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

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.