How I treat anticoagulant-refractory thrombotic antiphospholipid syndrome

Abstract

The standard treatment of thrombotic antiphospholipid syndrome (APS) is lifelong oral anticoagulation with a vitamin K antagonist (VKA), generally warfarin. A minority of patients with APS rethrombose despite seemingly adequate anticoagulation. These patients are deemed anticoagulant refractory. The management of anticoagulant-refractory APS is largely empirical and extrapolated from other clinically similar situations. Further options include increased VKA anticoagulation intensity or alternative antithrombotic strategies, including low-molecular-weight heparin, fondaparinux, the addition of antiplatelet therapy, and consideration of vascular options. Patients with anticoagulant-refractory thrombotic APS may have APS-associated thrombocytopenia, which necessitates balancing the risk of recurrent thrombosis vs bleeding to achieve adequate anticoagulation. The multiple mechanisms involved in the generation of the thrombotic phenotype in APS suggest that anticoagulation alone may not control thrombosis. Thus, other modalities, including adjunctive treatment (hydroxychloroquine, statins, and vitamin D) for APS-related thrombosis, merit consideration, as do immunomodulatory therapy and complement inhibition. Patients with APS may have coexistent systemic lupus erythematosus, which adds to the complexity of managing their thromboembolic disease. However, with attention to detail and judicious application of the limited data, it is possible to minimize the morbidity resulting from anticoagulant-refractory thrombotic APS. Multicenter studies are required to guide the sequence of interventions and their comparative efficacy in patients with anticoagulant-refractory thrombotic APS.