Resistance to activated protein C as an additional genetic risk factor in hereditary deficiency of protein S
(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.
(Less)
- author
- Zöller, Bengt LU ; Berntsdotter, Ann LU ; Garcia de Frutos, Pablo LU and Dahlbäck, Björn LU
- organization
- publishing date
- 1995-06-15
- type
- Contribution to journal
- publication status
- published
- subject
- 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
- pmid:7780138
- 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
- 2024-07-23 07:34:30
@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}}, 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}}, }