PMID- 37452405 OWN - NLM STAT- MEDLINE DCOM- 20230717 LR - 20230718 IS - 1470-7330 (Electronic) IS - 1740-5025 (Print) IS - 1470-7330 (Linking) VI - 23 IP - 1 DP - 2023 Jul 14 TI - Heparin reversal with protamine sulfate after Percutaneous Hepatic Perfusion (PHP): is less more? PG - 68 LID - 10.1186/s40644-023-00590-7 [doi] LID - 68 AB - PURPOSE: Percutaneous hepatic perfusion (PHP) is a palliative intraarterial therapy for unresectable hepatic malignancies. During PHP, high-dose melphalan is infused via the hepatic artery to saturate tumor in the liver with the chemotherapeutic substance. The venous hepatic blood is filtered by an extracorporeal melphalan specific filtration system. Blood clotting in the extracorporeal filter system is prevented by administering unfractionated heparin (UFH) in high doses, which might be reversed with protamine sulfate after the procedure. Aim of this retrospective two-center-study was to analyze the potential effect of UFH reversal with protamine sulfate on complication rates following PHP. MATERIALS AND METHODS: All patients receiving PHP treatment between 10/2014 and 04/2021 were classified according to their intraprocedural coagulation management: 92 patients/192 PHP received full UFH reversal with protamine (group(PROTAMINE)); 13 patients/21 PHP in group(REDUCED_PROTAMINE) received a reduced amount of protamine, and 28 patients/43 PHP did not receive UFH reversal with protamine (group(NO_PROTAMINE)). Periinterventional clinical reports, findings and laboratory values were retrospectively evaluated. Complications and adverse events were classified according to Common Terminology Criteria for Adverse Events (CTCAEv5.0). RESULTS: Thromboembolic events were recorded after 10 PHP procedures (5%) in group(PROTAMINE), six of which (3%) were major events (CTCAE grade 3-5). No (0%) thromboembolic events were recorded in group(REDUCED_PROTAMINE) and group(NO_PROTAMINE). Hemorrhagic events were registered after 24 PHP (13%) in group(PROTAMINE,) two of which (1%) were major (CTCAE grade 3-4). In group(REDUCED_PROTAMINE), only minor bleeding events were recorded, and one major hemorrhagic event was documented in group(NO_PROTAMINE) (2%). There was a significant difference between the percentage of post-interventional thrombopenia in group(PROTAMINE) (39%) and group(REDUCED_PROTAMINE) (14%) versus group(NO_PROTAMINE) (23%) (p=.00024). In group(PROTAMINE) one patient suffered from a severe anaphylactic shock after the administration of protamine. CONCLUSION: Our retrospective study implies that there might be a link between the practice of protamine sulfate administration to reverse the full hemodilutive effect of UFH after PHP and the post-interventional risk of thromboembolic events as well as clinically significant thrombopenia. Our data suggest that the standard use of protamine sulfate after PHP in low-risk patients without clinical signs of active bleeding should be critically re-evaluated. CI - (c) 2023. The Author(s). FAU - Facchetti, Nadia AU - Facchetti N AD - Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany. FAU - Hinrichs, Jan B AU - Hinrichs JB AD - Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany. FAU - Becker, Lena S AU - Becker LS AD - Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany. FAU - Schneider, Martin A AU - Schneider MA AD - Department of Radiology and Neuroradiology, Asklepios Clinic Hamburg-Barmbek, Hamburg, Germany. FAU - Bruning, Roland AU - Bruning R AD - Department of Radiology and Neuroradiology, Asklepios Clinic Hamburg-Barmbek, Hamburg, Germany. FAU - Rademacher, Jan AU - Rademacher J AD - Department of Anesthesiology, Asklepios Clinic Hamburg-Barmbek, Hamburg, Germany. FAU - Lenz, Jochen AU - Lenz J AD - Department of Anesthesiology, Asklepios Clinic Hamburg-Barmbek, Hamburg, Germany. FAU - Kudrass, Kirsten AU - Kudrass K AD - Department of Anesthesiology, Hannover Medical School, Hannover, Germany. FAU - Vogel, Arndt AU - Vogel A AD - Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany. FAU - Wacker, Frank K AU - Wacker FK AD - Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany. FAU - Dewald, Cornelia L A AU - Dewald CLA AUID- ORCID: 0000-0001-8805-2291 AD - Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany. dewald.cornelia@mh-hannover.de. LA - eng PT - Journal Article DEP - 20230714 PL - England TA - Cancer Imaging JT - Cancer imaging : the official publication of the International Cancer Imaging Society JID - 101172931 RN - 9005-49-6 (Heparin) RN - Q41OR9510P (Melphalan) RN - 0 (Protamines) SB - IM MH - Humans MH - *Heparin/therapeutic use MH - Melphalan MH - Retrospective Studies MH - Protamines/therapeutic use MH - *Thrombocytopenia/chemically induced/drug therapy MH - Perfusion PMC - PMC10349410 OTO - NOTNLM OT - Chemosaturation OT - Heparin neutralization OT - Percutaneous hepatic perfusion OT - Periprocedural safety OT - Protamine sulfate OT - Thromboembolism COIS- Frank K Wacker declares an institutional scientific grants from Siemens Healthineers, Promedicus Ltd. outside the submitted work and an institutional scientific grant from Delcath Ltd. related to the subject matter of the article. Roland Bruning has received financial support for presentations/meetings from Delcath Ltd. related to the subject matter of the article. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. CD, NF, LSB, MAS, JR, JL, KK, AV und JBH declare no conflicts of interest related to the subject matter of the article. EDAT- 2023/07/15 10:42 MHDA- 2023/07/17 06:42 PMCR- 2023/07/14 CRDT- 2023/07/14 23:40 PHST- 2023/03/10 00:00 [received] PHST- 2023/07/05 00:00 [accepted] PHST- 2023/07/17 06:42 [medline] PHST- 2023/07/15 10:42 [pubmed] PHST- 2023/07/14 23:40 [entrez] PHST- 2023/07/14 00:00 [pmc-release] AID - 10.1186/s40644-023-00590-7 [pii] AID - 590 [pii] AID - 10.1186/s40644-023-00590-7 [doi] PST - epublish SO - Cancer Imaging. 2023 Jul 14;23(1):68. doi: 10.1186/s40644-023-00590-7.