有静脉血栓栓塞史的成人基因检测的结果。

Jodi B Segal, Daniel J Brotman, Ashkan Emadi, Alejandro J Necochea, Lipika Samal, Lisa M Wilson, Matthew T Crim, Eric B Bass
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引用次数: 0

摘要

目的:探讨单独检测因子V Leiden (FVL)或联合凝血酶原G20210A检测是否能改善有静脉血栓栓塞(VTE)个人病史的成人的临床结果,或改善突变阳性个体的成年家庭成员的临床结果。数据来源:搜索MEDLINE, EMBASE, Cochrane图书馆,护理和相关健康文献累积索引,PsycInfo截止2008年12月。回顾方法:我们着重于这些测试的分析效度、临床效度和临床应用。每篇纳入的文章都经过了数据提取和研究质量评估的双重审查。当有足够的数据时,我们汇总了解决这些试验临床有效性的研究结果。其他证据汇总在证据表中。我们采用建议分级评估、发展和评估(GRADE)工作组推荐的方案对证据进行分级,评估影响个体研究质量的局限性、研究中观察到的直接效应的确定性、研究结果的准确性和强度,以及回答相关关键问题的数据的可用性(或缺乏)。每个子问题的证据被分为高、中、低三个等级。结果:我们检索了7777篇文献,纳入124篇。没有直接证据可以证明主要目标。然而,高质量的证据支持FVL和凝血酶原G20210A检测方法具有良好的分析效度的结论。大多数临床实验室都能准确地检测这些突变。先证FVL的杂合度[比值比(OR) =1.56(95%可信区间(CI) 1.14 ~ 2.12)]和纯合度[OR=2.65 (95% CI . 1.2 ~ 6.0)]可预测静脉血栓栓塞复发。FVL的杂合度预测家族成员的VTE [OR=3.5 (95% ci . 2.5 ~ 5.0)], FVL的纯合度[OR=18 (95% ci . 7.8 ~ 40)]也是如此。凝血酶原G20210A的杂合性不能预测先显子的复发[OR=1.45 (95% C.I. 0.96-2.2)]。凝血酶原G20210A在家族成员中的杂合性证据不足,凝血酶原G20210A的纯合性证据不足。一项研究支持临床医生可能根据测试结果改变管理方法的假设。有高级别证据表明抗凝可以减少FVL或凝血酶原G20210A先证患者的复发事件,然而,有低级别证据表明,治疗后的相对减少与没有突变的个体相当。有适度的证据支持这一结论,即测试的危害和益处都没有得到确凿的证明。决策分析模型表明,在选定的个体中,检测可能具有成本效益。结论:没有直接证据表明检测这些突变可以改善有静脉血栓栓塞病史的成年人或其成年家庭成员的临床结果。文献支持这样的结论:虽然这些检测具有很高的分析效度,但检测结果在预测这些人群的静脉血栓栓塞方面具有可变的临床效度,临床实用性较弱。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Outcomes of genetic testing in adults with a history of venous thromboembolism.

Objective: To address whether Factor V Leiden (FVL) testing alone, or in combination with prothrombin G20210A testing, leads to improved clinical outcomes in adults with a personal history of venous thromboembolism (VTE) or to improved clinical outcomes in adult family members of mutation-positive individuals.

Data sources: Searches of MEDLINE, EMBASE, The Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature, and PsycInfo through December 2008.

Review methods: We focused on the analytic validity, clinical validity, and clinical utility of these tests. Each included article underwent double review for data abstraction and assessment of study quality. We pooled the results of studies addressing the clinical validity of these tests when there were sufficient data. Other evidence was summarized in evidence tables. We graded the evidence by adapting a scheme recommended by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group by assessing the limitations affecting individual study quality, the certainty regarding the directness of the observed effects in the studies, the precision and strength of the findings, and the availability (or lack) of data to answer the relevant key question. Evidence for each sub-question was graded as high, moderate, or low.

Results: We reviewed 7,777 titles and included 124 articles. No direct evidence addressed the primary objective. However, high-grade evidence supported the conclusion that tests for the detection of FVL and prothrombin G20210A have excellent analytic validity. Most clinical laboratories test for these mutations accurately. Heterozygosity [odds ratio (OR) =1.56 (95 percent confidence interval (CI) 1.14 to 2.12)] and homozygosity [OR=2.65 (95 percent C.I. 1.2 to 6.0)] for FVL in probands are predictive of recurrent VTE. Heterozygosity for FVL predicts VTE in family members [OR=3.5 (95 percent C.I. 2.5 to 5.0)] as does homozygosity for FVL [OR=18 (95 percent C.I. 7.8 to 40)]. Heterozygosity for prothrombin G20210A is not predictive of recurrence in probands [OR=1.45 (95 percent C.I. 0.96-2.2)]. Evidence is insufficient about heterozygosity for prothrombin G20210A in family members and insufficient about homozygosity for prothrombin G20210A. A single study supported the hypothesis that clinicians might change management based on test results. There was high-grade evidence that anticoagulation reduces recurrent events in probands with FVL or prothrombin G20210A, however, there was low-grade evidence that the relative reduction with treatment is comparable to that seen in individuals without mutations. There was moderate evidence to support the conclusion that neither harms nor benefits of testing have been demonstrated conclusively. Decision-analysis models suggest that testing may be cost-effective in select individuals.

Conclusions: There is no direct evidence that testing for these mutations leads to improved clinical outcomes in adults with a history of VTE or their adult family members. The literature supports the conclusion that while these assays have high analytic validity, the test results have variable clinical validity for predicting VTE in these populations and have only weak clinical utility.

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