Coagulation activation and fibrinolytic imbalance in subjects with idiopathic antiphospholipid antibodies--a crucial role for acquired free protein S deficiency.
To 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 F1 + 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.
Ames
P R
PR
Department of Haematology, St Thomas' Hospital, London, UK.
Tommasino
C
C
Iannaccone
L
L
Brillante
M
M
Cimino
R
R
Brancaccio
V
V
D000328:Adult; D017153:Antibodies, Anticardiolipin / Q000097:blood; D017152:Antibodies, Antiphospholipid / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001778:Blood Coagulation Disorders / Q000097:blood / Q000276:immunology*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D005342:Fibrinolysis / Q000276:immunology*; D006801:Humans; D016682:Lupus Coagulation Inhibitor / Q000097:blood; D008297:Male; D008875:Middle Aged; D017293:Protein S / Q000378:metabolism; D018455:Protein S Deficiency / Q000276:immunology*; D013917:Thrombin / Q000096:biosynthesis; D013927:Thrombosis / Q000097:blood / Q000276:immunology*
D017153:Antibodies, Anticardiolipin; D017152:Antibodies, Antiphospholipid; D015415:Biomarkers; D016682:Lupus Coagulation Inhibitor; D017293:Protein S; D013917:Thrombin