How is thrombosis in antiphospholipid syndrome (APS) treated?

Updated: Nov 24, 2020
  • Author: Suneel Movva, MD; Chief Editor: Herbert S Diamond, MD  more...
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Answer

Perform full anticoagulation with intravenous or subcutaneous heparin followed by warfarin therapy. Based on the most recent evidence, a reasonable target for the international normalized ratio (INR) is 2.0-3.0 for venous thrombosis and 3.0 for arterial thrombosis. Patients with recurrent thrombotic events may require an INR of 3.0-4.0. For severe or refractory cases, a combination of warfarin and aspirin may be used. Treatment for significant thrombotic events in patients with APS is generally lifelong.

Direct oral anticoagulants (ie, direct thrombin inhibitors and factor Xa inhibitors such as rivaroxaban) have been used in patients who are warfarin intolerant/allergic or have poor anticoagulant control. [9, 21] However, studies of these agents in APS patients have largely proved disappointing.

In the Rivaroxaban for Antiphospholipid Syndrome (RAPS) trial—a controlled, open-label, phase II/III non-inferiority trial in 116 APS patients—the percentage change in endogenous thrombin potential at 42 days for rivaroxaban was inferior to that of warfarin. However, because no thromboembolic events occurred over the 210‐day follow‐up in either group, the investigators concluded that rivaroxaban might be an effective and safe alternative in patients with APS and previous venous thromboembolism (VTE). [22]

A cohort study in 176 APS patients followed for a median of 51 months reported an increased risk of recurrent thromboembolic events and recurrent VTE alone in patients receiving direct oral anticoagulants compared with those receiving warfarin. No differences were found between rivaroxaban and apixaban or among single-positive, double-positive, and triple-positive APS. [23]

The phase III Rivaroxaban in Thrombotic Antiphospholipid Syndrome (TRAPS) trial, which was conducted in high-risk APS patients triple-positive for lupus anticoagulant, anti-cardiolipin, and anti-β2-glycoprotein I antibodies of the same isotype, was terminated prematurely after the enrollment of 120 patients because of an excess rate of arterial thromboembolic events in patients on rivaroxaban: 12% (4 ischemic strokes and 3 myocardial infarctions) versus 0% in patients on warfarin, after 569 days’ follow‐up. [24]

In May 2019, the European Medicines Agency (EMA) issued a guidance statement recommending against the use of direct-acting oral anticoagulants (including rivaroxaban, apixaban, edoxaban, and dabigatran etexilate) for patients with a history of thrombosis who are diagnosed with APS, in particular those that are triple positive. This poses a challenge for clinicians, however, because current guidelines recommend direct oral anticoagulants for treatment of VTE. A proportion of patients with a first unprovoked VTE will have antiphospholipid antibodies, and some of those will have APS. However, when a patient presents with unprovoked VTE it is impossible to know whether APS is present, as the diagnosis of APS requires testing on two or more occasions at least 12 weeks apart. [25]

Rituximab can be considered for recurrent thrombosis despite adequate anticoagulation. A nonrandomized prospective study showed rituximab to be effective for noncriteria aPL manifestations (ie, thrombocytopenia and skin ulcers). [6]


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