Abstract 4943: Enhanced Stability of Plasminogen Activator Inhibitor-1 in Patients With Livedoid Vasculopathy
Livedoid vasculopathy (LV) is a chronic, recurrent, painful cutaneous disease with distinctive clinical features and an uncertain etiology. The skin lesions are recognizable by focal purpura, depigmentation and shallow ulcers. Thrombophilic conditions occur frequently in patients with LV. While no definitive treatment exists for LV, smoking cessation, antiplatelet therapy, immunosuppressive treatment, anabolic steroids are often included in the therapeutic ladder. Recently, a possible link between LV and impaired fibrinolysis was suggested and cutaneous LV lesions responded to tissue plasminogen activator (t-PA) infusion. Hence, inhibition of the fibrinolysis through plasminogen activator inhibitor-1 (PAI-1) activity may determine the disease course in patients with LV. In this study, we investigated PAI-1 Ag and activity levels in 8 patients with biopsy proven LV (mean age 33±18, M/F = 1, median disease duration 5 years). All patients received antiplatelet treatment with aspirin and/or dipyrimadole and 6 patients received anabolic steroids or immunosuppressive treatment. Fasting PAI-1 antigen and activity levels were measured at 9 AM in all patients. Both PAI-1 Ag levels were 44±11 (ng/ml) and PAI activity levels were 16±9 (U/ng/ml) were moderately elevated compared to age-matched controls. However, PAI-1 kinetic studies demonstrated, markedly enhanced stability of PAI-1 activities in plasma from patients with LV. Specific activity at 16 hours were significantly higher than expected activity levels (0.1±0.1 versus 0.001±0.001 u/ng/ml, p=0.028). In conclusion, enhanced stability of PAI-1 may contribute to the pathophysiology of LV, mediated via either binding with stablizing co-factors or by post-translational modification in the PAI-1 protein. Systemic or local treatment with PAI-1 inhibitors may offer potential treatment alternative in patients with LV.