TY - JOUR
T1 - Natural anticoagulants deficiency and the risk of venous thromboembolism
T2 - A meta-analysis of observational studies
AU - Di Minno, Matteo Nicola Dario
AU - Ambrosino, Pasquale
AU - Ageno, Walter
AU - Rosendaal, Frits
AU - Di Minno, Giovanni
AU - Dentali, Francesco
PY - 2015/5/1
Y1 - 2015/5/1
N2 - 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.
AB - 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.
KW - Antithrombin
KW - Protein C
KW - Protein S
KW - Venous thromboembolism
UR - http://www.scopus.com/inward/record.url?scp=84928598513&partnerID=8YFLogxK
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U2 - 10.1016/j.thromres.2015.03.010
DO - 10.1016/j.thromres.2015.03.010
M3 - Article
C2 - 25784135
AN - SCOPUS:84928598513
VL - 135
SP - 923
EP - 932
JO - Thrombosis Research
JF - Thrombosis Research
SN - 0049-3848
IS - 5
ER -