POS0874 CLOT LYSIS TIME PREDICTS RECURRENT DIGITAL ULCERS IN SYSTEMIC SCLEROSIS AFTER ONE YEAR OF FOLLOW-UP: A NESTED CASE-CONTROL STUDY
Authors: J. Colic, A. Antovic, I. Pruner, J. Vojinovic, N. Damjanov, M. Sefik Bukilica
Journal: Annals of the Rheumatic Diseases (2021)

Background: Digital ulcers (DU) are a common visible manifestation of vasculopathy in systemic sclerosis (SSc), which could be recurrent and associated with disability and mortality (1). Although vasculopathy is connected with impaired coagulation/fibrinolysis system and aberrant expression of adhesion molecules, there are few data about their role in developing recurrent DU. Objectives: To evaluate the possible role of Fibrin generation/Fibrinolysis parameters and adhesion molecules in the prediction of new ischaemic DU oncet during a 1-year follow-up and their impact on the time to new DU onset (TD). Methods: From 58 consecutive patients with SSc who fulfilled the 2013 ACR/EULAR SSc criteria and have never been treated with endothelin receptor antagonist, phosphodiesterase 5 inhibitors or prostanoids, a total of 38 patients with ever had DU, either active at inclusion or in past, were enrolled in a prospective cohort study. Each patient was given a “DU diary”. Demografic, clinical and serologycal data were recorded. The serum concentration of ICAM1 and E selectin were measured by ELISA. Haemostatic potential parameters: overall haemostasis (OHP), overall coagulation (OCP) and overall fibrinolysis (OFP) potential were assessed. Maximum absorbance (Cmax), reflects the fibrin clot density and clot lysis time (Lys50t0, time from initiation of clot formation to the time at which a 50% fall in absorbance from Cmax in the lysis assay), reflects fibrinolytic susceptibility, were calculated (2). Fibrin structure was visualised using scanning electron microscopy (SEM). Results: Over the follow-up period,18 patients (45.5%) developed new DU with the average TD of 7.4±2.9 months. There was no differance in ASA and CCB treatment among two groups (p&gt;0.05). The OFP value was significantly decreased (p&lt;0.01), Lys50t0 prolonged (p&lt;0.05), while OHP was increased (p&lt;0.05) in patients experienced new DU. Lys50t0 showed good validity in identifying patients with new DU oncet (AUC 0.683 95% CI 0.5 - 0.9). By multivariate analysis including clinical data in model the Lys50t0 (HR 1.2, 95% CI 1.1-1.3, p=0.018) and active DU at enrollment (HR 9.6, 95% CI 1.4-66.8, p=0.022) were identified as independent risk factors for the occurrence of new DU. TD was inversly correlated with ICAM1(p&lt;0.001), E selectin (p&lt;0.05), Cmax (p &lt;0.05) and Lys50t0 (p&lt;0.001). Model explaining 81.6% of the TD variability included Lys50t0 (β=- 0.55,p=0.003), E selectin (β=- 0.44,p=0.014) and fibrinogen (β=- 0.49,p=0.017). SEM revealed denser fibrin clots with thinner fibres in group experienced new DU compared to clots formed in plasma of patient without DU. Conclusion: Our results provide evidence that impaired fibrinolysis has critical role in the progression of microvascular disease, identifing clot lysis time as a strong predictor in the oncet of new digital ulcers in Systemic sclerosis. The higher level of E selectin and the longer lysis time are, the shorter is time until the onset of new digital ulcer. These results could be used in selection of patients at high risk of developing recurrent digital ulcer and therefore allow earlier therapeutic intervention. References: [1]Allanore Y, Distler O, Matucci-Cerinic M, Denton CP. Review: Defining a Unified Vascular Phenotype in Systemic Sclerosis. Arthritis Rheumatol. 2018 Feb;70(2):162-170 [2]Carter AM, et al. Heritability of clot formation, morphology, and lysis: the EuroCLOT study. Arterioscler Thromb Vasc Biol. 2007 Dec;27(12):2783-9. Figure 1. SEM images of fibrin network in 1 representative sample from a SSc patient with (A) and 1from patient without (B) new DU oncet Disclosure of Interests: None declared