Advanced

Pro- and anticoagulant properties of factor V in pathogenesis of thrombosis and bleeding disorders

Dahlbäck, Björn LU (2016) In International Journal of Laboratory Hematology 38. p.4-11
Abstract

Factor V (FV) serves an important role in the regulation of blood coagulation, having both pro- and anticoagulant properties. The circulating high molecular weight single-chain FV molecule undergoes a series of proteolytic cleavages during both activation of coagulation and during anticoagulant regulation of coagulation by activated protein C (APC). It is noteworthy that mutations in the factor V gene (F5) either cause thrombosis or bleeding. New insights into the importance and complexity of FV functions have been generated from elucidation of the pathogenic mechanisms of two familial mutations in the F5 gene. The first mutation was identified as a result of the discovery of APC resistance as the most common risk factor for venous... (More)

Factor V (FV) serves an important role in the regulation of blood coagulation, having both pro- and anticoagulant properties. The circulating high molecular weight single-chain FV molecule undergoes a series of proteolytic cleavages during both activation of coagulation and during anticoagulant regulation of coagulation by activated protein C (APC). It is noteworthy that mutations in the factor V gene (F5) either cause thrombosis or bleeding. New insights into the importance and complexity of FV functions have been generated from elucidation of the pathogenic mechanisms of two familial mutations in the F5 gene. The first mutation was identified as a result of the discovery of APC resistance as the most common risk factor for venous thrombosis. The mutation (FV Leiden) predicts the Arg506Gln replacement, which impairs the normal regulation of FVa by APC, as the Arg506 site is an important APC cleavage site. In addition, elucidation of APC resistance resulted in the discovery of the anticoagulant APC cofactor activity of FV. The second FV mutation (FVA2440G), identified in a family with an autosomal dominant bleeding disorder, has led to the discovery of an alternative splicing generating a previously unidentified FV isoform (FV-Short), which inhibits coagulation via an unexpected and intriguing mechanism involving the coagulation inhibitor TFPI-α. These are naturally occurring mutations in the F5 gene that have generated new knowledge on the role of FV in regulation of coagulation and the importance of genetic risk factors for thrombosis and bleeding.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
in press
subject
keywords
APC resistance, Bleeding disease, Coagulation, FV Leiden, Protein C, Protein S, TFPI, Venous thrombosis
in
International Journal of Laboratory Hematology
volume
38
pages
4 - 11
publisher
Wiley-Blackwell
external identifiers
  • Scopus:84968615996
ISSN
1751-5521
DOI
10.1111/ijlh.12508
language
English
LU publication?
yes
id
a313cfa9-d6db-4442-891b-785fb3aec05f
date added to LUP
2016-06-01 10:47:12
date last changed
2016-08-02 14:19:22
@misc{a313cfa9-d6db-4442-891b-785fb3aec05f,
  abstract     = {<p>Factor V (FV) serves an important role in the regulation of blood coagulation, having both pro- and anticoagulant properties. The circulating high molecular weight single-chain FV molecule undergoes a series of proteolytic cleavages during both activation of coagulation and during anticoagulant regulation of coagulation by activated protein C (APC). It is noteworthy that mutations in the factor V gene (F5) either cause thrombosis or bleeding. New insights into the importance and complexity of FV functions have been generated from elucidation of the pathogenic mechanisms of two familial mutations in the F5 gene. The first mutation was identified as a result of the discovery of APC resistance as the most common risk factor for venous thrombosis. The mutation (FV Leiden) predicts the Arg<sup>506</sup>Gln replacement, which impairs the normal regulation of FVa by APC, as the Arg506 site is an important APC cleavage site. In addition, elucidation of APC resistance resulted in the discovery of the anticoagulant APC cofactor activity of FV. The second FV mutation (FV<sup>A2440G</sup>), identified in a family with an autosomal dominant bleeding disorder, has led to the discovery of an alternative splicing generating a previously unidentified FV isoform (FV-Short), which inhibits coagulation via an unexpected and intriguing mechanism involving the coagulation inhibitor TFPI-α. These are naturally occurring mutations in the F5 gene that have generated new knowledge on the role of FV in regulation of coagulation and the importance of genetic risk factors for thrombosis and bleeding.</p>},
  author       = {Dahlbäck, Björn},
  issn         = {1751-5521},
  keyword      = {APC resistance,Bleeding disease,Coagulation,FV Leiden,Protein C,Protein S,TFPI,Venous thrombosis},
  language     = {eng},
  pages        = {4--11},
  publisher    = {ARRAY(0x9f35710)},
  series       = {International Journal of Laboratory Hematology},
  title        = {Pro- and anticoagulant properties of factor V in pathogenesis of thrombosis and bleeding disorders},
  url          = {http://dx.doi.org/10.1111/ijlh.12508},
  volume       = {38},
  year         = {2016},
}