Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Surgical Research Laboratory and Section of Hepatobiliary Surgery and Liver transplantation, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
J Thromb Haemost. 2020 Nov;18(11):2840-2851. doi: 10.1111/jth.15060. Epub 2020 Sep 10.
In vitro efficacy of pro- and antihemostatic drugs is profoundly different in patients with compensated cirrhosis and in those who have cirrhosis and are critically ill.
Here we assessed the efficacy of pro- and anticoagulant drugs in plasma of patients undergoing hepato-pancreato-biliary (HPB) surgery, which is associated with unique hemostatic changes.
We performed in vitro analyses on blood samples of 60 patients undergoing HPB surgery and liver transplantation: 20 orthotopic liver transplantations, 20 partial hepatectomies, and 20 pylorus-preserving pancreaticoduodenectomies. We performed thrombin generation experiments before and after in vitro addition of fresh frozen plasma (FFP), prothrombin complex concentrate (PCC), recombinant factor VIIa (rFVIIa), low molecular weight heparin (LMWH), unfractionated heparin, dabigatran, and rivaroxaban.
We showed that patients undergoing HPB surgery are in a hypercoagulable state by thrombin generation testing. FFP and rFVIIa had minimal effects on thrombin generation, whereas PCC had a more pronounced procoagulant effect in patients compared with controls. Dabigatran showed a more pronounced anticoagulant effect in patients compared with controls, whereas rivaroxaban and LMWH had a decreased anticoagulant effect in patients.
We demonstrate profoundly altered in vitro efficacy of commonly used anticoagulants, in patients undergoing HPB surgery compared with healthy controls, which may have implications for anticoagulant dosing in the early postoperative period. In the correction of perioperative bleeding complications, PCCs appear much more potent than FFP or rFVIIa, and PCCs may require conservative dosing and caution in use in patients undergoing HPB surgery.
在代偿性肝硬化患者和肝硬化伴危重症患者中，促凝和抗凝血药物的体外疗效有很大差异。
本研究评估了在肝胰胆（HPB）手术患者的血浆中使用促凝和抗凝药物的疗效，HPB 手术与独特的止血变化相关。
我们对 60 例接受 HPB 手术和肝移植的患者的血液样本进行了体外分析：20 例原位肝移植、20 例部分肝切除术和 20 例保留幽门的胰十二指肠切除术。我们在体外添加新鲜冷冻血浆（FFP）、凝血酶原复合物浓缩物（PCC）、重组因子 VIIa（rFVIIa）、低分子肝素（LMWH）、未分馏肝素、达比加群和利伐沙班前后进行了血栓生成实验。
我们通过血栓生成试验表明，接受 HPB 手术的患者处于高凝状态。FFP 和 rFVIIa 对血栓生成的影响很小，而 PCC 对患者的促凝作用比对照组更明显。与对照组相比，达比加群在患者中表现出更明显的抗凝作用，而利伐沙班和 LMWH 在患者中的抗凝作用降低。
与健康对照组相比，我们在接受 HPB 手术的患者中证明了常用抗凝剂的体外疗效发生了明显改变，这可能对术后早期抗凝剂的剂量调整有影响。在纠正围手术期出血并发症方面，PCC 似乎比 FFP 或 rFVIIa 更有效，在接受 HPB 手术的患者中，PCC 的使用剂量需要谨慎。
