Treating Donation After Circulatory Death Liver Grafts With Alteplase During Ex Situ Normothermic Machine Perfusion

IF 1.9 4区医学 Q2 SURGERY

Clinical Transplantation Pub Date : 2025-08-20 DOI:10.1111/ctr.70282

Rachel Todd, Leonie van Leeuwen, Andrew Rosowicz, Aritz Irizar, Antonios Arvelakis, Joseph DiNorcia, Marcelo Facciuto, Jang Moon, Chiara Rocha, Parissa Tabrizian, Leona Kim-Schluger, Sander S. Florman, M. Zeeshan Akhtar

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引用次数: 0

Abstract

Introduction

Normothermic machine perfusion (NMP) is increasing the safe utilization of donation after circulatory death livers. Historically, tissue plasminogen activator (tPA) has been administered intraoperatively to DCD graft recipients to reduce non-anastomotic biliary complications (NAS). Treating the liver during NMP offers a potentially safer administration, preventing systemic treatment of the recipient. In this retrospective study, we explore our center's experience of giving tPA with FFP during NMP and its effects on clinical chemistries during perfusion, intraoperative transfusions, and post-operative outcomes and clinical chemistries.

Methods

One hundred and twenty-seven livers were perfused using the OrganOx metra, including 56 DCD livers (tPA + NMP-DCD) that received a bolus of 10 mg tPA followed by a 90-min infusion of 40 mg. Sixty-five livers from donation after brain death donors underwent NMP without tPA (NMP-DBD). A historical, propensity-matched cohort of 78 livers from non-NMP DCD donor livers (n = 51) were an additional comparator group (tPA-DCD).

Results

Intraoperative transfusions, 30-day and 3-month patient survival, and 30-day and 3-month graft survival were not statistically different between the tPA-NMP-DCD and NMP-DBD groups, except for cell saver volumes (p = 0.0034). Less platelets and cryoprecipitate transfusions were observed in the tPA-NMP-DCD livers compared to historical tPA-DCD livers (p = 0.0021 and 0.0046, respectively). One incidence of primary non-function occurred in the tPA-DCD group, and the tPA-NMP-DCD arm had one case of ischemic cholangiopathy required re-transplant. There was a higher reoperation rate for hematoma evacuation in the NMP-DBD cohort. Minimum follow-up time was 5 months.

Conclusion

Our results continue to lend support to NMP providing a platform for administering tPA to donor livers, curtailing a potential risk to the recipient.

Summary

Administration of tissue plasminogen activator (tPA) can be safely administered during normothermic machine perfusion. For centers who traditionally deploy tPA in recipients for DCD donor livers, delivering during NMP is an alternative safer option sparing the reciepient from exposure.

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非原位恒温机器灌注阿替普酶治疗循环死亡肝移植捐献

常温机器灌注（NMP）提高了循环性死亡肝脏捐献的安全性。历史上，组织型纤溶酶原激活剂（tPA）已在术中给予DCD移植受者，以减少非吻合口胆道并发症（NAS）。在NMP期间治疗肝脏提供了一种潜在的更安全的给药，防止了受体的全身治疗。在这项回顾性研究中，我们探讨了本中心在NMP期间给予tPA与FFP的经验及其对灌注、术中输血、术后结局和临床化学的影响。方法采用OrganOx metra灌注127例肝脏，其中56例为DCD肝（tPA + NMP-DCD），先给药10mg tPA，再给药40mg tPA 90min。65例脑死亡供者的肝脏接受了不含tPA的NMP （NMP- dbd）。另一个比较组（tPA-DCD）是一个历史的、倾向匹配的队列，来自非nmp DCD供者肝脏的78个肝脏（n = 51）。结果tPA-NMP-DCD组与NMP-DBD组术中输血量、患者30天和3个月生存率、移植物30天和3个月生存率差异无统计学意义（p = 0.0034）。与历史tPA-DCD肝脏相比，tPA-NMP-DCD肝脏中血小板和低温沉淀输注量减少（p分别= 0.0021和0.0046）。tPA-DCD组有1例原发性无功能，tPA-NMP-DCD组有1例缺血性胆管病变需要再次移植。在NMP-DBD队列中，血肿清除的再手术率更高。最小随访时间为5个月。结论：我们的研究结果继续支持NMP，为tPA给药提供了一个平台，减少了对受体的潜在风险。组织纤溶酶原激活剂（tPA）的管理可以安全地给予常温机器灌注。对于传统上在DCD供体肝脏受者中使用tPA的中心来说，在NMP期间给予tPA是一种更安全的选择，可以使受者免受暴露。

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来源期刊

Clinical Transplantation 医学-外科

CiteScore

3.70

自引率

4.80%

发文量

286

审稿时长

2 months

期刊介绍： Clinical Transplantation: The Journal of Clinical and Translational Research aims to serve as a channel of rapid communication for all those involved in the care of patients who require, or have had, organ or tissue transplants, including: kidney, intestine, liver, pancreas, islets, heart, heart valves, lung, bone marrow, cornea, skin, bone, and cartilage, viable or stored. Published monthly, Clinical Transplantation’s scope is focused on the complete spectrum of present transplant therapies, as well as also those that are experimental or may become possible in future. Topics include: Immunology and immunosuppression; Patient preparation; Social, ethical, and psychological issues; Complications, short- and long-term results; Artificial organs; Donation and preservation of organ and tissue; Translational studies; Advances in tissue typing; Updates on transplant pathology;. Clinical and translational studies are particularly welcome, as well as focused reviews. Full-length papers and short communications are invited. Clinical reviews are encouraged, as well as seminal papers in basic science which might lead to immediate clinical application. Prominence is regularly given to the results of cooperative surveys conducted by the organ and tissue transplant registries. Clinical Transplantation: The Journal of Clinical and Translational Research is essential reading for clinicians and researchers in the diverse field of transplantation: surgeons; clinical immunologists; cryobiologists; hematologists; gastroenterologists; hepatologists; pulmonologists; nephrologists; cardiologists; and endocrinologists. It will also be of interest to sociologists, psychologists, research workers, and to all health professionals whose combined efforts will improve the prognosis of transplant recipients.