title: Clinical significance of hemostatic markers and thrombomodulin in systemic lupus erythematosus: evidence for a prothrombotic state.
abstract: Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder with overwhelming thrombotic states. The precise pathogenetic mechanisms underlying the prethrombotic state in SLE is not fully understood, but interactions between the antiphospholipid antibodies and antigen targets on the coagulation components have been incriminated to play fundamental roles. To evaluate this issue, 34 women with antiphospholipid antibody negative SLE were investigated for molecular markers of blood coagulation and fibrinolytic activity: prothrombin fragment1+2 (PF1+2), thrombin-antithrombin complex (TAT), plasmin-alpha2-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 Activity Index (SLEDAI). Concentrations of TAT, PAP, PF1+2 and sTM were significantly 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-ds 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 levels (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 both a prethrombotic state and a compensatory fibrinolytic process secondary to subclinical intravascular coagulation might coexist in SLE with elevated sTM levels, indicating impaired endothelial functions.
authors.affiliation: Department of Internal Medicine, Hacettepe University Faculty of Medicine, Ankara, Turkey.
authors.forename: S
authors.initials: S
authors.lastname: Kiraz
authors.forename: I
authors.initials: I
authors.lastname: Ertenli
authors.forename: M
authors.initials: M
authors.lastname: Benekli
authors.forename: I C
authors.initials: IC
authors.lastname: Haznedaroğlu
authors.forename: M
authors.initials: M
authors.lastname: Calgüneri
authors.forename: I
authors.initials: I
authors.lastname: Celik
authors.forename: S
authors.initials: S
authors.lastname: Apraş
authors.forename: S
authors.initials: S
authors.lastname: Kirazli
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood; D005260:Female; D006487:Hemostasis; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000276:immunology; D008875:Middle Aged; D018180:Thrombomodulin / Q000097:blood*; D013927:Thrombosis / Q000097:blood / Q000276:immunology
chemical_list: D001323:Autoantibodies; D018180:Thrombomodulin