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In vivo activation of coagulation during human liver transplantation is associated with activation of the intrinsic pathway: an observational cohort study

Year: 2025

Type: article

Abstract: Background Patients undergoing hepato-pancreato-biliary surgery experience substantial changes in their hemostatic system. The postoperative risk of venous thromboembolism is high, even in the presence of adequate thromboprophylaxis. Objectives As the hemostatic mechanisms underlying the thrombotic risk in these patients are incompletely studied, we aimed to identify the extent of in vivo activation of coagulation in relation to the activation of the intrinsic and extrinsic pathways. Methods We studied plasma samples before, during, and after surgery from patients undergoing orthotopic liver transplantation (OLT; n = 20), partial hepatectomy ( n = 20), and pylorus-preserving pancreaticoduodenectomy (PPPD; n = 20). Activation of coagulation was assessed by levels of thrombin-antithrombin (TAT) complexes and D-dimer. Intrinsic activation was assessed with ELISA detecting free factor (F)XIIa and C1-esterase inhibitor bound to coagulation FXIIa, FXIa, and plasma kallikrein. Extrinsic activation was assessed by quantification of FVIIa-antithrombin complexes. Results TAT and D-dimer were significantly elevated peri- and postoperatively in patients undergoing hepato-pancreato-biliary surgery. Markers of intrinsic pathway activation increased during OLT but not in patients undergoing partial hepatectomy or PPPD. Markers of extrinsic activation were low in all surgeries, even after adjustment for FVII zymogen levels. TAT and D-dimer were positively associated with intrinsic activation during OLT. Conclusion This study provides evidence that enhanced activation of coagulation during liver transplantation is mediated by the intrinsic pathway of coagulation, whereas the route of coagulation activation in patients undergoing partial hepatectomy and PPPD remains unclear.

Source: Research and Practice in Thrombosis and Haemostasis

DOI: 10.1016/j.rpth.2025.102872

Authors: Fynn L. Elvers, Jelle Adelmeijer, Sarah Bos, Coen Maas, William Bernal, Ton Lisman