Elvers Fynn L, Adelmeijer Jelle, Bos Sarah, Maas Coen, Bernal William, Lisman Ton
Surgical Research Laboratory and Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Gastroenterology, Treant Hospital, Emmen, The Netherlands.
Res Pract Thromb Haemost. 2025 Apr 24;9(4):102872. doi: 10.1016/j.rpth.2025.102872. eCollection 2025 May.
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.
As the hemostatic mechanisms underlying the thrombotic risk in these patients are incompletely studied, we aimed to identify the extent of activation of coagulation in relation to the activation of the intrinsic and extrinsic pathways.
We studied plasma samples before, during, and after surgery from patients undergoing orthotopic liver transplantation (OLT; = 20), partial hepatectomy ( = 20), and pylorus-preserving pancreaticoduodenectomy (PPPD; = 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.
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.
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.
接受肝胰胆手术的患者其止血系统会发生显著变化。即使采取了充分的血栓预防措施，术后静脉血栓栓塞的风险仍然很高。
由于这些患者血栓形成风险的止血机制尚未得到充分研究，我们旨在确定凝血激活程度与内源性和外源性途径激活之间的关系。
我们研究了接受原位肝移植（OLT；n = 20）、肝部分切除术（n = 20）和保留幽门的胰十二指肠切除术（PPPD；n = 20）的患者在手术前、手术期间和手术后的血浆样本。通过凝血酶 - 抗凝血酶（TAT）复合物和D - 二聚体水平评估凝血激活情况。通过ELISA检测游离因子（F）XIIa以及与凝血因子FXIIa、FXIa和血浆激肽释放酶结合的C1酯酶抑制剂来评估内源性激活。通过定量FVIIa - 抗凝血酶复合物评估外源性激活。
肝胰胆手术患者围手术期和术后TAT和D - 二聚体显著升高。内源性途径激活标志物在OLT期间增加，但在接受肝部分切除术或PPPD的患者中未增加。即使在调整FVII酶原水平后，所有手术中外源性激活标志物水平都很低。在OLT期间，TAT和D - 二聚体与内源性激活呈正相关。
本研究提供的证据表明，肝移植期间凝血激活增强是由凝血内源性途径介导的，而肝部分切除术和PPPD患者的凝血激活途径仍不清楚。
