Combined Administration of Fibrinogen and Factor XIII Concentrate Does Not Improve Dilutional Coagulopathy Superiorly Than Sole Fibrinogen Therapy: Results of an In-Vitro Thrombelastographic Study

The early administration of fibrinogen has gained wide acceptance for the treatment of major hemorrhage, whereas the substitution of coagulation factor XIII (FXIII) is only supported by a low level of evidence. This study aimed to answer the question of whether a combined therapy of fibrinogen/FXIII...

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Main Authors: Emmanuel Schneck, Marcus Muelich, Melanie Markmann, Fabian Edinger, Nina Cooper, Annette Moeller, Gregor Bein, Andreas Hecker, Christian Koch, Michael Sander, Matthias Wolff
Format: Article
Language:English
Published: MDPI AG 2021-05-01
Series:Journal of Clinical Medicine
Subjects:
Online Access:https://www.mdpi.com/2077-0383/10/10/2068
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author Emmanuel Schneck
Marcus Muelich
Melanie Markmann
Fabian Edinger
Nina Cooper
Annette Moeller
Gregor Bein
Andreas Hecker
Christian Koch
Michael Sander
Matthias Wolff
author_facet Emmanuel Schneck
Marcus Muelich
Melanie Markmann
Fabian Edinger
Nina Cooper
Annette Moeller
Gregor Bein
Andreas Hecker
Christian Koch
Michael Sander
Matthias Wolff
author_sort Emmanuel Schneck
collection DOAJ
description The early administration of fibrinogen has gained wide acceptance for the treatment of major hemorrhage, whereas the substitution of coagulation factor XIII (FXIII) is only supported by a low level of evidence. This study aimed to answer the question of whether a combined therapy of fibrinogen/FXIII substitution performs superiorly to sole fibrinogen administration in the treatment of dilutional coagulopathy. An in-vitro model of massive transfusion was used to compare the effect of combined fibrinogen/FXIII administration to that of sole fibrinogen therapy for the treatment of dilutional coagulopathy. For this purpose, the blood of red blood cell concentrates, fresh frozen plasma, and platelet concentrates were reconstituted in a ratio of 4:4:1, and then diluted with gelatin by 20% and 40%, respectively. Clot formation and stability were analyzed by thrombelastography. Both sole fibrinogen therapy (equivalent to 50 mg/kg) and the combined administration of fibrinogen (equivalent to 50 mg/kg) and FXIII (equivalent to 75 International Units (IU)/kg) increased fibrinogen-dependent mean clot firmness independently of the degree of dilution (20% dilution: 7 (6.3–7.8) mm; 20% dilution fibrinogen: 13.5 (13–17.3) mm; 20% dilution fibrinogen/FXIII: 16.5 (15.3–18.8) mm; 40% dilution: 3 (2–3.8) mm; 40% dilution fibrinogen: 8 (7–11.3) mm; 40% dilution fibrinogen/FXIII: 10 (8.3–11.8) mm; all <i>p</i> < 0.01). However, no differences were identified between the two treatment arms. Compared to fibrinogen therapy, no beneficial effect of the combined administration of fibrinogen and FXIII for the treatment of dilutional coagulopathy was detected in this in-vitro massive transfusion model. The result was independent of the degree of dilution.
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spelling doaj.art-5e9e957f76784211b71d22f26e8353fd2023-11-21T19:18:59ZengMDPI AGJournal of Clinical Medicine2077-03832021-05-011010206810.3390/jcm10102068Combined Administration of Fibrinogen and Factor XIII Concentrate Does Not Improve Dilutional Coagulopathy Superiorly Than Sole Fibrinogen Therapy: Results of an In-Vitro Thrombelastographic StudyEmmanuel Schneck0Marcus Muelich1Melanie Markmann2Fabian Edinger3Nina Cooper4Annette Moeller5Gregor Bein6Andreas Hecker7Christian Koch8Michael Sander9Matthias Wolff10Department of Anesthesiology, Operative Intensive Care Medicine and Pain Therapy, University Hospital of Giessen, 35392 Giessen, GermanyDepartment of Anesthesiology, Operative Intensive Care Medicine and Pain Therapy, University Hospital of Giessen, 35392 Giessen, GermanyDepartment of Anesthesiology, Operative Intensive Care Medicine and Pain Therapy, University Hospital of Giessen, 35392 Giessen, GermanyDepartment of Anesthesiology, Operative Intensive Care Medicine and Pain Therapy, University Hospital of Giessen, 35392 Giessen, GermanyInstitute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, 35392 Giessen, GermanyInstitute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, 35392 Giessen, GermanyInstitute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, 35392 Giessen, GermanyDepartment of General & Thoracic Surgery, University Hospital of Giessen, 35392 Giessen, GermanyDepartment of Anesthesiology, Operative Intensive Care Medicine and Pain Therapy, University Hospital of Giessen, 35392 Giessen, GermanyDepartment of Anesthesiology, Operative Intensive Care Medicine and Pain Therapy, University Hospital of Giessen, 35392 Giessen, GermanyDepartment of Anesthesiology, Operative Intensive Care Medicine and Pain Therapy, University Hospital of Giessen, 35392 Giessen, GermanyThe early administration of fibrinogen has gained wide acceptance for the treatment of major hemorrhage, whereas the substitution of coagulation factor XIII (FXIII) is only supported by a low level of evidence. This study aimed to answer the question of whether a combined therapy of fibrinogen/FXIII substitution performs superiorly to sole fibrinogen administration in the treatment of dilutional coagulopathy. An in-vitro model of massive transfusion was used to compare the effect of combined fibrinogen/FXIII administration to that of sole fibrinogen therapy for the treatment of dilutional coagulopathy. For this purpose, the blood of red blood cell concentrates, fresh frozen plasma, and platelet concentrates were reconstituted in a ratio of 4:4:1, and then diluted with gelatin by 20% and 40%, respectively. Clot formation and stability were analyzed by thrombelastography. Both sole fibrinogen therapy (equivalent to 50 mg/kg) and the combined administration of fibrinogen (equivalent to 50 mg/kg) and FXIII (equivalent to 75 International Units (IU)/kg) increased fibrinogen-dependent mean clot firmness independently of the degree of dilution (20% dilution: 7 (6.3–7.8) mm; 20% dilution fibrinogen: 13.5 (13–17.3) mm; 20% dilution fibrinogen/FXIII: 16.5 (15.3–18.8) mm; 40% dilution: 3 (2–3.8) mm; 40% dilution fibrinogen: 8 (7–11.3) mm; 40% dilution fibrinogen/FXIII: 10 (8.3–11.8) mm; all <i>p</i> < 0.01). However, no differences were identified between the two treatment arms. Compared to fibrinogen therapy, no beneficial effect of the combined administration of fibrinogen and FXIII for the treatment of dilutional coagulopathy was detected in this in-vitro massive transfusion model. The result was independent of the degree of dilution.https://www.mdpi.com/2077-0383/10/10/2068hemorrhagemajor bleedingcoagulationthrombelastometryimpedance aggregometrytrauma
spellingShingle Emmanuel Schneck
Marcus Muelich
Melanie Markmann
Fabian Edinger
Nina Cooper
Annette Moeller
Gregor Bein
Andreas Hecker
Christian Koch
Michael Sander
Matthias Wolff
Combined Administration of Fibrinogen and Factor XIII Concentrate Does Not Improve Dilutional Coagulopathy Superiorly Than Sole Fibrinogen Therapy: Results of an In-Vitro Thrombelastographic Study
Journal of Clinical Medicine
hemorrhage
major bleeding
coagulation
thrombelastometry
impedance aggregometry
trauma
title Combined Administration of Fibrinogen and Factor XIII Concentrate Does Not Improve Dilutional Coagulopathy Superiorly Than Sole Fibrinogen Therapy: Results of an In-Vitro Thrombelastographic Study
title_full Combined Administration of Fibrinogen and Factor XIII Concentrate Does Not Improve Dilutional Coagulopathy Superiorly Than Sole Fibrinogen Therapy: Results of an In-Vitro Thrombelastographic Study
title_fullStr Combined Administration of Fibrinogen and Factor XIII Concentrate Does Not Improve Dilutional Coagulopathy Superiorly Than Sole Fibrinogen Therapy: Results of an In-Vitro Thrombelastographic Study
title_full_unstemmed Combined Administration of Fibrinogen and Factor XIII Concentrate Does Not Improve Dilutional Coagulopathy Superiorly Than Sole Fibrinogen Therapy: Results of an In-Vitro Thrombelastographic Study
title_short Combined Administration of Fibrinogen and Factor XIII Concentrate Does Not Improve Dilutional Coagulopathy Superiorly Than Sole Fibrinogen Therapy: Results of an In-Vitro Thrombelastographic Study
title_sort combined administration of fibrinogen and factor xiii concentrate does not improve dilutional coagulopathy superiorly than sole fibrinogen therapy results of an in vitro thrombelastographic study
topic hemorrhage
major bleeding
coagulation
thrombelastometry
impedance aggregometry
trauma
url https://www.mdpi.com/2077-0383/10/10/2068
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