Hemophilia is an inherited bleeding disorder which is mainly X-linked recessive and therefore occurs almost exclusively in males. There are two main subtypes - hemophilia A (80%) and hemophilia B (20%).
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 post-operative 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 are relatively uncommon. The types of hemophilia are impossible to delineate clinically 6.
- haemophilic arthropathy
- osteopaenia and osteoporosis
- transfusion-related diseases:
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 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 occurring in almost all individuals
- haemophilic pseudotumor occurring 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, 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 leading causes of death. Life expectancy in those without HIV is ~62 years 2.
- ~15 times increased risk death from intracranial hemorrhage (~1/3 of all deaths)
- ~50 times increased risk 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.
- 2. Darby SC, Kan SW, Spooner RJ et-al. 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. Blood. 2007;110 (3): 815-25. doi:10.1182/blood-2006-10-050435 - Pubmed citation
- 3. Hermann G, Gilbert MS, Abdelwahab IF. Hemophilia: evaluation of musculoskeletal involvement with CT, sonography, and MR imaging. AJR Am J Roentgenol. 1992;158 (1): 119-23. AJR Am J Roentgenol (abstract) - Pubmed citation
- 4. Ng WH, Chu WC, Shing MK et-al. Role of imaging in management of hemophilic patients. AJR Am J Roentgenol. 2005;184 (5): 1619-23. AJR Am J Roentgenol (full text) - Pubmed citation
- 5. Franchini M, Mannucci PM. Past, present and future of hemophilia: a narrative review. Orphanet J Rare Dis. 2012;7 (1): 24. doi:10.1186/1750-1172-7-24 - Free text at pubmed - Pubmed citation
- 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