Moderate LMWH Anticoagulation Improves Success Rate of Hind Limb Allotransplantation in Mice

Barbara Kern, MD; Muhammad-Imtiaz Ashraf, PhD; Anja Reutzel-Selke, PhD; Joerg Mengwasser, PhD; Dietrich Polenz; Edward Michaelis, MD; Johann Pratschke, MD, PhD; Stefan G. Tullius, MD, PhD; Christian Witzel, MD, PhD; Igor M. Sauer, MD, PhD

doi:10.1097/GOX.0000000000005249

Plastic and Reconstructive Surgery, Global Open (Sep 2023)

Moderate LMWH Anticoagulation Improves Success Rate of Hind Limb Allotransplantation in Mice

Barbara Kern, MD,
Muhammad-Imtiaz Ashraf, PhD,
Anja Reutzel-Selke, PhD,
Joerg Mengwasser, PhD,
Dietrich Polenz,
Edward Michaelis, MD,
Johann Pratschke, MD, PhD,
Stefan G. Tullius, MD, PhD,
Christian Witzel, MD, PhD,
Igor M. Sauer, MD, PhD

Affiliations

Barbara Kern, MD: From the * Department of Surgery, Campus Charité Mitte | Campus Virchow Klinikum, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
Muhammad-Imtiaz Ashraf, PhD: From the * Department of Surgery, Campus Charité Mitte | Campus Virchow Klinikum, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
Anja Reutzel-Selke, PhD: From the * Department of Surgery, Campus Charité Mitte | Campus Virchow Klinikum, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
Joerg Mengwasser, PhD: From the * Department of Surgery, Campus Charité Mitte | Campus Virchow Klinikum, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
Dietrich Polenz: From the * Department of Surgery, Campus Charité Mitte | Campus Virchow Klinikum, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
Edward Michaelis, MD: ¶ Department of Pathology, Charité – Universitätsmedizin Berlin, Berlin, Germany
Johann Pratschke, MD, PhD: From the * Department of Surgery, Campus Charité Mitte | Campus Virchow Klinikum, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
Stefan G. Tullius, MD, PhD: ** Division of Transplant Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass.
Christian Witzel, MD, PhD: † Department of Plastic Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
Igor M. Sauer, MD, PhD: From the * Department of Surgery, Campus Charité Mitte | Campus Virchow Klinikum, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany

DOI: https://doi.org/10.1097/GOX.0000000000005249
Journal volume & issue: Vol. 11, no. 9
p. e5249

Abstract

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Background:. The mouse hind limb model represents a powerful research tool in vascularized composite tissue allotransplantation, but its applicability is limited due to poor graft survival (62%–83%). Vascular thrombosis and massive hemorrhage are the major causes for these drop-outs. We hypothesize that because of better anticoagulation effect and lower risk of thrombocytopenia, application of low molecular weight heparin (LMWH) will minimize vascular complications and enhance graft and animal survival. Methods:. Fifty allogeneic hind limb transplantations were performed (C57BL/6 to DBA/2 mice) using five different anticoagulation protocols. Bleeding and thromboembolic events were recorded macroscopically by postoperative hemorrhage and livid discoloration of the graft, respectively. Graft perfusion and survival were monitored daily by capillary-refill-time of graft toes within 2–3 seconds. Vascular congestion and tissue necrosis were examined by histological evaluation of hematoxylin-eosin-stained tissue sections. Results:. All transplantations were technically successful. Increase in thromboembolic events and a concomitant decrease in bleeding events were observed with the decreasing concentration of heparin in the perfusion solution. Although treatment of donor and recipient with low dose of LMWH could not reduce thromboembolic events, moderate dose effectively reduced these events. Compared with the poor outcome of graft perfusion with heparin alone, additional treatment of donor and recipient with low dose of LMWH improved graft and animal survival by 18%. Interestingly, animals treated with moderate dose of LMWH demonstrated 100% graft and animal survival. Conclusions:. Treatment of donor and recipient mice with a moderate dose of LMWH prevents vascular complications and improves the outcome of murine hind limb transplants.

Published in Plastic and Reconstructive Surgery, Global Open

ISSN: 2169-7574 (Online)
Publisher: Wolters Kluwer
Country of publisher: United States
LCC subjects: Medicine: Surgery
Website: http://www.prsgo.com

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