Factor XIII in primary antiphospholipid syndrome

Objective. To evaluate the clinical significance of factor XIII (FXIII) in primary antiphospholipid syndrome (APS). Methods. A cross-sectional study including patients with primary APS (n = 29), persistent carriers of idiopathic antiphospholipid antibodies (aPL) with no history of thrombosis (n = 14), thrombotic patients with inherited thrombophilia (n = 24), healthy controls (n = 28), and patients with mitral and aortic valve prosthesis (n = 32, as controls for FXIII only). FXIII and fibrinogen were measured by functional assays: IgG anticardiolipin antibody (aCL), IgG anti-beta(2)-glycoprotein 1 (anti-beta(2)-GPI), and plasminogen activator inhibitor (PAI) by immunoassay; and paraoxonase activity by paranitrophenol formation. Intima-media thickness (IMT) of carotid arteries was determined by high resolution sonography. Results. FXIII activity (FXIIIa) was highest in primary APS (p = 0.001), particularly in patients with multiple occlusions (n = 12) versus those with single occlusion (158 +/- 45% vs 118 +/- 38%; p = 0.02). In primary APS, FXIII positively correlated with PAI (p = 0.003) and fibrinogen (p = 0.005). Similarly in the thrombotic control group, FXIIIa correlated with PAI (p = 0.05) and fibrinogen (0.007). In primary APS, FXIIIa was related to the IMT of all carotid artery segments (p always < 0.01). In thrombotic controls FXIIIa correlated only to the IMT of the common carotid (p = 0.01). In primary APS, FXIIIa was strongly associated with IgG aCL and IgG anti-beta(2)-GPI (p = 0.005 for both). These associations were weaker in the aPL group (FXIIIa with IgG aCL, p = 0.02, with IgG anti-beta(2)-GPI, p = 0.04). Conclusion. Enhanced FXIII activity may contribute to atherothrombosis in primary APS via increased fibrin/fibrinogen cross-linking. This pathway is not exclusive to primary APS, being present also in thrombotic controls, but the presence of IgG aPL may favor a higher degree of FXIIIa activation in the primary APS group.