Fibrin Clot Structure and Function

Undas, Anetta; Ariëns, Robert A. S.

doi:10.1161/atvbaha.111.230631

Cited by 437 publications

(223 citation statements)

References 142 publications

Supporting

Mentioning

216

Contrasting

Order By: Relevance

“…Henschen estimated that there could be up to 1 million different forms of fibrinogen in the blood circulation [1]. While many of the minor alterations and polymorphisms are neutral and do not influence the structure and function of fibrinogen or its multimeric form fibrin, some of the larger alterations such as splice variation and particular single nucleotide polymorphisms such as AThr312Ala and BArg448Lys have been shown to influence structure and function of the fibrin clot [2].…”

Section: Fibrinogen Structurementioning

confidence: 99%

Fibrinogen splice variation and cross-linking: Effects on fibrin structure/function and role of fibrinogen γ′ as thrombomobulin II

Duval

Ariëns

2017

Matrix Biology

Self Cite

View full text Add to dashboard Cite

ReuseUnless indicated otherwise, fulltext items are protected by copyright with all rights reserved. The copyright exception in section 29 of the Copyright, Designs and Patents Act 1988 allows the making of a single copy solely for the purpose of non-commercial research or private study within the limits of fair dealing. The publisher or other rights-holder may allow further reproduction and re-use of this version -refer to the White Rose Research Online record for this item. Where records identify the publisher as the copyright holder, users can verify any specific terms of use on the publisher's website. TakedownIf you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ÔØ Å ÒÙ× Ö ÔØ A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT AbstractFibrin is an important matrix protein that provides the backbone to the blood clot, promoting tissue repair and wound healing. Its precursor fibrinogen is one of the most heterogenous proteins, with an estimated 1 million different forms due to alterations in glycosylation, oxidation, single nucleotide polymorphisms, splice variation and other variations. Furthermore, ligation by transglutamimase factor XIII (cross-linking) adds to the complexity of the fibrin network. The structure and function of the fibrin network is in part determined by this natural variation in the fibrinogen molecule, with major effects from slice variation and cross-linking. This mini-review will discuss the direct effects of fibrinogen EC and fibrinogen ' splice variation on clot structure and function and also discuss the additional role of fibrinogen ' as thrombomodulin II. Furthermore, the effects of crosslinking on clot function will be described. Splice variation and cross-linking are major determinants of the structure and function of fibrin and may therefore impact on diseases affecting bleeding, thrombosis and tissue repair.

show abstract

Section: Fibrinogen Structurementioning

confidence: 99%

Fibrinogen splice variation and cross-linking: Effects on fibrin structure/function and role of fibrinogen γ′ as thrombomobulin II

Duval

Ariëns

2017

Matrix Biology

Self Cite

View full text Add to dashboard Cite

show abstract

“…These molecules may interact with fibrinogen and change the mechanical properties of clots, which are essential to the effective function of fibrin. Clot properties that may vary include the pore size, fibrin diameter, rigidity, ease of fibrinolysis, and so on 208,396 (and some of these are correlated 361,397 ).…”

Section: -395mentioning

confidence: 99%

The simultaneous occurrence of both hypercoagulability and hypofibrinolysis in blood and serum during systemic inflammation, and the roles of iron and fibrin(ogen)

Kell

Pretorius

2014

Integrative Biology

127

View full text Add to dashboard Cite

Although the two phenomena are usually studied separately, we summarise a considerable body of literature to the effect that a great many diseases involve (or are accompanied by) both an increased tendency for blood to clot (hypercoagulability) and the resistance of the clots so formed (hypofibrinolysis) to the typical, 'healthy' or physiological lysis. We concentrate here on the terminal stages of fibrin formation from fibrinogen, as catalysed by thrombin. Hypercoagulability goes hand in hand with inflammation, and is strongly influenced by the fibrinogen concentration (and vice versa); this can be mediated via interleukin-6. Poorly liganded iron is a significant feature of inflammatory diseases, and hypofibrinolysis may change as a result of changes in the structure and morphology of the clot, which may be mimicked in vitro, and may be caused in vivo, by the presence of unliganded iron interacting with fibrin(ogen) during clot formation. Many of these phenomena are probably caused by electrostatic changes in the iron-fibrinogen system, though hydroxyl radical (OH ) formation can also contribute under both acute and (more especially) chronic conditions. Many substances are known to affect the nature of fibrin polymerised from fibrinogen, such that this might be seen as a kind of bellwether for human or plasma health. Overall, our analysis demonstrates the commonalities underpinning a variety of pathologies as seen in both hypercoagulability and hypofibrinolysis, and offers opportunities for both diagnostics and therapies.

show abstract

“…Moreover, MPO itself and MPO-derived reactive oxygen species have been shown to increase the expression of tissue factor, leading to a thrombotic state 91) , and influence erythrocyte deformation and aggregation, leading to membrane generation, rouleau formation and higher blood viscosity [92][93][94][95][96][97] . In addition, other cardiovascular risk factors (cigarette smoking, hyperglycemia) [98][99][100][101][102][103][104][105] and immune-inflammatory/oxidative stress-related factors (C-reactive protein, CD40 ligand, fibrinogen and D-dimer, lipoprotein (a)) 81, [106][107][108][109][110][111][112][113][114][115][116][117][118] have been reported to influence the platelet-fibrin clot structure and blood viscosity/erythrocyte aggregation. These findings are of considerable interest, since they suggest that some factors influencing blood thrombogenicity/ viscosity and erythrocyte properties (deformability and/or aggregability) may play important roles in the evolution of erythrocyte-rich large thrombi.…”

Section: )mentioning

confidence: 99%

Thrombus Aspiration Therapy and Coronary Thrombus Components in Patients with Acute ST-Elevation Myocardial Infarction

Yunoki

Naruko

Sugioka

et al. 2013

JAT

View full text Add to dashboard Cite

Inflammation and oxidative stress play key roles in atherosclerotic plaque instability, and plaque rupture/erosion and subsequent thrombus formation constitute the principal mechanisms of total vessel occlusion and acute ST-elevation myocardial infarction (STEMI). Plaque disruption triggers the formation of initial platelet aggregates that grow in association with an increase in fibrin formation, leading to persistent coronary flow obstruction and blood coagulation. The fibrin network may trap large numbers of erythrocytes and inflammatory cells to form an erythrocyte-rich thrombus. In fact, previous clinical studies have shown that not only platelet-rich white thrombi, but also erythrocyte-rich red thrombi can be visualized using angioscopy in patients with acute coronary syndrome. Recently, the development of thrombus aspiration and distal protection devices has significantly improved the clinical outcomes of percutaneous intervention in STEMI patients and has enabled the evaluation of antemortem coronary artery thrombi. This is important because previous autopsy studies were unable to differentiate coronary thrombi responsible for myocardial ischemia from postmortem clots. Using frozen samples of aspirated thrombi and specific monoclonal antibodies, we investigated the cellular components of thrombi (platelets, erythrocytes, fibrin and inflammatory cells, such as myeloperoxidase-positive cells) and pathologically evaluated the relationships between erythrocyterich thrombi and inflammation, oxidative stress and clinical outcomes in STEMI patients. Therefore, this review article focuses on the efficacy of thrombus aspiration therapy and the components of aspirated intracoronary thrombi in STEMI patients and presents the results of recent studies regarding the relationship between the composition of aspirated intracoronary thrombi and clinical outcomes.

show abstract

Fibrin Clot Structure and Function

Cited by 437 publications

References 142 publications

Fibrinogen splice variation and cross-linking: Effects on fibrin structure/function and role of fibrinogen γ′ as thrombomobulin II

Fibrinogen splice variation and cross-linking: Effects on fibrin structure/function and role of fibrinogen γ′ as thrombomobulin II

The simultaneous occurrence of both hypercoagulability and hypofibrinolysis in blood and serum during systemic inflammation, and the roles of iron and fibrin(ogen)

Thrombus Aspiration Therapy and Coronary Thrombus Components in Patients with Acute ST-Elevation Myocardial Infarction

Contact Info

Product

Resources

About