title: Rivaroxaban--an oral, direct Factor Xa inhibitor--has potential for the management of patients with heparin-induced thrombocytopenia.
abstract: Rivaroxaban is an oral, direct activated Factor Xa (FXa) inhibitor in advanced clinical development for the prevention and treatment of thromboembolic disorders. Currently available anticoagulants include unfractionated heparin (UFH) and low molecular weight heparins (LMWHs); however, their use can be restricted by heparin-induced thrombocytopenia (HIT). HIT is usually caused by the production of antibodies to a complex of heparin and platelet factor-4 (PF4). This study was performed to evaluate, in vitro, the potential of rivaroxaban as an anticoagulant for the management of patients with HIT. UFH, the LMWH enoxaparin, fondaparinux and the direct thrombin inhibitor argatroban were tested to enable comparative analyses. Rivaroxaban did not cause platelet activation or aggregation in the presence of HIT antibodies, unlike UFH and enoxaparin, suggesting that rivaroxaban does not cross-react with HIT antibodies. Furthermore, rivaroxaban did not cause the release of PF4 from platelets and did not interact with PF4, unlike UFH and enoxaparin. These findings suggest that rivaroxaban may be a suitable anticoagulant for the management of patients with HIT.
authors.affiliation: Cardiovascular Institute, Loyola University Chicago, Maywood, IL 60153, USA.
authors.forename: Jeanine M
authors.initials: JM
authors.lastname: Walenga
authors.forename: Margaret
authors.initials: M
authors.lastname: Prechel
authors.forename: Walter P
authors.initials: WP
authors.lastname: Jeske
authors.forename: Debra
authors.initials: D
authors.lastname: Hoppensteadt
authors.forename: Jyothi
authors.initials: J
authors.lastname: Maddineni
authors.forename: Omer
authors.initials: O
authors.lastname: Iqbal
authors.forename: Harry L
authors.initials: HL
authors.lastname: Messmore
authors.forename: Mamdouh
authors.initials: M
authors.lastname: Bakhos
mesh_terms: D000704:Analysis of Variance; D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D000990:Antithrombin III / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives; D001323:Autoantibodies / Q000276:immunology; D017984:Enoxaparin / Q000009:adverse effects; D005434:Flow Cytometry; D000077425:Fondaparinux; D006495:Heparin, Low-Molecular-Weight / Q000009:adverse effects*; D006801:Humans; D009025:Morpholines / Q000627:therapeutic use*; D010875:Pipecolic Acids / Q000009:adverse effects; D015539:Platelet Activation; D010974:Platelet Aggregation / Q000187:drug effects; D010978:Platelet Factor 4 / Q000009:adverse effects; D011134:Polysaccharides / Q000009:adverse effects; D000069552:Rivaroxaban; D013449:Sulfonamides; D013876:Thiophenes / Q000627:therapeutic use*; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000925:Anticoagulants; D001323:Autoantibodies; D017984:Enoxaparin; D006495:Heparin, Low-Molecular-Weight; D009025:Morpholines; D010875:Pipecolic Acids; D011134:Polysaccharides; D013449:Sulfonamides; D013876:Thiophenes; D010978:Platelet Factor 4; D000990:Antithrombin III; D001120:Arginine; D000069552:Rivaroxaban; C031942:argatroban; D000077425:Fondaparinux