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

Abstract

\n\nHeparin is the most commonly used injectable anticoagulant for many indications,\nranging from the treatment of atrial fibrillation to the prevention of clotting in patients\nundergoing surgery. Currently, only argatroban and bivalirudin are FDA approved for the management\nof heparin induced thrombocytopenia (HIT) in the United States, both of which are direct\nthrombin inhibitors. The agents being reviewed, apixaban and rivaroxaban, are oral direct factor\nXa (FXa) inhibitors. Currently, neither has FDA approval for use in HIT. The objective of this review\nis to summarize the current evidence available regarding the use of oral factor Xa inhibitors\nfor the treatment of HIT.\n\n\n\nA literature search was conducted using Medline and Ovid Embase. Search terms included\nheparin-induced thrombocytopenia, HIT, apixaban, rivaroxaban, Xa Inhibitor, direct thrombin\ninhibitor, NOAC, and DOAC. Studies and case reports were included if they evaluated the efficacy\nand safety of oral FXa inhibitors for the treatment of HIT. Additional literature and case reports\nwere found through bibliographic review.\n\n\n\nCurrently, available literature includes an in vitro study with apixaban,\ncase reports, and retrospective and prospective cohort studies. The in vitro study evaluated the interaction\nbetween apixaban and platelets in the presence of HIT antibodies, which assessed its potential\nfor use in HIT management. Fourteen case reports and one case series were also identified, of\nwhich six described treatment with apixaban and eight with rivaroxaban. Lastly, four cohort\nstudies were published evaluating the use of direct acting oral anticoagulants (DOACs), including\noral factor Xa inhibitors in patients with HIT. Although there are no published randomized control\ntrials evaluating the use of FXa inhibitors in the management of HIT, there are several findings that\nmay guide clinicians on the use of these agents in practice.\n\n\n\nAs indicated by the case reports, case series and cohort studies detailing clinical use\nand described in this manuscript, there are data and positive patient outcomes that support the potential\nuse of these agents for HIT, and are an impetus for future studies.\n