Enhanced Fibrinolysis in Lung Cancer Patients: A Functional Assessment Using Lysis Slope Time and Fibrinolytic Biomarkers
Anuha Vellanki, Prakasha Kempaiah, Alexander Pohlman, Fakiha Siddiqui, Walter Jeske, Debra Hoppensteadt, Jeanine Walenga, Jean Amiral, W. Keith Jones, Jawed Fareed, Zaid AbdelsattarBackground
Surgery is the cornerstone of treatment for lung cancer. However, cancer and surgery can both independently affect thrombosis and hemostasis with interrelated, but unclear mechanisms. There are currently poor methods of detection and prediction of subsequent complications. In this context, we aim to evaluate levels of fibrinolysis in peri-operative lung cancer patients, via two different approaches, to identify potential biological mechanisms and trends around surgery.
Methods
Plasma samples were collected from patients undergoing lung resection preoperatively (day 0; n = 77) and postoperatively (day 1; n = 81). Blood bank plasma served as the control (n=24). Plasma lysis slope times were measured using the Lysis Timer, an automated assay that measures the rate of fibrin clot formation and subsequent tPA-stimulated clot breakdown in plasma. PAI-1 and tPA antigen levels were quantified and compared to fibrinolytic activity as measured on the lysis timer.
Results
A total of 84 patients were included. Preoperative (day 0) samples were available for 77 patients and postoperative (day 1) samples for 81 patients, and 24 blood bank plasma samples served as controls. Control samples demonstrated a median lysis slope time of 56.5 min. Patients undergoing lung resection showed significantly shorter plasma lysis slope times both preoperatively (median 33 min, p = 0.0051) and on postoperative day 1 (median 34 min, p = 0.0020) compared with controls, with no significant paired difference between day 0 and day 1 using the Wilcoxon signed-rank test (median day 0: 33 min; median day 1: 32 min; p = 0.7602). PAI-1 antigen levels were significantly elevated in patients both preoperatively and postoperatively compared with controls, with no significant paired difference between day 0 and day 1 (p = 0.4816). tPA antigen levels increased postoperatively and were significantly higher than both controls (p = 0.0009) and paired preoperative levels (p < 0.0001).
Conclusion
Lung cancer patients demonstrated shorter ex vivo plasma lysis slope times compared with controls, suggesting altered fibrinolytic potential under standardized assay conditions. These differences may contribute to postoperative complications, but the findings should be interpreted as assay-specific and require further study with larger longitudinal cohorts, medication-adjusted models, and additional in vivo coagulation/fibrinolysis markers.