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Complement activation and altered fibrin clot properties in obstetric antiphospholipid syndrome: impact on
Magdalena Piróg1, Michał Ząbczyk2,3, Joanna Natorska2,3
1Gynecological Endocrinology Department, Jagiellonian University Medical College, Ul. Kopernika 23, 31-501, Krakow, Poland. magda.m.pulka@gmail.com.
Background:
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.
Objectives:
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.
Methods:
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 (KS) 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.
Results:
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 (KS, 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%).
Conclusion:
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. Key Points • Enhanced complement activation with increased thrombin generation and prothrombotic fibrin clot phenotype is observed in women with OAPS. • Higher C5a and C5b-9 in women with OAPS are observed in women with lower chances of live births during follow-up.
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