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Thromb Res. 2015 May;135(5):923-32. doi: 10.1016/j.thromres.2015.03.010. Epub 2015 Mar 13.

Natural anticoagulants deficiency and the risk of venous thromboembolism: a meta-analysis of observational studies.

Author information

1
Department of Clinical Medicine and Surgery, Reference Centre for Coagulation Disorders, Federico II University, Naples, Italy; Unit of cell and molecular biology in cardiovascular diseases, Centro Cardiologico Monzino, IRCCS, Milan, Italy. Electronic address: dario.diminno@hotmail.it.
2
Department of Clinical Medicine and Surgery, Reference Centre for Coagulation Disorders, Federico II University, Naples, Italy.
3
Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy.
4
Department of Thrombosis and Hemostasis, Leiden University, Leiden, The Netherlands.

Abstract

INTRODUCTION:

Natural anticoagulants deficiency (antithrombin [AT], protein C [PC], protein S [PS]) is a rare, but potent risk factor for venous thromboembolism (VTE). We performed a meta-analysis of observational studies evaluating the impact of inherited natural anticoagulants deficiency on VTE risk.

MATERIALS AND METHODS:

Case-control and cohort studies evaluating the association of these abnormalities with VTE were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases.

RESULTS:

Twenty-one studies were included in the analysis. Thirteen studies (3,452 cases and 11,562 controls) showed an increased risk of first VTE in AT deficient subjects compared to controls (OR: 16.26, 95%CI:9.90-26.70; P<0.00001). An increased risk of first VTE was also found in PC (11 studies, 2,554 cases and 9,355 controls; OR: 7.51, 95%CI:3.21-17.52; P<0.00001) and PS deficient patients (14 studies, 4,955 cases and 9,267 controls; OR: 5.37; 95%CI:2.70-10.67; P<0.00001) compared to controls. Evaluating the risk of VTE recurrence, we found a significant association with AT (4 studies, 142 cases and 1,927 controls; OR: 3.61; 95%CI:1.46-8.95; P=0.006) and with PC (2 studies, 80 cases and 546 controls; OR: 2.94; 95%CI:1.43-6.04; P=0.03), but not with PS deficiency (2 studies, 57 cases and 589 controls; OR: 2.52; 95%CI:0.89-7.16; P=0.08). Sensitivity and subgroup analyses confirmed these results. The association among natural anticoagulants deficiency and VTE was maximal for patients with unprovoked events.

CONCLUSION:

The VTE risk is increased in patients with natural anticoagulants deficiency, but additional studies are warranted to better assess the risk of VTE recurrence.

KEYWORDS:

Antithrombin; Protein C; Protein S; Venous thromboembolism

PMID:
25784135
DOI:
10.1016/j.thromres.2015.03.010
[Indexed for MEDLINE]

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