Primignani Massimo, Martinelli Ida, Bucciarelli Paolo, Battaglioli Tullia, Reati Raffaella, Fabris Federica, Dell'era Alessandra, Pappalardo Emanuela, Mannucci Pier Mannuccio
Gastroenterology and Gastrointestinal Endoscopy Service, Department of Internal Medicine and Dermatology, IRCCS Maggiore Hospital and University of Milano, Milan, Italy.
Hepatology. 2005 Mar;41(3):603-8. doi: 10.1002/hep.20591.
Scant information exists on the role of thrombophilia in extrahepatic portal vein obstruction (EHPVO). We studied 65 patients with EHPVO, 500 with deep vein thrombosis (DVT) of the lower limbs, and 700 healthy controls referred for thrombophilia screening, including the search for gain-of-function mutations in genes encoding coagulation factor V (factor V Leiden) and prothrombin (prothrombin G20210A); antithrombin, protein C, and protein S deficiency; and hyperhomocysteinemia. At least one abnormality in the thrombophilia screening was found in 40% of patients with either EHPVO or lower limb DVT and in 13% of controls, for odds ratios of 4.0 (95% CI, 2.3-7.0) and 4.4 (95% CI, 3.3-5.9), respectively. Statistically significant associations with EHPVO were observed for the prothrombin G20210A mutation (odds ratio, 8.1; 95% CI, 3.8-17.5) and the deficiencies of antithrombin, protein C, or protein S taken together (odds ratio, 4.5; 95% CI, 1.1-18.0). The odds ratio for the prothrombin G20210A was approximately twice that for lower limb DVT. Patients with factor V Leiden had an odds ratio for EHPVO of 0.8 (95% CI, 0.1-6.4) and for lower limb DVT of 7.5 (95% CI, 4.4-13.0). The odds ratio for EHPVO in patients with hyperhomocysteinemia was 2.0 (95% CI, 0.9-4.9). At variance with lower limb DVT, oral contraceptive use was not associated with an increased risk of EHPVO. Myeloproliferative disorders were diagnosed in 35% of patients with EHPVO. In conclusion, the risk for EHPVO is increased in the presence of thrombophilia resulting from the prothrombin G20210A mutation and from the deficiencies of the naturally occurring anticoagulant proteins, but not from factor V Leiden.
关于血栓形成倾向在肝外门静脉阻塞（EHPVO）中的作用，现有信息很少。我们研究了65例EHPVO患者、500例下肢深静脉血栓形成（DVT）患者以及700名因血栓形成倾向筛查前来就诊的健康对照者，筛查内容包括寻找编码凝血因子V（因子V莱顿）和凝血酶原（凝血酶原G20210A）的基因中的功能获得性突变；抗凝血酶、蛋白C和蛋白S缺乏；以及高同型半胱氨酸血症。在EHPVO患者或下肢DVT患者中，40%的患者在血栓形成倾向筛查中至少发现一项异常，而在对照者中这一比例为13%，优势比分别为4.0（95%CI，2.3 - 7.0）和4.4（95%CI，3.3 - 5.9）。凝血酶原G20210A突变（优势比，8.1；95%CI，3.8 - 17.5）以及抗凝血酶、蛋白C或蛋白S缺乏合并存在（优势比，4.5；95%CI，1.1 - 18.0）与EHPVO存在统计学显著关联。凝血酶原G20210A的优势比约为下肢DVT的两倍。携带因子V莱顿的患者发生EHPVO的优势比为0.8（95%CI，0.1 - 6.4），发生下肢DVT的优势比为7.5（95%CI，4.4 - 13.0）。高同型半胱氨酸血症患者发生EHPVO的优势比为2.0（95%CI，0.9 - 4.9）。与下肢DVT不同，口服避孕药的使用与EHPVO风险增加无关。35%的EHPVO患者被诊断为骨髓增殖性疾病。总之，由凝血酶原G20210A突变以及天然抗凝蛋白缺乏导致的血栓形成倾向会增加EHPVO风险，但因子V莱顿不会。
