Clarification of the risk for venous thrombosis associated with hereditary protein S deficiency by investigation of a large kindred with a characterized gene defect
(1998) In Annals of Internal Medicine 128(1). p.8-14- Abstract
BACKGROUND: Protein S is an important regulatory protein of the coagulation cascade. The risk for venous thrombosis associated with protein S deficiency has been uncertain because all previous risk estimates used phenotypic evaluation alone, which can be ambiguous.
OBJECTIVE: To quantitate the risk for thrombosis associated with a characterized protein S gene mutation that causes a Gly295-->Val substitution and protein S deficiency.
DESIGN: Retrospective study of a single extended family.
SETTING: University hospital referral center.
PARTICIPANTS: A 122-member protein S-deficient family, in which 44 members had a recently characterized gene defect.
MEASUREMENTS: Comprehensive history of thrombosis,... (More)
BACKGROUND: Protein S is an important regulatory protein of the coagulation cascade. The risk for venous thrombosis associated with protein S deficiency has been uncertain because all previous risk estimates used phenotypic evaluation alone, which can be ambiguous.
OBJECTIVE: To quantitate the risk for thrombosis associated with a characterized protein S gene mutation that causes a Gly295-->Val substitution and protein S deficiency.
DESIGN: Retrospective study of a single extended family.
SETTING: University hospital referral center.
PARTICIPANTS: A 122-member protein S-deficient family, in which 44 members had a recently characterized gene defect.
MEASUREMENTS: Comprehensive history of thrombosis, history of exposure to acquired risk factors for thrombosis, levels of total and free protein S antigen, and genotype for the mutation causing the Gly295-->Val substitution.
RESULTS: Kaplan-Meier analysis of thrombosis-free survival showed that the probability of remaining free of thrombosis at 30 years of age is 0.5 (95% CI, 0.33 to 0.66) for carriers of the Gly295-->Val mutation compared with 0.97 (CI, 0.93 to 1.0) for normal family members (P < 0.001). In a multivariate Cox regression model that included smoking and obesity, the mutation was a strong independent risk factor for thrombosis (hazard ratio, 11.5 [CI, 4.33 to 30.6]; P < 0.001). For free (but not total) protein S antigen levels, the distributions of persons with and persons without the mutation did not overlap.
CONCLUSIONS: Protein S deficiency, as defined by the presence of a causative gene mutation or a reduced level of free protein S antigen, is a strong independent risk factor for venous thrombosis in a clinical affected family.
(Less)
- author
- Simmonds, R E ; Ireland, H ; Lane, D A ; Zöller, B LU ; García de Frutos, P and Dahlbäck, B LU
- organization
- publishing date
- 1998-01-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Adolescent, Adult, Aged, Aged, 80 and over, Chi-Square Distribution, Child, Disease-Free Survival, Female, Heterozygote, Humans, Male, Middle Aged, Mutation, Phenotype, Protein S Deficiency, Regression Analysis, Risk Factors, Thrombophlebitis, Journal Article, Research Support, Non-U.S. Gov't
- in
- Annals of Internal Medicine
- volume
- 128
- issue
- 1
- pages
- 7 pages
- publisher
- American College of Physicians
- external identifiers
-
- pmid:9424998
- scopus:0031964419
- ISSN
- 0003-4819
- DOI
- 10.7326/0003-4819-128-1-199801010-00002
- language
- English
- LU publication?
- yes
- id
- b102906f-429e-4d2b-9c3d-09f1f12f9cc2
- date added to LUP
- 2017-10-19 15:13:27
- date last changed
- 2024-01-29 07:13:31
@article{b102906f-429e-4d2b-9c3d-09f1f12f9cc2, abstract = {{<p>BACKGROUND: Protein S is an important regulatory protein of the coagulation cascade. The risk for venous thrombosis associated with protein S deficiency has been uncertain because all previous risk estimates used phenotypic evaluation alone, which can be ambiguous.</p><p>OBJECTIVE: To quantitate the risk for thrombosis associated with a characterized protein S gene mutation that causes a Gly295-->Val substitution and protein S deficiency.</p><p>DESIGN: Retrospective study of a single extended family.</p><p>SETTING: University hospital referral center.</p><p>PARTICIPANTS: A 122-member protein S-deficient family, in which 44 members had a recently characterized gene defect.</p><p>MEASUREMENTS: Comprehensive history of thrombosis, history of exposure to acquired risk factors for thrombosis, levels of total and free protein S antigen, and genotype for the mutation causing the Gly295-->Val substitution.</p><p>RESULTS: Kaplan-Meier analysis of thrombosis-free survival showed that the probability of remaining free of thrombosis at 30 years of age is 0.5 (95% CI, 0.33 to 0.66) for carriers of the Gly295-->Val mutation compared with 0.97 (CI, 0.93 to 1.0) for normal family members (P < 0.001). In a multivariate Cox regression model that included smoking and obesity, the mutation was a strong independent risk factor for thrombosis (hazard ratio, 11.5 [CI, 4.33 to 30.6]; P < 0.001). For free (but not total) protein S antigen levels, the distributions of persons with and persons without the mutation did not overlap.</p><p>CONCLUSIONS: Protein S deficiency, as defined by the presence of a causative gene mutation or a reduced level of free protein S antigen, is a strong independent risk factor for venous thrombosis in a clinical affected family.</p>}}, author = {{Simmonds, R E and Ireland, H and Lane, D A and Zöller, B and García de Frutos, P and Dahlbäck, B}}, issn = {{0003-4819}}, keywords = {{Adolescent; Adult; Aged; Aged, 80 and over; Chi-Square Distribution; Child; Disease-Free Survival; Female; Heterozygote; Humans; Male; Middle Aged; Mutation; Phenotype; Protein S Deficiency; Regression Analysis; Risk Factors; Thrombophlebitis; Journal Article; Research Support, Non-U.S. Gov't}}, language = {{eng}}, month = {{01}}, number = {{1}}, pages = {{8--14}}, publisher = {{American College of Physicians}}, series = {{Annals of Internal Medicine}}, title = {{Clarification of the risk for venous thrombosis associated with hereditary protein S deficiency by investigation of a large kindred with a characterized gene defect}}, url = {{http://dx.doi.org/10.7326/0003-4819-128-1-199801010-00002}}, doi = {{10.7326/0003-4819-128-1-199801010-00002}}, volume = {{128}}, year = {{1998}}, }