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

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 ), 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 (lower quartile, <6 × 10  cm ; 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 (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.