Understanding Hemophilia A
The Blood Clotting Process
In a healthy person, proteins called clotting factors work together to stop bleeding when there is injury to a blood vessel. Deficiencies in certain factors can lead to different types of bleeding disorders, such as hemophilia A or B.1
Clotting factors activate each other in a specific order to form a blood clot, or coagulate. This process is called the coagulation cascade.
There are two pathways in the coagulation cascade that can be triggered by different types of injuries. These pathways then converge on a common pathway that leads to a blood clot. The image above is a simplified depiction of the coagulation cascade and its pathways.
Hemophilia A is a rare but serious genetic bleeding disorder in which people do not have enough of or have defective factor VIII.
The lack of factor VIII disrupts the completion of the coagulation cascade, resulting in blood clots that form more slowly, or that do not form at all.
People with hemophilia A may bleed longer after an injury or may experience internal bleeding, including into the joints.2
Minor injuries like paper cuts are typically not a serious problem for people with hemophilia A because the body has other mechanisms to stop external bleeding from those types of injuries.3
Living with Hemophilia A
Hemophilia occurs more frequently in males than females.
1 in 5,000
The majority of hemophilia A cases are inherited.
But in about one-third of cases it is caused by spontaneous genetic changes.2
Without treatment, people with hemophilia A can experience:4
that can lead to a buildup of blood in the area (hematoma)
into muscles and joints, which can lead to long term disability or joint disease
SPONTANEOUS INTERNAL BLEEDING
which can be life threatening if it occurs in vital organs such as the brain
following injury or surgery
The level and frequency of bleeding depends on the severity of the disorder. Hemophilia is classified as mild, moderate or severe depending on how much functional clotting factor a person has.
Caring for Hemophilia A
Standard treatment for hemophilia A includes factor VIII replacement therapy, which temporarily restores factor VIII levels to help complete the coagulation cascade and allow blood clots to form.
Factor VIII replacement therapy infusions can be given in response to an injury or bleed, or prophylactically to prevent bleeding.5
The current standard of care is regular intravenous injections (requiring access to a vein) of factor VIII replacement therapy 2-3 times per week.6
Hemophilia A With Inhibitors
Inhibitors have represented a major challenge in hemophilia care.
About 25 to 30 percent of people with severe hemophilia A develop factor VIII antibodies, called inhibitors, at some point in their lifetime.7
Inhibitors can block replacement factor VIII and stop it from working properly.8
People with hemophilia A who have developed inhibitors have a 70 percent higher risk of death compared to those without inhibitors.9
For people with severe hemophilia A with inhibitors, it is difficult, if not impossible, to obtain a level of factor VIII sufficient to control bleeding.10
Immune tolerance induction (ITI) is one treatment option for people with inhibitors. This is where very high doses of factor VIII are given over a long period of time in an effort to train the body to recognize and tolerate the treatment without reacting to it.11
However, ITI treatment can take many years and has been shown to be ineffective in about 30 percent of people.12, 13
Bypassing agents (BPA) are a treatment option for people with hemophilia A who develop high levels of inhibitors, and are infused either as on-demand (episodic) or as preventative (prophylaxis) treatment to control bleeding. BPAs may need to be taken often, which can require frequent intravenous infusions or the long-term use of a device surgically implanted into a blood vein.14
Research is underway to develop new treatment approaches for people with hemophilia A and to help reduce the burden of frequent intravenous infusions.
1 NHF. Types of Bleeding Disorders. https://www.hemophilia.org/Bleeding-Disorders/Types-of-Bleeding-Disorders. Accessed June 30, 2016.
2 NHF. Hemophilia A. https://www.hemophilia.org/Bleeding-Disorders/Types-of-Bleeding-Disorders/Hemophilia-A. Accessed June 30, 2016.
3 Mayo Clinic. Hemophilia definition. http://www.mayoclinic.org/diseases-conditions/hemophilia/basics/definition/con-20029824. 2014. Accessed June 30, 2016.
4 CDC. Hemophilia facts. http://www.cdc.gov/ncbddd/hemophilia/facts.html. 2014. Accessed June 30, 2016.
5 HFA. Treatment of hemophilia. http://www.hemophiliafed.org/bleeding-disorders/hemophilia/treatment. Accessed June 30, 2016.
6 Porada C, et al. Hemophilia A: an ideal disease to correct in utero. Front Pharmacol. 2014; 5:276.
7 NIH. How is Hemophilia Treated? http://www.nhlbi.nih.gov/health/health-topics/topics/hemophilia/treatment. Accessed July 8, 2016.
8 Whelan SF, et al. Distinct characteristics of antibody responses against factor VIII in healthy individuals and in different cohorts of hemophilia A patients. Blood 2013; 121:1039–48.
9 Centers of Disease Control and Prevention. Does having an inhibitor increase the risk of death among US males with severe hemophilia A?. https://www.cdc.gov/ncbddd/hemophilia/features/inhibitor-severe-hemophilia-a.html.
10 American Society of Hematology Blood Journal. F8 gene mutation type and inhibitor development in patients with severe hemophilia A: systematic review and meta-analysis.
11 HFA. Treatment & Eradication of Inhibitors. http://www.hemophiliafed.org/bleeding-isorders/inhibitors/treatment-eradication-inhibitors. Accessed July 8, 2016.
12 Valentino LA, et al. US Guidelines for immune tolerance induction in patients with haemophilia A and inhibitors. Haemophilia 2015; 21: 559-67.
13 Rocino A, et al. Immune tolerance induction in patients with haemophilia a and inhibitors: effectiveness and cost analysis in an European Cohort (The ITER Study). Haemophilia 2015:10.
14 Hemophilia Federation of America. Bleeding Management of Inhibitors. http://www.hemophiliafed.org/bleedingdisorders/inhibitors/bleeding-management-of-inhibitors.