Types of hemophilia
The primary forms of hemophilia include Hemophilia A and Hemophilia B. However, we can also include acquired hemophilia as a separate entity:
› Hemophilia A
It is caused by defective or insufficient production of Factor VIII. This clotting factor is commonly produced in the liver’s vascular endothelium. Thus, liver transplantation usually corrects the problem in individuals with hemophilia A. This clotting factor works in association with the von Willebrand factor, which stabilizes and protects factor VIII from degradation.
The affected gene in hemophilia A is located on the Xq28 region of the chromosome X, which is found in the long arm, and it is known as F8C. It’s a very large gene, encoding for a protein with 2332 amino acids. In 40% of cases, the genetic defect comes from an inversion of the gene, but the remaining 60% of cases are caused by a point mutation, an insertion, or a deletion of the gene. The result is a dysfunctional or deficient FVIII, an abnormal cascade of coagulation, and excessive bleeding. The most common manifestation is joint bleeding, and intracranial hemorrhage usually appears in young patients before turning 18 years old.
› Hemophilia B
It is caused by defective or insufficient production of Factor IX. This problem disrupts the coagulation cascade, and excessive hemorrhage, usually located in the joints, and in the central nervous system, the muscles, pulmonary system, gastrointestinal tract, and other organs. It is less frequent as compared to hemophilia A, but shares many similarities. Factor IX is also synthesized in the hepatocyte and has a half-life of 18 to 24 hours. Like FVIII, FIX is also inactive in the blood, and when activated, they work together to activate factor X, which converts fibrinogen into fibrin and stops bleeding. Factor IX gene is located in the region Xq27, which is also found on the long arm of chromosome X. This gene is also known as F9, and encodes for a shorter protein (415 amino acids) as compared to FVIII. Deletions and point mutations are the most common cause of the disease. The clinical manifestations are basically the same as hemophilia A.
› Acquired hemophilia
It is caused by the formation of antibodies against clotting factors. It may cause a type of hemophilia A or hemophilia B, which appears later in life instead of being born with it. Around 30% of patients with severe cases of hemophilia A and 3-5% of patients with hemophilia B develop antibodies against clotting factor VIII, which may or may not be affected by a genetic mutation. Such inhibitors are immunoglobulin G subclass 4. When they are in contact with clotting factors, they neutralize their clotting effects in the coagulation cascade. This condition can be usually found in older adults (50 years old and later on). It is often associated with a collagen vascular disease or an adverse drug reaction against penicillin or another drug. A patient with very high levels of antibodies against FVIII should be evaluated for lymphoproliferative malignancies and other cancer types.