DOCSLIB.ORG

Outcomes of Genetic Testing in Adults with a History of Venous Thromboembolism

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Outcomes of Genetic Testing in Adults with a History of Venous Thromboembolism Evidence Report/Technology Assessment Number 180 Outcomes of Genetic Testing in Adults with a History of Venous Thromboembolism Prepared for: Agency for Healthcare Research and Quality U.S. Department of Health and Human Services http://www.ahrq.gov Contract No. HHSA 290-2007-10061-I Prepared by: The Johns Hopkins University Evidence-based Practice Center Investigators Jodi B. Segal, M.D., M.P.H. Daniel J. Brotman, M.D. Ashkan Emadi, M.D., Ph.D. Alejandro J. Necochea, M.D., M.P.H. Lipika Samal, M.D. Lisa M. Wilson, M.S. Matthew T. Crim, M.Sc., M.A. Eric B. Bass, M.D., M.P.H. AHRQ Publication No. 09-E011 June 2009 i 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. ii This document is in the public domain and may be used and reprinted without permission except those copyrighted materials noted for which further reproduction is prohibited without the specific permission of copyright holders. 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. iii Preface The Agency for Healthcare Research and Quality (AHRQ), through its Evidence-Based Practice Centers (EPCs), sponsors the development of evidence reports and technology assessments to assist public- and private-sector organizations in their efforts to improve the quality of health care in the United States. This report was requested and funded by the Centers for Disease Control and Prevention (CDC), Office of Public Health Genomics (OPHG). The reports and assessments provide organizations with comprehensive, science-based information on common, costly medical conditions and new health care technologies. The EPCs systematically review the relevant scientific literature on topics assigned to them by AHRQ and conduct additional analyses when appropriate prior to developing their reports and assessments. To bring the broadest range of experts into the development of evidence reports and health technology assessments, AHRQ encourages the EPCs to form partnerships and enter into collaborations with other medical and research organizations. The EPCs work with these partner organizations to ensure that the evidence reports and technology assessments they produce will become building blocks for health care quality improvement projects throughout the Nation. The reports undergo peer review prior to their release. AHRQ expects that the EPC evidence reports and technology assessments will inform individual health plans, providers, and purchasers as well as the health care system as a whole by providing important information to help improve health care quality. We welcome comments on this evidence report. They may be sent by mail to the Task Order Officer named below at: Agency for Healthcare Research and Quality, 540 Gaither Road, Rockville, MD 20850, or by e-mail to [email protected]. Carolyn M. Clancy, M.D. Jean Slutsky, P.A., M.S.P.H. Director Director, Center for Outcomes and Evidence Agency for Healthcare Research and Quality Agency for Healthcare Research and Quality Beth A. Collins Sharp, Ph.D., R.N. Gurvaneet Randhawa, M.D., M.P.H. Acting Director, EPC Program Task Order Officer, Center for Outcomes and Agency for Healthcare Research and Quality Evidence Agency for Healthcare Research and Quality Thomas R. Frieden, M.D., M.P.H. Director Centers for Disease Control and Prevention iv Acknowledgments The EPC thanks Renee F. Wilson, Dr. Olaide Odelola, and Ritu Sharma for their assistance with the final assembly and formatting of this report, and Dr. Gurvaneet Randhawa for his valuable insight. v Structured 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. v Contents Executive Summary.........................................................................................................................1 Evidence Report...........................................................................................................................15 Chapter 1. Introduction .................................................................................................................17 Venous Thromboembolism........................................................................................................3 Diagnosis and Treatment ...........................................................................................................4 Genetic Mutations Associated with VTE: FVL and Prothrombin G20210A............................4 Methods for Identifying Mutations............................................................................................5 Objectives of this Evidence Report............................................................................................5 Chapter 2. Methods..........................................................................................................................7 Establishing a Technical Expert Panel.......................................................................................7 Analytic Framework ..................................................................................................................7
Load more

Recommended publications
  • Mutation in the Prothrombin Gene G20210A As a Cause of Cerebral Venous Thrombosis
    Hindawi Publishing Corporation Case Reports in Medicine Volume 2012, Article ID 828050, 3 pages doi:10.1155/2012/828050 Case Report Mutation in the Prothrombin Gene G20210A as a Cause of Cerebral Venous Thrombosis Jorge A. Arroyave1 and Jairo Quinones˜ 2 1 Internal Medicine, Universidad CES, Medell´ın, Colombia 2 Neuroinmunology, Clinical Neurology, Fundacion´ Cl´ınica Valle del Lili, Cali, Colombia Correspondence should be addressed to Jorge A. Arroyave, [email protected] Received 8 February 2012; Accepted 21 February 2012 Academic Editor: Mamede de Carvalho Copyright © 2012 J. A. Arroyave and J. Quinones.˜ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Introduction. Cerebral venous sinus thrombosis (CVST) is a rare form of cerebrovascular disease, which may manifest clinically by a wide variety of signs and symptoms. It has been associated with multiple risk factors including genetic or acquired blood disorders, infections, and trauma. Case Report. Man of 17 years who presented with 10 days of intense global headache with nausea and vomiting and subsequent onset of mild hemiparesis and hypoesthesia in right hemibody. Studies show venous thrombosis of the superior longitudinal sinus. It was identified a gene mutation in prothrombin G20210A as a probable cause of the thrombosis. Conclusions. Substitution of guanine for adenine at nucleotide 20210 in the coding region of the prothrombin gene is the second most common primary thrombophilia. Multiple cases of CVST have been associated with this mutation. In the presence of CVST must be considered the primary studies for thrombophilia gene mutations, including prothrombin G20210A.
    [Show full text]
  • The Underrecognized Prothrombotic Vascular Disease of COVID-19
    Journal Articles 2020 The underrecognized prothrombotic vascular disease of COVID-19. KP Cohoon G Mahé AC Spyropoulos Zucker School of Medicine at Hofstra/Northwell, [email protected] Follow this and additional works at: https://academicworks.medicine.hofstra.edu/articles Part of the Internal Medicine Commons Recommended Citation Cohoon K, Mahé G, Spyropoulos A. The underrecognized prothrombotic vascular disease of COVID-19.. 2020 Jan 01; 4(5):Article 6487 [ p.]. Available from: https://academicworks.medicine.hofstra.edu/articles/ 6487. Free full text article. This Article is brought to you for free and open access by Donald and Barbara Zucker School of Medicine Academic Works. It has been accepted for inclusion in Journal Articles by an authorized administrator of Donald and Barbara Zucker School of Medicine Academic Works. For more information, please contact [email protected]. Received: 6 May 2020 | Revised: 16 May 2020 | Accepted: 21 May 2020 DOI: 10.1002/rth2.12396 LETTER TO THE EDITOR The underrecognized prothrombotic vascular disease of COVID-19 We have read with interest “COVID-19-associated coagulopathy around elevated markers of hypercoagulability, including D-dimer, and thromboembolic disease: Commentary on an interim expert tissue factor expression, fibrinogen levels, factor VIII levels, guidance” recently provided by Cannegieter and Klok.1 This com- short-activated partial thromboplastin time, platelet binding, and mentary exemplifies the importance that venous thromboembolism thrombin formation.8 Based on well-defined clinical and laboratory (VTE) and atheroembolism may be underrepresented and a cause parameters, a proposal for staging COVID-19 coagulopathy may for increased morbidity and mortality among coronavirus disease provide treatment algorithms stratified into 3 stages.9 However, 2019 (COVID-19) patients.
    [Show full text]
  • Spontaneous Deep Vein Thrombosis in Hemophilia A: a Case Report Murat Bicer, Murat Yanar* and Oktay Tuydes
    Open Access Case report Spontaneous deep vein thrombosis in hemophilia A: a case report Murat Bicer, Murat Yanar* and Oktay Tuydes Address: Department of Cardiac Surgery, Kalp Damar Cerrahisi Anabilim Dali Görükle Yerles¸kesi, Nilüfer Bursa 16059, Turkey Email: MB - [email protected]; MY* - [email protected]; OT - [email protected] * Corresponding author Received: 4 March 2009 Accepted: 5 July 2009 Published: 11 September 2009 Cases Journal 2009, 2:6390 doi: 10.4076/1757-1626-2-6390 This article is available from: http://casesjournal.com/casesjournal/article/view/6390 © 2009 Bicer et al.; licensee Cases Network Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Venous thromboembolus is an important cause of hospital acquired morbidity and mortality. Venous thrombosis is a very rare occurrence in patients with haemophilia A. The thrombosis originated from the right main and external iliac veins, and effects the cranial segments of the main, deep and superficial femoral veins as an acute phase thrombus. Neither any local anatomic compression nor any predisposing thrombophilic risk factors were identified. We treated the patient with enoxaparine 1 mg/kg twice a day subcutaneously and then started oral anticoagulation with warfarin. Introduction was warmer and 2 cm larger than the left lower extremity in Venous thromboembolus is an important cause of hospital circumference. According to the visual analog scale, the acquired morbidity and mortality [1]. Hemophilia A is pain score was 6.
    [Show full text]
  • Thrombocytopenia and Intracranial Venous Sinus Thrombosis After “COVID-19 Vaccine Astrazeneca” Exposure
    Journal of Clinical Medicine Article Thrombocytopenia and Intracranial Venous Sinus Thrombosis after “COVID-19 Vaccine AstraZeneca” Exposure Marc E. Wolf 1,2 , Beate Luz 3, Ludwig Niehaus 4 , Pervinder Bhogal 5, Hansjörg Bäzner 1,2 and Hans Henkes 6,7,* 1 Neurologische Klinik, Klinikum Stuttgart, D-70174 Stuttgart, Germany; [email protected] (M.E.W.); [email protected] (H.B.) 2 Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, D-68167 Mannheim, Germany 3 Zentralinstitut für Transfusionsmedizin und Blutspendedienst, Klinikum Stuttgart, D-70174 Stuttgart, Germany; [email protected] 4 Neurologie, Rems-Murr-Klinikum Winnenden, D-71364 Winnenden, Germany; [email protected] 5 Department of Interventional Neuroradiology, The Royal London Hospital, Barts NHS Trust, London E1 1FR, UK; [email protected] 6 Neuroradiologische Klinik, Klinikum Stuttgart, D-70174 Stuttgart, Germany 7 Medical Faculty, University Duisburg-Essen, D-47057 Duisburg, Germany * Correspondence: [email protected]; Fax: +49-711-278-345-09 Abstract: Background: As of 8 April 2021, a total of 2.9 million people have died with or from the coronavirus infection causing COVID-19 (Corona Virus Disease 2019). On 29 January 2021, the European Medicines Agency (EMA) approved a COVID-19 vaccine developed by Oxford University Citation: Wolf, M.E.; Luz, B.; and AstraZeneca (AZD1222, ChAdOx1 nCoV-19, COVID-19 vaccine AstraZeneca, Vaxzevria, Cov- Niehaus, L.; Bhogal, P.; Bäzner, H.; ishield). While the vaccine prevents severe course of and death from COVID-19, the observation of Henkes, H. Thrombocytopenia and pulmonary, abdominal, and intracranial venous thromboembolic events has raised concerns. Objec- Intracranial Venous Sinus Thrombosis after “COVID-19 Vaccine tive: To describe the clinical manifestations and the concerning management of patients with cranial AstraZeneca” Exposure.
    [Show full text]
  • Disseminated Intravascular Coagulation and Coagulation Disorders Carl-Erik Dempfle
    Disseminated intravascular coagulation and coagulation disorders Carl-Erik Dempfle Purpose of review Abbreviations An update on recent developments in diagnosis and treatment aPTT activated partial thromboplastin time of disseminated intravascular coagulation. DAA drotrecogin a (activated) DIC disseminated intravascular coagulation Recent findings FRM fibrin-related marker Disseminated intravascular coagulation is defined as a typical ISTH International Society for Thrombosis and Hemostasis disease condition with laboratory findings indicating massive # coagulation activation and reduction in procoagulant capacity. 2004 Lippincott Williams & Wilkins 0952-7907 Clinical syndromes associated with the condition are consumption coagulopathy, sepsis-induced purpura fulminans, and viral hemorrhagic fevers. Consumption coagulopathy is Introduction observed in patients with sepsis, aortic aneurysms, acute The diagnosis of disseminated intravascular coagulation promyelocytic leukemia, and other disseminated malignancies. (DIC) is based on the combination of a disease condition Sepsis-induced purpura fulminans is characterized by with laboratory findings indicating massive coagulation microvascular occlusion causing hemorrhagic necrosis of the activation and reduction in procoagulant capacity (Table skin and organ failure. Viral hemorrhagic fevers result in 1). Current scoring systems include elevated fibrin- massively increased tissue factor production in monocytes and related markers (FRMs), prolonged prothrombin time, macrophages, inducing microvascular
    [Show full text]
  • OFC Vol. 17/4
    CLINICAL PRACTICE ○○○○○○○○○○○○○○○○○ Prevalence of Factor V Leiden, Prothrombin G20210A, and MTHFR C677T Mutations in 200 Healthy Jordanians SUHAIR S EID, GHADA RIHANI ○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○○ Thrombophilia is now considered a multi-causal condition, Ghada Rihani is Chief Officer Immunology and Molecular with interplay of acquired genetic risk factors. In order to Laboratory, King Hussein Medical Centre, Jordan. estimate the frequency of the factor V Leiden, prothrombin G20210A, and MTHFR C677T mutations in the Jorda- Address for correspondence: Suhair S Eid, PO Box 143 855, nian population, we screened 200 healthy Jordanian indi- Amman 11814, Jordan. (+9626) 581-8531, (+9626) 566- Downloaded from viduals. 40% were females. Mean age was 32.1 years for males 2260 (fax). [email protected] and 30.0 years for female participants. A PCR method de- tected 15.0% factor V Leiden (87% heterozygous, 13% ho- Thrombosis risk factors predispose towards thrombosis but, mozygous), 2% prothrombin G20210A (100% heterozy- due to the episodic nature of thrombosis, interaction with gous), and 24% MTHFR C677T (67% heterozygous, 33% other components is required before onset of the clinical homozygous). disorder. A well-established genetic predisposition to throm- http://hwmaint.clsjournal.ascls.org/ bosis is a single point mutation in the gene encoding coagu- We conclude that the prevalence of factor V Leiden and lation factor V (G1691A) leading to factor V Leiden (FVL) MTHFR C677T is elevated in this population of Jordani- which was identified as the molecular basis for the pheno- ans. However the incidence of G20210A is relatively low. type of activated protein C resistance (APC-R) in the ma- jority of affected individuals.1,2 This mutation is associated Quantification of these genetic thrombosis risk factors in vari- with a five- to ten-fold risk for heterozygotes and 80-fold ous populations will contribute to a better understanding of risk for homozygotes.3 the interaction of genetic and environmental risk factors.
    [Show full text]
  • 1 FACTOR V LEIDEN, PROTHROMBIN G20210A, and MTHFR
    Factor V Leiden, Prothrombin G20210A, and MTHFR C677T Polymorphisms in Cancer Patients with Venous Thromboembolism Item Type text; Electronic Dissertation Authors Lattimore, Lois Eileen Publisher The University of Arizona. Rights Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. Download date 09/10/2021 17:40:06 Link to Item http://hdl.handle.net/10150/193768 ! ! "! FACTOR V LEIDEN, PROTHROMBIN G20210A, and MTHFR C677T POLYMORPHISMS IN CANCER PATIENTS WITH VENOUS THROMBOEMBOLISM by Lois Eileen Lattimore ________________________ Copyright © Lois Eileen Lattimore 2010 A Scholarly Inquiry Project Submitted to the Faculty of the COLLEGE OF NURSING In Partial Fulfillment of the Requirements For the Degree of DOCTOR OF NURSING PRACTICE In the Graduate College THE UNIVERSITY OF ARIZONA 2 0 1 0 ! ! #! THE UNIVERSITY OF ARIZONA GRADUATE COLLEGE As members of the Practice Inquiry Committee, we certify that we have read the practice inquiry prepared by Lois Eileen Lattimore entitled $%&'()!*!+,-.,/0!1)('2)(34-/! 5#6#"6%0!%/.!3'2$)!&788'!1(+93()12-:3:!-/!&%/&,)!1%'-,/':!;-'2! *,/(<:!'2)(34(,34(+-:3 and recommend that it be accepted as fulfilling the practice inquiry requirement for the Degree of Doctor of Nursing Practice. ____________________________________________ October 14, 2010 Ida M. (Ki) Moore, DNSc, RN, FAAN ____________________________________________ October 14, 2010 Leslie Ritter, PhD, RN ____________________________________________ October 14, 2010 Matthew J. Gallek, PhD, RN, CNRN Final approval and acceptance of this practice inquiry is contingent upon the candidate’s submission of the final copies of the practice inquiry to the Graduate College.
    [Show full text]
  • Is Inherited Thrombophilia a Risk Factor for Arterial Stroke?
    J Neurol Neurosurg Psychiatry 1998;65:617 617 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.65.5.617 on 1 November 1998. Downloaded from EDITORIAL COMMENTARY Is inherited thrombophilia a risk factor for arterial stroke? The term thrombophilia describes an increased tendency there is a striking association between both V Leiden and to clinical thrombosis associated with laboratory evidence prothrombin G20210A mutations and cerebral venous of abnormal haemostasis. Causes include inherited defi- thrombosis.45 ciencies of natural anticoagulants (antithrombin, protein What is the relevance of these findings for clinical prac- C, and protein S), polymorphisms causing resistance to tice? It seems reasonable to continue to screen patients activated protein C (factor V Leiden mutation) or disturb- younger than 50 presenting with ischaemic stroke for ing the normal proclot or anticlot balance (prothrombin thrombophilia, recognising that positive results have to be G20210A mutation), and disorders which are polygenic or interpreted with caution. Firstly, inherited abnormalities of interact with dietary and environmental factors (high this type are found in a significant proportion of the normal factor VIII and hyperhomocysteinaemia). Inherited throm- population, often without any history of thrombosis. bophilias, most commonly factor V Leiden and high VIII, Secondly, concentrations of protein C, protein S, and anti- are risk factors in most cases of venous thromboembolism thrombin are depressed after stroke. The blood tests 1 under the age of 40. It is therefore tempting to assume that should be repeated at least 3 months after the acute event a similar relation will be found in arterial thrombosis, espe- before concluding that inherited deficiency is present.
    [Show full text]
  • Laboratory Bulletin... Updates and Information from Rex Healthcare and Rex Outreach
    Laboratory Bulletin... Updates and Information from Rex Healthcare and Rex Outreach August 2000 Issue Number 49 Prothrombin G20210A and Introduction: Since the 1960s, several genetic disorders that contribute to venous thrombosis have been characterized. Protein S, Protein C and antithrombin deficiency Venous are rare autosomal dominant disorders, have a relatively high risk for thrombosis and Thrombosis are well know. In the 1990’s the link between hyperhomocysteinemia and thrombosis has been established. Recently, the two most common causes of familial thrombophilia, Factor V Leiden and Prothrombin G20210A, have become known. Prothrombin G20210A is prothrombin (factor II) with a single substitution of adenine for guanine at position 20210 that results in increased risk for thrombosis. Decreased levels of prothrombin are associated with increased risk for hemorrhage, whereas elevated prothrombin levels have been associated with increased risk for venous thrombosis. The mechanism whereby this genetic defect results in increased levels of prothrombin is unknown. Prevalence: Factor V Leiden occurs in 5% of the general population and in about 20% of patients with venous thrombosis. Prothrombin G20210A occurs in less than half as many people as factor V Leiden and is almost absent in nonwhites and Asians. About 32% of the causes of deep vein thrombosis can be attributed to known hereditary conditions (Table 1). The rest of the cases are due to acquired risk factors or undiscovered genetic disorders. Table 1. Prevalence of Inherited Risk Factors in Caucasians* Prevalence in Prevalence in general population patient with DVT Relative Risk factor (%) (%) risk Factor V Leiden 5 20 7 Prothrombin G20210A 2 6 3 Protein C deficiency 0.2 – 0.4 3 7 Protein S deficiency 0.7 2 10 Antithrombin deficiency 0.02 1 5 Hyperhomocystinemia 1:335,000 0.1 2.5 *DVT = deep vein thrombosis Clinical Importance: Many investigators believe that the G20210A genetic defect alone is usually not sufficient for the development of venous thrombosis.
    [Show full text]
  • Prothrombin G20210A Mutation
    PATIENT INFORMATION Prothrombin G20210A Mutation What is prothrombin? Prothrombin is one of the blood clotting factors, the condition known as prothrombin G20210A is due to a mutation of the prothrombin gene. It tends to cause blood to become “stickier”, due to higher levels of prothrombin. How does the problem come about? Prothrombin G20210A is an inherited condition. If one parent has the faulty gene there is a 50:50 chance that a child will inherit it. Very rarely both parents will have the faulty gene. Prothrombin G20210A and venous thrombosis Venous thrombosis means blood clots developing in the veins – usually deep vein thrombosis of the leg and more rarely in the lungs – pulmonary embolism. People with the prothrombin G20210A mutation have a slightly increased risk of blood clots, which can be higher if there are also hereditary risk factor such as: Factor V Leiden or Protein S deficiency present. The large majority of people with the mutation will never have a problem. Prothrombin G20210A mutation is not associated with blood clots in the arteries which cause the majority of heart attacks, strokes and peripheral vascular disease (thrombosis in leg arteries). How do I reduce the risks? · Lead a physically active life · Eat a healthy diet and avoid becoming overweight · Avoid smoking · Avoid long period of immobility · Seek advice before major surgery or when likely to be immobile for long periods. Working with you, for you Women with prothrombin G20210A should also seek medical advice before: · Taking the oral contraceptive pill. · Hormone replacement therapy. · When or if they become pregnant. · When undergoing major surgery.
    [Show full text]
  • Factor II (Prothrombin) 20210 G -->A
    Factor II (Prothrombin) 20210 G -->A This test is used in the evaluation of patients with deep vein thrombosis or pulmonary embolism, women with premature myocardial infarction, a family history of deep vein thrombosis or the prothrombin 20210A mutation, or the presence of another known genetic hypercoagulability condition. Testing Method and Background This test utilizes the eSensor® Thrombophilia Risk Test (TRT) is an in vitro diagnostic for the detection and genotyping of Factor II (Prothrombin) G20210A, Factor V (Factor V Leiden) G1691A and MTHFR (human 5, 10 methylenetetrahydrofolate reductase gene) C677T and A1298C using isolated genomic DNA. The eSensor® technology uses a solid-phase electrochemical method for determining the genotyping status. Inherited Thrombosis is associated with congenital predisposing risk factors such as Factor II (Prothrombin, FII)1 and Factor V (Leiden, FV) proteins involved in the blood coagulation enzyme activity cascade. The FII and FV mutations are present in ~2% and 5% of individuals with N. European ancestry respectively, but at much lower levels in other populations. Factor V Leiden is inherited in an autosomal dominant manner. Highlights of Factor II (Prothrombin) Testing Targeted Region FII: Genotyping of the 20210 G -->A mutation Add on Thrombophilia Risk Testing Same blood specimen can be used for genotyping Factor V (Factor V Leiden) 1691G>A and MTHFR (human 5, 10 methylenetetrahydrofolate reductase gene) C677T and A1298C mutations. Ordering Information Get started (non-HFHS): Print a Genetic
    [Show full text]
  • Factor II/Prothrombin Testing for Thrombophilia
    Lab Management Guidelines V1.0.2020 Factor II/Prothrombin Testing for Thrombophilia MOL.TS.166.A v1.0.2020 Procedures addressed The inclusion of any procedure code in this table does not imply that the code is under management or requires prior authorization. Refer to the specific Health Plan's procedure code list for management requirements. Procedure addressed by this guideline Procedure code F2 Targeted Mutation Analysis 81240 What is prothrombin thrombophilia Definition Prothrombin thrombophilia is a genetic disorder that increases one’s risk for developing abnormal blood clots (venous thromboembolism or VTE).1 Prothrombin thrombophilia is caused by a genetic change, or mutation, in the F2 gene called G20210A (20210G>A or c.*97G>A).1-3 o The F2 gene produces a protein that helps to initiate the formation of blood clots.1 o The prothrombin mutation is a gain of function mutation that shifts the F2 gene into overdrive, increasing one’s risk of VTE.1 o The prothrombin mutation is one of several mutations linked to an increase risk for blood clotting.2,3 The formation of abnormal blood clots can lead to conditions like deep vein thrombosis (DVT) and pulmonary embolism.1,2 There has been conflicting evidence about the association of inherited thrombophilias and other pregnancy complications, such as severe preeclampsia, intrauterine growth restriction, and placental abruption. 4,5 About 1-3% of the European population have at least one prothrombin mutation.1,2,4 o Inheriting one prothrombin mutation (heterozygous) increases one’s risk for developing VTE approximately 2-fold to 4-fold compared to non-carriers.1,6 o First-degree relatives of an individual who is heterozygous for the G20210A mutation are at 50% risk of carrying the same mutation.7 © 2020 eviCore healthcare.
    [Show full text]