Alejandro J Necochea

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

CONTEXT Testing for genetic risks for venous thromboembolism (VTE) is common, but the safety and utility of such testing need review. OBJECTIVES To define rates of recurrent VTE among adults with VTE with a factor V Leiden (FVL) or prothrombin G20210A mutation compared with those without such mutations; to define rates of VTE among family members of adults with a FVL or prothrombin G20210A mutation according to presence or absence of a mutation; and to assess whether testing adults with VTE for FVL or prothrombin G20210A improves outcomes. DATA SOURCES We searched MEDLINE, EMBASE, the Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature, and PsycInfo through December 2008. STUDY SELECTION Studies were included if they assessed rates of VTE in individuals with a history of VTE who were tested for FVL or prothrombin G20210A or in family members of individuals with these mutations. Studies assessing the harms and benefits associated with testing were also included. DATA EXTRACTION Two investigators abstracted data and assessed study quality. We pooled the odds of VTE associated with the mutations using random-effects models. We assessed the strength of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. RESULTS We reviewed 7777 titles and included 46 articles. Heterozygosity (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.14-2.12) and homozygosity (OR, 2.65; 95% CI, 1.2-6.0) for FVL in probands are predictive of recurrent VTE compared with individuals without FVL. Heterozygosity for FVL predicts VTE in family members (OR, 3.5; 95% CI, 2.5-5.0), as does homozygosity for FVL (OR, 18; 95% CI, 7.8-40) compared with family members of adults without FVL. Heterozygosity for prothrombin G20210A is not predictive of recurrent VTE in probands compared with individuals without prothrombin G20210A (OR, 1.45; 95% CI, 0.96-2.2). Evidence is insufficient regarding the predictive value of prothrombin G20210A homozygosity for recurrent VTE and the risk of VTE in family members of individuals with prothrombin G20210A. High-grade evidence supports that anticoagulation reduces recurrent VTE events in probands with either mutation. Low-grade evidence supports that this risk reduction is similar to that in individuals with a history of VTE and without mutations. CONCLUSIONS Patients with FVL are at increased risk of recurrent VTE compared with patients with VTE without this mutation. However, it is unknown whether testing for FVL or prothrombin G20210A improves outcomes in adults with VTE or in family members of those with a mutation.

Reduction of Regulated Medical Waste Using Lean Sigma Results in Financial Gains for Hospital

This article describes how anesthesiologists can lead innovation and process improvement focused on regulated medical waste reduction and cost savings using a process improvement methodology known as Lean Sigma.

Analytic validity of genetic tests to identify factor V Leiden and prothrombin G20210A

The objective of this study is to systematically review methods for detecting Factor V Leiden or prothrombin G20210A. English‐language literature from MEDLINE®, EMBASE®, The Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature, PsycInfo©, 2000‐December 2008. Studies assessed methods for detection of these mutations in at least 10 human blood samples and reported concordance, discordance, or reproducibility. Two investigators abstracted data on the sample selection criteria, test operators, DNA extraction, experimental test, reference standard, commercial instruments, concordance rates, explanation of any discordance, and whether discordance resolved after repetition. We assessed strength of the evidence using the GRADE criteria. We reviewed 7,777 titles and included 66 articles. The majority of the reviewed studies used PCR‐RFLP or AS‐PCR as the reference standard. The studies demonstrated that commercially available and precommercial tests have high analytic validity with all having greater than 99% concordance with the reference standard. With a few exceptions, discordance resolved with repetition of the test, suggesting operator or administrative errors were responsible for the discordant results. In the quality assurance studies, greater than 98% of laboratories demonstrated high, even perfect, accuracy when asked to diagnose a sample with a known mutation. The majority of errors came from a limited number of laboratories. Although not all methods may be accurate, there is high‐grade evidence that genetic tests for the detection of FVL and prothrombin G20210A have excellent analytic validity. There is high‐grade evidence that most, but not all, clinical laboratories test for FVL and prothrombin G20210A accurately. Am. J. Hematol., 2010.