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Outcomes of Genetic Testing in Adults with a History of Venous Thromboembolism
Evidence Reports/Technology Assessments, No. 180
Investigators: Jodi B Segal, MD, MPH, Daniel J Brotman, MD, Ashkan Emadi, MD, PhD, Alejandro J Necochea, MD, MPH, Lipika Samal, MD, Lisa M Wilson, MS, Matthew T Crim, MSc, MA, and Eric B Bass, MD, MPH.
Author Information and AffiliationsStructured Abstract
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 & 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.
Contents
- Preface
- Acknowledgments
- Executive Summary
- 1. Introduction
- 2. Methods
- 3. Results
- Results of the Search
- Key Question 1: Association of FVL testing, alone, or in combination with prothrombin G20210A testing, with improved clinical outcomes in adults with a personal history of VTE or in adult family members of mutation-positive individuals as a result of medical, personal, or public health decision making
- Key Question 2: Analytic validity of tests to identify FVL and prothrombin G20210A mutations
- Key Question 3: Clinical Validity of Testing for FVL and/or Prothrombin G202010A
- Key Question 4 Clinical Utility of Testing for FVL and/or Prothrombin G202010A
- 4. Discussion
- Key Question 1: Association of FVL Testing, Alone or in Combination With Prothrombin G20210A Testing, With Improved Clinical Outcomes in Adults With a Personal History of VTE or in Adult Family Members of Mutation-positive Individuals
- Key Question 2: Analytic Validity of Tests to Identify FVL and Prothrombin G20210A Mutations
- Key Question 3: Clinical Validity of Testing for FVL and Prothrombin G20210A Mutations
- Key Question 4 Clinical Utility of Testing for FVL and Prothrombin G20210A Mutations
- Summary of the Evidence
- Limitations of This Report
- Implications for Future Research
- References
- Acronyms
- Appendixes
Prepared for: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services.1 Contract No. 290-2007-10061-I. Prepared by: Johns Hopkins University Evidence-based Practice Center.
Suggested citation:
Segal JB, Brotman DJ, Emadi A, Necochea AJ, Samal L, Wilson LM, Crim MT, Bass EB. Outcomes of Genetic Testing in Adults with a History of Venous Thromboembolism. Evidence Report/Technology Assessment No. 180. (Prepared by Johns Hopkins University Evidence-based Practice Center under contract no. HHSA 290-2007-10061-I). AHRQ Publication No. 09-E011. Rockville, MD. Agency for Healthcare Research and Quality.
This report is based on research conducted by the Johns Hopkins University Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. HHSA 290-2007-10061-I). The findings and conclusions in this document are those of the author(s), who are responsible for its content, and do not necessarily represent the views of AHRQ. No statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.
The information in this report is intended to help clinicians, employers, policymakers, and others make informed decisions about the provision of health care services. This report is intended as a reference and not as a substitute for clinical judgment.
This report may be used, in whole or in part, as the basis for the development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.
- 1
540 Gaither Road, Rockville, MD 20850. www
.ahrq.gov
- Review Predictive value of factor V Leiden and prothrombin G20210A in adults with venous thromboembolism and in family members of those with a mutation: a systematic review.[JAMA. 2009]Review Predictive value of factor V Leiden and prothrombin G20210A in adults with venous thromboembolism and in family members of those with a mutation: a systematic review.Segal JB, Brotman DJ, Necochea AJ, Emadi A, Samal L, Wilson LM, Crim MT, Bass EB. JAMA. 2009 Jun 17; 301(23):2472-85.
- Recommendations from the EGAPP Working Group: routine testing for Factor V Leiden (R506Q) and prothrombin (20210G>A) mutations in adults with a history of idiopathic venous thromboembolism and their adult family members.[Genet Med. 2011]Recommendations from the EGAPP Working Group: routine testing for Factor V Leiden (R506Q) and prothrombin (20210G>A) mutations in adults with a history of idiopathic venous thromboembolism and their adult family members.Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. Genet Med. 2011 Jan; 13(1):67-76.
- Review Analytic validity of genetic tests to identify factor V Leiden and prothrombin G20210A.[Am J Hematol. 2010]Review Analytic validity of genetic tests to identify factor V Leiden and prothrombin G20210A.Emadi A, Crim MT, Brotman DJ, Necochea AJ, Samal L, Wilson LM, Bass EB, Segal JB. Am J Hematol. 2010 Apr; 85(4):264-70.
- Do Factor V Leiden and Prothrombin G20210A Mutations Predict Recurrent Venous Thromboembolism in Older Patients?[Am J Med. 2017]Do Factor V Leiden and Prothrombin G20210A Mutations Predict Recurrent Venous Thromboembolism in Older Patients?Méan M, Limacher A, Stalder O, Angelillo-Scherrer A, Alberio L, Fontana P, Beer HJ, Rodondi N, Lämmle B, Aujesky D. Am J Med. 2017 Oct; 130(10):1220.e17-1220.e22. Epub 2017 Jun 9.
- Review Combined oral contraceptives, thrombophilia and the risk of venous thromboembolism: a systematic review and meta-analysis.[J Thromb Haemost. 2016]Review Combined oral contraceptives, thrombophilia and the risk of venous thromboembolism: a systematic review and meta-analysis.van Vlijmen EF, Wiewel-Verschueren S, Monster TB, Meijer K. J Thromb Haemost. 2016 Jul; 14(7):1393-403. Epub 2016 Jun 16.
- Outcomes of Genetic Testing in Adults with a History of Venous ThromboembolismOutcomes of Genetic Testing in Adults with a History of Venous Thromboembolism
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