Document Detail

Mechanisms of fibrin polymerization and clinical implications.
MedLine Citation:
PMID:  23305734     Owner:  NLM     Status:  MEDLINE    
Research on all stages of fibrin polymerization, using a variety of approaches including naturally occurring and recombinant variants of fibrinogen, x-ray crystallography, electron and light microscopy, and other biophysical approaches, has revealed aspects of the molecular mechanisms involved. The ordered sequence of fibrinopeptide release is essential for the knob-hole interactions that initiate oligomer formation and the subsequent formation of 2-stranded protofibrils. Calcium ions bound both strongly and weakly to fibrin(ogen) have been localized, and some aspects of their roles are beginning to be discovered. Much less is known about the mechanisms of the lateral aggregation of protofibrils and the subsequent branching to yield a 3-dimensional network, although the αC region and B:b knob-hole binding seem to enhance lateral aggregation. Much information now exists about variations in clot structure and properties because of genetic and acquired molecular variants, environmental factors, effects of various intravascular and extravascular cells, hydrodynamic flow, and some functional consequences. The mechanical and chemical stability of clots and thrombi are affected by both the structure of the fibrin network and cross-linking by plasma transglutaminase. There are important clinical consequences to all of these new findings that are relevant for the pathogenesis of diseases, prophylaxis, diagnosis, and treatment.
John W Weisel; Rustem I Litvinov
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2013-01-10
Journal Detail:
Title:  Blood     Volume:  121     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-08     Completed Date:  2013-05-07     Revised Date:  2014-03-09    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1712-9     Citation Subset:  AIM; IM    
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MeSH Terms
Biopolymers / chemistry*,  metabolism
Blood Coagulation Disorders / diagnosis*,  therapy*
Fibrin / chemistry*,  metabolism
Grant Support
Reg. No./Substance:
0/Biopolymers; 9001-31-4/Fibrin

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