THE ROLE OF THE TISSUE FACTOR PATHWAY IN THE HYPERCOAGULABLE STATE INPATIENTS WITH THE ANTIPHOSPHOLIPID SYNDROME

The antiphospholipid syndrome (APS) is characterised by both arterial and venous thrombosis, recurrent pregnancy loss and thrombocytopaenia in association with antiphospholipid antibodies (aPL). To explore furt her the pathogenesis of thrombosis in APS, we evaluated the behaviour of tissue factor (TF) pathway in patients with APS. Plasma antigen lev els of soluble TF and tissue factor pathway inhibitor (TFPI), a physio logical regulator of TF dependent coagulation activation, were measure d in 57 APS patients (36 primary and 21 secondary to systemic lupus er ythematosus). Significantly elevated levels of both TF and TFPI were f ound in AP-S patients compared with 25 healthy controls (279 +/- 15 vs . 217 +/- 17 pg/ml, p = 0.01; 56.24 +/- 2.00 vs. 47.92 +/- 2.22 ng/ml, p = 0.01, respectively), suggesting in vivo upregulation of TF pathwa y in patients with APS. By flow-cytometry, monocytes from a healthy do nor displayed higher TF antigen expression when incubated in the prese nce of APS plasmas than in control plasmas (24.23 +/- 3.11 vs. 12.78 /- 1.57%, p = 0.002). Peripheral blood mononuclear cells (PBMC) also e xpressed more procoagulant activity (PCA) when incubated in the presen ce of APS plasmas than in control plasmas (1.80 +/- 0.12 vs. 1.35 +/- 0.054, p = 0.001) implying that TF up-regulation in APS was reproducib le in vitro. Human monoclonal anticardiolipin antibodies induced PCA o n PBMC and also TF mRNA on both PBMC and human umbilical vein endothel ial cells shown by reverse-transcription polymerase chain reaction. Th ese data strongly suggest that the TF pathway is implicated in the pat hogenesis of aPL related thrombosis.