{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T15:00:44Z","timestamp":1778857244767,"version":"3.51.4"},"reference-count":101,"publisher":"Georg Thieme Verlag KG","issue":"08","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Thromb Hemost"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The factor V Leiden (FVL) polymorphism is known as the most common inherited risk factor for venous thrombosis. In turn, FVL is the leading cause of an activated protein C resistance (APCR) phenotype, in which the addition of exogenous activated protein C to plasma does not result in the expected anticoagulant effect. In the routine laboratory approach to the formal diagnosis of FVL, an initial positive screening plasma-based method for APCR is often performed, and only if needed, this is followed by a confirmatory DNA-based assay for FVL. Multiple methods with accepted sensitivity and specificity for determining an APCR\/FVL phenotype are commonly categorized into two separate groups: (1) screening plasma-based assays, including qualitative functional clot-based assays, for APCR, and (2) confirmatory DNA-based molecular assays, entailing several tests and platforms, including polymerase chain reaction-based and non-PCR-based techniques, for FVL. This review will describe the methodological aspects of each laboratory test and prepare suggestions on the indication of APCR and FVL testing and method selection.<\/jats:p>","DOI":"10.1055\/s-0043-1770773","type":"journal-article","created":{"date-parts":[[2023,7,10]],"date-time":"2023-07-10T23:06:56Z","timestamp":1689030416000},"page":"1067-1083","source":"Crossref","is-referenced-by-count":7,"title":["Laboratory Diagnosis of Activated Protein C Resistance and Factor V Leiden"],"prefix":"10.1055","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9735-4830","authenticated-orcid":false,"given":"Mehran","family":"Bahraini","sequence":"additional","affiliation":[{"name":"Department of Hematology and Blood Transfusion, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alieh","family":"Fazeli","sequence":"additional","affiliation":[{"name":"Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akbar","family":"Dorgalaleh","sequence":"additional","affiliation":[{"name":"Hamin Pazhuhan Tis Institute, Tehran, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2023,7,10]]},"reference":[{"issue":"03","key":"ref1","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1097\/MBC.0b013e3283424883","article-title":"Inherited and acquired factor V deficiency","volume":"22","author":"G Lippi","year":"2011","journal-title":"Blood Coagul Fibrinolysis"},{"issue":"02","key":"ref2","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1532\/IJH97.03149","article-title":"Progress in the understanding of the protein C anticoagulant pathway","volume":"79","author":"B Dahlb\u00e4ck","year":"2004","journal-title":"Int J Hematol"},{"issue":"01","key":"ref3","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1111\/j.1538-7836.2005.01590.x","article-title":"Inherited defects of coagulation factor V: the hemorrhagic side","volume":"4","author":"R Asselta","year":"2006","journal-title":"J Thromb Haemost"},{"issue":"04","key":"ref4","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1182\/blood.V91.4.1140","article-title":"Factor V Cambridge: a new mutation (Arg306\u2013>Thr) associated with resistance to activated protein C","volume":"91","author":"D Williamson","year":"1998","journal-title":"Blood"},{"issue":"06","key":"ref5","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1213\/01.ANE.0000113545.03192.FD","article-title":"Factor V Leiden and perioperative risk","volume":"98","author":"B S Donahue","year":"2004","journal-title":"Anesth Analg"},{"issue":"03","key":"ref6","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1073\/pnas.90.3.1004","article-title":"Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C","volume":"90","author":"B Dahlb\u00e4ck","year":"1993","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1016\/S0140-6736(05)80081-9","article-title":"Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study","volume":"342","author":"T Koster","year":"1993","journal-title":"Lancet"},{"issue":"02","key":"ref8","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1055\/s-0038-1650556","article-title":"Factor V enhances the cofactor function of protein S in the APC-mediated inactivation of factor VIII: influence of the factor VR506Q mutation","volume":"76","author":"K V\u00e1radi","year":"1996","journal-title":"Thromb Haemost"},{"issue":"46","key":"ref9","doi-asserted-by":"crossref","first-page":"27852","DOI":"10.1074\/jbc.270.46.27852","article-title":"Effects of protein S and factor Xa on peptide bond cleavages during inactivation of factor Va and factor VaR506Q by activated protein C","volume":"270","author":"J Rosing","year":"1995","journal-title":"J Biol Chem"},{"issue":"01","key":"ref10","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1159\/000315141","article-title":"Factor V is an anticoagulant cofactor for activated protein C during inactivation of factor Va","volume":"37","author":"T J Cramer","year":"2010","journal-title":"Pathophysiol Haemost Thromb"},{"issue":"11","key":"ref11","doi-asserted-by":"crossref","first-page":"3075","DOI":"10.1182\/blood.V112.11.3075.3075","article-title":"Factor V as anticoagulant cofactor for activated protein C in factor Va inactivation","volume":"112","author":"T J Cramer","year":"2008","journal-title":"Blood"},{"issue":"04","key":"ref12","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1055\/s-0034-1544003","article-title":"Diagnostics in venous thromboembolism: from origin to future prospects","volume":"41","author":"G Lippi","year":"2015","journal-title":"Semin Thromb Hemost"},{"issue":"03","key":"ref13","first-page":"809","article-title":"Combined effect of factor V Leiden and prothrombin 20210A on the risk of venous thromboembolism-pooled analysis of 8 case-control studies including 2310 cases and 3204 controls","volume":"86","author":"J Emmerich","year":"2001","journal-title":"Thromb Haemost"},{"issue":"07","key":"ref14","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1055\/s-0039-1694772","article-title":"Genetic testing for thrombophilia-related genes: observations of testing patterns for factor V Leiden (G1691A) and prothrombin gene \u201cMutation\u201d(G20210A)","volume":"45","author":"E J Favaloro","year":"2019","journal-title":"Semin Thromb Hemost"},{"issue":"244","key":"ref15","first-page":"232840","article-title":"Acquired activated protein C resistance, thrombophilia and adverse pregnancy outcomes: a study performed in an Irish cohort of pregnant women","volume":"2011","author":"S Sedano-Balb\u00e1s","year":"2011","journal-title":"J Pregnancy"},{"issue":"06","key":"ref16","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1055\/s-0038-1648978","article-title":"Laboratory diagnosis of APC-resistance: a critical evaluation of the test and the development of diagnostic criteria","volume":"72","author":"H de Ronde","year":"1994","journal-title":"Thromb Haemost"},{"issue":"09","key":"ref17","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1093\/clinchem\/43.9.1678","article-title":"Factor V Leiden and other coagulation factor mutations affecting thrombotic risk","volume":"43","author":"R M Bertina","year":"1997","journal-title":"Clin Chem"},{"issue":"04","key":"ref18","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1002\/jcla.20470","article-title":"Evolving methods for single nucleotide polymorphism detection: factor V Leiden mutation detection","volume":"25","author":"H Oh","year":"2011","journal-title":"J Clin Lab Anal"},{"issue":"05","key":"ref19","doi-asserted-by":"crossref","first-page":"577","DOI":"10.5858\/2002-126-0577-APCRTF","article-title":"Activated protein C resistance, the factor V Leiden mutation, and a laboratory testing algorithm","volume":"126","author":"E M Van Cott","year":"2002","journal-title":"Arch Pathol Lab Med"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1016\/S0140-6736(94)90494-4","article-title":"Modified APC resistance assay for patients on oral anticoagulants","volume":"344","author":"M Trossa\u00ebrt","year":"1994","journal-title":"Lancet"},{"issue":"03","key":"ref21","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/0049-3848(96)00075-8","article-title":"Factor V Leiden-dependent APC resistance: improved sensitivity and specificity of the APC resistance test by plasma dilution in factor V-depleted plasma","volume":"82","author":"M Gouault-Heilmann","year":"1996","journal-title":"Thromb Res"},{"issue":"04","key":"ref22","first-page":"715","article-title":"Low levels of protein S activity in factor V depleted plasma used in APC resistance test","volume":"80","author":"M S Samama","year":"1998","journal-title":"Thromb Haemost"},{"issue":"06","key":"ref23","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1055\/s-0037-1613954","article-title":"A new dilution for the modified APTT-based assay for activated protein C resistance: improvement of the reliability in patients with a lupus anticoagulant","volume":"83","author":"N Benattar","year":"2000","journal-title":"Thromb Haemost"},{"issue":"02","key":"ref24","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1055\/s-0038-1649817","article-title":"False positive activated protein C resistance test due to anti-phospholipid antibodies is corrected by platelet extract","volume":"74","author":"J R Martorell","year":"1995","journal-title":"Thromb Haemost"},{"issue":"06","key":"ref25","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/0049-3848(96)00043-6","article-title":"APC resistance in neonates and infants: adjustment of the APTT-based method","volume":"81","author":"U Nowak-G\u00f6ttl","year":"1996","journal-title":"Thromb Res"},{"issue":"02","key":"ref26","doi-asserted-by":"crossref","first-page":"247","DOI":"10.4103\/IJPM.IJPM_899_19","article-title":"Comparative analysis of \u201cAPTT vs RVVT\u201d based activated protein C resistance assay in the diagnosis of Factor V Leiden mutation","volume":"63","author":"M A Baig","year":"2020","journal-title":"Indian J Pathol Microbiol"},{"issue":"01","key":"ref27","first-page":"1","article-title":"The changing face of activated protein C resistance testing\u2014a 10-year retrospective","volume":"5","author":"E Dean","year":"2020","journal-title":"Ann Blood"},{"issue":"03","key":"ref28","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1055\/s-0038-1655984","article-title":"Screening for the FV:Q506 mutation\u2013evaluation of thirteen plasma-based methods for their diagnostic efficacy in comparison with DNA analysis","volume":"77","author":"A Tripodi","year":"1997","journal-title":"Thromb Haemost"},{"issue":"05","key":"ref29","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1309\/AJCP7YBJ6URTVCWP","article-title":"Comparison of Russell viper venom-based and activated partial thromboplastin time-based screening assays for resistance to activated protein C","volume":"130","author":"A Z Herskovits","year":"2008","journal-title":"Am J Clin Pathol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1159\/000092430","article-title":"The use of snake venom-derived compounds for new functional diagnostic test kits in the field of haemostasis","volume":"34","author":"R Schoni","year":"2005","journal-title":"Pathophysiol Haemost Thromb"},{"issue":"01","key":"ref31","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.thromres.2006.06.015","article-title":"Clinical evaluation of a new functional test for detection of activated protein C resistance (Pefakit APC-R Factor V Leiden) at two centers in Europe and the USA","volume":"119","author":"R Sch\u00f6ni","year":"2007","journal-title":"Thromb Res"},{"issue":"07","key":"ref32","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1097\/MBC.0b013e3282891e2f","article-title":"Clinical evaluation of a functional prothrombin time-based assay for identification of factor V Leiden carriers in a group of Italian patients with venous thrombosis","volume":"18","author":"G Gessoni","year":"2007","journal-title":"Blood Coagul Fibrinolysis"},{"key":"ref33","first-page":"137","volume-title":"Laboratory testing for activated protein C resistance (APCR)","author":"S Mohammed","year":"2017"},{"issue":"01","key":"ref34","first-page":"23","article-title":"Functional activated protein C resistance assays: correlation with factor V DNA analysis is better with RVVT-than APTT-based assays","volume":"56","author":"E J Favaloro","year":"1999","journal-title":"Br J Biomed Sci"},{"issue":"04","key":"ref35","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1080\/003130202760120526","article-title":"A 9-year retrospective assessment of laboratory testing for activated protein C resistance: evolution of a novel approach to thrombophilia investigations","volume":"34","author":"E J Favaloro","year":"2002","journal-title":"Pathology"},{"issue":"08","key":"ref36","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1515\/cclm-2019-1160","article-title":"Laboratory testing for activated protein C resistance: rivaroxaban induced interference and a comparative evaluation of andexanet alfa and DOAC Stop to neutralise interference","volume":"58","author":"E J Favaloro","year":"2020","journal-title":"Clin Chem Lab Med"},{"issue":"06","key":"ref37","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.thromres.2005.06.011","article-title":"Activated protein C resistance: the influence of ABO-blood group, gender and age","volume":"117","author":"E J Favaloro","year":"2006","journal-title":"Thromb Res"},{"issue":"05","key":"ref38","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1055\/s-0039-1692703","article-title":"Current and emerging direct oral anticoagulants: state-of-the-art","volume":"45","author":"G Lippi","year":"2019","journal-title":"Semin Thromb Hemost"},{"issue":"02","key":"ref39","doi-asserted-by":"crossref","first-page":"49","DOI":"10.21037\/aob.2018.12.04","article-title":"Oral anticoagulants around the world: an updated state-of-the art analysis","volume":"3","author":"G Lippi","year":"2018","journal-title":"Ann Blood"},{"issue":"06","key":"ref40","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1515\/cclm-2018-1041","article-title":"Danger of false negative (exclusion) or false positive (diagnosis) for 'congenital thrombophilia' in the age of anticoagulants","volume":"57","author":"E J Favaloro","year":"2019","journal-title":"Clin Chem Lab Med"},{"issue":"02","key":"ref41","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.thromres.2019.05.013","article-title":"Neutralising rivaroxaban induced interference in laboratory testing for lupus anticoagulant (LA): a comparative study using DOAC Stop and andexanet alfa","volume":"180","author":"E J Favaloro","year":"2019","journal-title":"Thromb Res"},{"issue":"04","key":"ref42","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1097\/PAT.0000000000000252","article-title":"The effect of dabigatran on haemostasis tests: a comprehensive assessment using in vitro and ex vivo samples","volume":"47","author":"R Bonar","year":"2015","journal-title":"Pathology"},{"issue":"06","key":"ref43","first-page":"491","article-title":"Interference of direct oral anticoagulants in haemostasis assays: high potential for diagnostic false positives and false negatives","volume":"15","author":"E J Favaloro","year":"2017","journal-title":"Blood Transfus"},{"issue":"06","key":"ref44","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.pathol.2020.05.006","article-title":"Oral anticoagulation therapy: an update on usage, costs and associated risks","volume":"52","author":"E J Favaloro","year":"2020","journal-title":"Pathology"},{"issue":"S 01","key":"ref45","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1111\/ijlh.13196","article-title":"The effect of DOACs on laboratory tests and their removal by activated carbon to limit interference in functional assays","volume":"42","author":"T Exner","year":"2020","journal-title":"Int J Lab Hematol"},{"issue":"03","key":"ref46","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1515\/cclm-2019-0650","article-title":"DOAC-Remove abolishes the effect of direct oral anticoagulants on activated protein C resistance testing in real-life venous thromboembolism patients","volume":"58","author":"M Kopytek","year":"2020","journal-title":"Clin Chem Lab Med"},{"issue":"12","key":"ref47","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.thromres.2019.11.001","article-title":"Potential usefulness of activated charcoal (DOAC remove\u00ae) for dRVVT testing in patients receiving Direct Oral AntiCoagulants","volume":"184","author":"G Jourdi","year":"2019","journal-title":"Thromb Res"},{"issue":"S 01","key":"ref48","doi-asserted-by":"crossref","first-page":"S109","DOI":"10.1016\/j.pathol.2020.01.374","article-title":"Neutralisation of rivaroxaban interference on APCR, FVIII and FIX assays by DOAC-StoP And andexanet ALFA","volume":"52","author":"E Dean","year":"2020","journal-title":"Pathology"},{"issue":"06","key":"ref49","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1160\/TH10-11-0767","article-title":"Molecular basis of hereditary factor V deficiency in India: identification of four novel mutations and their genotype-phenotype correlation","volume":"105","author":"A Chapla","year":"2011","journal-title":"Thromb Haemost"},{"issue":"05","key":"ref50","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1055\/s-0039-1687906","article-title":"A comprehensive overview of coagulation factor V and congenital factor V deficiency","volume":"45","author":"S Tabibian","year":"2019","journal-title":"Semin Thromb Hemost"},{"issue":"03","key":"ref51","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1055\/s-0038-1650290","article-title":"\u201cPseudo homozygous\u201d activated protein C resistance due to double heterozygous factor V defects (factor V Leiden mutation and type I quantitative factor V defect) associated with thrombosis: report of two cases belonging to two unrelated kindreds","volume":"75","author":"P Simioni","year":"1996","journal-title":"Thromb Haemost"},{"issue":"02","key":"ref52","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1046\/j.1365-2141.2003.04620.x","article-title":"Two novel factor V null mutations associated with activated protein C resistance phenotype\/genotype discrepancy","volume":"123","author":"Y Dargaud","year":"2003","journal-title":"Br J Haematol"},{"issue":"04","key":"ref53","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1002\/ajh.21617","article-title":"Analytic validity of genetic tests to identify factor V Leiden and prothrombin G20210A","volume":"85","author":"A Emadi","year":"2010","journal-title":"Am J Hematol"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/369064a0","article-title":"Mutation in blood coagulation factor V associated with resistance to activated protein C","volume":"369","author":"R M Bertina","year":"1994","journal-title":"Nature"},{"key":"ref55","volume-title":"Rodak's Hematology-E-Book: Clinical Principles and Applications","author":"E M Keohane","year":"2019"},{"issue":"07","key":"ref56","doi-asserted-by":"crossref","first-page":"2503","DOI":"10.1093\/nar\/17.7.2503","article-title":"Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS)","volume":"17","author":"C R Newton","year":"1989","journal-title":"Nucleic Acids Res"},{"issue":"01","key":"ref57","first-page":"1","article-title":"Amplification-refractory mutation system (ARMS) analysis of point mutations","volume":"7","author":"S Little","year":"1995","journal-title":"Curr Protoc Hum Genet"},{"issue":"06","key":"ref58","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1002\/(SICI)1098-2825(1996)10:6<414::AID-JCLA17>3.0.CO;2-#","article-title":"ARMS test for diagnosis of factor VLeiden mutation, a common cause of inherited thrombotic tendency","volume":"10","author":"C N Yandava","year":"1996","journal-title":"J Clin Lab Anal"},{"issue":"06","key":"ref59","doi-asserted-by":"crossref","first-page":"M361","DOI":"10.1136\/mp.49.6.M361","article-title":"Development of a rapid DNA screening procedure for the Factor V Leiden mutation","volume":"49","author":"G A Scobie","year":"1996","journal-title":"Clin Mol Pathol"},{"key":"ref60","volume-title":"Clinical Evaluation and Diagnostic Tests for Neuromuscular Disorders","author":"T E Bertorini","year":"2002"},{"key":"ref61","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-59259-726-0","volume-title":"Principles of Molecular Medicine","author":"J L Jameson","year":"1998"},{"issue":"02","key":"ref62","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1055\/s-0037-1614463","article-title":"Multiplex PCR for one-step determination of the G20210A variation and the factor V Leiden mutation by denaturing gradient gel electrophoresis (DGGE)","volume":"81","author":"S Patri","year":"1999","journal-title":"Thromb Haemost"},{"key":"ref63","first-page":"145","volume-title":"Denaturing gradient gel electrophoresis (DGGE)","author":"F Strathdee","year":"2013"},{"issue":"18","key":"ref64","doi-asserted-by":"crossref","first-page":"3055","DOI":"10.1002\/elps.1150191802","article-title":"Polymerase chain reaction-single strand conformation polymorphism or how to detect reliably and efficiently each sequence variation in many samples and many genes","volume":"19","author":"S Jaeckel","year":"1998","journal-title":"Electrophoresis"},{"issue":"03","key":"ref65","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1055\/s-0037-1614497","article-title":"A whole blood, multiplex PCR detection method for factor V Leiden and the prothrombin G20210A variant","volume":"81","author":"S Keeney","year":"1999","journal-title":"Thromb Haemost"},{"issue":"03","key":"ref66","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1177\/107602960300900307","article-title":"Detection of factor V Leiden by PCR-SSCP using GMA precast Elchrom scientific gels","volume":"9","author":"A M Simundic","year":"2003","journal-title":"Clin Appl Thromb Hemost"},{"issue":"01","key":"ref67","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1055\/s-0037-1614436","article-title":"Simultaneous genotyping for factor V Leiden and prothrombin G20210A variant by a multiplex PCR-SSCP assay on whole blood","volume":"81","author":"M Meyer","year":"1999","journal-title":"Thromb Haemost"},{"issue":"02","key":"ref68","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S1084-8592(99)80037-X","article-title":"Non-PCR-dependent detection of the factor V Leiden mutation from genomic DNA using a homogeneous invader microtiter plate assay","volume":"4","author":"D Ryan","year":"1999","journal-title":"Mol Diagn"},{"key":"ref69","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1093\/clinchem\/46.8.1051","article-title":"Genotyping of factor V G1691A (Leiden) without the use of PCR by invasive cleavage of oligonucleotide probes","volume":"46","author":"M J Hessner","year":"2000","journal-title":"Clin Chem"},{"issue":"02","key":"ref70","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S1525-1578(10)60623-X","article-title":"A multi-site study for detection of the factor V (Leiden) mutation from genomic DNA using a homogeneous invader microtiter plate fluorescence resonance energy transfer (FRET) assay","volume":"2","author":"M Ledford","year":"2000","journal-title":"J Mol Diagn"},{"issue":"17","key":"ref71","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.cca.2018.11.016","article-title":"Direct blood PCR: TaqMan-probe based detection of the venous thromboembolism associated mutations factor V Leiden and prothrombin c.20210G>A without DNA extraction","volume":"488","author":"K Geiger","year":"2019","journal-title":"Clin Chim Acta"},{"issue":"04","key":"ref72","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1006\/mcpr.2000.0313","article-title":"Factor V Leiden genotyping using real-time fluorescent polymerase chain reaction","volume":"14","author":"J Sanders Sevall","year":"2000","journal-title":"Mol Cell Probes"},{"issue":"12","key":"ref73","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1515\/CCLM.2004.255","article-title":"Rapid combined genotyping of factor V, prothrombin and methylenetetrahydrofolate reductase single nucleotide polymorphisms using minor groove binding DNA oligonucleotides (MGB probes) and real-time polymerase chain reaction","volume":"42","author":"M Louis","year":"2004","journal-title":"Clin Chem Lab Med"},{"issue":"05","key":"ref74","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1097\/00001721-200307000-00012","article-title":"Evaluation of the Roche LightCycler: a simple and rapid method for direct detection of factor V Leiden and prothrombin G20210A genotypes from blood samples without the need for DNA extraction","volume":"14","author":"P C Cooper","year":"2003","journal-title":"Blood Coagul Fibrinolysis"},{"issue":"12","key":"ref75","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.1093\/clinchem\/43.12.2262","article-title":"Real-time fluorescence genotyping of factor V Leiden during rapid-cycle PCR","volume":"43","author":"M J Lay","year":"1997","journal-title":"Clin Chem"},{"issue":"04","key":"ref76","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S1084-8592(98)80041-6","article-title":"Detection and identification of base alterations within the region of factor V Leiden by fluorescent melting curves","volume":"3","author":"E Lyondagger","year":"1998","journal-title":"Mol Diagn"},{"issue":"01","key":"ref77","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1586\/14737159.1.1.92","article-title":"Mutation detection using fluorescent hybridization probes and melting curve analysis","volume":"1","author":"E Lyon","year":"2001","journal-title":"Expert Rev Mol Diagn"},{"issue":"06","key":"ref78","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.2144\/03346pf01","article-title":"The LightTyper: high-throughput genotyping using fluorescent melting curve analysis","volume":"34","author":"C D Bennett","year":"2003","journal-title":"Biotechniques"},{"issue":"04","key":"ref79","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/ng1201-365","article-title":"Minimum information about a microarray experiment (MIAME)-toward standards for microarray data","volume":"29","author":"A Brazma","year":"2001","journal-title":"Nat Genet"},{"key":"ref80","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1126\/science.270.5235.467","article-title":"Quantitative monitoring of gene expression patterns with a complementary DNA microarray","volume":"270","author":"M Schena","year":"1995","journal-title":"Science"},{"issue":"02","key":"ref81","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.yexmp.2009.06.002","article-title":"Evaluation of the Nanosphere Verigene System and the Verigene F5\/F2\/MTHFR Nucleic Acid Tests","volume":"87","author":"J A Lefferts","year":"2009","journal-title":"Exp Mol Pathol"},{"issue":"08","key":"ref82","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1039\/b603963d","article-title":"Subfemtomolar electrochemical detection of target DNA by catalytic enlargement of the hybridized gold nanoparticle labels","volume":"131","author":"M Rochelet-Dequaire","year":"2006","journal-title":"Analyst (Lond)"},{"issue":"03","key":"ref83","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1586\/14737159.6.3.287","article-title":"Microelectronic array system for molecular diagnostic genotyping: Nanogen NanoChip 400 and molecular biology workstation","volume":"6","author":"D Keen-Kim","year":"2006","journal-title":"Expert Rev Mol Diagn"},{"issue":"09","key":"ref84","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1093\/clinchem\/48.9.1406","article-title":"Determination of the factor V Leiden single-nucleotide polymorphism in a commercial clinical laboratory by use of NanoChip microelectronic array technology","volume":"48","author":"J G Evans","year":"2002","journal-title":"Clin Chem"},{"issue":"04","key":"ref85","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1309\/3VTR7TL2X7TXL0QY","article-title":"Diagnostic single nucleotide polymorphism analysis of factor V Leiden and prothrombin 20210G > A. A comparison of the Nanogen Eelectronic Microarray with restriction enzyme digestion and the Roche LightCycler","volume":"119","author":"I Schrijver","year":"2003","journal-title":"Am J Clin Pathol"},{"issue":"12","key":"ref86","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1038\/s41436-018-0322-z","article-title":"Venous thromboembolism laboratory testing (factor V Leiden and factor II c.*97G>A), 2018 update: a technical standard of the American College of Medical Genetics and Genomics (ACMG)","volume":"20","author":"S Zhang","year":"2018","journal-title":"Genet Med"},{"issue":"02","key":"ref87","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1097\/00125817-200103000-00009","article-title":"American College of Medical Genetics consensus statement on factor V Leiden mutation testing","volume":"3","author":"W W Grody","year":"2001","journal-title":"Genet Med"},{"issue":"12","key":"ref88","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.1038\/s41436-021-01108-x","article-title":"Addendum: American College of Medical Genetics consensus statement on factor V Leiden mutation testing","volume":"23","author":"S Bhatt","year":"2021","journal-title":"Genet Med"},{"issue":"07","key":"ref89","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1161\/01.CIR.0000051864.28048.01","article-title":"Factor V Leiden protects against blood loss and transfusion after cardiac surgery","volume":"107","author":"B S Donahue","year":"2003","journal-title":"Circulation"},{"issue":"08","key":"ref90","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.1182\/blood.V89.8.2817","article-title":"Factor V Leiden (resistance to activated protein C) increases the risk of myocardial infarction in young women","volume":"89","author":"F R Rosendaal","year":"1997","journal-title":"Blood"},{"issue":"11","key":"ref91","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.5858\/2002-126-1304-CUOFVL","article-title":"Clinical utility of factor V Leiden (R506Q) testing for the diagnosis and management of thromboembolic disorders","volume":"126","author":"R D Press","year":"2002","journal-title":"Arch Pathol Lab Med"},{"issue":"01","key":"ref92","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/GIM.0b013e3181faa0f2","article-title":"Factor V Leiden thrombophilia","volume":"13","author":"J L Kujovich","year":"2011","journal-title":"Genet Med"},{"issue":"16","key":"ref93","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1001\/jama.1997.03540400055031","article-title":"Ethnic distribution of factor V Leiden in 4047 men and women. Implications for venous thromboembolism screening","volume":"277","author":"P M Ridker","year":"1997","journal-title":"JAMA"},{"key":"ref94","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1016\/S0140-6736(95)91803-5","article-title":"World distribution of factor V Leiden","volume":"346","author":"D C Rees","year":"1995","journal-title":"Lancet"},{"issue":"12","key":"ref95","first-page":"1305","article-title":"Factor V Leiden mutation and the risk of venous thromboembolism in pregnant women","volume":"86","author":"D Tormene","year":"2001","journal-title":"Haematologica"},{"issue":"02","key":"ref96","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1111\/j.1479-828X.2000.tb01144.x","article-title":"Factor V Leiden as a risk factor for miscarriage and reduced fertility","volume":"40","author":"S N Bar\u00e9","year":"2000","journal-title":"Aust N Z J Obstet Gynaecol"},{"issue":"02","key":"ref97","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1182\/blood-2002-02-0343","article-title":"Functional characterization of recombinant FV Hong Kong and FV Cambridge","volume":"100","author":"E Norstr\u00f8m","year":"2002","journal-title":"Blood"},{"issue":"15","key":"ref98","doi-asserted-by":"crossref","first-page":"2420","DOI":"10.1182\/blood-2013-10-530089","article-title":"Novel FV mutation (W1920R, FVNara) associated with serious deep vein thrombosis and more potent APC resistance relative to FVLeiden","volume":"123","author":"K Nogami","year":"2014","journal-title":"Blood"},{"issue":"03","key":"ref99","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1046\/j.1365-2141.2003.04624.x","article-title":"Factor V I359T: a novel mutation associated with thrombosis and resistance to activated protein C","volume":"123","author":"A D Mumford","year":"2003","journal-title":"Br J Haematol"},{"issue":"07","key":"ref100","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1111\/jth.13339","article-title":"Identification and functional characterization of a novel F5 mutation (Ala512Val, FVB onn ) associated with activated protein C resistance","volume":"14","author":"B Pezeshkpoor","year":"2016","journal-title":"J Thromb Haemost"},{"issue":"12","key":"ref101","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1007\/s00277-008-0543-3","article-title":"Factor V HR2 haplotype: a risk factor for venous thromboembolism in individuals with absence of Factor V Leiden","volume":"87","author":"Z K Otrock","year":"2008","journal-title":"Ann Hematol"}],"container-title":["Seminars in Thrombosis and Hemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0043-1770773.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:03:09Z","timestamp":1738281789000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0043-1770773"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,10]]},"references-count":101,"journal-issue":{"issue":"08","published-online":{"date-parts":[[2024,10,11]]},"published-print":{"date-parts":[[2024,11]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0043-1770773","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0094-6176","1098-9064"],"issn-type":[{"value":"0094-6176","type":"print"},{"value":"1098-9064","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,10]]}}}