Non-Warfarin Oral Anticoagulants in Anti-Phospholipid Syndrome

Abstract

Introduction: Anti-Phospholipid Syndrome (APS) is a serious and deadly disorder leading to a significant risk of thrombi, requiring lifelong therapeutic anticoagulation. Traditionally, the vitamin K antagonist (VKA) warfarin has been considered standard of care in this patient population. However, the VKAs require frequent laboratory monitoring, have a narrow therapeutic window, numerous drug interactions and dietary restrictions. Due to these factors, many patients suffer recurrent thrombi and/or major bleeding, warranting therapy modification or switching to parenteral anticoagulants. The non-warfarin oral anticoagulants (NOACs), specifically the direct Xa inhibitors apixaban and rivaroxaban, have been approved for the treatment of venous thromboembolism and represent attractive options for these patients.Methods: We designed a retrospective analysis of all patients at the University of Virginia with APS that were treated with either apixaban or rivaroxaban since September 2011. All patients were required to have a definitive diagnosis of APS [defined by the Sydney criteria as an arterial or venous thrombosis and IgM and/or IgG anti-cardiolipin antibody >40GLP, IgG and/or IgM beta-2 glycoprotein >99th percentile, and/or positive lupus anticoagulant (e.g. prolonged silica clot time or dilute Russell viper venom time)]. Patients were reviewed for recurrent thrombi, severe bleeding or other complications that led to changes in their management.Results: Sixty-six patients were identified with suspected APS, with 18 being treated with a NOAC. Of these, 10 had definitive APS per the Sydney criteria and were analyzed. 6/10 (60%) were treated with apixaban and 4/10 (40%) were treated with rivaroxaban. No patients developed severe bleeding or thrombotic complications and none required changes of their therapy. 30% started a NOAC as the first line outpatient regimen with the remaining 70% being previously treated with other anticoagulants. 7/10 (70%) were treated with warfarin and 3 patients were treated with fondaparinux before changing to a NOAC. Reasons for stopping warfarin were difficulty managing INRs (33%) or thrombi while on warfarin (66%). Of those previously on fondaparinux, reasons for changing therapy were transient ischemic attack (33%), difficulty with injections (33%) and cost (33%). Of these 10 patients, safe and effective anticoagulation with a NOAC was noted for up to 36 months without adverse effects.Conclusion: Apixaban and rivaroxaban showed to be a safe and effective first line outpatient regimen for patients with APS or patients with APS who develop recurrent thrombi on warfarin or parenteral anticoagulation. Further prospective studies are needed before their use should be considered standard of care.Table 1Patients with Anti-Phospholipid Syndrome Treated with Non-Warfarin Oral AnticoagulantPatientFirst Positive TestSecond Positive TestSerum Testing Performed off WarfarinAnticoagulantLength of Treatment (in months)Bleeding ComplicationsThrombotic ComplicationsPrior Anticoagulant UseReason Therapy was Changed1Cardiolipin IgG 52, β2 IgG >112Cardiolipin IgG 76, β2 IgG >112; RVVT prolongedNoApixaban8NoneNoneYes (warfarin)Difficult to control INR2Cardiolipin IgG >15;RVVT prolongedCardiolipin IgG >15;RVVT prolongedYesApixaban6NoneNoneYes (warfarin)Difficult to control INR3Cardiolipin & β2 >112Cardiolipin & β2 >112YesApixaban2NoneNoneYes (warfarin)Stroke while on warfarin4Cardiolipin IgM 66, β2 IgM 68Cardiolipin IgM 98, β2 IgM 87YesApixaban8NoneNoneNoN/A5β2 IgG 122;+ LACardiolipin & β2 >112NoApixaban7NoneNoneYes (warfarin)Multiple strokes while on warfarin6β2 IgM 29;+ LACardiolipin IgM 50, β2 IgM 74RVVT prolongedYesApixaban4NoneNoneYes (Fondaparinux)Difficulty with injections7Cardiolipin IgG 73Cardiolipin IgG & β2 IgG>112;RVVT prolongedYesRivaroxaban36NoneNoneYes (warfarin & fondaparinux)Thrombi on warfarin & fondaparinux8Cardiolipin IgG>112;RVVT prolongedCardiolipin IgG>112Yes*Rivaroxaban2NoneNoneYes (warfarin)Difficult to control INR9Cardiolipin IgM & β2 IgM>112Cardiolipin IgM & β2 IgM>112Yes*Rivaroxaban15NoneNoneNoN/A10β2 IgG>100RVVT prolongedβ2 IgG>100;RVVT prolongedNoRivaroxaban31NoneNoneYes (warfarin & fondaparinux)Thrombi on warfarin & fondaparinux*Second serum testing drawn while on rivaroxaban DisclosuresOff Label Use: Apixaban and rivaroxaban use in patients with Anti-phospholipid Syndrome.