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Resistance to activated protein C as an additional genetic risk factor in hereditary deficiency of protein S

Zöller, Bengt LU orcid ; Berntsdotter, Ann LU ; Garcia de Frutos, Pablo LU and Dahlbäck, Björn LU (1995) In Blood 85(12). p.3518-3523
Abstract

Inherited resistance to activated protein C (APC), which is caused by a single point mutation in the gene for factor V, is a common risk factor for thrombosis. In this study, the prevalence of APC resistance in 18 unrelated thrombosis-prone families with inherited protein S deficiency was investigated to determine its role as additional genetic risk factor for thrombosis. In addition, a detailed evaluation of the clinical manifestations in these families was performed. Venous thrombotic events had occurred in 47% of the protein S-deficient patients (64/136) and in 7% of relatives without protein S deficiency (14/191). As estimated from Kaplan-Meier analysis, 50% of protein S-deficient family members and 12% of those without protein S... (More)

Inherited resistance to activated protein C (APC), which is caused by a single point mutation in the gene for factor V, is a common risk factor for thrombosis. In this study, the prevalence of APC resistance in 18 unrelated thrombosis-prone families with inherited protein S deficiency was investigated to determine its role as additional genetic risk factor for thrombosis. In addition, a detailed evaluation of the clinical manifestations in these families was performed. Venous thrombotic events had occurred in 47% of the protein S-deficient patients (64/136) and in 7% of relatives without protein S deficiency (14/191). As estimated from Kaplan-Meier analysis, 50% of protein S-deficient family members and 12% of those without protein S deficiency had had manifestation of venous thromboembolism at the age of 45 years. The age at the first thrombotic event ranged from 10 to 81 years (mean, 32.5 years) and a large intrafamilial and interfamilial variability in expression of thrombotic symptoms was seen. The factor V gene mutation related to APC resistance was present in 6 (38%) of 16 probands available for testing; in total, the mutation was found in 7 (39%) of the 18 families. In family members with combined defects, 72% (13/18) had had thrombosis as compared with 19% (4/21) of those with only protein S deficiency and 19% (4/21) of those with only the factor V mutation. In conclusion, APC resistance was found to be highly prevalent in thrombosis-prone families with protein S deficiency and was an additional genetic risk factor for thrombosis in these families. The results suggest thrombosis-prone families with protein S deficiency often to be affected by yet another genetic defect.

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Contribution to journal
publication status
published
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keywords
Adolescent, Adult, Aged, Aged, 80 and over, Child, Family, Female, Humans, Male, Middle Aged, Point Mutation, Prevalence, Protein C, Protein S Deficiency, Risk Factors, Thrombosis, Journal Article, Research Support, Non-U.S. Gov't
in
Blood
volume
85
issue
12
pages
6 pages
publisher
American Society of Hematology
external identifiers
  • pmid:7780138
  • scopus:0029016883
ISSN
0006-4971
language
English
LU publication?
yes
id
4c08b285-26f9-403d-9693-4d4285d7bf14
date added to LUP
2017-11-02 11:05:55
date last changed
2024-01-29 06:05:27
@article{4c08b285-26f9-403d-9693-4d4285d7bf14,
  abstract     = {{<p>Inherited resistance to activated protein C (APC), which is caused by a single point mutation in the gene for factor V, is a common risk factor for thrombosis. In this study, the prevalence of APC resistance in 18 unrelated thrombosis-prone families with inherited protein S deficiency was investigated to determine its role as additional genetic risk factor for thrombosis. In addition, a detailed evaluation of the clinical manifestations in these families was performed. Venous thrombotic events had occurred in 47% of the protein S-deficient patients (64/136) and in 7% of relatives without protein S deficiency (14/191). As estimated from Kaplan-Meier analysis, 50% of protein S-deficient family members and 12% of those without protein S deficiency had had manifestation of venous thromboembolism at the age of 45 years. The age at the first thrombotic event ranged from 10 to 81 years (mean, 32.5 years) and a large intrafamilial and interfamilial variability in expression of thrombotic symptoms was seen. The factor V gene mutation related to APC resistance was present in 6 (38%) of 16 probands available for testing; in total, the mutation was found in 7 (39%) of the 18 families. In family members with combined defects, 72% (13/18) had had thrombosis as compared with 19% (4/21) of those with only protein S deficiency and 19% (4/21) of those with only the factor V mutation. In conclusion, APC resistance was found to be highly prevalent in thrombosis-prone families with protein S deficiency and was an additional genetic risk factor for thrombosis in these families. The results suggest thrombosis-prone families with protein S deficiency often to be affected by yet another genetic defect.</p>}},
  author       = {{Zöller, Bengt and Berntsdotter, Ann and Garcia de Frutos, Pablo and Dahlbäck, Björn}},
  issn         = {{0006-4971}},
  keywords     = {{Adolescent; Adult; Aged; Aged, 80 and over; Child; Family; Female; Humans; Male; Middle Aged; Point Mutation; Prevalence; Protein C; Protein S Deficiency; Risk Factors; Thrombosis; Journal Article; Research Support, Non-U.S. Gov't}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{12}},
  pages        = {{3518--3523}},
  publisher    = {{American Society of Hematology}},
  series       = {{Blood}},
  title        = {{Resistance to activated protein C as an additional genetic risk factor in hereditary deficiency of protein S}},
  volume       = {{85}},
  year         = {{1995}},
}