Complement activation and altered fibrin clot properties in obstetric antiphospholipid syndrome: impact on thromboembolism and pregnancy

Prothrombotic fibrin clot properties and increased thrombin generation were observed in obstetric antiphospholipid syndrome (OAPS), but the role of complement in the prothrombotic state is unclear.

This study aimed to determine whether circulating C5a and C5b-9 levels are associated with fibrin clot phenotype and thrombin generation in women with OAPS, and to assess their prognostic value for thrombotic events and obstetric outcomes during long-term follow-up.

In this retrospective study, in 57 women with OAPS, and 57 controls matched for age, weight, and the type of obstetric complications complement components including C5a and C5b-9 levels, along with endogenous thrombin potential (ETP), plasma fibrin clot permeability (K_S) and clot lysis time (CLT) were determined at baseline. During a median follow-up of 54 months venous/arterial TE and live births were recorded.

OAPS patients compared to controls had higher circulating C5a (+ 95.7%) and C5b-9 (+ 44.8%; both p < 0.05), that were positively associated with IgG anticardiolipin, anti-ß-2-glycoprotein I, and antiphosphatidylserine/prothrombin antibodies. Elevated C5a and C5b-9 correlated with reduced clot permeability (K_S, r = -0.42 and r = -0.63), prolonged CLT (r = 0.27 and r = 0.48), and higher thrombin generation (ETP, r = 0.33 and r = 0.39, respectively). Women with higher baseline C5a and C5b-9 (per 1 unit; OR = 0.79, 95% CI: 0.65–0.95, p = 0.013 and OR = 0.98, 95% CI: 0.97–0.99, p = 0.003, respectively) had a lower odd of experiencing pregnancy failure (n = 26, 45.6%).

Determination of complement components along with fibrin clot properties may be helpful to differentiate women with OAPS with a greater risk of negative pregnancy outcomes.