THROMBOSIS IN PRIMARY ANTIPHOSPHOLIPID SYNDROME - A PIVOTAL ROLE FOR MONOCYTE TISSUE FACTOR EXPRESSION

Objective. The antiphospholipid syndrome (APS) is a disorder of recurr ent thrombosis, pregnancy loss, and thrombocytopenia associated with t he production of anticardiolipin antibodies (aCL) and lupus anticoagul ant (LAC). The mechanisms of thrombus formation remain unknown. Tissue factor (TF), an inducible cell glycoprotein, is a major initiator of coagulation in vivo. The present study was therefore undertaken to inv estigate TF expression and procoagulant activity on monocytes from pat ients with primary APS and its correlation mith thrombotic events. Met hods. Three groups of patients were studied: group 1 comprised 23 prim ary APS patients with thrombosis, group 2 consisted of 10 primary APS patients without thrombosis, and group 3 contained 20 patients with th rombosis but without antiphospholipid antibodies, Twenty age- and sex- matched healthy blood donors were used as controls (group 1). Anticard iolipin antibodies were measured by enzyme-linked immunosorbent assay (ELISA) and LAC by standard methodology, Cell surface expression of TF on monocytes was assessed by flow cytometry. The amount of TF in cell lysates (TFAg) and soluble TFAg plasma levels were analyzed by ELISA, and the TF-related procoagulant activity (PCA-TF) on intact cells and cell lysates by a chromogenic assay, Le,els of the cytokines that inf luence TF production, i.e., tumor necrosis factor alpha (TNF alpha) an d interleukin-1 beta (IL-1 beta), were determined by ELISA. Results. C ell surface expression of TF was increased in group 1 (mean+/-SEM 50.2 +/-4% positive cells) compared with group 2 (14.6+/-1.6%), group 3 (16 .8+/-3.7%), and group 4 (14.1+/-1.6%). TFAg levels were also elevated in group 1 (215.8+/-11.2 pg/10(6)) compared with group 2 (150.8+/-15.2 ), group 3 (101.4+/-14.8), and group 4 (80.32+/-5.5). PCA-TF on intact cells and cell lysates was significantly increased in group 1 (148.8/-16.3 units/10(5) lysate cells, compared with 54.5+/-11.9, 38.6+/-9.7 , and 22.5+/-3.1 in groups 2, 3, and 4, respectively), Among group 1 p atients, there was a significant increase in the degree of TF expressi on in those positive for IgG aCL, but not in those positive for IgM aC L or LAC. TNF alpha and IL-1 beta plasma levels did not differ signifi cantly between any of the groups. Conclusion. These results suggest th at monocyte TF expression is directly involved in the pathogenesis of thrombotic complications in patients with the primary APS.