COAGULATION ACTIVATION AND FIBRINOLYTIC IMBALANCE IN SUBJECTS WITH IDIOPATHIC ANTIPHOSPHOLIPID ANTIBODIES - A CRUCIAL ROLE FOR ACQUIRED FREE PROTEIN-S DEFICIENCY

To explore the coa,coagulation/fibrinolytic balance and its relation w ith free protein S (f-PS) in subjects with antiphospholipid antibodies (aPLs) outside the setting of autoimmune inflammatory disorders, we c arried out a cross-sectional study on 18 thrombotic patients with prim ary antiphospholipid syndrome and 18 apparently healthy subjects with persistence of idiopathic aPLs. Prothrombin fragment 1+2 (F1+2), throm bin-antithrombin complex (TAT) and D-Dimer (D-D) were taken as markers of thrombin generation and fibrin turnover. Mean F1+2 levels were hig her in thrombotic (p=0.005) and non-thrombotic subjects (p=0.0001) tha n 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 co ntrols. Within both groups, mean F1+2 levels were higher in subjects w ho had low f-PS levels compared to those with normal f-PS levels (p=0. 01). Gender analysed data revealed blunted tPA release (venous occlusi on test) in thrombotic females (from 16.80+/-9.79 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 pat ient groups females had higher mean PAI than males (p <0.0002) and tha n control females (p <0.02), Low free protein S was found in 100% of n on-thrombotic and in 90% of thrombotic patients with defective fibrino lysis. These data are consistent with increased thrombin generation, a ccelerated fibrin turnover and fibrinolysis abnormalities also in asym ptomatic carriers of aPLs and highlight a central role for acquired f- PS deficiency in the thrombotic tendency of the antiphospholipid syndr ome.