Di Minno Matteo Nicola Dario, Ambrosino Pasquale, Ageno Walter, Rosendaal Frits, Di Minno Giovanni, Dentali Francesco
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.
Department of Clinical Medicine and Surgery, Reference Centre for Coagulation Disorders, Federico II University, Naples, Italy.
Thromb Res. 2015 May;135(5):923-32. doi: 10.1016/j.thromres.2015.03.010. Epub 2015 Mar 13.
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.
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.
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.
The VTE risk is increased in patients with natural anticoagulants deficiency, but additional studies are warranted to better assess the risk of VTE recurrence.
天然抗凝剂缺乏（抗凝血酶[AT]、蛋白C[PC]、蛋白S[PS]）是静脉血栓栓塞症（VTE）的一种罕见但强效的风险因素。我们对评估遗传性天然抗凝剂缺乏对VTE风险影响的观察性研究进行了荟萃分析。
在PubMed、科学网、Scopus和EMBASE数据库中系统检索评估这些异常与VTE关联的病例对照研究和队列研究。
分析纳入了21项研究。13项研究（3452例病例和11562例对照）显示，与对照组相比，AT缺乏受试者首次发生VTE的风险增加（比值比[OR]：16.26，95%置信区间[CI]：9.90 - 26.70；P < 0.00001）。在PC缺乏患者（11项研究，2554例病例和9355例对照；OR：7.51，95%CI：3.21 - 17.52；P < 0.00001）和PS缺乏患者（14项研究，4955例病例和9267例对照；OR：5.37；95%CI：2.70 - 10.67；P < 0.00001）中也发现首次发生VTE的风险高于对照组。在评估VTE复发风险时，我们发现与AT（4项研究，142例病例和1927例对照；OR：3.61；95%CI：1.46 - 8.95；P = 0.006）和PC（2项研究，80例病例和546例对照；OR：2.94；95%CI：1.43 - 6.04；P = 0.03）存在显著关联，但与PS缺乏无关（2项研究，57例病例和589例对照；OR：2.52；95%CI：0.89 - 7.16；P = 0.08）。敏感性分析和亚组分析证实了这些结果。对于无诱因事件患者，天然抗凝剂缺乏与VTE之间的关联最为显著。
天然抗凝剂缺乏患者发生VTE的风险增加，但需要更多研究来更好地评估VTE复发风险。
