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Hemophilia is an inherited bleeding disorder that is mainly X-linked recessive and therefore occurs almost exclusively in males. There are two main subtypes: hemophilia A (80%) and hemophilia B (20%).
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The incidence of hemophilia A is around 1 in 5000 male births, and the incidence of hemophilia B is around 1 in 25,000-30,000 male births.
Most patients present with a bleeding diathesis. In severe cases, patients present during the neonatal or infantile period or with clinically significant bleeding (e.g. cephalohematoma, or postoperative bleeding). In adolescents and adults, hemorrhage typically manifests as bleeding into joints (hemarthrosis) and muscles, whereas bleeding in other more clinically significant sites such as intracranially or gastrointestinal is relatively uncommon. The types of hemophilia are impossible to delineate clinically 6.
Creutzfeldt-Jacob disease: very rare
The main forms of hemophilia are inheritable X-linked recessive diseases 6, with ~70% considered familial and ~30% considered sporadic 8. Generally, severity is graded depending on baseline factor activity:
mild: factor activity 6-40% of normal
moderate: factor activity 1-5% of normal
severe: factor activity <1% of normal
~80% of cases
F8 gene mutation, on the long arm of the X-chromosome
inherited as an X-linked recessive condition
coagulation factor VIII deficiency or absence
a.k.a. Christmas disease
~20% of cases
F9 gene mutation, on the long arm of the X-chromosome
inherited as an X-linked recessive condition
coagulation factor IX deficiency or absence
a.k.a. Rosenthal syndrome
<1% of cases
most common in the Ashkenazi Jewish population
F11 gene mutation, on the long arm of chromosome 4
inherited as an autosomal recessive or dominant condition
coagulation factor XI deficiency or absence
The hallmark of the disease is hemorrhage, particularly into joints and/or soft tissue, with several radiological consequences:
haemophilic arthropathy occurs in almost all individuals
haemophilic pseudotumor occurs in ~2%
soft tissue hematoma formation may lead to contractures 3
serious life-threatening hemorrhage (intracranial, thoracic, abdominal)
Treatment and prognosis
Treatment depends on the type, general severity, and current clinical state, and can be delivered episodically or prophylactically. Options for treatment include factor products (plasma-derived or recombinant) or novel medications such as emicizumab 10.
Prognosis depends on the severity and on the presence or absence of transfusion-related disease. Complications from HIV and cirrhosis are the leading causes of death. Life expectancy in those without HIV is ~62 years 2.
~15 times increased risk of death from intracranial hemorrhage (~1/3 of all deaths)
~50 times increased risk of death from non-intracranial hemorrhage
- 1. National Heart, Lung, and Blood Institute. Hemophilia. NHLBI Diseases and Conditions Index. Available at http://www.nhlbi.nih.gov/health/dci/Diseases/hemophilia/hemophilia_all.html.
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- 6. Coppola A, Di Capua M, Di Minno MN et-al. Treatment of hemophilia: a review of current advances and ongoing issues. J Blood Med. 2012;1: 183-95. doi:10.2147/JBM.S6885 - Free text at pubmed - Pubmed citation
- 7. Seo JY, Jang MA, Kim HJ et-al. Sequence variation data of F8 and F9 genes in functionally validated control individuals: implications on the molecular diagnosis of hemophilia. Blood Res. 2013;48 (3): 206-10. doi:10.5045/br.2013.48.3.206 - Free text at pubmed - Pubmed citation
- 8. Kasper CK, Lin JC. Prevalence of sporadic and familial haemophilia. Haemophilia. 2007;13 (1): 90-2. doi:10.1111/j.1365-2516.2006.01397.x - Pubmed citation
- 9. Gomez K, Bolton-Maggs P. Factor XI deficiency. (2008) Haemophilia. 14 (6): 1183. doi:10.1111/j.1365-2516.2008.01667.x - Pubmed
- 10. Johnny Mahlangu, Johannes Oldenburg, Ido Paz-Priel, Claude Negrier, Markus Niggli, M. Elisa Mancuso, Christophe Schmitt, Victor Jiménez-Yuste, Christine Kempton, Christophe Dhalluin, Michael U. Callaghan, Willem Bujan, Midori Shima, Joanne I. Adamkewicz, Elina Asikanius, Gallia G. Levy, Rebecca Kruse-Jarres. Emicizumab Prophylaxis in Patients Who Have Hemophilia A without Inhibitors. (2018) New England Journal of Medicine. 379 (9): 811-822. doi:10.1056/NEJMoa1803550 - Pubmed