For a study, researchers sought to evaluate thrombin generation, fibrin formation, structure, and fibrinolytic status in systemic sclerosis (SSc) patients about the development of digital ulcers (DUs) across the course of the disease. Investigators examined endothelial dysfunction, thrombin production, overall hemostatic capability, and fibrin clot turbidity in plasma from 58 patients with systemic sclerosis (39 with DU history and 19 DU-naive) and 46 matched healthy controls (HCs). Using scanning electron microscopy (SEM), the fibrin structure was viewed. Lastly, 39 patients with a history of DUs were followed for 1.5 years, and the predictive efficacy of all studied markers for the beginning of new DUs was investigated. Patients with DUs had significantly increased endogenous thrombin potential (ETP) and delayed clot lysis time (CLT) compared to HCs. CLT was lengthened in individuals with DUs relative to those without, demonstrating good validity in diagnosing DUs with an area under 0.70 (95% CI: 0.60–0.80). Independently, the levels of ETP and intercellular adhesion molecule 1 were linked with CLT. During the time of follow-up, 20 patients developed new DUs. CLT was lengthened (P<0.001) in individuals with fresh bouts of DU, particularly those with recurrent DUs. Regression analysis revealed that the visual analog scale for Raynaud’s phenomenon and CLT were predictors of new DUs (OR 1.1, 95% CI 1.0–1.1 and OR 1.2, 95% CI 1.1–1.3, respectively). SEM confirmed that patients with new DUs had denser fibrin clots. The outcomes implied that defective fibrinolysis might play an increasing role in the pathophysiology of digital vasculopathy and its development in SSc.