Evaluation of the prothrombotic potential of four-factor prothrombin complex concentrate (4F-PCC) in animal models.

<h4>Objectives</h4>Acquired coagulopathy may be associated with bleeding risk. Approaches to restore haemostasis include administration of coagulation factor concentrates, but there are concerns regarding potential prothrombotic risk. The present study assessed the prothrombotic potentia...

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Autores principales:	Subhajit Ghosh, Wilfred Krege, Baerbel Doerr, Marcel Mischnik, Ingo Pragst, Gerhard Dickneite, Eva Herzog
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bdfb1062e4ee47e8ba770c579dd6c0b7
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spelling	oai:doaj.org-article:bdfb1062e4ee47e8ba770c579dd6c0b72021-12-02T20:17:15ZEvaluation of the prothrombotic potential of four-factor prothrombin complex concentrate (4F-PCC) in animal models.1932-620310.1371/journal.pone.0258192https://doaj.org/article/bdfb1062e4ee47e8ba770c579dd6c0b72021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0258192https://doaj.org/toc/1932-6203<h4>Objectives</h4>Acquired coagulopathy may be associated with bleeding risk. Approaches to restore haemostasis include administration of coagulation factor concentrates, but there are concerns regarding potential prothrombotic risk. The present study assessed the prothrombotic potential of four-factor prothrombin complex concentrate (4F-PCC) versus activated PCC (aPCC) and recombinant factor VIIa (rFVIIa), using three preclinical animal models.<h4>Methods</h4>The first model was a modified Wessler model of venous stasis-induced thrombosis in rabbit, focusing on dilutional coagulopathy; the second model employed the same system but focused on direct oral anticoagulant reversal (i.e. edoxaban). The third model assessed the prothrombotic impact of 4F-PCC, aPCC and rFVIIa in a rat model of ferric chloride-induced arterial thrombosis.<h4>Results</h4>In the first model, thrombi were observed at aPCC doses ≥10 IU/kg (therapeutic dose 100 IU/kg) and rFVIIa doses ≥50 μg/kg (therapeutic dose 90 μg/kg), but not 4F-PCC 50 IU/kg (therapeutic dose 50 IU/kg). The impact of 4F-PCC (up to 300 IU/kg) on thrombus formation was evident from 10 minutes post-administration, but not at 24 hours post-administration; this did not change with addition of tranexamic acid and/or fibrinogen concentrate. 4F-PCC-induced thrombus formation was lower after haemodilution versus non-haemodilution. In the second model, no prothrombotic effect was confirmed at 4F-PCC 50 IU/kg. The third model showed lower incidence of thrombus formation for 4F-PCC 50 IU/kg versus aPCC (50 U/kg) and rFVIIa (90 μg/kg).<h4>Conclusions</h4>These results suggest that 4F-PCC has a low thrombotic potential versus aPCC or rFVIIa, supporting the clinical use of 4F-PCC for the treatment of coagulopathy-mediated bleeding.Subhajit GhoshWilfred KregeBaerbel DoerrMarcel MischnikIngo PragstGerhard DickneiteEva HerzogPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10, p e0258192 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Subhajit Ghosh Wilfred Krege Baerbel Doerr Marcel Mischnik Ingo Pragst Gerhard Dickneite Eva Herzog Evaluation of the prothrombotic potential of four-factor prothrombin complex concentrate (4F-PCC) in animal models.
description	<h4>Objectives</h4>Acquired coagulopathy may be associated with bleeding risk. Approaches to restore haemostasis include administration of coagulation factor concentrates, but there are concerns regarding potential prothrombotic risk. The present study assessed the prothrombotic potential of four-factor prothrombin complex concentrate (4F-PCC) versus activated PCC (aPCC) and recombinant factor VIIa (rFVIIa), using three preclinical animal models.<h4>Methods</h4>The first model was a modified Wessler model of venous stasis-induced thrombosis in rabbit, focusing on dilutional coagulopathy; the second model employed the same system but focused on direct oral anticoagulant reversal (i.e. edoxaban). The third model assessed the prothrombotic impact of 4F-PCC, aPCC and rFVIIa in a rat model of ferric chloride-induced arterial thrombosis.<h4>Results</h4>In the first model, thrombi were observed at aPCC doses ≥10 IU/kg (therapeutic dose 100 IU/kg) and rFVIIa doses ≥50 μg/kg (therapeutic dose 90 μg/kg), but not 4F-PCC 50 IU/kg (therapeutic dose 50 IU/kg). The impact of 4F-PCC (up to 300 IU/kg) on thrombus formation was evident from 10 minutes post-administration, but not at 24 hours post-administration; this did not change with addition of tranexamic acid and/or fibrinogen concentrate. 4F-PCC-induced thrombus formation was lower after haemodilution versus non-haemodilution. In the second model, no prothrombotic effect was confirmed at 4F-PCC 50 IU/kg. The third model showed lower incidence of thrombus formation for 4F-PCC 50 IU/kg versus aPCC (50 U/kg) and rFVIIa (90 μg/kg).<h4>Conclusions</h4>These results suggest that 4F-PCC has a low thrombotic potential versus aPCC or rFVIIa, supporting the clinical use of 4F-PCC for the treatment of coagulopathy-mediated bleeding.
format	article
author	Subhajit Ghosh Wilfred Krege Baerbel Doerr Marcel Mischnik Ingo Pragst Gerhard Dickneite Eva Herzog
author_facet	Subhajit Ghosh Wilfred Krege Baerbel Doerr Marcel Mischnik Ingo Pragst Gerhard Dickneite Eva Herzog
author_sort	Subhajit Ghosh
title	Evaluation of the prothrombotic potential of four-factor prothrombin complex concentrate (4F-PCC) in animal models.
title_short	Evaluation of the prothrombotic potential of four-factor prothrombin complex concentrate (4F-PCC) in animal models.
title_full	Evaluation of the prothrombotic potential of four-factor prothrombin complex concentrate (4F-PCC) in animal models.
title_fullStr	Evaluation of the prothrombotic potential of four-factor prothrombin complex concentrate (4F-PCC) in animal models.
title_full_unstemmed	Evaluation of the prothrombotic potential of four-factor prothrombin complex concentrate (4F-PCC) in animal models.
title_sort	evaluation of the prothrombotic potential of four-factor prothrombin complex concentrate (4f-pcc) in animal models.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/bdfb1062e4ee47e8ba770c579dd6c0b7
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Evaluation of the prothrombotic potential of four-factor prothrombin complex concentrate (4F-PCC) in animal models.

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