Congenital and acquired activated protein C resistance.
(2003) In Seminars in Vascular Medicine 3(1). p.33-46- Abstract
- Resistance to the anticoagulant action of activated protein C, APC resistance, is a highly prevalent risk factor for venous thrombosis among individuals of Caucasian origin. In most cases, APC resistance is associated with a single missense mutation in the gene for coagulation factor V (FVLeiden), which predicts the replacement of Arg506 with a Gln at one of the cleavage sites for APC in factor V. Factor V is a Janus-faced protein with dual functions, serving as an essential nonenzymatic cofactor in both pro- and anticoagulant pathways. Procoagulant factor Va, generated after proteolysis by thrombin or factor Xa, is a cofactor to factor Xa in the activation of prothrombin, whereas anticoagulant factor V, generated after proteolysis by APC,... (More)
- Resistance to the anticoagulant action of activated protein C, APC resistance, is a highly prevalent risk factor for venous thrombosis among individuals of Caucasian origin. In most cases, APC resistance is associated with a single missense mutation in the gene for coagulation factor V (FVLeiden), which predicts the replacement of Arg506 with a Gln at one of the cleavage sites for APC in factor V. Factor V is a Janus-faced protein with dual functions, serving as an essential nonenzymatic cofactor in both pro- and anticoagulant pathways. Procoagulant factor Va, generated after proteolysis by thrombin or factor Xa, is a cofactor to factor Xa in the activation of prothrombin, whereas anticoagulant factor V, generated after proteolysis by APC, functions as a cofactor in the APC-mediated degradation of FVIIIa. The FVLeiden mutation affects the anticoagulant response to APC at two distinct levels of the coagulation pathway, as it impairs degradation of both activated factor V and activated factor VIII, the latter effect inasmuch as FVLeiden is a poor APC cofactor. Several other genetic traits, some of them quite common, are known to affect the anticoagulant response to APC, but none of them cause the same severe APC-resistance phenotype as FVLeiden and their importance as risk factors for thrombosis is unclear. A poor APC response may also result from acquired conditions, some of which are clearly involved in the pathogenesis of venous thrombosis. Venous thrombosis is a typical multifactorial disease, the pathogenesis of which involves multiple gene-gene and gene-environment interactions. In many patients with severe thrombophilia, APC resistance is found as a contributing risk factor. (Less)
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https://lup.lub.lu.se/record/124124
- author
- Nicolaes, Gerry A F and Dahlbäck, Björn LU
- organization
- publishing date
- 2003
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Seminars in Vascular Medicine
- volume
- 3
- issue
- 1
- pages
- 33 - 46
- publisher
- Georg Thieme Verlag
- external identifiers
-
- scopus:0042383418
- ISSN
- 1528-9648
- DOI
- 10.1055/s-2003-38331
- language
- English
- LU publication?
- yes
- id
- f2502c6b-4457-4169-b859-853578484276 (old id 124124)
- date added to LUP
- 2016-04-01 11:46:09
- date last changed
- 2022-05-14 03:38:46
@article{f2502c6b-4457-4169-b859-853578484276,
abstract = {{Resistance to the anticoagulant action of activated protein C, APC resistance, is a highly prevalent risk factor for venous thrombosis among individuals of Caucasian origin. In most cases, APC resistance is associated with a single missense mutation in the gene for coagulation factor V (FVLeiden), which predicts the replacement of Arg506 with a Gln at one of the cleavage sites for APC in factor V. Factor V is a Janus-faced protein with dual functions, serving as an essential nonenzymatic cofactor in both pro- and anticoagulant pathways. Procoagulant factor Va, generated after proteolysis by thrombin or factor Xa, is a cofactor to factor Xa in the activation of prothrombin, whereas anticoagulant factor V, generated after proteolysis by APC, functions as a cofactor in the APC-mediated degradation of FVIIIa. The FVLeiden mutation affects the anticoagulant response to APC at two distinct levels of the coagulation pathway, as it impairs degradation of both activated factor V and activated factor VIII, the latter effect inasmuch as FVLeiden is a poor APC cofactor. Several other genetic traits, some of them quite common, are known to affect the anticoagulant response to APC, but none of them cause the same severe APC-resistance phenotype as FVLeiden and their importance as risk factors for thrombosis is unclear. A poor APC response may also result from acquired conditions, some of which are clearly involved in the pathogenesis of venous thrombosis. Venous thrombosis is a typical multifactorial disease, the pathogenesis of which involves multiple gene-gene and gene-environment interactions. In many patients with severe thrombophilia, APC resistance is found as a contributing risk factor.}},
author = {{Nicolaes, Gerry A F and Dahlbäck, Björn}},
issn = {{1528-9648}},
language = {{eng}},
number = {{1}},
pages = {{33--46}},
publisher = {{Georg Thieme Verlag}},
series = {{Seminars in Vascular Medicine}},
title = {{Congenital and acquired activated protein C resistance.}},
url = {{http://dx.doi.org/10.1055/s-2003-38331}},
doi = {{10.1055/s-2003-38331}},
volume = {{3}},
year = {{2003}},
}