Effect of α2-plasmin inhibitor heterogeneity on the risk of venous thromboembolism.

INTRODUCTION

Alpha2-plasmin inhibitor (α2-PI) has a heterogeneous composition in the plasma. Both N- and C-terminal cleavages occur that modify the function of the molecule. C-terminal cleavage converts the plasminogen-binding form (PB-α2-PI) to a non-plasminogen-binding form (NPB-α2-PI). N-terminal cleavage by soluble fibroblast activation protein (sFAP) results in a form shortened by 12 amino acids, which is more quickly cross-linked to fibrin. The p.Arg6Trp polymorphism of α2-PI affects N-terminal cleavage. In this work, we aimed to investigate the association between α2-PI heterogeneity and the risk of venous thromboembolism.

MATERIALS AND METHODS

Two hundred and eighteen patients with venous thromboembolism (VTE) and the same number of age and sex-matched healthy controls were enrolled. Total-α2-PI, PB-α2-PI and NPB-α2-PI antigen levels, α2-PI activity, sFAP antigen levels and p.Arg6Trp polymorphism were investigated.

RESULTS

Total-α2-PI and NPB-α2-PI levels were significantly elevated in VTE patients, while PB-α2-PI levels did not change. Elevated NPB-α2-PI levels independently associated with VTE risk (adjusted OR: 9.868; CI: 4.095-23.783). Soluble FAP levels were significantly elevated in the VTE group, however, elevated sFAP levels did not show a significant association with VTE risk. The α2-PI p.Arg6Trp polymorphism did not influence VTE risk, however, in the case of elevated sFAP levels the carriage of Trp6 allele associated with lower VTE risk.

CONCLUSION

Our results showed that the elevation of total-α2-PI levels in VTE is caused by the elevation of NPB-α2-PI levels. Elevated sFAP level or p.Arg6Trp polymorphism alone did not influence VTE risk. However, an interaction can be detected between the polymorphism and high sFAP levels.