Coagulation Activation and Fibrinolytic imbalance in Subjects with Idiopathic Antiphospholipid Antibodies -A Crucial Role for Acquired Free Protein S Deficiency

Abstract

SummaryTo explore the coagulation/fibrinolytic balance and its relation with free protein S (f-PS) in subjects with antiphospholipid antibodies (aPLs) outside the setting of autoimmune inflammatory disorders, we carried out a cross-sectional study on 18 thrombotic patients with primary antiphospholipid syndrome and 18 apparently healthy subjects with persistence of idiopathic aPLs. Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT) and D-Dimer (D-D) were taken as markers of thrombin generation and fibrin turnover. Mean F1+2 levels were higher in thrombotic (p = 0.006) and non-thrombotic subjects (p = 0.0001) than in controls as were those of D-D (p <0.0001 and p = 0.003 respectively). TAT levels did not differ. Lower mean levels of f-PS were found in thrombotic (p = 0.0006) and non-thrombotic subjects (p = 0.002) than in controls. Within both groups, mean Fl+2 levels were higher in subjects who had low f-PS levels compared to those with normal f-PS levels (p = 0.01). Gender analysed data revealed blunted tPA release (venous occlusion test) in thrombotic females (from 16.80 ± 0.79 to 21.3 ± 3.9 ng/nl, NS) but not in thrombotic males (from 18.2 ± 2.0 to 33.7 ± 4.9 ng/ml, p = 0.01) nor in asymptomatic subjects of either sex. Also, in both patient groups females had higher mean PAI than males (p <0.0002) and than control females (p <0.02). Low free protein S was found in 100% of non-thrombotic and in 90% of thrombotic patients with defective fibrinolysis. These data are consistent with increased thrombin generation, accelerated fibrin turnover and fibrinolysis abnormalities also in asymptomatic carriers of aPLs and highlight a central role for acquired f-PS deficiency in the thrombotic tendency of the antiphospholipid syndrome.