Clinical significance of hemostatic markers and thrombomodulin in systemiclupus erythematosus: evidence for a prothrombotic state

Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder with o verwhelming thrombotic stales. The precise pathogenetic mechanisms underlyi ng the prethrombotic slate in SLE is not fully understood, bur interactions between the antiphospholipid antibodies and antigen targets on the coagula tion components have been incriminated to play fundamental roles. To evalua te this issue, 34 women with antiphospholipid antibody negative SLE were in vestigated for molecular markers of blood coagulation and frbrinolytic acti vity: prothrombin fragmnent(1+2) (PF1+2), thrombin-antithrombin complex (TA T), plasmin-alpha(2)-antiplasmin inhibitor complex (PAP), and tissue factor pathway inhibitor (TFPI). We also analysed plasma soluble thrombomodulin ( sTM) levels. SLE disease activity was determined using the SLE Disease Acti vity Index (SLEDAI). Concentrations of TAT, PAP, PF1+2 and sTM were signifi cantly elevated (P<0.0001, P=0.0002, P<0.0001, and P<0.0001, respectively), while TFPI antigen levels were found to be reduced (P<0.0001) in patients with SLE compared to the control group. In patients with active SLE, anti-d s DNA levels were correlated positively with plasma TAT (P<0.05), PF1+2 (P< 0.05), and sTM (P<0.01) concentrations and negatively with plasma TFPI leve ls (P<0.05). SLEDAI scores were correlated positively with plasma TAT (P<0. 01), PF1+2 (<0.01), and sTM (P<0.01) levels. This study illustrates that bo th a prethrombotic stale and a compensatory fibrinolytic process secondary to subclinical intravascular coagulation might coexist in SLE with elevated sTM levels, indicating impaired endothelial functions.