Table of Contents
Definition of Hemophilia
A group of inherited genetic disorders in which certain clotting factors are deficient or absent, resulting in clotting dysfunction. People who have hemophilia tend to bleed easily and longer than normal. Some forms of hemophilia carry substantial risk for life-threatening hemorrhage (bleeding).
Types of Hemophilia
Doctors classify hemophilia according to the deficient clotting factor, which may be missing from the blood, present in subnormal quantities, or present but defective. About 85 percent of people who have hemophilia have hemophilia A, a deficiency of clotting factor VIII (also called antihemophilic factor A). The remaining 15 percent have hemophilia B, a deficiency of clotting factor IX (also called Christmas factor, antihemophilic factor B, or plasma thromboplastin).
Hemophilia B was once called Christmas disease-named after the family in which doctors first identified the clotting factor IX deficiency- and distinguished this type of hemophilia from the classic hemophilia A. Hemophilia C, which is very rare in the United States, is a deficiency of clotting factor XI (also called plasma thromboplastin antecedent).
The most common types of hemophilia, hemophilia A and hemophilia B, are inherited X-linked chromosomal disorders, meaning they nearly always only affect males. The daughters of a man who has hemophilia A or B will all carry the defective gene, though the sons will have normal clotting factor genes.
The son of a carrier has a 50 percent chance of having hemophilia; the daughter of a carrier has a 50 percent chance of also carrying the defective genes.
Rarely, hemophilia A or B occurs through spontaneous gene mutation. In such circumstances it is possible for a woman to have the disorder. Hemophilia C, which primarily affects people who are of Ashkenazi Jewish descent, is an autosomal disorder that affects men and women equally though is very rare.
Symptoms and Diagnostic Path
Excessive bleeding is the most common symptom of hemophilia A or B, which often first manifests after circumcision. The more severe the hemophilia, the earlier in life symptoms become apparent. Some men may not experience symptoms until adulthood, while others experience lifethreatening hemorrhage with common childhood injuries such as nosebleed (epistaxis) and trauma such as a cut.
The diagnostic path includes blood tests that measure clotting times, platelet aggregation, blood cell counts, and the presence of clotting factors VIII, IX, and XI, and the von Willebrand factor. The findings of these tests, along with personal and family medical histories, are generally conclusive of the diagnosis.
The amount of functional clotting factor in the blood determines the severity of the hemophilia. Clotting factor presence above 10 percent generally produces only mild to moderate symptoms; clotting factor presence below 1 percent, which occurs in about 70 percent of people who have hemophilia, generally produces severe symptoms. Life-threatening hemorrhage is the most significant consequence of hemophilia.
Treatment Options and Outlook
The goal of treatment is generally to raise the deficient clotting factor to 30 percent, or 50 to 100 percent during episodes of active bleeding, depending on the site. Treatment may be transfusions with fresh frozen plasma or plasma cryoprecipitate, both of which contain clotting factors VIII and IX, or with clotting factor concentrates.
The more often these treatments are necessary, however, the greater the likelihood the person will develop antibodies to the clotting factors that subsequently prevents these treatments from having any effect. In such situations the doctor may administer porcine-derived forms of clotting factor VIII or prothrombin complex concentrate, which bypass some of the steps in the coagulation cascade to avoid antibody activation.
A promising treatment for mild hemophilia A is the synthetic hormone desmopressin. Also called DDAVP, desmopressin is an analog (close chemical relative) of the endogenous hormone vasopressin, which the pituitary gland secretes. Administered intravenously or via nasal spray, desmopressin causes the body to increase blood levels of clotting factors VIII and IX. However, desmopressin has little effect in people who have hemophilia B. Desmopressin may affect other aspects of the coagulation cascade and can elevate the blood pressure.
Blood product treatments for hemophilia carry the risk of infection with various pathogens that current blood screening technology cannot detect including hepatitis a, human T-lymphotropic virus 1 (HTLV-1), west Nile virus, malaria, and also cytomegalovirus (CMV). Though infection with human immunodeficiency virus (HIV) was a significant problem during the 1980s, screening procedures in effect today have nearly eliminated the risk for acquiring HIV/AIDS through donated blood products.
Many people who have hemophilia are able to enjoy a high quality of life with ongoing medical monitoring and lifestyle choices to reduce the risk for traumatic injury. However, complications such as joint damage due to frequent bleeding can limit physical activities. Gastrointestinal bleeding is also a potential complication.
Risk Factors and Preventive Measures
Genetic inheritance is the only known risk factor. Health experts encourage people who have hemophilia, know they carry the gene defect for hemophilia, or have a family history of unusual bleeding to discuss family planning with a genetic counselor who can advise of the risks that children will either carry or have hemophilia.
Much research currently focuses on perfecting recombinant technologies to provide clotting factor therapies free from risk of infection and antibody development. Other research efforts are exploring the potential for gene therapy that can repair the damaged genes, though this potential has not yet yielded practical results.