Low borderline plasma levels of antithrombin, protein C and protein S are risk factors for venous thromboembolism

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Abstract

Background: Inherited deficiencies of antithrombin (AT), protein C (PC) and protein S (PS) are risk factors for venous thromboembolism (VTE). They are usually defined by laboratory cut-offs (in our setting 81, 70 and 63IUdL-1, respectively), which give only a rough idea of the VTE risk associated with plasma levels of these proteins. Objectives: We investigated whether the risk of VTE associated with the plasma deficiencies of AT, PC or PS has a dose-response effect, and whether low borderline levels of these proteins are associated with an increased risk of VTE, both in the whole study population and separately in carriers of either factor V Leiden or G20210A prothrombin gene mutation. Patients/Methods: A case-control study of 1401 patients with a first objectively-documented VTE and 1847 healthy controls has been carried out. Results: A dose-response effect on the VTE risk was observed for all the three anticoagulant proteins. Compared with individuals with AT, PC or PS levels >100IU/dL, the adjusted odds ratio (95%CI) of VTE was 2.00 (1.44-2.78) for AT levels between 76 and 85IUdL-1, 2.21 (1.54-3.18) and 1.84 (1.31-2.59) for PC and PS levels between 61 and 75IUdL-1. The risk of unprovoked VTE in factor V Leiden or prothrombin G20210A carriers appears 2 to 3-fold increased when levels of AT or PS are low borderline. Conclusions: Low borderline plasma levels of AT, PC and PS are associated with a 2-fold increased risk of VTE and should be considered in the assessment of the individual VTE risk.

Original languageEnglish
Pages (from-to)1783-1791
Number of pages9
JournalJournal of Thrombosis and Haemostasis
Volume10
Issue number9
DOIs
Publication statusPublished - Sep 2012

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Antithrombin Proteins
Protein S
Venous Thromboembolism
Protein C
Protein C Deficiency
Prothrombin
Antithrombins
Anticoagulants
Case-Control Studies
Blood Proteins
Proteins
Odds Ratio

Keywords

  • Antithrombin
  • Protein C
  • Protein S
  • Risk factors
  • Venous thromboembolism

ASJC Scopus subject areas

  • Hematology

Cite this

@article{b37a89d7524845d3bbfd2ec9d65cb5e7,
title = "Low borderline plasma levels of antithrombin, protein C and protein S are risk factors for venous thromboembolism",
abstract = "Background: Inherited deficiencies of antithrombin (AT), protein C (PC) and protein S (PS) are risk factors for venous thromboembolism (VTE). They are usually defined by laboratory cut-offs (in our setting 81, 70 and 63IUdL-1, respectively), which give only a rough idea of the VTE risk associated with plasma levels of these proteins. Objectives: We investigated whether the risk of VTE associated with the plasma deficiencies of AT, PC or PS has a dose-response effect, and whether low borderline levels of these proteins are associated with an increased risk of VTE, both in the whole study population and separately in carriers of either factor V Leiden or G20210A prothrombin gene mutation. Patients/Methods: A case-control study of 1401 patients with a first objectively-documented VTE and 1847 healthy controls has been carried out. Results: A dose-response effect on the VTE risk was observed for all the three anticoagulant proteins. Compared with individuals with AT, PC or PS levels >100IU/dL, the adjusted odds ratio (95{\%}CI) of VTE was 2.00 (1.44-2.78) for AT levels between 76 and 85IUdL-1, 2.21 (1.54-3.18) and 1.84 (1.31-2.59) for PC and PS levels between 61 and 75IUdL-1. The risk of unprovoked VTE in factor V Leiden or prothrombin G20210A carriers appears 2 to 3-fold increased when levels of AT or PS are low borderline. Conclusions: Low borderline plasma levels of AT, PC and PS are associated with a 2-fold increased risk of VTE and should be considered in the assessment of the individual VTE risk.",
keywords = "Antithrombin, Protein C, Protein S, Risk factors, Venous thromboembolism",
author = "P. Bucciarelli and Passamonti, {S. M.} and E. Biguzzi and F. Gianniello and F. Franchi and Mannucci, {P. M.} and I. Martinelli",
year = "2012",
month = "9",
doi = "10.1111/j.1538-7836.2012.04858.x",
language = "English",
volume = "10",
pages = "1783--1791",
journal = "Journal of Thrombosis and Haemostasis",
issn = "1538-7933",
publisher = "Wiley-Blackwell",
number = "9",

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TY - JOUR

T1 - Low borderline plasma levels of antithrombin, protein C and protein S are risk factors for venous thromboembolism

AU - Bucciarelli, P.

AU - Passamonti, S. M.

AU - Biguzzi, E.

AU - Gianniello, F.

AU - Franchi, F.

AU - Mannucci, P. M.

AU - Martinelli, I.

PY - 2012/9

Y1 - 2012/9

N2 - Background: Inherited deficiencies of antithrombin (AT), protein C (PC) and protein S (PS) are risk factors for venous thromboembolism (VTE). They are usually defined by laboratory cut-offs (in our setting 81, 70 and 63IUdL-1, respectively), which give only a rough idea of the VTE risk associated with plasma levels of these proteins. Objectives: We investigated whether the risk of VTE associated with the plasma deficiencies of AT, PC or PS has a dose-response effect, and whether low borderline levels of these proteins are associated with an increased risk of VTE, both in the whole study population and separately in carriers of either factor V Leiden or G20210A prothrombin gene mutation. Patients/Methods: A case-control study of 1401 patients with a first objectively-documented VTE and 1847 healthy controls has been carried out. Results: A dose-response effect on the VTE risk was observed for all the three anticoagulant proteins. Compared with individuals with AT, PC or PS levels >100IU/dL, the adjusted odds ratio (95%CI) of VTE was 2.00 (1.44-2.78) for AT levels between 76 and 85IUdL-1, 2.21 (1.54-3.18) and 1.84 (1.31-2.59) for PC and PS levels between 61 and 75IUdL-1. The risk of unprovoked VTE in factor V Leiden or prothrombin G20210A carriers appears 2 to 3-fold increased when levels of AT or PS are low borderline. Conclusions: Low borderline plasma levels of AT, PC and PS are associated with a 2-fold increased risk of VTE and should be considered in the assessment of the individual VTE risk.

AB - Background: Inherited deficiencies of antithrombin (AT), protein C (PC) and protein S (PS) are risk factors for venous thromboembolism (VTE). They are usually defined by laboratory cut-offs (in our setting 81, 70 and 63IUdL-1, respectively), which give only a rough idea of the VTE risk associated with plasma levels of these proteins. Objectives: We investigated whether the risk of VTE associated with the plasma deficiencies of AT, PC or PS has a dose-response effect, and whether low borderline levels of these proteins are associated with an increased risk of VTE, both in the whole study population and separately in carriers of either factor V Leiden or G20210A prothrombin gene mutation. Patients/Methods: A case-control study of 1401 patients with a first objectively-documented VTE and 1847 healthy controls has been carried out. Results: A dose-response effect on the VTE risk was observed for all the three anticoagulant proteins. Compared with individuals with AT, PC or PS levels >100IU/dL, the adjusted odds ratio (95%CI) of VTE was 2.00 (1.44-2.78) for AT levels between 76 and 85IUdL-1, 2.21 (1.54-3.18) and 1.84 (1.31-2.59) for PC and PS levels between 61 and 75IUdL-1. The risk of unprovoked VTE in factor V Leiden or prothrombin G20210A carriers appears 2 to 3-fold increased when levels of AT or PS are low borderline. Conclusions: Low borderline plasma levels of AT, PC and PS are associated with a 2-fold increased risk of VTE and should be considered in the assessment of the individual VTE risk.

KW - Antithrombin

KW - Protein C

KW - Protein S

KW - Risk factors

KW - Venous thromboembolism

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U2 - 10.1111/j.1538-7836.2012.04858.x

DO - 10.1111/j.1538-7836.2012.04858.x

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