Longitudinal coagulation-fibrinolysis dynamics are associated with survival in amyotrophic lateral sclerosis: a...

Background: Amyotrophic lateral sclerosis (ALS) has been associated with thromboembolic risk. However, whether dynamic coagulation-fibrinolysis markers provide prognostic information in ALS remains insufficiently defined. Methods: We conducted a prospective cohort study of 151 patients with ALS, including repeated coagulation measurements in a longitudinal subset (n = 58), and assessed directional validation in the independent Answer ALS (AALS) cohort (n = 270). Survival analyses, longitudinal modeling, and plasma proteomic analyses were used to examine associations between coagulation-fibrinolysis dynamics, functional decline, and survival. Results: Higher baseline fibrinogen (FIB) was independently associated with shorter survival (HR = 2.19; 95% confidence interval (CI), 1.40-3.44). In the longitudinal subset, a steeper increase in D-dimer (DD) was associated with shorter survival (HR = 1.012; 95% CI, 1.001-1.024) and lower ALSFRS-R scores over time (β = -0.013; 95% CI, -0.016 to -0.009). Directionally consistent validation was observed in AALS using rescaled SomaScan-derived DD trajectories (HR = 1.0002; 95% CI, 1.0000-1.0004). Plasma proteomics showed reduced tetranectin, a fibrinolysis-related protein, in ALS; slower tetranectin decline was associated with longer survival using rescaled SomaScan-derived tetranectin trajectories (HR = 0.996; 95% CI, 0.993-0.998). Conclusions: These findings suggest that longitudinal coagulation-fibrinolysis markers may help identify a survival-related biomarker profile in ALS, involving higher baseline FIB, steeper rising DD, and reduced or more rapidly declining tetranectin.