Hypercoagulable State in Patients With Antiphospholipid Syndrome Is Related to High Induced Tissue Factor Expression on Monocytes and to Low Free Protein S

Abstract

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 previous thrombosis, 12 with SLE and aPLs but no thrombosis, 15 with SLE without aPLs or thrombosis, 11 with primary antiphospholipid syndrome with thrombosis, and 6 asymptomatic subjects with aPLs) to investigate 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 disrupted cells was measured after plasma incubation for 6 hours at 37°C with normal mononuclear cells. Hemostasis regulatory proteins, prothrombin fragment 1+2, and thrombin–antithrombin III complex levels were determined. Increased TF expression and procoagulant activity were observed using plasma samples from SLE patients with aPLs and thrombosis ( P <.01) and from primary antiphospholipid syndrome patients ( P <.01) but not from patients with SLE and aPLs but no thrombosis, patients with SLE without aPLs, or asymptomatic patients with aPLs. Purified aPL immunoglobulins from one primary antiphospholipid syndrome and two SLE patients added to normal plasma showed a significant increase in both TF expression and procoagulant activity ( P <.05) compared with purified aPL from two SLE patients without thrombosis. The addition of nonspecific IgG from three SLE patients without aPLs and from three control subjects did not 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 fragment 1+2 and thrombin–antithrombin III values ( P <.01). These observations may contribute to a further understanding of the thrombotic risk in aPL patients.