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Fibrin(ogen) in human disease: both friend and foe.

ABSTRACT: Fibrinogen is an abundant protein synthesized in the liver, present in human blood plasma at concentrations ranging from 1.5-4 g/L in healthy individuals with a normal half-life of 3-5 days. With fibrin, produced by thrombin-mediated cleavage, fibrinogen plays important roles in many physiological processes. Indeed, the formation of a stable blood clot, containing polymerized and cross-linked fibrin, is crucial to prevent blood loss and drive wound healing upon vascular injury. A balance between clotting, notably the conversion of fibrinogen to fibrin, and fibrinolysis, the proteolytic degradation of the fibrin mesh, is essential. Disruption of this equilibrium can cause disease in distinct manners. While some pathological conditions are the consequence of altered levels of fibrinogen, others are related to structural properties of the molecule. The source of fibrinogen expression and the localization of fibrin(ogen) protein also have clinical implications. Low levels of fibrinogen expression have been detected in extra-hepatic tissues, including carcinomas, potentially contributing to disease. Fibrin(ogen) deposits at aberrant sites including the central nervous system or kidney, can also be pathological. In this review, we discuss disorders in which fibrinogen and fibrin are implicated, highlighting mechanisms that may contribute to disease.

SUBMITTER: Vilar R

PROVIDER: S-EPMC7012490 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Fibrin(ogen) in human disease: both friend and foe.

Vilar Rui R Fish Richard J RJ Casini Alessandro A Neerman-Arbez Marguerite M

Haematologica 20200131 2

Fibrinogen is an abundant protein synthesized in the liver, present in human blood plasma at concentrations ranging from 1.5-4 g/L in healthy individuals with a normal half-life of 3-5 days. With fibrin, produced by thrombin-mediated cleavage, fibrinogen plays important roles in many physiological processes. Indeed, the formation of a stable blood clot, containing polymerized and cross-linked fibrin, is crucial to prevent blood loss and drive wound healing upon vascular injury. A balance between ...[more]

PMID: 31949010

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Project description:ObjectiveManagement of coagulopathy in chronic liver disease (CLD) poses a challenge for critical care physicians. Prothrombinex®-VF is a low-volume product with rapid onset of action. Evidence for its efficacy and safety in CLD is limited and cases of acute intravascular coagulation and fibrinolysis (AICF) and/or disseminated intravascular coagulation (DIC) have been reported. Our objective was to evaluate the role of Prothrombinex®-VF in reversal of coagulopathy and the incidence AICF/DIC, thromboembolic events and mortality.MethodsThis was a retrospective, multi-centre study of Prothrombinex®-VF use in CLD across 11 hospitals over a 2-year period, excluding those on therapeutic anticoagulation. Patients were subclassified into acute on chronic liver failure (ACLF), acute decompensation (ADC) and compensated cirrhosis. Reversal of coagulopathy was defined as international normalised ratio (INR) <1.5× upper limit normal (ULN), prothrombin time <1.5× ULN, activated partial thromboplastin time <1.5× ULN and fibrinogen >1 g/L. Markers of AICF/DIC were recorded.ResultsThirty CLD patients were included, and the median model for end-stage liver disease score was 23.5. Acute bleeding was the most common indication for Prothrombinex®-VF (60%). All had baseline coagulopathy and the majority did not achieve reversal. Key indicators of AICF/DIC were mainly observed in those with ACLF; bleeding from mucosa or lines (53%), worsening hypofibrinogenaemia (60%), worsening thrombocytopaenia (60%). The ADC and compensated cirrhosis groups were relatively unaffected. Incidence of venous thromboembolism was 6%. Overall mortality was 43% and 70% in ACLF.ConclusionProthrombinex®-VF did not lead to meaningful reversal of coagulopathy and should be used with caution in CLD. Patients with ACLF were more likely to develop AICF/DIC following Prothrombinex®-VF, although the association is uncertain. Further studies are needed to evaluate the safety and efficacy of Prothrombinex®-VF use in CLD.

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Fibrin(ogen) in human disease: both friend and foe.

Publications

Fibrin(ogen) in human disease: both friend and foe.

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