{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T13:29:31Z","timestamp":1780406971081,"version":"3.54.1"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"858","license":[{"start":{"date-parts":[[1997,4,1]],"date-time":"1997-04-01T00:00:00Z","timestamp":859852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1997,4,1]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>Although the nature of haemophilia has been understood for thousands of years, knowledge of its molecular genetics is recent. These X-linked bleeding disorders have diverse underlying DNA defects and, in 1992, DNA inversion within the X chromosome was found to explain half of the most serious cases of haemophilia A. The life-span and quality-of-life for patients with haemophilia had improved steadily throughout the early 1980s but the principal cause of death remained intracranial haemorrhage until the epidemic of HIV infection due to contaminated factor concentrates. Infection with hepatitis C virus is almost universal for patients treated with clotting factors before 1985. No curative treatment is available for hepatitis C at present. Knowledge of the transmission of viruses in concentrates has led to important developments in processing techniques to eliminate them. Recombinant technology has produced factor VIII and, more recently, factor IX concentrate which is likely to be very safe. Development of inhibitors to factor concentrates (especially factor VIII) remains one of the most serious complications of haemophilia. The variety of treatments available testifies to the lack of a single universally efficacious one. The use of prophylactic treatment has been conclusively demonstrated to result in a preservation of joint function in severely affected patients who might otherwise develop significant joint problems. The many facets of the care of patients with severe haemophilia, ranging from dental care to genetic counselling, can be advantageously co-ordinated in a haemophilia comprehensive care centre.<\/jats:p>","DOI":"10.1136\/pgmj.73.858.201","type":"journal-article","created":{"date-parts":[[2008,12,29]],"date-time":"2008-12-29T21:49:00Z","timestamp":1230587340000},"page":"201-206","source":"Crossref","is-referenced-by-count":23,"title":["Haemophilia"],"prefix":"10.1093","volume":"73","author":[{"given":"M R","family":"Cahill","sequence":"first","affiliation":[{"name":"Haemophilia Comprehensive Care Centre, Royal London Hospital , Whitechapel, London E1 1BB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B T","family":"Colvin","sequence":"additional","affiliation":[{"name":"Haemophilia Comprehensive Care Centre, Royal London Hospital , Whitechapel, London E1 1BB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[1997,4,1]]},"reference":[{"key":"ref_1","article-title":"It had been recognised since 1972 that hepatitis B and non-A, non-B hepatitis could be transmitted by clotting factor concentrates'6. With the recognition that concentrate transmitted HIV infection to haemophilia patients, efforts to produce virally inactivated concentrates were intensified.3' These have culminated in the production of a generation of products which are safe and free from lipid-coated viruses. Some products have undergone double viral inactivation steps - for example, dry heating or ultrafiltration may be combined with a chemical inactivation step such as the use of solvent detergent processes or sodium thiocyanate'1. Thanks to these measures there have been no cases of seroconversion from HIV, hepatitis B or C recorded in the UK since 1986. Despite this significant achievement, caution is warranted because documented transmission ofhepatitis A and parvovirus B 19 have occurred in Europe39'40 and this indicates that non-lipid coated viruses can escape inactivation procedures","unstructured":"It had been recognised since 1972 that hepatitis B and non-A, non-B hepatitis could be transmitted by clotting factor concentrates'6. With the recognition that concentrate transmitted HIV infection to haemophilia patients, efforts to produce virally inactivated concentrates were intensified.3' These have culminated in the production of a generation of products which are safe and free from lipid-coated viruses. Some products have undergone double viral inactivation steps - for example, dry heating or ultrafiltration may be combined with a chemical inactivation step such as the use of solvent detergent processes or sodium thiocyanate'1. Thanks to these measures there have been no cases of seroconversion from HIV, hepatitis B or C recorded in the UK since 1986. Despite this significant achievement, caution is warranted because documented transmission ofhepatitis A and parvovirus B 19 have occurred in Europe39'40 and this indicates that non-lipid coated viruses can escape inactivation procedures."},{"key":"ref_2","article-title":"Haemophilia, with special reference to the Talmud. Heb Med J'","volume":"165","author":"Katznelson, J.L.","unstructured":"Katznelson JL. Haemophilia, with special reference to the Talmud. Heb Med J' 1956: I; 165.","journal-title":"1956"},{"issue":"6","key":"ref_3","first-page":"1","article-title":"An account of haemorrhagic disposition existing in certain families","volume":"1803","author":"Otto, J.C.","unstructured":"Otto JC. An account of haemorrhagic disposition existing in certain families. 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Factor VIII gene rearrangements in patients with severe haemophilia A. Lancet 1994; 343: 329-30.","journal-title":"Lancet"},{"key":"ref_10","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","year":"1993","unstructured":"Lakich D, Kazazian Jr HH, Antonarakis SE, Gitschier J. Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A. Nature Genet 1993; 5: 236-41.","journal-title":"Nature Genet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.1093\/nar\/20.suppl.2027","article-title":"Haemophilia B: Database of point mutations and short additions and deletions-third edition","volume":"(suppl):","author":"Giannelli, F.; Green, P.M.; High, K.A.","year":"1992","unstructured":"Giannelli F, Green PM, High KA, et al. Haemophilia B: Database of point mutations and short additions and deletions-third edition. Nucleic Acid Res 1992; 20 (suppl): 2027-63.","journal-title":"Nucleic Acid Res"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/324380a0","article-title":"Recurrent mutations in haemophilia A give evidence of CpG mutation hot-spots","volume":"324","author":"true","year":"1986","unstructured":"Youssoufian H, Kazazian Jr HH, Philips DG, et al. Recurrent mutations in haemophilia A give evidence of CpG mutation hot-spots. Nature 1986; 324: 380-2.","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1055\/s-0038-1646370","article-title":"B: Genetic basis of haemophilia A","volume":"66","author":"Gitschier, J.; Kogan, S.; Diamond, C.; Levinson","year":"1991","unstructured":"Gitschier J, Kogan S, Diamond C, Levinson B: Genetic basis of haemophilia A. 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JAMA 1972; 221: 510.","journal-title":"JAMA"},{"key":"ref_18","first-page":"1619","volume":"310","author":"C, Lee C.A.Hepatitis; haemophilia","year":"1995","unstructured":"Lee CA. Hepatitis C and haemophilia. (editorial) BM3t 1995; 310: 1619-20."},{"key":"ref_19","first-page":"555","article-title":"The progression of HCVassociated liver disease in a cohort of haemophilic patients","volume":"87","author":"Telfer, P.; Sabin, C.; Devereux, H.; Scott, F.; Dusheiko, G.; Lee, C.","year":"1994","unstructured":"Telfer P, Sabin C, Devereux H, Scott F, Dusheiko G, Lee C. The progression of HCVassociated liver disease in a cohort of haemophilic patients. 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N Engl J Med 1981; 305: 717 - 21.","journal-title":"N Engl J Med"},{"issue":"2","key":"ref_28","first-page":"1193","article-title":"Successful use of recombinant factor VIIa in a patient with severe haemophilia A during synovectomy","volume":"1988","author":"Hedner, U.; Glazer, S.; Pigel, K.","unstructured":"Hedner U, Glazer S, Pigel K et al. Successful use of recombinant factor VIIa in a patient with severe haemophilia A during synovectomy. Lancet 1988: 2: 1193.","journal-title":"Lancet"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1056\/NEJM198804143181503","article-title":"Induction of immune tolerance in patients with haemophilia and antibodies to factor VIII by combined treatment with intravenous IgG, cyclophosphamide and factor VIII","volume":"318","year":"1988","unstructured":"Nilsson IM, Berntorp E, Zettervall 0. Induction of immune tolerance in patients with haemophilia and antibodies to factor VIII by combined treatment with intravenous IgG, cyclophosphamide and factor VIII. N Eng J Med 1988; 318: 947-50.","journal-title":"N Eng J Med"},{"key":"ref_30","first-page":"577","article-title":"The role of intensive plasma exchange in the prevention and managment of haemorrhage in patients with inhibitors to factor VIII","volume":"47","author":"Slocombe, G.W.; Newland, A.C.; Colvin, M.P.; Colvin, B.T.","year":"1981","unstructured":"Slocombe GW, Newland AC, Colvin MP, Colvin BT. The role of intensive plasma exchange in the prevention and managment of haemorrhage in patients with inhibitors to factor VIII. 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NHS Health Service Guidelines, 1993; 20.","journal-title":"NHS Health Service Guidelines"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1136\/bmj.2.6090.814","article-title":"Regional co-ordinator for haemophilia in domiciliary practice","volume":"2","author":"Colvin, B.T.; Aston, C.; Davis, G.; Jenkins, G.C.; Dormandy, K.M.","year":"1977","unstructured":"Colvin BT, Aston C, Davis G, Jenkins GC, Dormandy KM. Regional co-ordinator for haemophilia in domiciliary practice. BMJ 1977; 2: 814-5.","journal-title":"BMJ"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1111\/j.1365-2516.1995.tb00062.x","article-title":"Implementation of a nurse practitioner policy for the requisition and administration of drugs in a haemophilia comprehensive care centre","volume":"1","author":"Cahill, M.R.; Woosey, C.P.; Hayden, S.M.; MacClean, M.; Colvin, B.T.","year":"1995","unstructured":"Cahill MR, Woosey CP, Hayden SM, MacClean M, Colvin BT. 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