{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:25:49Z","timestamp":1791419149337,"version":"4.3.3"},"reference-count":75,"publisher":"Georg Thieme Verlag KG","issue":"06","license":[{"start":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T00:00:00Z","timestamp":1671667200000},"content-version":"vor","delay-in-days":21,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hamostaseologie"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hemophilia A and hemophilia B are rare congenital, recessive X-linked disorders caused by lack or deficiency of clotting factor VIII (FVIII) or IX (FIX), respectively. The severity of the disease depends on the reduction of coagulation FVIII or FIX activity levels, which is determined by the type of the pathogenic variants in the genes encoding the two factors (F8 and F9, respectively). Molecular genetic analysis is widely applied in inherited bleeding disorders. The outcome of genetic analysis allows genetic counseling of affected families and helps find a link between the genotype and the phenotype. Genetic analysis in hemophilia has tremendously improved in the last decades. Many new techniques and modifications as well as analysis softwares became available, which made the genetic analysis and interpretation of the data faster and more accurate. Advances in genetic variant detection strategies facilitate identification of the causal variants in up to 97% of patients. In this review, we discuss the milestones in genetic analysis of hemophilia and highlight the importance of identification of the causative genetic variants for genetic counseling and particularly for the interpretation of the clinical presentation of hemophilia patients.<\/jats:p>","DOI":"10.1055\/a-1945-9429","type":"journal-article","created":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T23:30:11Z","timestamp":1671751811000},"page":"390-399","source":"Crossref","is-referenced-by-count":37,"title":["Insights into the Molecular Genetic of Hemophilia A and Hemophilia B: The Relevance of Genetic Testing in Routine Clinical Practice"],"prefix":"10.1055","volume":"42","author":[{"given":"Behnaz","family":"Pezeshkpoor","sequence":"additional","affiliation":[{"name":"Institute of Experimental Hematology and Transfusion Medicine, Medical Faculty, University of Bonn, University Hospital Bonn, Bonn, Germany"},{"name":"Center for Rare Diseases Bonn (ZSEB), University Clinic Bonn, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Oldenburg","sequence":"additional","affiliation":[{"name":"Institute of Experimental Hematology and Transfusion Medicine, Medical Faculty, University of Bonn, University Hospital Bonn, Bonn, Germany"},{"name":"Center for Rare Diseases Bonn (ZSEB), University Clinic Bonn, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Pavlova","sequence":"additional","affiliation":[{"name":"Institute of Experimental Hematology and Transfusion Medicine, Medical Faculty, University of Bonn, University Hospital Bonn, Bonn, Germany"},{"name":"Center for Rare Diseases Bonn (ZSEB), University Clinic Bonn, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2022,12,22]]},"reference":[{"issue":"11","key":"ref1","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1111\/jth.12672","article-title":"Definitions in hemophilia: communication from the SSC of the ISTH","volume":"12","author":"V S Blanchette","year":"2014","journal-title":"J Thromb Haemost"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1016\/S0140-6736(11)61139-2","article-title":"Modern haemophilia care","volume":"379","author":"E Berntorp","year":"2012","journal-title":"Lancet"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/190372a0","article-title":"Gene action in the X-chromosome of the mouse (Mus musculus L.)","volume":"190","author":"M F Lyon","year":"1961","journal-title":"Nature"},{"issue":"02","key":"ref4","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s00439-011-1013-x","article-title":"Mary Lyon and the hypothesis of random X chromosome inactivation","volume":"130","author":"P S Harper","year":"2011","journal-title":"Hum Genet"},{"issue":"04","key":"ref5","doi-asserted-by":"crossref","first-page":"e280","DOI":"10.1111\/hae.12448","article-title":"Prospective observational cohort studies for studying rare diseases: the European PedNet Haemophilia Registry","volume":"20","author":"K Fischer","year":"2014","journal-title":"Haemophilia"},{"issue":"01","key":"ref6","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1111\/hae.13637","article-title":"Recommendations for the clinical interpretation of genetic variants and presentation of results to patients with inherited bleeding disorders. A UK Haemophilia Centre Doctors' Organisation Good Practice Paper","volume":"25","author":"K Gomez","year":"2019","journal-title":"Haemophilia"},{"issue":"02","key":"ref7","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1111\/hae.14186","article-title":"Genetic causes of haemophilia in women and girls","volume":"27","author":"C H Miller","year":"2021","journal-title":"Haemophilia"},{"issue":"06","key":"ref8","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1111\/j.1538-7836.2009.03346.x","article-title":"Molecular mechanisms underlying hemophilia A phenotype in seven females","volume":"7","author":"A Pavlova","year":"2009","journal-title":"J Thromb Haemost"},{"issue":"02","key":"ref9","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1182\/blood.V85.2.599.599","article-title":"A skewed lyonization phenomenon as cause of hemophilia A in a female patient","volume":"85","author":"M Acquila","year":"1995","journal-title":"Blood"},{"issue":"10","key":"ref10","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1002\/ajh.21219","article-title":"Female monozygotic twins discordant for hemophilia A due to nonrandom X-chromosome inactivation","volume":"83","author":"C M Bennett","year":"2008","journal-title":"Am J Hematol"},{"issue":"04","key":"ref11","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1111\/jth.12854","article-title":"Phenotype-genotype correlations in hemophilia A carriers are consistent with the binary role of the phase between F8 and X-chromosome inactivation","volume":"13","author":"C P Radic","year":"2015","journal-title":"J Thromb Haemost"},{"issue":"13","key":"ref12","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1182\/blood-2014-08-532820","article-title":"Rare bleeding disorders: diagnosis and treatment","volume":"125","author":"R Palla","year":"2015","journal-title":"Blood"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1038\/312326a0","article-title":"Characterization of the human factor VIII gene","volume":"312","author":"J Gitschier","year":"1984","journal-title":"Nature"},{"issue":"06","key":"ref14","first-page":"867","article-title":"Moderately severe hemophilia A resulting from Glu\u2013Gly substitution in exon 7 of the factor VIII gene","volume":"42","author":"H Youssoufian","year":"1988","journal-title":"Am J Hum Genet"},{"issue":"04","key":"ref15","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1086\/302065","article-title":"Methylation levels at selected CpG sites in the factor VIII and FGFR3 genes, in mature female and male germ cells: implications for male-driven evolution","volume":"63","author":"O El-Maarri","year":"1998","journal-title":"Am J Hum Genet"},{"issue":"02","key":"ref16","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1055\/s-0037-1615015","article-title":"Small deletion\/insertion mutations within poly-A runs of the factor VIII gene mitigate the severe haemophilia A phenotype","volume":"79","author":"J Oldenburg","year":"1998","journal-title":"Thromb Haemost"},{"issue":"05","key":"ref17","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1002\/em.22087","article-title":"Mechanisms of DNA damage, repair, and mutagenesis","volume":"58","author":"N Chatterjee","year":"2017","journal-title":"Environ Mol Mutagen"},{"issue":"01","key":"ref18","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1182\/blood.V99.1.168","article-title":"Recurrent inversion breaking intron 1 of the factor VIII gene is a frequent cause of severe hemophilia A","volume":"99","author":"R D Bagnall","year":"2002","journal-title":"Blood"},{"issue":"07","key":"ref19","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1093\/hmg\/4.7.1217","article-title":"Investigation of the factor VIII intron 22 repeated region (int22h) and the associated inversion junctions","volume":"4","author":"J A Naylor","year":"1995","journal-title":"Hum Mol Genet"},{"issue":"03","key":"ref20","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/ng1193-236","article-title":"Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A","volume":"5","author":"D Lakich","year":"1993","journal-title":"Nat Genet"},{"issue":"07","key":"ref21","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1093\/hmg\/3.7.1035","article-title":"Factor VIII gene inversions causing severe hemophilia A originate almost exclusively in male germ cells","volume":"3","author":"J P Rossiter","year":"1994","journal-title":"Hum Mol Genet"},{"issue":"05","key":"ref22","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s004390050981","article-title":"A deletion\/insertion leading to the generation of a direct repeat as a result of slipped mispairing and intragenic recombination in the factor VIII gene","volume":"104","author":"K Tavassoli","year":"1999","journal-title":"Hum Genet"},{"issue":"01","key":"ref23","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1055\/s-0037-1613146","article-title":"First molecular characterization of an unequal homologous Alu-mediated recombination event responsible for hemophilia","volume":"88","author":"F Vidal","year":"2002","journal-title":"Thromb Haemost"},{"issue":"01","key":"ref25","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.tig.2013.09.007","article-title":"Hemophilia B Leyden and once mysterious cis-regulatory mutations","volume":"30","author":"A PW Funnell","year":"2014","journal-title":"Trends Genet"},{"issue":"02","key":"ref26","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/BF00319731","article-title":"Haemophilia A: carrier detection by DNA analysis","volume":"57","author":"R Schwaab","year":"1988","journal-title":"Blut"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/1471-2350-9-53","article-title":"Mutation spectrum of 122 hemophilia A families from Taiwanese population by LD-PCR, DHPLC, multiplex PCR and evaluating the clinical application of HRM","volume":"9","author":"S-Y Lin","year":"2008","journal-title":"BMC Med Genet"},{"issue":"16","key":"ref28","doi-asserted-by":"crossref","first-page":"7405","DOI":"10.1073\/pnas.88.16.7405","article-title":"Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene","volume":"88","author":"M Higuchi","year":"1991","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"07","key":"ref29","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1373\/clinchem.2004.046490","article-title":"Genotyping the hemophilia inversion hotspot by use of inverse PCR","volume":"51","author":"L C Rossetti","year":"2005","journal-title":"Clin Chem"},{"issue":"05","key":"ref30","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1111\/j.1538-7836.2008.02926.x","article-title":"Developing a new generation of tests for genotyping hemophilia-causative rearrangements involving int22h and int1h hotspots in the factor VIII gene","volume":"6","author":"L C Rossetti","year":"2008","journal-title":"J Thromb Haemost"},{"issue":"07","key":"ref31","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1056\/NEJMp1400788","article-title":"Genotype-phenotype correlation\u2013promiscuity in the era of next-generation sequencing","volume":"371","author":"J T Lu","year":"2014","journal-title":"N Engl J Med"},{"issue":"07","key":"ref32","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1002\/humu.22332","article-title":"Targeted next-generation sequencing can replace Sanger sequencing in clinical diagnostics","volume":"34","author":"B Sikkema-Raddatz","year":"2013","journal-title":"Hum Mutat"},{"issue":"04","key":"ref33","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1111\/hae.12908","article-title":"Design and application of a 23-gene panel by next-generation sequencing for inherited coagulation bleeding disorders","volume":"22","author":"J M Bastida","year":"2016","journal-title":"Haemophilia"},{"issue":"05","key":"ref34","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"S Richards","year":"2015","journal-title":"Genet Med"},{"issue":"01","key":"ref35","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1160\/TH16-05-0375","article-title":"Application of a molecular diagnostic algorithm for haemophilia A and B using next-generation sequencing of entire F8, F9 and VWF genes","volume":"117","author":"J M Bastida","year":"2017","journal-title":"Thromb Haemost"},{"issue":"08","key":"ref36","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1111\/jth.14945","article-title":"Strengths and limitations of high-throughput sequencing for the diagnosis of inherited bleeding and platelet disorders","volume":"18","author":"F Ver Donck","year":"2020","journal-title":"J Thromb Haemost"},{"issue":"S 11","key":"ref37","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1186\/1471-2105-14-S11-S1","article-title":"Computational tools for copy number variation (CNV) detection using next-generation sequencing data: features and perspectives","volume":"14","author":"M Zhao","year":"2013","journal-title":"BMC Bioinformatics"},{"issue":"03","key":"ref38","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1177\/1073110517737531","article-title":"The continuing evolution of ethical standards for genomic sequencing in clinical care: restoring patient choice","volume":"45","author":"S M Wolf","year":"2017","journal-title":"J Law Med Ethics"},{"issue":"08","key":"ref39","doi-asserted-by":"crossref","first-page":"e12637","DOI":"10.1002\/rth2.12637","article-title":"Hemostatic phenotypes and genetic disorders","volume":"5","author":"F Ver Donck","year":"2021","journal-title":"Res Pract Thromb Haemost"},{"issue":"02","key":"ref40","doi-asserted-by":"crossref","first-page":"167","DOI":"10.5482\/HAMO-13-08-0043","article-title":"F8 genetic analysis strategies when standard approaches fail","volume":"34","author":"B Pezeshkpoor","year":"2014","journal-title":"Hamostaseologie"},{"issue":"S 02","key":"ref41","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.1055\/s-0037-1617062","article-title":"VKCFD2 - from clinical phenotype to molecular mechanism","volume":"36","author":"K J Czogalla","year":"2016","journal-title":"Hamostaseologie"},{"issue":"S 06","key":"ref42","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1111\/hae.13501","article-title":"Women with bleeding disorders: clinical and psychological issues","volume":"24","author":"C McLintock","year":"2018","journal-title":"Haemophilia"},{"issue":"03","key":"ref43","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1111\/j.1365-2141.2008.07391.x","article-title":"Preimplantation genetic diagnosis of haemophilia","volume":"144","author":"S Lavery","year":"2009","journal-title":"Br J Haematol"},{"issue":"07","key":"ref44","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1111\/jth.14825","article-title":"The experiences and attitudes of hemophilia carriers around pregnancy: a qualitative systematic review","volume":"18","author":"M C Punt","year":"2020","journal-title":"J Thromb Haemost"},{"issue":"06","key":"ref45","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1007\/s10897-015-9834-8","article-title":"Uptake of genetic counseling, knowledge of bleeding risks and psychosocial impact in a South African cohort of female relatives of people with hemophilia","volume":"24","author":"A Gillham","year":"2015","journal-title":"J Genet Couns"},{"issue":"06","key":"ref46","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1007\/s10897-017-0112-9","article-title":"\u201cIt was a lot tougher than I thought it would be\u201d. A qualitative study on the changing nature of being a hemophilia carrier","volume":"26","author":"C von der Lippe","year":"2017","journal-title":"J Genet Couns"},{"issue":"01","key":"ref47","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1046\/j.1365-2516.2000.00353.x","article-title":"Reproductive choices of women in families with haemophilia","volume":"6","author":"R A Kadir","year":"2000","journal-title":"Haemophilia"},{"issue":"04","key":"ref48","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1111\/j.1538-7836.2010.03768.x","article-title":"Preimplantation genetic diagnosis for hemophilia A using indirect linkage analysis and direct genotyping approaches","volume":"8","author":"A D Laurie","year":"2010","journal-title":"J Thromb Haemost"},{"issue":"02","key":"ref49","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1046\/j.1365-2516.1999.00295.x","article-title":"Prenatal diagnosis of haemophilia","volume":"5","author":"R C Ljung","year":"1999","journal-title":"Haemophilia"},{"issue":"06","key":"ref50","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1111\/hae.12247","article-title":"Third trimester amniocentesis for diagnosis of inherited bleeding disorders prior to delivery","volume":"19","author":"J Cutler","year":"2013","journal-title":"Haemophilia"},{"issue":"04","key":"ref51","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1046\/j.1365-2141.1999.01631.x","article-title":"Origin of mutation in sporadic cases of haemophilia A","volume":"106","author":"R C Ljung","year":"1999","journal-title":"Br J Haematol"},{"issue":"01","key":"ref52","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1086\/321285","article-title":"Somatic mosaicism in hemophilia A: a fairly common event","volume":"69","author":"M Leuer","year":"2001","journal-title":"Am J Hum Genet"},{"issue":"06","key":"ref53","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1111\/j.1365-2516.2009.02003.x","article-title":"Mosaics and haemophilia","volume":"15","author":"C K Kasper","year":"2009","journal-title":"Haemophilia"},{"issue":"03","key":"ref54","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1111\/hae.13975","article-title":"Genetic mosaicism in haemophilia: a practical review to help evaluate the risk of transmitting the disease","volume":"26","author":"N Lannoy","year":"2020","journal-title":"Haemophilia"},{"issue":"06","key":"ref55","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1111\/hae.12516","article-title":"Prenatal diagnosis of haemophilia in Sweden now more commonly used for psychological preparation than termination of pregnancy","volume":"20","author":"A M\u00e5rtensson","year":"2014","journal-title":"Haemophilia"},{"issue":"01","key":"ref56","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1111\/hex.12602","article-title":"The role of experiential knowledge within attitudes towards genetic carrier screening: a comparison of people with and without experience of spinal muscular atrophy","volume":"21","author":"F K Boardman","year":"2018","journal-title":"Health Expect"},{"issue":"03","key":"ref57","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1182\/blood-2016-12-755017","article-title":"Noninvasive detection of F8 int22h-related inversions and sequence variants in maternal plasma of hemophilia carriers","volume":"130","author":"I Hudecova","year":"2017","journal-title":"Blood"},{"issue":"03","key":"ref58","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1182\/blood.2019000658","article-title":"Timing of inhibitor development in more than 1000 previously untreated patients with severe hemophilia A","volume":"134","author":"H M van den Berg","year":"2019","journal-title":"Blood"},{"issue":"01","key":"ref59","doi-asserted-by":"crossref","first-page":"123","DOI":"10.3324\/haematol.2019.239160","article-title":"Inhibitor incidence in an unselected cohort of previously untreated patients with severe haemophilia B: a PedNet study","volume":"106","author":"C Male","year":"2021","journal-title":"Haematologica"},{"issue":"13","key":"ref60","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1182\/blood-2014-08-535328","article-title":"FVIII inhibitors: pathogenesis and avoidance","volume":"125","author":"J Astermark","year":"2015","journal-title":"Blood"},{"issue":"12","key":"ref61","doi-asserted-by":"crossref","first-page":"2922","DOI":"10.1182\/blood-2011-09-379453","article-title":"F8 gene mutation type and inhibitor development in patients with severe hemophilia A: systematic review and meta-analysis","volume":"119","author":"S C Gouw","year":"2012","journal-title":"Blood"},{"issue":"S 06","key":"ref62","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/j.1365-2516.2006.01361.x","article-title":"Genetic risk factors for inhibitors to factors VIII and IX","volume":"12","author":"J Oldenburg","year":"2006","journal-title":"Haemophilia"},{"issue":"07","key":"ref63","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1111\/jth.12990","article-title":"Inhibitor development and mortality in non-severe hemophilia A","volume":"13","author":"C L Eckhardt","year":"2015","journal-title":"J Thromb Haemost"},{"issue":"15","key":"ref64","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1182\/blood-2014-02-546127","article-title":"Molecular and clinical predictors of inhibitor risk and its prevention and treatment in mild hemophilia A","volume":"124","author":"G Castaman","year":"2014","journal-title":"Blood"},{"issue":"S 77","key":"ref65","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/ejh.12495","article-title":"Genetic risk factors for inhibitors in haemophilia A","volume":"94","author":"E Bardi","year":"2015","journal-title":"Eur J Haematol"},{"issue":"07","key":"ref66","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1055\/s-0033-1354426","article-title":"Defining severity of hemophilia: more than factor levels","volume":"39","author":"A Pavlova","year":"2013","journal-title":"Semin Thromb Hemost"},{"issue":"03","key":"ref67","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1055\/s-0037-1613824","article-title":"Effect of the factor V Leiden mutation on the clinical expression of severe hemophilia A","volume":"83","author":"D H Lee","year":"2000","journal-title":"Thromb Haemost"},{"issue":"02","key":"ref68","doi-asserted-by":"crossref","first-page":"347","DOI":"10.3390\/jcm10020347","article-title":"Familial multiple coagulation factor deficiencies (FMCFDs) in a large cohort of patients - a single-center experience in genetic diagnosis","volume":"10","author":"B Preisler","year":"2021","journal-title":"J Clin Med"},{"issue":"02","key":"ref69","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1055\/s-0037-1615679","article-title":"Symptomatic onset of severe hemophilia A in childhood is dependent on the presence of prothrombotic risk factors","volume":"85","author":"C Escuriola Ettingshausen","year":"2001","journal-title":"Thromb Haemost"},{"issue":"05","key":"ref70","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1111\/j.1538-7836.2007.02447.x","article-title":"Phenotype of severe hemophilia A and plasma levels of risk factors for thrombosis","volume":"5","author":"K van Dijk","year":"2007","journal-title":"J Thromb Haemost"},{"issue":"04","key":"ref71","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1111\/j.1365-2141.2007.06693.x","article-title":"Contribution of natural anticoagulant and fibrinolytic factors in modulating the clinical severity of haemophilia patients","volume":"138","author":"S Shetty","year":"2007","journal-title":"Br J Haematol"},{"issue":"06","key":"ref72","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1111\/jth.12902","article-title":"Evaluation of von Willebrand factor phenotypes and genotypes in hemophilia A patients with and without identified F8 mutations","volume":"13","author":"B Boylan","year":"2015","journal-title":"J Thromb Haemost"},{"issue":"06","key":"ref73","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1002\/pbc.23120","article-title":"Therapeutic consequences for misdiagnosis of type 2N von Willebrand disease","volume":"57","author":"M Gupta","year":"2011","journal-title":"Pediatr Blood Cancer"},{"issue":"02","key":"ref74","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1053\/beha.2001.0138","article-title":"Type 2N von Willebrand disease: clinical manifestations, pathophysiology, laboratory diagnosis and molecular biology","volume":"14","author":"C Mazurier","year":"2001","journal-title":"Best Pract Res Clin Haematol"},{"issue":"05","key":"ref75","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1160\/TH13-08-0690","article-title":"Haemophilia A mutations in patients with non-severe phenotype associated with a discrepancy between one-stage and chromogenic factor VIII activity assays","volume":"111","author":"A Pavlova","year":"2014","journal-title":"Thromb Haemost"},{"issue":"04","key":"ref76","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1046\/j.1365-2141.1999.01460.x","article-title":"Diagnostic importance of the two-stage factor VIII:C assay demonstrated by a case of mild haemophilia associated with His1954\u2013>Leu substitution in the factor VIII A3 domain","volume":"105","author":"D M Keeling","year":"1999","journal-title":"Br J Haematol"}],"container-title":["H\u00e4mostaseologie"],"original-title":[],"language":"de","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-1945-9429.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T23:33:13Z","timestamp":1671751993000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-1945-9429"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12]]},"references-count":75,"journal-issue":{"issue":"06","published-online":{"date-parts":[[2022,12,22]]},"published-print":{"date-parts":[[2022,12]]}},"URL":"https:\/\/doi.org\/10.1055\/a-1945-9429","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0720-9355","2567-5761"],"issn-type":[{"value":"0720-9355","type":"print"},{"value":"2567-5761","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12]]}}}