When the body responds normally to a tear in a blood vessel, a chain reaction of proteins, called clotting factors, act together in a specific order to form a blood clot. There are at least eleven clotting factors in the body. The deficiency of any one of these factors results in a bleeding disorder.
Common Bleeding Disorders
Hemophilia A & B
Hemophilia A is an x-linked genetic bleeding disorder which results in prolonged bleeding. It is also known as Factor VIII Deficiency because of the body's inability to produce enough of the blood clotting factor VIII.
Hemophilia B is also an x-linked genetic bleeding disorder which results in prolonged bleeding. It results from the body's inability to produce enough blood clotting Factor IX, and is sometimes called Factor IX Deficiency. It may occasionally be referred to as Christmas Disease in reference to the name of the first patient with the disease to be studied.
The severity of symptoms of Hemophilia A or B can range from mild to severe. In addition to prolonged bleeding time, bleeding within joints may lead to swelling, pain, and permanent joint damage.
Another form of the disorder, Acquired Hemophilia, is not caused by inherited gene mutations but by the development of antibodies (inhibitors), directed against plasma coagulation factors; most frequently FVIII.
von Willebrand's Disease
von WIllebrand's Disease (vWD) is congenital bleeding disorder in women which passes genetically as an autosomal recessive trait. It is caused by deficient or defective von Willebrand factor (Factor III), a blood protein that controls platelet activity. The bleeding tendency manifests at an early age. Easy bruising, bleeding in the intestinal tract during surgery, and excess loss of blood during menstruation are common. It is the most common form of bleeding disorder. It is named for the Finnish physician Erik von Willebrand who discovered it.
Factor products are either derived from human plasma or developed through monoclonal or recombinant technologies. In the 1980s and early 1990s, infectious diseases such as AIDS and Hepatitis A were transmitted to Hemophilia patients through infected plasma used in the manufacturing of factor products. Due to the addition of purification processes to ensure a safe product, no cases of viral transmission through the plasma supply have been documented since the mid-1990s. Although the manufacturing industry has tightened its production standards, viral safety continues to be a concern among the bleeding disorders community.
In Hemophilia A and B patients being treated with anti-hemophilic factor products, the development of inhibitors is an ongoing concern. Inhibitors are the result of an immune response to the introduction of foreign factor proteins. Mistaking the factor proteins as infectious, the immune system destroys the proteins needed to treat a bleed, resulting in the infusion being ineffective, the bleeding continuing, and the factor being wasted. Inhibitors cannot be prevented and may occur at anytime. The treatment of an inhibitor is costly, time consuming, and demanding. Approximately 30% of people with Hemophilia A will develop inhibitors; usually between the 5th and 50th factor infusion and in rare cases, later in life; while 2-3% of people with hemophilia B will develop inhibitors.
While scientists do not know exactly what causes inhibitors, risk factors that have been shown in some studies to possibly play a role include:
- Type of hemophilia gene defect
- Frequency and amount of treatment (inhibitors typically occur within the first 50 times factor is used)
- Family history of inhibitors
- Type of factor treatment product
- Presence of other immune disorder
Inhibitor patients fall into three categories. Those who are:
- Transient and disappear without treatment
- Disappear with immune tolerance induction
- Persistent and high-titer
Transient inhibitors may be fairly common but infrequently diagnosed because they do not noticeably affect the efficacy of treatment.
Although a blood test for inhibitors is usually performed annually by the Hemophilia Treatment Center, one should also be performed if factor replacement is ineffective or prior to surgery.
The goal of treatment for a hemophilia patient with an inhibitor is two-fold: to control the bleeding episode and to eliminate the inhibitor. The approach to treatment is dependent upon the titer level of the inhibitor, how the inhibitor level responds to an infusion, and the severity of the bleed.
Some inhibitors are transient and disappear without treatment. In patients with persistent inhibitors, a course of treatment called Immune Tolerance Induction is common. Immune Tolerance Induction involves overwhelming the immune system through administering a high dosage of factor on a regular basis, usually at least several days per week. The course of treatment may span several years, making it time consuming and costly.
Scharrer I, Bray GL, Neutzling O. Incidence of inhibitors in haemophilia A patients a review of recent studies of recombinant and plasma-derived factor VIII concentrates. Haemophilia 1999; 5: 145-154.
Abshire T, Kenet G. Recombinant factor VIIa: review of efficacy, dosing regimens and safety in patients with congenital and acquired factor VIII or IX inhibitors. J Thromb Haemost 2004; 2: 899-909.
Lacroix, R.N., Sylvie, Nora Schwetz, R.N., Andrea Pritchard, R.N., Kathy Mulder, B.P.T., and Nichan Zourikian, B.P.T. All About Inhibitors. 1999, Canadian Hemophilia Society.