Dual impairment of thrombotic and fibrinolytic pathways assessed by the global thrombosis test predicts adverse clinical outcomes after percutaneous coronary intervention

Background / Introduction The Global Thrombosis Test (GTT) simultaneously assesses thrombotic status (Occlusion Time, OT) and fibrinolytic capacity (Lysis Time, LT) using native blood under physiological shear. While prolonged LT (≥3,000 s) is an established marker of impaired fibrinolysis, the prognostic role of markedly prolonged OT—reflecting bleeding tendency—and its combination with prolonged LT (dual impairment) remain unexplored in patients undergoing percutaneous coronary intervention (PCI). Purpose To evaluate the prognostic significance of dual impairment of thrombotic and fibrinolytic pathways (OT ≥750 s and LT ≥3,000 s) for major adverse cardiovascular events (MACE; a composite of all-cause death, myocardial infarction, stroke, and revascularisation), all-cause mortality, and bleeding in patients undergoing PCI. Methods We prospectively enrolled 2,000 consecutive PCI patients (41.5% acute coronary syndrome) at two centres. GTT was performed prior to or within 24 hours of the index procedure. Dual impairment was defined as OT ≥750 and LT ≥3,000 s. The primary endpoints were MACE (all-cause death, myocardial infarction, stroke, and revascularisation), all-cause death, and bleeding (BARC ≥2) over a median 42-month follow-up. Multivariable Cox regression adjusted for age, hypertension, diabetes, haemoglobin, smoking, and ACS presentation. Results Among 2,000 patients (mean age 66.8 years, 70.3% male), 289 (14.5%) had dual impairment. They were older (69.3 vs. 66.4 years, p<0.001), had more diabetes (47.7% vs. 35.0%, p<0.001), lower haemoglobin (13.2 vs. 14.0 g/dL, p<0.001), higher fibrinogen (337 vs. 309 mg/dL, p<0.001), elevated D-dimer (0.52 vs. 0.37 µg/mL, p<0.001), and prolonged aPTT (35.4 vs. 33.7 s, p<0.001). On multivariable analysis, dual impairment independently predicted all-cause death (HR 2.39, 95% CI 1.45–3.94, p<0.001) and MACE (HR 1.73, 95% CI 1.18–2.53, p=0.005), with a trend for bleeding (HR 1.48, 95% CI 0.93–2.36, p=0.095). Single-pathway impairment showed no significant risk increase, indicating a synergistic effect (Figure). Conclusion(s) Concurrent impairment of both thrombotic and fibrinolytic pathways by GTT identifies a high-risk subgroup with a 2.4-fold increase in mortality and 1.7-fold increase in MACE after PCI. This synergistic dual impairment phenotype provides unique prognostic information by capturing both ischaemic and haemorrhagic vulnerability in a single bedside test.