Background/Purpose: Oral direct oral anticoagulants (DOACs) are approved for the treatment of venous thrombosis and the prevention of venous/arterial thrombosis. There is growing information from case reports and series where DOACs have been used in antiphospholipid syndrome (APS) patients with controversial results. Thus, our objective was to systematically review the literature for DOAC use in APS.

Methods: We reviewed the literature (Pubmed, Cochrane Library, congress abstracts books, and the reference lists of studies) without language restrictions. Medical subject heading terms were: “antiphospholipid syndrome”, “direct oral anticoagulants”, “oral direct inhibitors of thrombin”, “oral direct inhibitors of  factor Xa”, “rivaroxaban”, “dabigatran”, “apixaban”, and “edoxaban”. In a systematic fashion, we recorded the type of the study, DOACs used, indication for DOAC use, follow-up time, and outcomes.

Results: As of April 2016, we identified seven case reports and four case series, which included 99 APS patients (primary APS: 38; APS associated with lupus: 23; and unspecified: 38) treated with DOACs (rivaroxaban: 84; dabigatran: 14; and apixaban: 1) (Table). Direct oral anticoagulants were used due to: international normalized ratio (INR) lability in 69 patients; recurrent thrombosis on warfarin in 12; first line therapy in 12; and life-threatening bleeding on warfarin in 5. The follow up time varied between 1- 39 months (mean ± SD: 12.9 ± 8.6 months) (not specified in two studies). Recurrent vascular events (including two superficial venous thrombosis and one transient ischemic attack) were reported in 17 (17%) patients; and minor bleeding in 4 (4%) patients. The frequency of recurrence was not different between the patients who used rivaroxaban (18%) or dabigatran (14%) (p: 0.85), or between the patients with (30%) or without (16%) a previous history of recurrence (p: 0.43).

Conclusion: Based on our systematic literature review of DOAC-receiving APS patients, approximately 20% of patients develop thrombosis during a mean follow-up of 12 months. Given the publication bias and also the low evidence level study designs, e.g., case reports and series, it is difficult to have strong clinical recommendations based on the current literature. Ongoing randomized controlled clinical trials evaluating DOACs in APS will determine if these agents can be incorporated into the management of APS patients.  Table: Direct Oral Anticoagulated (DOAC)-treated APS Patients

PAPS: primary antiphospholipid syndrome; SAPS: APS associated with other autoimmune diseases; NR: no report; AT: arterial thrombosis; VT: vein thrombosis; SVT: superficial vein thrombosis; TIA: transient ischemic attack; m: months; f/u: follow-up; QD: daily; BID: twice a day; * median; **: only time to recurrence was reported ( median: 90days;