Efficacy of Direct Oral Anticoagulants (DOAC) in Patients with Antiphospholipid Antibody Syndrome (APS)

Introduction: The definition of APS had evolved over time. Based on the revised classification criteria for APS presence of one of the clinical criteria (vascular thrombosis or pregnancy related morbidity) along with laboratory criteria met at least 12 weeks apart (positive lupus anticoagulant (LA) or Ig G or Ig M Anticardiolipin antibodies (aCL) with medium or high titers (>40 GPL or MPL units respectively) or Ig G or Ig M Anti Beta2GP1 antibodies in a titer >99% percentile. Warfarin had been the backbone of antithrombotic therapy in patients with APS. The efficacy of DOAC is not established in a prospective randomized clinical trial yet. Information from large retrospective pooled analysis remains unclear. We performed a single center retrospective study at the University of Nebraska Medical Center to study the efficacy of DOACs in this thrombophilia.

Methods: We identified 82 patients from our thrombosis clinic who had established long-term care with known diagnosis of APS of whom 28 patients were on DOACs. 4 patients were excluded due to either lack of necessary diagnostic lab values other than vague mentioning in the history or other clear concurrent strong provoking factors for thrombosis. We did a descriptive analysis of these patients including age at initiation of DOAC, gender, type of thrombosis (arteria or venous: A/V), history of miscarriages in women, APS diagnostic laboratory data, met the diagnostic criteria, reason for using DOAC, Any thrombosis on DOAC, prior history of autoimmune disorders, renal functions, liver functions and the median duration of DOAC. Median and range of the values are descried. If the same patient failed multiple anticoagulants their data was used in the analysis separately (6 patients).

Results: Out of the 24 patients included in the analysis, 14 patients had met the revised stringent criteria for APS and the rest had either missing follow up value or did not meet the criteria. Median age of 49 (27-81), 2 patients with arterial thrombosis, 6 had both A&V and the rest with only V thrombosis. Out of the 16 women 5 had history of miscarriages in the past. 7 had negative LA, median Ig G aCL of 14(1-120 GPL units), Ig M aCL of 19 (1-50), Ig G anti beta2GP1 Ab of 2 (1-134 GPL), Ig M Anti beta2GP1 b of 13 (2-150). Reason for switching Anticoagualtion (AC): AC failure: 5 patients, labile INR: 7 patients, patient or provider preference: 8 patients and rest due to organ dysfunctions or bleeding complications. Only 2 patients (8%) had thrombosis recurrence on DOAC-one with positive D dimer with no thrombosis and the other with thrombosis. 5 patients had additional thrombophilia like Factor V leiden mutation, prothrombin gene mutation or myeloproliferative neoplasms or elevated CRP. 10 patients had concurrent autoimmune disorders. Rivaroxaban was the most commonly used DOAC followed by apixaban, dabigatran and edoxaban. One patient on Rivaroxaban experienced uterine major bleeding, one of Dabigatran had GI bleeding. Median duration of DOAC use is 31 months.

Conclusion: DOACs appear to be safe to use as anticoagulation as antithrombotic therapy in APS with around 8% chance of thrombosis recurrence. Prospective randomized studies are needed to answer this question definitively.