Thrombotic Antiphospholipid Syndrome and Direct Oral Anticoagulants: Unmet Needs and Review of the Literature.

Patients with thrombotic antiphospholipid syndrome (APS) require long-term anticoagulation due to the high-thrombotic recurrence risk. Vitamin K antagonists (VKA) have been traditionally considered the standard of care in thrombotic APS. Nevertheless, the risk of recurrence persists with VKA. There are publications considering different intensities of anticoagulation with VKA; however, the standard-intensity anticoagulation (international normalized ratio between 2.0 and 3.0) is the most recommended. Furthermore, there is no consensus on the role of antiplatelet treatment in thrombotic APS. Nonvitamin K antagonist oral anticoagulants (NOACs) have emerged as an alternative to VKA for many indications. There are, however, discrepancies regarding the management with NOACs in thrombotic APS. In this review, we update the different clinical trials with NOACs in venous, arterial, and microvascular thrombosis and suggest how these patients should be managed in agreement with the expert panels. Although scarce data are published regarding the current role of NOACs in thrombotic APS, the clinical trials failed to demonstrate noninferiority of NOACs compared with VKA, especially in patients with triple antiphospholipid antibodies positivity and/or arterial thrombosis. Single or double antiphospholipid positivity should be analyzed on a case-by-case basis. In addition, we focus on different areas of uncertainty that still remain in thrombotic APS and NOACs. To summarize, emerging clinical trials are needed to provide robust data on the management of thrombotic APS.