Elevated lipoprotein(a) as a new risk factor of cerebral venous sinus thrombosis: association with fibrin clot properties

Abstract

Elevated lipoprotein(a) [Lp(a)] has been reported to be associated with prothrombotic clot phenotype. We hypothesized that increased Lp(a) contributes to cerebral venous sinus thrombosis (CVST) and its recurrence in relation to clot features. In 80 consecutive patients (aged 39.36 ± 10.18 years, 61 women) following the first CVST after anticoagulation withdrawal, we assessed Lp(a) levels and plasma clot properties. Recurrence of CVST was recorded during follow-up (median 53, interquartile range 40–59 months). Lp(a) levels were inversely associated with clot permeability (Ks, r = − 0.58, P < 0.001) and the rate of D-dimer release from clots in the presence of tissue plasminogen activator (r = − 0.27, P = 0.017) along with increased maximum absorbance of fibrin gels (r = 0.42, P < 0.001) and maximum D-dimer levels achieved during lysis (D–Dmax, r = 0.29, P = 0.01). Recurrence of CVST was observed in 12 patients (15%) after median follow-up of 26 months. Lp(a) concentrations were higher in patients with recurrence of CVST compared to the remainder (14.15 [8.85–25.25] vs. 28.3 [18.9–35.6] mg/dL; P = 0.001). The risk of recurrent CVST was fourfold higher among 17 (21.25%) patients with Lp(a) > 30 mg/dL compared to the remainder (adjusted hazard ratio, 3.9; 95% confidence interval [CI] 1.23–12.4). Recurrence of CVST was associated with 14% lower Ks (P = 0.001) and 10% higher D–Dmax (P = 0.008), with no differences in other clot features. Multiple logistic regression model showed that CVST recurrence was independently associated with Lp(a) (odds ratio 1.09, 95% CI 1.02–1.16). Increased Lp(a) characterizes subjects at elevated risk of recurrent CVST after anticoagulation withdrawal, which could be partly explained by formation of denser fibrin clots.