COAGULATION ACTIVATION AND FIBRINOLYTIC IMBALANCE IN SUBJECTS WITH IDIOPATHIC ANTIPHOSPHOLIPID ANTIBODIES - A CRUCIAL ROLE FOR ACQUIRED FREE PROTEIN-S DEFICIENCY
Prj. Ames et al., COAGULATION ACTIVATION AND FIBRINOLYTIC IMBALANCE IN SUBJECTS WITH IDIOPATHIC ANTIPHOSPHOLIPID ANTIBODIES - A CRUCIAL ROLE FOR ACQUIRED FREE PROTEIN-S DEFICIENCY, Thrombosis and haemostasis, 76(2), 1996, pp. 190-194
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.