Advanced

Resistance to activated protein C, the FV:Q506 allele, and venous thrombosis

Dahlbäck, Björn LU ; Hillarp, A. LU ; Rosen, S. and Zöller, Bengt LU (1996) In Annals of Hematology 72(4). p.166-176
Abstract

Vitamin K-dependent protein C is an important regulator of blood coagulation. After its activation on the endothelial cell surface by thrombin bound to thrombomodulin, it cleaves and inactivates procoagulant cofactors Va and VIIIa, protein S and intact factor V working as cofactors. Until recently, genetic defects of protein C or protein S were, together with antithrombin III deficiency, the established major causes of familial venous thromboembolism, but they were found in fewer than 5-10% of patients with thrombosis. In 1993, inherited resistance to activated protein C (APC) was described as a major risk factor for venous thrombosis. It is found in up to 60% of patients with venous thrombosis. In more than 90% of cases, the molecular... (More)

Vitamin K-dependent protein C is an important regulator of blood coagulation. After its activation on the endothelial cell surface by thrombin bound to thrombomodulin, it cleaves and inactivates procoagulant cofactors Va and VIIIa, protein S and intact factor V working as cofactors. Until recently, genetic defects of protein C or protein S were, together with antithrombin III deficiency, the established major causes of familial venous thromboembolism, but they were found in fewer than 5-10% of patients with thrombosis. In 1993, inherited resistance to activated protein C (APC) was described as a major risk factor for venous thrombosis. It is found in up to 60% of patients with venous thrombosis. In more than 90% of cases, the molecular background for the APC resistance is a single point mutation in the factor V gene, which predicts substitution of an arginine (R) at position 506 by a glutamine (Q). Mutated factor V (FV:Q506) is activated by thrombin or factor Xa in normal way, but impaired inactivation of mutated factor Va by APC results in life-long hypercoagulability. The prevalence of the FV:Q506 allele in the general population of Western countries varies between 2 and 15%, whereas it is not found in several other populations with different ethnic backgrounds. Owing to the high prevalence of FV:Q506 in Western populations, it occasionally occurs in patients with deficiency of protein S, protein C, or antithrombin III. Individuals with combined defects suffer more severely from thrombosis, and often at a younger age, than those with single defects, suggesting severe thrombophilia to be a multigenetic disease.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
APC-resistance, Factor V, Protein C, Protein S, Thrombosis, activated protein C, antithrombin III, blood clotting factor 5, protein C, protein S, amino acid substitution, antithrombin deficiency, blood clotting, clinical feature, gene frequency, human, multifactorial inheritance, point mutation, priority journal, review, risk factor, thrombophilia, vein thrombosis
in
Annals of Hematology
volume
72
issue
4
pages
11 pages
publisher
Springer Verlag
external identifiers
  • scopus:0029864822
ISSN
0939-5555
DOI
10.1007/s002770050157
language
English
LU publication?
yes
id
ac4b48e3-11b5-4145-b54e-483cef4fdae4
date added to LUP
2017-10-19 16:27:58
date last changed
2017-11-07 14:35:06
@article{ac4b48e3-11b5-4145-b54e-483cef4fdae4,
  abstract     = {<p>Vitamin K-dependent protein C is an important regulator of blood coagulation. After its activation on the endothelial cell surface by thrombin bound to thrombomodulin, it cleaves and inactivates procoagulant cofactors Va and VIIIa, protein S and intact factor V working as cofactors. Until recently, genetic defects of protein C or protein S were, together with antithrombin III deficiency, the established major causes of familial venous thromboembolism, but they were found in fewer than 5-10% of patients with thrombosis. In 1993, inherited resistance to activated protein C (APC) was described as a major risk factor for venous thrombosis. It is found in up to 60% of patients with venous thrombosis. In more than 90% of cases, the molecular background for the APC resistance is a single point mutation in the factor V gene, which predicts substitution of an arginine (R) at position 506 by a glutamine (Q). Mutated factor V (FV:Q506) is activated by thrombin or factor Xa in normal way, but impaired inactivation of mutated factor Va by APC results in life-long hypercoagulability. The prevalence of the FV:Q506 allele in the general population of Western countries varies between 2 and 15%, whereas it is not found in several other populations with different ethnic backgrounds. Owing to the high prevalence of FV:Q506 in Western populations, it occasionally occurs in patients with deficiency of protein S, protein C, or antithrombin III. Individuals with combined defects suffer more severely from thrombosis, and often at a younger age, than those with single defects, suggesting severe thrombophilia to be a multigenetic disease.</p>},
  author       = {Dahlbäck, Björn and Hillarp, A. and Rosen, S. and Zöller, Bengt},
  issn         = {0939-5555},
  keyword      = {APC-resistance,Factor V,Protein C,Protein S,Thrombosis,activated protein C,antithrombin III,blood clotting factor 5,protein C,protein S,amino acid substitution,antithrombin deficiency,blood clotting,clinical feature,gene frequency,human,multifactorial inheritance,point mutation,priority journal,review,risk factor,thrombophilia,vein thrombosis},
  language     = {eng},
  number       = {4},
  pages        = {166--176},
  publisher    = {Springer Verlag},
  series       = {Annals of Hematology},
  title        = {Resistance to activated protein C, the FV:Q506 allele, and venous thrombosis},
  url          = {http://dx.doi.org/10.1007/s002770050157},
  volume       = {72},
  year         = {1996},
}