Correlation of thrombophilia and hypofibrinolysis with pulmonary embolism following total hip arthroplasty - An analysis of genetic factors
Correlation of thrombophilia and hypofibrinolysis with pulmonary embolism following total hip arthroplasty - An analysis of genetic factors
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DOI：
10.2106/00004623-200212000-00006
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发表时间：
2002-12-01
影响因子：
5.3
通讯作者：
Salvati, EA
中科院分区：
文献类型：
--
作者：
Westrich, GH;Weksler, BB;Salvati, EA
背景：与全髋关节置换术相关的血栓栓塞风险增加是多因素造成的。我们评估了在全髋关节置换术后发生肺栓塞的患者中，通过新的血栓形成倾向和低纤溶基因筛查试验显示的异常患病率是否高于匹配的对照患者。14例全髋关节置换术后有记录的肺栓塞患者和14例匹配的对照组患者，这些患者接受了全髋关节置换术，但没有任何血栓栓塞的临床指征评估血栓形成倾向和纤溶功能减退的风险。止血功能试验包括凝血酶原时间评价;活化部分凝血活酶时间;纤维蛋白原水平，血清同型半胱氨酸，蛋白C和S，抗凝血酶111;活化蛋白C抗性;和稀释罗素蝰蛇毒时间。对凝血因子V Leiden、凝血酶原启动子G20210 A、亚甲基四氢叶酸还原酶C677 T、纤溶酶原激活物抑制剂-1 4G/4G和血小板糖蛋白IIb/IIIa A1/A2或A2/A2突变进行分子遗传学检测。肺栓塞组（24例异常）中确定的遗传性嗜血栓性异常的总数高于对照组（15例异常）。只有肺栓塞患者凝血酶原G20210 A突变为杂合性或纯合性（14例患者中有4例;与对照组相比p = 0.05），抗凝血酶III水平降低（13例患者中有3例;与对照组相比p = 0.10）。与对照组相比，肺栓塞患者更有可能出现至少一种嗜血栓性异常：14例肺栓塞患者中有7例抗凝血酶-III水平较低或凝血酶原G20210 A基因突变，而对照组14例患者中无一例（Fisher精确检验，p < 0.01）。凝血酶原G20210 A基因突变的存在与肺栓塞显著相关（r = 0.41，p = 0.03），至少存在一处异常（抗凝血酶-III水平低或存在凝血酶原G20210 A基因突变）结论：全髋关节置换术后发生肺栓塞的患者中遗传性血栓形成倾向和纤溶功能低下的发生率高于未发生肺栓塞的患者。多个遗传性血栓形成基因多态性的存在，特别是凝血酶原G20210 A和抗凝血酶III，而不是任何单一的遗传性血栓形成前异常，似乎信号增加血栓栓塞风险的患者接受全髋关节置换术。这些测试的未来改进和可用性将可能允许术前识别血栓栓塞遗传易感性增加的患者。
Background: The increased thromboembolic risk associated with total hip arthroplasty is multifactorial. We assessed whether the prevalence of abnormalities shown by newer genetic screening tests for thrombophilia and hypofibrinolysis was higher in patients in whom pulmonary embolism had developed after total hip arthroplasty than it was in matched control patients.Methods: Fourteen patients with documented pulmonary embolism after total hip arthroplasty and fourteen matched control patients who had undergone total hip arthroplasty without any clinical indication of thromboembolism were evaluated for risks of thrombophilia and hypofibrinolysis. Functional tests of hemostasis included evaluations of prothrombin time; activated partial thromboplastin time; levels of fibrinogen, serum homocysteine, protein C and S, and antithrombin 111; activated protein-C resistance; and dilute Russell viper venom time. Molecular genetic testing was performed for factor-V Leiden, prothrombin promoter G20210A, methylenetetrahydrofolate reductase C677T, plasminogen activator inhibitor-1 4G/4G, and platelet glycoprotein IIb/IIIa A1/A2 or A2/A2 mutations.Results: The total number of genetic thrombophilic abnormalities identified was higher in the pulmonary embolism group (twenty-four abnormalities) than in the control group (fifteen abnormalities). Only patients with pulmonary embolism were found to have heterozygosity or homozygosity for the prothrombin G20210A mutation (four of fourteen patients; p = 0.05 compared with the control group) and a decreased antithrombin-Ill level (three of thirteen patients; p = 0.10 compared with the control group). Patients with pulmonary embolism were much more likely than control patients to have at least one thrombophilic abnormality: seven of fourteen patients with pulmonary embolism had a low antithrombin-Ill level or the prothrombin G20210A gene mutation compared with none of the fourteen in the control group (Fisher exact test, p < 0.01). The presence of the prothrombin G20210A gene mutation was significantly correlated with pulmonary embolism (r = 0.41, p = 0.03), as was the presence of least one abnormality (a low antithrombin-III level or the presence of the prothrombin G20210A gene mutation) (r = 0.58, p = 0.001).Conclusions: Genetic thrombophilia and hypofibrinolysis were more frequent in patients who had had pulmonary embolism after total hip arthroplasty than in those who had not. The presence of multiple genetic thrombophilic polymorphisms, particularly prothrombin G20210A and antithrombin III, rather than any single genetic prothrombotic abnormality, appears to signal an increased thromboembolic risk in patients undergoing total hip arthroplasty. Future refinements and availability of these tests will likely allow preoperative identification of patients with an increased genetic predisposition for thromboembolism.