Antiphosphatidylserine/prothrombin complex antibodies as a determinant of prothrombotic plasma fibrin clot properties in patients with antiphospholipid syndrome

摘要

Abstract Background Antiphosphatidylserine/prothrombin complex ( aPS / PT ) antibodies are recognized as a marker for antiphospholipid syndrome ( APS ). Dense and poorly lysable fibrin clots occur in thrombotic APS . Compact clots predict thromboembolism, but determinants of the unfavorable clot phenotype remain unknown in APS . We hypothesized that elevated aPS / PT antibodies determine unfavorable clot features. Methods In a cohort study involving 124 consecutive patients with thrombotic APS , we measured at baseline plasma fibrin clot permeability ( K s ), efficiency of fibrinolysis (clot lysis time, CLT ), and turbidity (off anticoagulation) along with immunoglobulin (Ig)G/IgM aPS / PT . During follow‐up, symptomatic thromboembolic events were recorded. Results Elevated IgG and IgM aPS / PT antibodies 30?international enzyme units ( UI ) were detected in 54.8% and 42.7% of APS patients, including 76.2% and 54% of lupus anticoagulant‐ ( LA , n ?=?63) positive patients, respectively. Elevated IgG and IgM aPS / PT antibodies predicted low K s (lower quartile, 6?×?10 ?9 ?cm 2 ; odds ratio [ OR ]?=?5.93, 95% confidence interval [ CI ] 2.09‐16.82 and OR ?=?11.79, 95% CI 4.10‐33.92) and prolonged CLT (top quartile, ≥116?min; OR ?=?4.85, 95% CI 2.42‐25.07 and OR ?=?6.04, 95% CI 2.42‐15.07). No such associations were observed for anticardiolipin or β2‐glycoprotein I antibodies or LA presence. During follow‐up (median 72.5, range 66‐83?months), thromboembolic events observed in 32 (26.7%, 4.6%/year) patients were independently predicted by IgG aPS / PT antibodies 30? UI (hazard ratio [ HR ]?=?3.04, 95% CI 1.20‐8.88) and low K s ( HR ?=?3.00, 95% CI 1.41‐6.50). Conclusions We identified aPS / PT antibodies as a determinant of denser and poorly lysable plasma fibrin clot formation in APS patients. The association of elevated aPS / PT antibodies with thromboembolism in APS could be at least in part mediated by prothrombotic clot properties.