Oral Factor Xa (FXa) Inhibitors for Treatment of Heparin-induced Thrombocytopenia (HIT)

Abstract

Background:: Heparin is the most commonly used injectable anticoagulant for many indications, ranging from the treatment of atrial fibrillation to the prevention of clotting in patients undergoing surgery. Currently, only argatroban and bivalirudin are FDA approved for the management of heparin induced thrombocytopenia (HIT) in the United States, both of which are direct thrombin inhibitors. The agents being reviewed, apixaban and rivaroxaban, are oral direct factor Xa (FXa) inhibitors. Currently, neither has FDA approval for use in HIT. The objective of this review is to summarize the current evidence available regarding the use of oral factor Xa inhibitors for the treatment of HIT. Methods:: A literature search was conducted using Medline and Ovid Embase. Search terms included heparin-induced thrombocytopenia, HIT, apixaban, rivaroxaban, Xa Inhibitor, direct thrombin inhibitor, NOAC, and DOAC. Studies and case reports were included if they evaluated the efficacy and safety of oral FXa inhibitors for the treatment of HIT. Additional literature and case reports were found through bibliographic review. Results and Discussion: Currently, available literature includes an in vitro study with apixaban, case reports, and retrospective and prospective cohort studies. The in vitro study evaluated the interaction between apixaban and platelets in the presence of HIT antibodies, which assessed its potential for use in HIT management. Fourteen case reports and one case series were also identified, of which six described treatment with apixaban and eight with rivaroxaban. Lastly, four cohort studies were published evaluating the use of direct acting oral anticoagulants (DOACs), including oral factor Xa inhibitors in patients with HIT. Although there are no published randomized control trials evaluating the use of FXa inhibitors in the management of HIT, there are several findings that may guide clinicians on the use of these agents in practice. Conclusion:: As indicated by the case reports, case series and cohort studies detailing clinical use and described in this manuscript, there are data and positive patient outcomes that support the potential use of these agents for HIT, and are an impetus for future studies.