{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:05:31Z","timestamp":1783987531514,"version":"3.55.0"},"reference-count":78,"publisher":"Georg Thieme Verlag KG","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Thromb Hemost"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The human coagulation system has resulted from thousands of years of evolutionary pressure, finely balancing the competing risks of lethal hemorrhage and catastrophic thrombosis. There are several examples of the close interaction between the two opposing sides of hemostasis. A paradigmatic case is offered by the factor V Leiden mutation. Emerging approximately 22,000 years ago, this gain-of-function variant is now expressed in approximately 5% of Caucasians. While it now significantly elevates the risk of venous thromboembolism, it historically provided crucial evolutionary advantages, including reduced peripartum blood loss, enhanced iron stores, improved fertility, and increased embryo implantation rates. Conversely, congenital hypocoagulable states, such as hemophilia, demonstrate the other side of the coin. With modern therapeutic advances now extend the life expectancy of individuals with hemophilia, clinicians are increasingly managing age-related comorbidities. While experimental models suggest a chr onic hypocoagulable state might mitigate the risk of occlusive cardiovascular events or suppress cancer metastasis, clinical and epidemiological data remain conflicting. Mild factor deficiencies may offer some protection against ischemic heart disease, but overall cardiovascular and oncological risk profiles in patients with hemophilia increasingly mirror those of the aging general population. This review explores the genetic and environmental forces that shape this homeostatic equilibrium, illustrating how historical survival mechanisms influence modern disease patterns.<\/jats:p>","DOI":"10.1055\/a-2905-4308","type":"journal-article","created":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T00:20:58Z","timestamp":1783124458000},"source":"Crossref","is-referenced-by-count":0,"title":["Human Evolution: Between Hemorrhage and Thrombosis"],"prefix":"10.1055","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8795-0580","authenticated-orcid":false,"given":"Massimo","family":"Franchini","sequence":"additional","affiliation":[{"name":"Carlo Poma Hospital, Italy","department":["Department of Transfusion Medicine and Hematology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Zani","sequence":"additional","affiliation":[{"name":"Carlo Poma Hospital, Italy","department":["Department of Transfusion Medicine and Hematology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Focosi","sequence":"additional","affiliation":[{"name":"Azienda USL Toscana Nord-Ovest, Nuovo Ospedale Apuane, Italy","department":["Division of Immunohematology and Transfusion Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"issue":"03","key":"ref1","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s11739-008-0171-x","article-title":"Mankind adaptation and present human health","volume":"3","author":"F Contaldo","year":"2008","journal-title":"Intern Emerg Med"},{"issue":"08","key":"ref2","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1007\/s11739-013-1017-8","article-title":"Human genome, environment and medical practice","volume":"8","author":"G Di Minno","year":"2013","journal-title":"Intern Emerg Med"},{"issue":"01","key":"ref3","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s11739-008-0100-z","article-title":"The hemostatic balance revisited through the lessons of mankind evolution","volume":"3","author":"M Franchini","year":"2008","journal-title":"Intern Emerg Med"},{"issue":"02","key":"ref4","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.thromres.2009.11.003","article-title":"Factor V Leiden and hemophilia","volume":"125","author":"M Franchini","year":"2010","journal-title":"Thromb Res"},{"issue":"03","key":"ref5","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1055\/s-0031-1273091","article-title":"Factor V Leiden in women: a thrombotic risk factor or an evolutionary advantage?","volume":"37","author":"M Franchini","year":"2011","journal-title":"Semin Thromb Hemost"},{"issue":"06","key":"ref6","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1177\/1076029611412370","article-title":"Factor V Leiden and natural selection","volume":"17","author":"N Akar","year":"2011","journal-title":"Clin Appl Thromb Hemost"},{"issue":"01","key":"ref7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1182\/asheducation-2016.1.1","article-title":"Inherited thrombophilia: a double-edged sword","volume":"2016","author":"S Middeldorp","year":"2016","journal-title":"Hematology (Am Soc Hematol Educ Program)"},{"issue":"15","key":"ref8","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.2174\/092986708784638852","article-title":"Carriership of Factor V Leiden and evolutionary selection advantage","volume":"15","author":"P G Lindqvist","year":"2008","journal-title":"Curr Med Chem"},{"issue":"32","key":"ref9","doi-asserted-by":"crossref","first-page":"3676","DOI":"10.2174\/0929867322666151001121707","article-title":"On the evolutionary advantage of coagulation factor V Leiden (FVL)","volume":"22","author":"P G Lindqvist","year":"2015","journal-title":"Curr Med Chem"},{"issue":"01","key":"ref10","first-page":"23","article-title":"Evolution of factor V Leiden","volume":"110","author":"T E van Mens","year":"2013","journal-title":"Thromb Haemost"},{"key":"ref11","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":"02","key":"ref12","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1182\/blood.V89.2.397","article-title":"A single genetic origin for a common Caucasian risk factor for venous thrombosis","volume":"89","author":"A Zivelin","year":"1997","journal-title":"Blood"},{"issue":"01","key":"ref13","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1055\/s-0037-1614222","article-title":"Factor V Q506 mutation (activated protein C resistance) associated with reduced intrapartum blood loss\u2013a possible evolutionary selection mechanism","volume":"79","author":"P G Lindqvist","year":"1998","journal-title":"Thromb Haemost"},{"issue":"04","key":"ref14","first-page":"1122","article-title":"Improved hemoglobin status and reduced menstrual blood loss among female carriers of factor V Leiden\u2013an evolutionary advantage?","volume":"86","author":"P G Lindqvist","year":"2001","journal-title":"Thromb Haemost"},{"issue":"03","key":"ref15","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/s11239-008-0293-z","article-title":"The Factor V Leiden mutation is associated with a higher blood haemoglobin concentration in women below 50 of the Malm\u00f6 Thrombophilia Study (MATS)","volume":"28","author":"N Isma","year":"2009","journal-title":"J Thromb Thrombolysis"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1016\/S0140-6736(01)06354-1","article-title":"Selection pressure for the factor-V-Leiden mutation and embryo implantation","volume":"358","author":"W G\u00f6pel","year":"2001","journal-title":"Lancet"},{"issue":"04","key":"ref17","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1093\/humrep\/dei422","article-title":"Gender-specific association of the factor V Leiden mutation with fertility and fecundity in a historic cohort. The Leiden 85-Plus Study","volume":"21","author":"F M van Dunn\u00e9","year":"2006","journal-title":"Hum Reprod"},{"issue":"11","key":"ref18","doi-asserted-by":"crossref","first-page":"2332","DOI":"10.1093\/humrep\/dex287","article-title":"Factor V Leiden is associated with increased sperm count","volume":"32","author":"T E van Mens","year":"2017","journal-title":"Hum Reprod"},{"key":"ref19","first-page":"752","article-title":"Women with factor V leiden mutation and unexplained recurrent miscarriage have a shorter time to pregnancy than non-carriers; an evolutionary advantage?","volume":"9","author":"T E van Mens","year":"2011","journal-title":"J Thromb Haemost"},{"issue":"10","key":"ref20","doi-asserted-by":"crossref","first-page":"2979","DOI":"10.1182\/blood.V97.10.2979","article-title":"Polymorphisms of clotting factors modify the risk for primary intracranial hemorrhage","volume":"97","author":"J Corral","year":"2001","journal-title":"Blood"},{"issue":"07","key":"ref21","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":"09","key":"ref22","doi-asserted-by":"crossref","first-page":"3085","DOI":"10.1182\/blood-2003-06-1789","article-title":"Survival advantage associated with heterozygous factor V Leiden mutation in patients with severe sepsis and in mouse endotoxemia","volume":"102","author":"B A Kerlin","year":"2003","journal-title":"Blood"},{"issue":"10","key":"ref23","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1056\/NEJM200103083441001","article-title":"Efficacy and safety of recombinant human activated protein C for severe sepsis","volume":"344","author":"G R Bernard","year":"2001","journal-title":"N Engl J Med"},{"issue":"06","key":"ref24","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1111\/jth.12876","article-title":"Survival advantage of heterozygous factor V Leiden carriers in murine sepsis","volume":"13","author":"E Kerschen","year":"2015","journal-title":"J Thromb Haemost"},{"issue":"06","key":"ref25","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1097\/CCM.0b013e318174373d","article-title":"Factor V Leiden mutation is associated with improved 30-day survival in patients with acute respiratory distress syndrome","volume":"36","author":"M Adamzik","year":"2008","journal-title":"Crit Care Med"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"S239","DOI":"10.1097\/01.CCM.0000126122.34119.D1","article-title":"Effect of factor V Leiden polymorphism in severe sepsis and on treatment with recombinant human activated protein C","volume":"32","author":"S B Yan","year":"2004","journal-title":"Crit Care Med"},{"issue":"03","key":"ref27","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1177\/1076029613494470","article-title":"Lack of association between factor V Leiden and sepsis: a meta-analysis","volume":"21","author":"J Zhang","journal-title":"Clin Appl Thromb Hemost"},{"issue":"12","key":"ref28","doi-asserted-by":"crossref","first-page":"4666","DOI":"10.1182\/blood-2005-12-5158","article-title":"Prothrombin 20210G>A is an ancestral prothrombotic mutation that occurred in whites approximately 24,000 years ago","volume":"107","author":"A Zivelin","year":"2006","journal-title":"Blood"},{"issue":"05","key":"ref29","doi-asserted-by":"crossref","first-page":"809","DOI":"10.3324\/haematol.2016.160432","article-title":"Pathophysiological consequences and benefits of HFE mutations: 20 years of research","volume":"102","author":"I Hollerer","year":"2017","journal-title":"Haematologica"},{"issue":"04","key":"ref30","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1111\/j.1365-2141.2009.08005.x","article-title":"Co-morbidities and quality of life in elderly persons with haemophilia","volume":"148","author":"M Franchini","year":"2010","journal-title":"Br J Haematol"},{"issue":"07","key":"ref31","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.3324\/haematol.2022.282407","article-title":"How we manage cardiovascular disease in patients with hemophilia","volume":"108","author":"M Franchini","year":"2023","journal-title":"Haematologica"},{"issue":"04","key":"ref32","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1111\/bjh.18085","article-title":"Cardiovascular disease in hereditary haemophilia: the challenges of longevity","volume":"197","author":"S Shapiro","year":"2022","journal-title":"Br J Haematol"},{"issue":"05","key":"ref33","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1007\/s11739-023-03331-7","article-title":"Hemophilia patients: are they naturally anticoagulated?","volume":"18","author":"A Tripodi","year":"2023","journal-title":"Intern Emerg Med"},{"issue":"05","key":"ref34","doi-asserted-by":"crossref","first-page":"e406","DOI":"10.1111\/hae.13069","article-title":"How to compare cardiovascular disease and risk factors in elderly patients with haemophilia with the general population","volume":"22","author":"K Berger","year":"2016","journal-title":"Haemophilia"},{"issue":"01","key":"ref35","doi-asserted-by":"crossref","first-page":"100007","DOI":"10.1016\/j.rpth.2022.100007","article-title":"Prevalence of selected bleeding and thrombotic events in persons with hemophilia versus the general population: a scoping review","volume":"7","author":"A D Shapiro","year":"2022","journal-title":"Res Pract Thromb Haemost"},{"issue":"03","key":"ref36","doi-asserted-by":"crossref","first-page":"e156","DOI":"10.1111\/hae.12596","article-title":"Cardiovascular disease prevalence and relevance in haemophilia: a scoping review","volume":"21","author":"I Rizwan","year":"2015","journal-title":"Haemophilia"},{"issue":"01","key":"ref37","doi-asserted-by":"crossref","first-page":"e35","DOI":"10.1111\/j.1365-2516.2011.02684.x","article-title":"Does haemophilia protect against ischaemic cardiovascular disease?","volume":"18","author":"D E Fransen Van De Putte","year":"2012","journal-title":"Haemophilia"},{"issue":"01","key":"ref38","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1182\/hematology.2025000773","article-title":"The aging hemophilia patient","volume":"2025","author":"M Lewandowska","year":"2025","journal-title":"Hematology (Am Soc Hematol Educ Program)"},{"issue":"09","key":"ref39","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1182\/blood-2013-11-453159","article-title":"Cardiovascular risk in patients with hemophilia","volume":"123","author":"P W Kamphuisen","year":"2014","journal-title":"Blood"},{"issue":"02","key":"ref40","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/j.1538-7836.2008.03201.x","article-title":"Cardiovascular disease in patients with hemophilia","volume":"7","author":"A Tuinenburg","year":"2009","journal-title":"J Thromb Haemost"},{"issue":"01","key":"ref41","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1002\/ajh.20339","article-title":"Prevalence and risk factors for heart disease among males with hemophilia","volume":"79","author":"R Kulkarni","year":"2005","journal-title":"Am J Hematol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/S0140-6736(03)14021-4","article-title":"Decreased mortality of ischaemic heart disease among carriers of haemophilia","volume":"362","author":"A Sr\u00e1mek","year":"2003","journal-title":"Lancet"},{"issue":"06","key":"ref43","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1111\/hae.12768","article-title":"Cardiovascular disease (CVD) in Canadians with haemophilia: age-related CVD in Haemophilia Epidemiological Research (ARCHER study)","volume":"21","author":"L Minuk","year":"2015","journal-title":"Haemophilia"},{"issue":"18","key":"ref44","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.2217\/cer-2021-0120","article-title":"Estimating the risk of thrombotic events in people with congenital hemophilia A using US claims data","volume":"10","author":"I Faghmous","year":"2021","journal-title":"J Comp Eff Res"},{"issue":"03","key":"ref45","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.thromres.2014.12.027","article-title":"Prevalence and risk factors of atherothrombotic events among 1054 hemophilia patients: a population-based analysis","volume":"135","author":"J D Wang","year":"2015","journal-title":"Thromb Res"},{"issue":"03","key":"ref46","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1182\/bloodadvances.2021005260","article-title":"Reduced cardiovascular morbidity in patients with hemophilia: results of a 5-year multinational prospective study","volume":"6","author":"P Van Der Valk","year":"2022","journal-title":"Blood Adv"},{"issue":"02","key":"ref47","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.advms.2018.06.001","article-title":"Cardiovascular comorbidities in a United States patient population with hemophilia A: a comprehensive chart review","volume":"63","author":"T J Humphries","year":"2018","journal-title":"Adv Med Sci"},{"issue":"11","key":"ref48","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1182\/bloodadvances.2018018226","article-title":"A cross-sectional analysis of cardiovascular disease in the hemophilia population","volume":"2","author":"S L Sood","year":"2018","journal-title":"Blood Adv"},{"issue":"06","key":"ref49","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1111\/hae.14647","article-title":"Prevalence of comorbid conditions among older males with haemophilia receiving care in haemophilia treatment centers in the United States","volume":"28","author":"J M Soucie","year":"2022","journal-title":"Haemophilia"},{"issue":"03","key":"ref50","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1111\/hae.12092","article-title":"Incidence, mortality rates and causes of deaths in haemophilia patients in Sweden","volume":"19","author":"S L\u00f6vdahl","year":"2013","journal-title":"Haemophilia"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.thromres.2019.07.017","article-title":"Hypertension and cardiovascular diseases in Swedish persons with haemophilia - a longitudinal registry study","volume":"181","author":"S L\u00f6vdahl","year":"2019","journal-title":"Thromb Res"},{"issue":"03","key":"ref52","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1111\/j.1365-2516.2009.02188.x","article-title":"Mortality and causes of death in Italian persons with haemophilia, 1990-2007","volume":"16","author":"A Tagliaferri","year":"2010","journal-title":"Haemophilia"},{"issue":"03","key":"ref53","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1111\/jth.15182","article-title":"Mortality, life expectancy, and causes of death of persons with hemophilia in the Netherlands 2001-2018","volume":"19","author":"S Hassan","year":"2021","journal-title":"J Thromb Haemost"},{"issue":"02","key":"ref54","first-page":"437","article-title":"Mortality among males with hemophilia: relations with source of medical care","volume":"96","author":"J M Soucie","year":"2000","journal-title":"Blood"},{"issue":"04","key":"ref55","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1111\/j.1365-2516.2010.02463.x","article-title":"Prevalence and risk factors of cardiovascular disease (CVD) events among patients with haemophilia: experience of a single haemophilia treatment centre in the United States (US)","volume":"17","author":"A A Sharathkumar","year":"2011","journal-title":"Haemophilia"},{"issue":"03","key":"ref56","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1182\/blood-2006-10-050435","article-title":"Mortality rates, life expectancy, and causes of death in people with hemophilia A or B in the United Kingdom who were not infected with HIV","volume":"110","author":"S C Darby","year":"2007","journal-title":"Blood"},{"issue":"07","key":"ref57","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1161\/hc3501.094232","article-title":"Decreased coagulability has no clinically relevant effect on atherogenesis: observations in individuals with a hereditary bleeding tendency","volume":"104","author":"A Sr\u00e1mek","year":"2001","journal-title":"Circulation"},{"issue":"01","key":"ref58","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/j.1538-7836.2011.04499.x","article-title":"Factor VIII deficiency does not protect against atherosclerosis","volume":"10","author":"S Biere-Rafi","year":"2012","journal-title":"J Thromb Haemost"},{"issue":"01","key":"ref59","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/j.1538-7836.2011.04514.x","article-title":"Coronary artery calcification score and carotid intima\u2013media thickness in patients with hemophilia","volume":"10","author":"M Zwiers","year":"2012","journal-title":"J Thromb Haemost"},{"issue":"02","key":"ref60","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1111\/hae.70187","article-title":"Carotid intima-media thickness as a marker of subclinical atherosclerosis in adolescents with severe haemophilia","volume":"32","author":"A Trillo","year":"2026","journal-title":"Haemophilia"},{"issue":"01","key":"ref61","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/j.1538-7836.2011.04542.x","article-title":"Reduced cardiovascular mortality in hemophilia despite normal atherosclerotic load","volume":"10","author":"M Makris","year":"2012","journal-title":"J Thromb Haemost"},{"issue":"05","key":"ref62","first-page":"207","article-title":"The effect of haemophilia and von Willebrand disease on arterial thrombosis: a systematic review","volume":"68","author":"S Biere-Rafi","year":"2010","journal-title":"Neth J Med"},{"issue":"06","key":"ref63","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1016\/j.jtha.2023.02.029","article-title":"Cancer-associated thrombosis: enhanced awareness and pathophysiologic complexity","volume":"21","author":"A Falanga","year":"2023","journal-title":"J Thromb Haemost"},{"issue":"06","key":"ref64","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1111\/hae.14423","article-title":"All-cause mortality and causes of death in persons with haemophilia: a systematic review and meta-analysis","volume":"27","author":"A U Alam","year":"2021","journal-title":"Haemophilia"},{"issue":"01","key":"ref65","first-page":"26","article-title":"Haemophilia and cancer: a personal perspective","volume":"11","author":"M Franchini","year":"2013","journal-title":"Blood Transfus"},{"issue":"03","key":"ref66","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1111\/j.1365-2516.2009.02128.x","article-title":"Malignancy in patients with haemophilia: a review of the literature","volume":"16","author":"A L Dunn","year":"2010","journal-title":"Haemophilia"},{"issue":"06","key":"ref67","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1111\/j.1582-4934.2009.00702.x","article-title":"Are haemophiliacs protected against cancer development? Prospective controlled studies are needed","volume":"13","author":"M Franchini","year":"2009","journal-title":"J Cell Mol Med"},{"issue":"04","key":"ref68","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.ctrv.2009.01.001","article-title":"Hemophilia and cancer: a new challenge for hemophilia centers","volume":"35","author":"M Franchini","year":"2009","journal-title":"Cancer Treat Rev"},{"issue":"06","key":"ref69","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.3390\/jcm13061770","article-title":"Haemophilia and cancer: a literature review","volume":"13","author":"E Zanon","year":"2024","journal-title":"J Clin Med"},{"issue":"01","key":"ref70","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/j.1365-2516.2010.02364.x","article-title":"Does haemophilia influence cancer-related mortality in HIV-negative patients?","volume":"17","author":"W Miesbach","year":"2011","journal-title":"Haemophilia"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"2622","DOI":"10.1111\/j.1582-4934.2008.00316.x","article-title":"Experimental melanoma metastasis in lungs of mice with congenital coagulation disorders","volume":"12","author":"L W Br\u00fcggemann","year":"2008","journal-title":"J Cell Mol Med"},{"issue":"05","key":"ref72","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1111\/j.1538-7836.2006.01883.x","article-title":"Experimental metastasis and primary tumor growth in mice with hemophilia A","volume":"4","author":"F Langer","year":"2006","journal-title":"J Thromb Haemost"},{"issue":"05","key":"ref73","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1046\/j.1365-2516.1998.00179.x","article-title":"Causes of death in Canadians with haemophilia 1980-1995","volume":"4","author":"I R Walker","year":"1998","journal-title":"Haemophilia"},{"issue":"01","key":"ref74","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1111\/j.1538-7836.2011.04566.x","article-title":"Cancers in patients with hemophilia: a retrospective study from the Italian Association of Hemophilia Centers","volume":"10","author":"A Tagliaferri","year":"2012","journal-title":"J Thromb Haemost"},{"issue":"03","key":"ref75","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1111\/j.1538-7836.2006.01808.x","article-title":"Mortality and causes of death in patients with hemophilia, 1992-2001: a prospective cohort study","volume":"4","author":"I Plug","year":"2006","journal-title":"J Thromb Haemost"},{"issue":"06","key":"ref76","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1111\/hae.12450","article-title":"Increased cancer risk in patients with haemophilia A: a nationwide population-based 14-year study in Taiwan","volume":"20","author":"C J Liu","year":"2014","journal-title":"Haemophilia"},{"issue":"04","key":"ref77","doi-asserted-by":"crossref","first-page":"E55","DOI":"10.1002\/ajh.23947","article-title":"Incidence and survival of cancers among 1,054 hemophilia patients: a nationwide and 14-year cohort study","volume":"90","author":"Y C Huang","year":"2015","journal-title":"Am J Hematol"},{"issue":"06","key":"ref78","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1097\/MBC.0000000000000339","article-title":"Malignancies in Swedish persons with haemophilia: a longitudinal registry study","volume":"27","author":"S L\u00f6vdahl","year":"2016","journal-title":"Blood Coagul Fibrinolysis"}],"container-title":["Seminars in Thrombosis and Hemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2905-4308.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T23:13:34Z","timestamp":1783984414000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2905-4308"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,3]]},"references-count":78,"URL":"https:\/\/doi.org\/10.1055\/a-2905-4308","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0094-6176","1098-9064"],"issn-type":[{"value":"0094-6176","type":"print"},{"value":"1098-9064","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,7,3]]},"published":{"date-parts":[[2026,7,3]]}}}