The characteristic phenotype of Hemophilia A is a tendency to bleed.1,2
Hemophilia A results from missing or defective clotting protein factor VIII (FVIII), and the frequency and severity of bleeding manifestations generally correlates with the degree of FVIII deficiency.1,2
Hemophilia A is typically an X-linked recessive genetic disorder that most often affects males, with an incidence of approximately 1 in 5,000 male births.1,2 Between 2012 and 2018, there were an estimated 20,000 to 33,000 males with Hemophilia A living in the U.S.
Children can inherit Hemophilia A from a father with Hemophilia A, or from a mother who is a carrier.1,2,3 Around one-third of people with Hemophilia A have no prior family history (spontaneous). Females with hemophilia are rare, but may result in females with both X chromosomes affected or when one X chromosome is inactive — females account for 3% of people with Hemophilia A.
Acquired Hemophilia A (AHA), a rare autoimmune form of Hemophilia A in which an individual develops autoantibodies to FVIII, has an estimated incidence of 1.5 to 2 cases per million per year.4,5,6,7 It is more common in the elderly, with a median age of 73.9 at diagnosis, and can affect men and women equally.
In some cases, infant boys with genetic risk factors are tested shortly after birth.2 In other cases, testing is done after clinical suspicion of hemophilia due to symptoms.
Due to a variety of chromosomal abnormalities, the symptoms of hemophilia can vary greatly from one patient to another and they correlate to plasma FVIII levels.1 Severe Hemophilia A is typically diagnosed at a very young age due to joint bleeds or intramuscular bleeding, bleeding associated with a minor medical procedure (venipuncture, circumcision, central line placement, or heel prick), mucocutaneous bleeding, or extracranial bleeding.1,2
Individuals with mild Hemophilia A may rarely experience spontaneous bleeding, but can experience major bleeding with trauma or surgery.1 Individuals with moderate Hemophilia A may experience occasional spontaneous bleeding, and are at risk for prolonged bleeding with minor trauma or surgery. When including mild and moderate cases, 36% of Hemophilia A cases were expected to be undiagnosed in the U.S. based on data from 2016.8
FVIII is a glycoprotein synthesized mainly in hepatocytes.9,10,11,12 Von Willebrand Factor (VWF) stabilizes FVIII, protects it from premature proteolysis, and transfers it to the site of endothelial injuries.
In primary hemostasis, which involves the formation of a platelet plug after endothelial injury, VWF:FVIII complex is critical for the recruitment and activation of platelets, and binding to collagen.10,11,13 In this process, FVIII is freed from VWF, which activates FVIII. Activated FVIII plays a role in secondary hemostasis, which is the process of forming a stable fibrin clot.14
FVIII deficiencies, which can result from a variety of mutations to the FVIII gene, lead to varying degrees of inability to form a stable fibrin clot and thus stop bleeding.1,14
Navigating Hemophilia A
Even a single bleed in an individual with Hemophilia A may be life-threatening or lead to debilitating joint disease.1,15,16 Therefore, prevention of all bleeds is the goal of optimal hemophilia patient care.17,18
One of the most serious complications of factor treatment is neutralizing antibodies to FVIII (FVIII inhibitors).1,2 Testing for inhibitors is required in any individual with hemophilia in the following circumstances:1
When clinical or laboratory response to concentrate is suboptimal;
Before and after a switch of treatment;
Before elective invasive procedures; and
Within 4 weeks after intensive treatment (≥5 consecutive days of clotting factor administration) or before surgery
Srivastava A, Santagostino E, Dougall A, et al. Haemophilia. 2020;26(S6):1-158.
Centers for Disease Control and Prevention. What is Hemophilia? Available at: https://www.cdc.gov/ncbddd/hemophilia/facts.html. Updated June 3, 2019. Accessed October 24, 2022.
World Federation of Hemophilia. Report on the Annual Global Survey, 2018. Available at: http://www1.wfh.org/publications/files/pdf-1731.pdf. Accessed October 24, 2022.
Collins P, Baudo F, Huth-Kuhne A, et al. BMC Res Notes. 2010;3:161.
Kessler CM and Knöbl P. Eur J Haematol. 2015;95(Suppl 81):36-44.
Sakurai Y and Takeda T. J Immunol Res. 2014;2014:1-10.
Knoebl P, Marco P, Baudo F, et al. J Thromb Haemost. 2012;10(4):622-631.
Brouwer ES, et al. Presented at ISTH 2019, Melbourne; Poster PB1420.
Mazurkiewicz-Pisarek A, Plucienniczak G, Ciach T, et al. Acta Biochim Pol. 2016;63(1):11-16.
This site is intended only for healthcare professionals registered to practice in the U.S. and is intended to provide balanced, scientific, and evidence-based answers to unsolicited medical questions. The information is not intended as medical advice and may be incomplete. This resource may include information that has not been approved by the U.S. Food and Drug Administration (FDA). Takeda does not recommend the use of any Takeda product beyond the approved labeling. Any decisions regarding the usage of a Takeda product beyond the approved labeling is left to the discretion of the healthcare professional.
Choose an option that describes you:
By clicking on this option, I certify that I am a U.S. healthcare professional.
Select a product and enter keywords to search for specific product information
Congress materials may include information about investigational use(s) of compounds/products that are not approved for use by the U.S. Food and Drug Administration (FDA) and/or are inconsistent with the Prescribing Information. Takeda does not recommend the use of any Takeda product beyond the approved labeling. Any decisions regarding the usage of a Takeda product beyond the approved labeling is left to the discretion of the healthcare professional. Takeda makes no representations about whether investigational compounds or unapproved uses will be approved by the FDA.