Evidence map›Paper›PMID 34614035›Full record

ArticlePloS one2021

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

Subhajit Ghosh, Wilfred Krege, Baerbel Doerr, Marcel Mischnik, Ingo Pragst, Gerhard Dickneite, Eva Herzog

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.7field-weighted citation impact, top 30% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Subhajit GhoshDepartment of Pharmacology and Toxicology, CSL Behring GmbH, Marburg, Germany.
Wilfred KregeDepartment of Pharmacology and Toxicology, CSL Behring GmbH, Marburg, Germany.
Baerbel DoerrDepartment of Pharmacology and Toxicology, CSL Behring GmbH, Marburg, Germany.
Marcel MischnikDepartment of Pharmacology and Toxicology, CSL Behring GmbH, Marburg, Germany.
Ingo PragstDepartment of Clinical Research and Development, CSL Behring GmbH, Marburg, Germany.
Gerhard DickneiteDepartment of Pharmacology and Toxicology, CSL Behring GmbH, Marburg, Germany.
Eva HerzogDepartment of Pharmacology and Toxicology, CSL Behring GmbH, Marburg, Germany.
Behringwerke (Germany) · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesAcquired 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.

methodsThe 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.

resultsIn 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).

conclusionsThese 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.

Indexed as

AnimalsArteriesBlood Coagulation FactorsFactor VIIaFemaleHemodilutionRabbitsRatsRats, Sprague-DawleyRecombinant ProteinsThrombosisTime FactorsTranexamic AcidBlood Coagulation FactorsFactor VIIaprothrombin complex concentratesrecombinant FVIIaRecombinant ProteinsTranexamic Acid

Identifiers

PMID34614035
PMCPMC8494364
OpenAlexW3204741514

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.