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Elevated levels of prothrombin activation fragment 1 + 2 in plasma from patients with heterozygous Arg506 to Gln mutation in the factor V gene (APC-resistance) and/or inherited protein S deficiency

Zöller, Bengt LU ; Holm, Johan LU ; Svensson, Peter LU and Dahlbäck, B LU (1996) In Thrombosis and Haemostasis 75(2). p.270-274
Abstract

Inherited resistance to activated protein C (APC-resistance), caused by a point mutation in the factor V gene leading to replacement of Arg(R)506 with a Gln (Q), and inherited protein S deficiency are associated with functional impairment of the protein C anticoagulant system, yielding lifelong hypercoagulability and increased risk of thrombosis. APC-resistance is often an additional genetic risk factor in thrombosis-prone protein S deficient families. The plasma concentration of prothrombin fragment 1 + 2 (F1 + 2), which is a marker of hypercoagulable states, was measured in 205 members of 34 thrombosis-prone families harbouring the Arg506 to Gln mutation (APC-resistance) and/or inherited protein S deficiency. The plasma concentration... (More)

Inherited resistance to activated protein C (APC-resistance), caused by a point mutation in the factor V gene leading to replacement of Arg(R)506 with a Gln (Q), and inherited protein S deficiency are associated with functional impairment of the protein C anticoagulant system, yielding lifelong hypercoagulability and increased risk of thrombosis. APC-resistance is often an additional genetic risk factor in thrombosis-prone protein S deficient families. The plasma concentration of prothrombin fragment 1 + 2 (F1 + 2), which is a marker of hypercoagulable states, was measured in 205 members of 34 thrombosis-prone families harbouring the Arg506 to Gln mutation (APC-resistance) and/or inherited protein S deficiency. The plasma concentration of F1 + 2 was significantly higher both in 38 individuals carrying the FV:Q506 mutation in heterozygous state (1.7 +/- 0.7 nM; mean +/- SD) and in 48 protein S deficient cases (1.9 +/- 0.9 nm), than in 100 unaffected relatives (1.3 +/- 0.5 nM). Warfarin therapy decreased the F1 + 2 levels, even in those four patients who had combined defects (0.5 +/- 0.3 nM). Our results agree with the hypothesis that individuals with APC-resistance or protein S deficiency have an imbalance between pro- and anti-coagulant forces leading to increased thrombin generation and a hypercoagulable state.

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keywords
Adolescent, Adult, Aged, Aged, 80 and over, Biomarkers, Child, Disease Susceptibility, Factor V, Factor V Deficiency, Female, Humans, Male, Middle Aged, Peptide Fragments, Point Mutation, Protein S Deficiency, Prothrombin, Thromboembolism, Warfarin, Journal Article, Research Support, Non-U.S. Gov't
in
Thrombosis and Haemostasis
volume
75
issue
2
pages
5 pages
publisher
F K Schattauer Verlag Gmbh
external identifiers
  • scopus:0029878085
ISSN
0340-6245
language
English
LU publication?
yes
id
454ba16d-3c2c-4ab3-bcd3-7dcd50753c9d
date added to LUP
2017-10-19 15:29:55
date last changed
2017-11-08 08:07:40
@article{454ba16d-3c2c-4ab3-bcd3-7dcd50753c9d,
  abstract     = {<p>Inherited resistance to activated protein C (APC-resistance), caused by a point mutation in the factor V gene leading to replacement of Arg(R)506 with a Gln (Q), and inherited protein S deficiency are associated with functional impairment of the protein C anticoagulant system, yielding lifelong hypercoagulability and increased risk of thrombosis. APC-resistance is often an additional genetic risk factor in thrombosis-prone protein S deficient families. The plasma concentration of prothrombin fragment 1 + 2 (F1 + 2), which is a marker of hypercoagulable states, was measured in 205 members of 34 thrombosis-prone families harbouring the Arg506 to Gln mutation (APC-resistance) and/or inherited protein S deficiency. The plasma concentration of F1 + 2 was significantly higher both in 38 individuals carrying the FV:Q506 mutation in heterozygous state (1.7 +/- 0.7 nM; mean +/- SD) and in 48 protein S deficient cases (1.9 +/- 0.9 nm), than in 100 unaffected relatives (1.3 +/- 0.5 nM). Warfarin therapy decreased the F1 + 2 levels, even in those four patients who had combined defects (0.5 +/- 0.3 nM). Our results agree with the hypothesis that individuals with APC-resistance or protein S deficiency have an imbalance between pro- and anti-coagulant forces leading to increased thrombin generation and a hypercoagulable state.</p>},
  author       = {Zöller, Bengt and Holm, Johan and Svensson, Peter and Dahlbäck, B},
  issn         = {0340-6245},
  keyword      = {Adolescent,Adult,Aged,Aged, 80 and over,Biomarkers,Child,Disease Susceptibility,Factor V,Factor V Deficiency,Female,Humans,Male,Middle Aged,Peptide Fragments,Point Mutation,Protein S Deficiency,Prothrombin,Thromboembolism,Warfarin,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {2},
  pages        = {270--274},
  publisher    = {F K Schattauer Verlag Gmbh},
  series       = {Thrombosis and Haemostasis},
  title        = {Elevated levels of prothrombin activation fragment 1 + 2 in plasma from patients with heterozygous Arg506 to Gln mutation in the factor V gene (APC-resistance) and/or inherited protein S deficiency},
  volume       = {75},
  year         = {1996},
}