HYPERCOAGULABLE STATE IN PATIENTS WITH ANTIPHOSPHOLIPID SYNDROME IS RELATED TO HIGH INDUCED TISSUE FACTOR EXPRESSION ON MONOCYTES AND TO LOW FREE PROTEIN-S

Antiphospholipid antibodies (aPLs) are associated with thrombosis, but the mechanisms of this thrombotic tendency are unknown. We studied 56 patients (12 with systemic lupus erythematosus [SLE] and aPLs and pre vious thrombosis, 12 with SLE and aPLs but no thrombosis, 15 with SLE without aPLs or thrombosis, 11 with primary antiphospholipid syn drome with thrombosis, and 6 asymptomatic subjects with aPLs) to investigat e the ability of aPLs to induce tissue factor (TF) expression on human normal monocytes. A double direct immunofluorescence technique (anti- CD14 and anti-TF) was used, and procoagulant activity in viable and di srupted cells was measured after plasma incubation for 6 hours at 37 d egrees C with normal mononuclear cells. Hemostasis regulatory proteins , prothrombin fragment 1+2, and thrombin-antithrombin III complex leve ls were determined, Increased TF expression and procoagulant activity were observed using plasma samples from SLE patients with aPLs and thr ombosis (P<.01) and from primary antiphospholipid syndrome patients (P <.01) but not from patients with SLE and aPLs but no thrombosis, patie nts with SLE without aPLs, or asymptomatic patients with aPLs. Purifie d aPL immunoglobulins from one primary antiphospholipid syndrome and t wo SLE patients added to normal plasma showed a significant increase i n both TF expression and procoagulant activity (P<.05) compared with p urified aPL from two SLE patients without thrombosis, The addition of nonspecific IgG from three SLE patients without aPLs and from three co ntrol subjects did nor increase TF expression. Low free protein S was seen in eight patients. Increased TF expression and low free protein S correlated with thrombosis (P<.01) and with higher prothrombin fragme nt 1+2 and thrombin-antithrombin III values (P<.01). These observation s may contribute to a further understanding of the thrombotic risk in aPL patients.