THROMBIN GENERATION MEASURED EX-VIVO FOLLOWING MICROVASCULAR INJURY IS INCREASED IN SLE PATIENTS WITH ANTIPHOSPHOLIPID-PROTEIN ANTIBODIES

Antiphospholipid-protein antibodies (APA) include lupus-type anticoagu lant (LA) and antibodies recognizing complexes of anionic phospholipid s (e.g. cardiolipin) and proteins (e.g. prothrombin and beta(2)-glycop rotein I). The presence of APA is associated with an increased risk of both arterial and venous thrombosis. However, the pathogenic mechanis m leading to thrombosis in patients with APA remains unclear. We studi ed 32 patients with systemic lupus erythematosus (SLE) who were divide d into two groups depending on the presence (n = 19) or absence (n = 1 3) of APA. Healthy volunteers (n = 12) marched by age and sex served a s controls. In all subjects LA and IgG class anticardiolipin antibodie s (ACA) were determined. Thrombin generation was monitored ex vivo mea suring fibrinopeptide A (FPA) and prothrombin fragment F1 + 2 (F1 + 2) in blood emerging from a skin microvasculature injury, collected at 3 0 second intervals. In subjects with antiphospholipid antibodies mean FPA and F1 + 2 concentrations were significantly higher at most blood sampling times than in controls. In some SLE patients with APA the pro cess of thrombin generation was clearly disturbed and very high concen trations of fibrinopeptide A were detected already in the first sample s collected. Two minutes after skin incision SLE patients without APA produced slightly more FPA, but not F1 + 2, as compared to healthy sub jects. Mathematical model applied to analyze the thrombin generation k inetics revealed that APA patients generated significantly greater amo unts of thrombin than healthy controls (p = 0.02 for either marker). I n contrast, in the same patients generation of thrombin in recalcified plasma in vitro was delayed pointing to the role of endothelium in th e phenomenon studied. In summary, these data show for the first time t hat in SLE patients with antiphospholipid-protein antibodies thrombin generation after small blood vessel injury is markedly increased. Enha nced thrombin generation might explain thrombotic tendency observed in these patients.