence of HIT antibodies was evaluated by the 14C-serotonin release assay (SRA; washed platelets) and the heparin-induced platelet aggregation assay (PA-HIT; platelet-rich plasma). A consistent absence of platelet activation by apixaban (0.05-50 mg/mL) was observed: SRA (n = 35) 11 + 4% and PA-HIT (n = 37) 8 + 3% (mean + standard error of the mean; positive is >20%) versus heparin (0.1 U/mL) 82 + 3% SRA and 78 + 6% PA-HIT (P < 0.01) versus enoxaparin (10 mg/mL) 73 + 5% SRA and 62 + 7% PA-HIT. Apixaban may provide an option for oral anticoagulation in patients with HIT, particularly for extended management and prevention.