Background The prevention of catastrophic antiphospholipid syndrome (CAPS), a rare complication of antiphospholipid syndrome (APS), is a major goal. The role of precipitating factors in CAPS development is well known. However, little is known about the specific role of anticoagulant treatment as a potential precipitating factor for CAPS. We analyzed precipitating factors of CAPS in a large series of patients, and we focused on anticoagulation immediately before CAPS episodes.

Methods We retrospectively analyzed patients in the French multicenter APS/systemic lupus erythematosus database with at least one CAPS episode. Then we compared each patient with known APS before CAPS with two non-CAPS APS patients matched for age, sex, center and APS phenotype.

Results We included 112 CAPS patients (70% female, mean age 43±15 years). At least one standard precipitating factor of CAPS was observed for 67 patients (64%), mainly infections (n=28, 27%), pregnancy (n=23, 22%), and surgery (n=16, 15%).

Before the CAPS episode, 67 (60%) patients already had a diagnosis of APS. Of the 61 treated with anticoagulants, 32 (48%) received vitamin K antagonists (VKA), 23 (34%) heparin, and 2 (3%) a direct oral anticoagulant. They were less likely than their matched APS patients without CAPS to receive VKA (48% vs 66%, P=0.001). Among those treated with VKA, 72% had a subtherapeutic INR < 2, versus 28% in APS patients without CAPS (P<0.001). Finally, if we excluded pregnant patients (n=14) for whom the effect of treatment versus pregnancy is impossible to differentiate, among the 47 remaining cases, 32 (68%) had either a recent introduction of DOAC (n=2), a planned bridging therapy (n=9) or a VKA treatment with INR <2 (n=21).

Conclusions These results strongly suggest that suboptimal anticoagulation management is a trigger of CAPS in patients with thrombotic APS.