Human Fibrinogen: Molecular and Genetic Aspects of Congenital Disorders

Tiscia, Giovanni Luca; Margaglione, Maurizio

doi:10.3390/ijms19061597

Cited by 55 publications

(47 citation statements)

References 82 publications

(81 reference statements)

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“…) and forms part of the acute phase response as part of the coagulation cascade (Tiscia and Margaglione, 2018). In camelids, fibrinogen is a biomarker for stress and infection (Greunz et al, 2018;El-Bahr and El-Deeb, 2016;El-Deeb and Buczinski, 2015).…”

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confidence: 99%

Deiminated proteins in extracellular vesicles and serum of llama (Lama glama)—Novel insights into camelid immunity

Criscitiello

Kraev

Lange

2020

Molecular Immunology

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A B S T R A C TPeptidylarginine deiminases (PADs) are phylogenetically conserved calcium-dependent enzymes which posttranslationally convert arginine into citrulline in target proteins in an irreversible manner, causing functional and structural changes in target proteins. Protein deimination causes generation of neo-epitopes, affects gene regulation and also allows for protein moonlighting. Furthermore, PADs have been found to be a phylogenetically conserved regulator for extracellular vesicle (EVs) release. EVs are found in most body fluids and participate in cellular communication via transfer of cargo proteins and genetic material. In this study, post-translationally deiminated proteins in serum and serum-EVs are described for the first time in camelids, using the llama (Lama glama L. 1758) as a model animal. We report a poly-dispersed population of llama serum EVs, positive for phylogenetically conserved EV-specific markers and characterised by TEM. In serum, 103 deiminated proteins were overall identified, including key immune and metabolic mediators including complement components, immunoglobulin-based nanobodies, adiponectin and heat shock proteins. In serum, 60 deiminated proteins were identified that were not in EVs, and 25 deiminated proteins were found to be unique to EVs, with 43 shared deiminated protein hits between both serum and EVs. Deiminated histone H3, a marker of neutrophil extracellular trap formation, was also detected in llama serum. PAD homologues were identified in llama serum by Western blotting, via cross reaction with human PAD antibodies, and detected at an expected 70 kDa size. This is the first report of deiminated proteins in serum and EVs of a camelid species, highlighting a hitherto unrecognized post-translational modification in key immune and metabolic proteins in camelids, which may be translatable to and inform a range of human metabolic and inflammatory pathologies.

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confidence: 99%

Deiminated proteins in extracellular vesicles and serum of llama (Lama glama)—Novel insights into camelid immunity

Criscitiello

Kraev

Lange

2020

Molecular Immunology

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“…Fibrinogen has a functional role as the fibrin polymer precursor for the enzymatic process of coagulation [1]. The severity of coagulation disorders frequently depends on the circulating fibrinogen levels.…”

Section: Introductionmentioning

confidence: 99%

“…This is a glycoprotein with a molecular weight of 340 KDa, which is synthesized in the liver and has plasma concentrations between 1.5 and 3.5 g/L. In some cases, such as in pregnancy, baseline levels may be higher [1].…”

Section: Introductionmentioning

confidence: 99%

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Observational Safety Study of Clottafact® Fibrinogen Concentrate: Real-World Data in Mexico

et al. 2020

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Background and Objective The use of fibrinogen concentrate to treat or prevent major bleeding with regard to potential adverse reactions has not been free of controversy. Our objective was to perform a post-authorization safety study to describe the use of Clottafact ® (LFB Biomedicaments) fibrinogen concentrate in real-life medical practice in Mexico. Methods This was a prospective, observational study that collected and evaluated information between January 2017 and June 2019 related to suspected serious adverse reactions (SUSARs) during and after Clottafact ® infusion. Results Information from 40 subjects was analyzed; 43% were women (n = 17), mean age was 39.05 ± 26.8 years (range 0-91 years). The medical specialties included in this analysis were cardiac surgery − 52.5% of the cases, gynecology/obstetrics − 17.5%, general surgery and orthopedics − 12.5% each, and hematology and neurosurgery − 2.5%, respectively. Mean plasma fibrinogen levels before and after Clottafact ® infusion were 2.58 g/L and 4.02 g/L; p = 0.001, respectively. The mean Clottafact ® dose was 2.20 ± 0.77 g. One patient presented SUSARs (dry mouth and dysgeusia) with drug administration, which ceased after treatment discontinuation. Conclusions In this real-life post-marketing study, the safety profile of Clottafact ® was very similar to previous reports. Thus, Clottafact ® shows a favorable safety profile in clinical practice. Key Points Clottafact ® showed a favorable safety profile in clinical practice in Mexico. Clottafact® human fibrinogen concentrate usage profile is considered safe in real-world conditions for the treatment of acquired or congenital fibrinogen deficiency.

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“…Peptide aus dem Fibrinogenmolekül ab, das Fibrinopeptid A von der α-Kette und das Fibrinopeptid B von der β-Kette[1]. Die gebildeten Fibrinmonomere polymerisieren spontan zu einem unlöslichen Gel.…”

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Schwangerschaftsbegleitende Behandlung bei hereditärer Dysfibrinogenämie nach wiederkehrendem Schwangerschaftsverlust

Zimmermann

Peisl

Geisen

et al. 2019

Transfusionsmedizin

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ZusammenfassungEine Dysfibrinogenämie kann zu Blutungen oder Thrombosen sowie zu Geburtskomplikationen führen. Letztere beinhalten frühzeitige Schwangerschaftsverluste, Blutungen, vorzeitige Plazentaablösung und Thrombosen. Es gibt nur wenige Fallberichte mit Behandlungsempfehlungen für Schwangerschaften bei betroffenen Frauen. Wir berichten über eine inzwischen 34-jährige Frau, bei der es zwischen 2013 und 2015 zu 4 aufeinanderfolgenden Frühaborten kam. Bei der Vorstellung in unserer Ambulanz berichtete die Patientin von einer Neigung zu Blutergüssen, aber keine weiteren Blutungen und keine thromboembolischen Ereignisse. Laboruntersuchungen ergaben einen verminderten Quick-Wert, eine verlängerte Thrombinzeit, eine stark verlängerte Reptilasezeit und Fibrinogenkonzentrationen von 67 mg/dl (Clauss-Methode) und 387 mg/dl (Immunturbidimetrie). Bei der Patientin wurde eine Dysfibrinogenämie diagnostiziert. Die molekularbiologische Untersuchung ergab die Mutation c.103C>T (p.Arg35Cys) im Exon 2 des FGA-Gens (Synonym Aα 16Arg→Cys-Substitution). Während der 5. und 6. Schwangerschaft wurde die Patientin mit einem niedermolekularen Heparin unter Verwendung der empfohlenen Prophylaxedosis für erhöhtes Thromboserisiko behandelt. Gleichzeitig erhielt die Patientin 3 × wöchentlich Fibrinogenkonzentrat (3 × 2 g pro Woche). Darunter verliefen beide Schwangerschaften ereignislos. Schwangerschaftskomplikationen wurden in vielen Fällen berichtet, wenn der funktionell aktive Fibrinogenspiegel unter 0,6 g/l lag (Clauss-Methode). Nach der erstmaligen Feststellung einer Dysfibrinogenämie bei einer Frau ohne offensichtliche Blutungsneigung und ohne thromboembolische Ereignisse in der Anamnese erscheint aus unserer Sicht die empfehlenswerte Vorgehensweise, Fibrinogen zu substituieren und gleichzeitig niedermolekulare Heparine zu geben, um sowohl Blutungen als auch Thrombosen und Schwangerschaftsverluste zu verhindern.

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Human Fibrinogen: Molecular and Genetic Aspects of Congenital Disorders

Cited by 55 publications

References 82 publications

Deiminated proteins in extracellular vesicles and serum of llama (Lama glama)—Novel insights into camelid immunity

Deiminated proteins in extracellular vesicles and serum of llama (Lama glama)—Novel insights into camelid immunity

Observational Safety Study of Clottafact® Fibrinogen Concentrate: Real-World Data in Mexico

Schwangerschaftsbegleitende Behandlung bei hereditärer Dysfibrinogenämie nach wiederkehrendem Schwangerschaftsverlust

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