FRI0232 ALTERED FIBRIN CLOT PROPERTIES IN PATIENTS WITH SYSTEMIC SCLEROSIS

Abstract

Background:Vasculopathy in Systemic sclerosis (SSc) is connected with the activation of coagulation. However, the fibrinolytic activity still remains unclear since the most preliminary evidences are discordant (1, 2).Objectives:To assess the haemostatic function, fibrin clot density and clot lysis time in SSc patients and healthy controls (HC) to determine their relation to disease findings.Methods:Patients who fulfilled the 2013 ACR/EULAR SSc criteria and have never been treated with endothelin receptor antagonist, phosphodiesterase 5 inhibitors or prostanoids were eligibile. Our study included 58 SSc patients [36 limited (lcSSc) and 22 diffuse cutaneous SSc (dcSSc)] and 46 sex/age-matched HC. Clinical evaluation of patients was performed, including high-resolution CT (HRCT), pulmonary function tests and the revised EUSTAR activity index. The interstitial lung disease (ILD) group (n = 15) was defined as moderate or severe changes on HRCT, with a forced vital capacity (FVC) < 85% predicted, without evidence of significant pulmonary arterial hypertension. The serum concentration of ICAM1 and von Willebrand factor antigen (VWF) were measured by ELISA. Haemostatic potential parameters; including overall haemostasis (OHP), overall coagulation (OCP) and overall fibrinolysis (OFP) potential, were assessed and endogenous thrombin potential (ETP) was determined. Maximum absorbance (Cmax), reflects the fibrin clot density and clot lysis time (Lys50t0), reflects fibrinolytic susceptibility, were calculated from OHP and OCP curves (3). Fibrin structure was visualised using scanning electron microscopy (SEM).Results:The OFP value was significantly decreased, Lys50t0 prolonged (p<0.05), while OHP and ETP were increased (p<0.05) in patients. In dSSc group ETP, OHP, Cmax and Lys50t0 were higher compared to HC (p<0.05). In SSc group, a positive association was found between coagulation parameters (OCP, OHP, Cmax) and the erythrocyte sedimentation rate (ESR), fibrinogen and ICAM1 (respectively p<0.05). Lys50t0 was positively correlated with ICAM1, ESR and VWF (respectively p<0.001, p<0.05, p<0.05). An inverse correlation was found between Cmax and both the diffusing capacity of the lungs for carbon monoxide (r=-0.408, p<0.01) and FVC (r=-0.318, p<0.01). Increased Cmax was found in ILD respect to HC (p<0.01). Denser plasma clot was associated with active disease (p<0.01). Longer Lys50t0 was observed in pitting scars group (p<0.01). Prolonged Lys50t0 was independently predicted by ICAM1 (OR 1.12, 95% CI 1.03–1.2, p<0.01).Conclusion:Our results provide evidences of denser plasma fibrin clot among patients with lung involvement and impaired fibrinolysis, selectively presented among SSc patients with piting scars. Thus, these patients might be at risk for thrombotic complications. Raised ICAM-1 levels could reflect impaired fibrinolysis, giving insight the important role of this molecule in endothelial homeostasis.References:[1]Cerinic MM, et al. Blood coagulation, fibrinolysis, and markers of endothelial dysfunction in systemic sclerosis. Semin Arthritis Rheum. 2003;32:285–95[2]Lippi G, et al. Plasma D-dimer concentration in patients with systemic sclerosis.Thromb J. 2006;4:2.[3]Carter AM, et al. Heritability of clot formation, morphology, and lysis: the EuroCLOT study. Arterioscler Thromb Vasc Biol. 2007 Dec;27(12):2783-9Figure 1.SEM images of fibrin network in 1 representative sample from a SSc (A) and 1from HC sample (B).Disclosure of Interests:Jelena Colic: None declared, Aleksandra Antovic: None declared, Iva Pruner: None declared, Jelena Vojinovic Consultant of: Roche, Abbvie, Pfizer, MSD, Speakers bureau: Roche, Abbvie, Pfizer, MSD, Mirjana Sefik Bukilica: None declared, Nemanja Damjanov Grant/research support from: from AbbVie, Pfizer, and Roche, Consultant of: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, Speakers bureau: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche