Protein S levels and the risk of venous thrombosis: results from the MEGA case-control study

M.R. Pintao, D.D. Ribeiro, I.D. Bezemer, A.A. Garcia, M.C.H. de Visser, Catharina Jacoba Maria Doggen, W.M. Lijfering, P.H. Reitsma, F.R. Rosendaal

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34 Citations (Scopus)

Abstract

In thrombophilic families, protein S deficiency is clearly associated with venous thrombosis. We aimed to determine whether the same holds true in a population-based case-control study (n=5317). Subjects were regarded protein S deficient when protein S levels were <2.5th percentile of the controls. Free- and total protein S deficiency was not associated with venous thrombosis: free protein S <53 U/dL, odds ratio [OR] 0.82 (95%CI, 0.56-1.21) and total protein S <68 U/dL, OR 0.90 (95%CI, 0.62-1.31). When lower cut-off values were applied, it appeared that subjects at risk of venous thrombosis could be identified at levels <0.10th percentile of free protein S (<33 U/dL, OR 5.4; 95% CI, 0.61-48.8). In contrast, even extremely low total protein S levels were not associated with venous thrombosis. PROS1 was sequenced in 48 subjects with free protein S level <1st percentile (<46 U/dL), and copy number variations were investigated in 2718 subjects, including all subjects with protein S (free or total) <2.5th percentile. Mutations in PROS1 were detected in five patients and five controls reinforcing the observation that inherited protein S deficiency is rare in the general population. Protein S testing and PROS1 testing should not be considered in unselected patients with venous thrombosis.
Original languageEnglish
Pages (from-to)3210-3219
Number of pages10
JournalBlood
Volume122
Issue number18
DOIs
Publication statusPublished - 6 Sep 2013

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Protein S
Venous Thrombosis
Case-Control Studies
Protein S Deficiency
Odds Ratio
Population
Testing
Mutation

Keywords

  • METIS-297974
  • IR-87359

Cite this

Pintao, M. R., Ribeiro, D. D., Bezemer, I. D., Garcia, A. A., de Visser, M. C. H., Doggen, C. J. M., ... Rosendaal, F. R. (2013). Protein S levels and the risk of venous thrombosis: results from the MEGA case-control study. Blood, 122(18), 3210-3219. https://doi.org/10.1182/blood-2013-04-499335
Pintao, M.R. ; Ribeiro, D.D. ; Bezemer, I.D. ; Garcia, A.A. ; de Visser, M.C.H. ; Doggen, Catharina Jacoba Maria ; Lijfering, W.M. ; Reitsma, P.H. ; Rosendaal, F.R. / Protein S levels and the risk of venous thrombosis: results from the MEGA case-control study. In: Blood. 2013 ; Vol. 122, No. 18. pp. 3210-3219.
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abstract = "In thrombophilic families, protein S deficiency is clearly associated with venous thrombosis. We aimed to determine whether the same holds true in a population-based case-control study (n=5317). Subjects were regarded protein S deficient when protein S levels were <2.5th percentile of the controls. Free- and total protein S deficiency was not associated with venous thrombosis: free protein S <53 U/dL, odds ratio [OR] 0.82 (95{\%}CI, 0.56-1.21) and total protein S <68 U/dL, OR 0.90 (95{\%}CI, 0.62-1.31). When lower cut-off values were applied, it appeared that subjects at risk of venous thrombosis could be identified at levels <0.10th percentile of free protein S (<33 U/dL, OR 5.4; 95{\%} CI, 0.61-48.8). In contrast, even extremely low total protein S levels were not associated with venous thrombosis. PROS1 was sequenced in 48 subjects with free protein S level <1st percentile (<46 U/dL), and copy number variations were investigated in 2718 subjects, including all subjects with protein S (free or total) <2.5th percentile. Mutations in PROS1 were detected in five patients and five controls reinforcing the observation that inherited protein S deficiency is rare in the general population. Protein S testing and PROS1 testing should not be considered in unselected patients with venous thrombosis.",
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author = "M.R. Pintao and D.D. Ribeiro and I.D. Bezemer and A.A. Garcia and {de Visser}, M.C.H. and Doggen, {Catharina Jacoba Maria} and W.M. Lijfering and P.H. Reitsma and F.R. Rosendaal",
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Pintao, MR, Ribeiro, DD, Bezemer, ID, Garcia, AA, de Visser, MCH, Doggen, CJM, Lijfering, WM, Reitsma, PH & Rosendaal, FR 2013, 'Protein S levels and the risk of venous thrombosis: results from the MEGA case-control study' Blood, vol. 122, no. 18, pp. 3210-3219. https://doi.org/10.1182/blood-2013-04-499335

Protein S levels and the risk of venous thrombosis: results from the MEGA case-control study. / Pintao, M.R.; Ribeiro, D.D.; Bezemer, I.D.; Garcia, A.A.; de Visser, M.C.H.; Doggen, Catharina Jacoba Maria; Lijfering, W.M.; Reitsma, P.H.; Rosendaal, F.R.

In: Blood, Vol. 122, No. 18, 06.09.2013, p. 3210-3219.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Protein S levels and the risk of venous thrombosis: results from the MEGA case-control study

AU - Pintao, M.R.

AU - Ribeiro, D.D.

AU - Bezemer, I.D.

AU - Garcia, A.A.

AU - de Visser, M.C.H.

AU - Doggen, Catharina Jacoba Maria

AU - Lijfering, W.M.

AU - Reitsma, P.H.

AU - Rosendaal, F.R.

PY - 2013/9/6

Y1 - 2013/9/6

N2 - In thrombophilic families, protein S deficiency is clearly associated with venous thrombosis. We aimed to determine whether the same holds true in a population-based case-control study (n=5317). Subjects were regarded protein S deficient when protein S levels were <2.5th percentile of the controls. Free- and total protein S deficiency was not associated with venous thrombosis: free protein S <53 U/dL, odds ratio [OR] 0.82 (95%CI, 0.56-1.21) and total protein S <68 U/dL, OR 0.90 (95%CI, 0.62-1.31). When lower cut-off values were applied, it appeared that subjects at risk of venous thrombosis could be identified at levels <0.10th percentile of free protein S (<33 U/dL, OR 5.4; 95% CI, 0.61-48.8). In contrast, even extremely low total protein S levels were not associated with venous thrombosis. PROS1 was sequenced in 48 subjects with free protein S level <1st percentile (<46 U/dL), and copy number variations were investigated in 2718 subjects, including all subjects with protein S (free or total) <2.5th percentile. Mutations in PROS1 were detected in five patients and five controls reinforcing the observation that inherited protein S deficiency is rare in the general population. Protein S testing and PROS1 testing should not be considered in unselected patients with venous thrombosis.

AB - In thrombophilic families, protein S deficiency is clearly associated with venous thrombosis. We aimed to determine whether the same holds true in a population-based case-control study (n=5317). Subjects were regarded protein S deficient when protein S levels were <2.5th percentile of the controls. Free- and total protein S deficiency was not associated with venous thrombosis: free protein S <53 U/dL, odds ratio [OR] 0.82 (95%CI, 0.56-1.21) and total protein S <68 U/dL, OR 0.90 (95%CI, 0.62-1.31). When lower cut-off values were applied, it appeared that subjects at risk of venous thrombosis could be identified at levels <0.10th percentile of free protein S (<33 U/dL, OR 5.4; 95% CI, 0.61-48.8). In contrast, even extremely low total protein S levels were not associated with venous thrombosis. PROS1 was sequenced in 48 subjects with free protein S level <1st percentile (<46 U/dL), and copy number variations were investigated in 2718 subjects, including all subjects with protein S (free or total) <2.5th percentile. Mutations in PROS1 were detected in five patients and five controls reinforcing the observation that inherited protein S deficiency is rare in the general population. Protein S testing and PROS1 testing should not be considered in unselected patients with venous thrombosis.

KW - METIS-297974

KW - IR-87359

U2 - 10.1182/blood-2013-04-499335

DO - 10.1182/blood-2013-04-499335

M3 - Article

VL - 122

SP - 3210

EP - 3219

JO - Blood

JF - Blood

SN - 0006-4971

IS - 18

ER -