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

Zöller, Bengt LU ; 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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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
  • scopus:0029016883
ISSN
0006-4971
language
English
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yes
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4c08b285-26f9-403d-9693-4d4285d7bf14
date added to LUP
2017-11-02 11:05:55
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2017-11-09 14:22:30
@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},
  keyword      = {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},
}