There are several types of hemophilia, the rare bleeding disorder in which the blood fails to clot properly. Hemophilia A and B are the most common types, while hemophilia C is relatively rare.
Additionally, there is an acquired form of the disease, which results from a fault in the body’s immune system that causes it to attack and destroy certain blood clotting proteins, called clotting factors.
Most cases of hemophilia are caused by mutations in genes encoding the clotting proteins, which cause the body to produce small amounts of that particular clotting factor.
The type of hemophilia a patient has depends on the specific clotting factors that person is missing.
Hemophilia A, also known as classical hemophilia, occurs when mutations in the F8 gene cause the body to produce low levels of clotting factor VIII (FVIII). These mutations typically are inherited, although they also may occur spontaneously.
The F8 gene is found on the X chromosome, of which males inherit only one copy; females inherit two copies. Because of this, hemophilia A tends to affect more men — who inherit only a faulty X chromosome from their mothers — than women.
Hemophilia A can be considered mild, moderate, or severe, depending on FVIII activity levels. In healthy people, these levels typically range between 50–150%. In patients with mild hemophilia A, FVIII activity levels usually range between 5–40%. Among those with moderate cases, FVIII activity levels range between 1–5%, while in people with severe hemophilia A, they drop to less than 1%.
The onset of symptoms in hemophilia A often varies with age and disease severity.
Individuals with mild cases may not experience significant bleeding until having surgery, sustaining a serious injury, or experiencing other major trauma. As such, the condition may remain undiagnosed until adulthood.
Conversely, severe hemophilia A may be caught early on in infants and young children, as they can bleed excessively from the mouth or develop large swellings under the scalp known as “goose eggs” after bumping their heads.
Treatment for hemophilia A typically consists of supplying FVIII to patients intravenously, or directly into the bloodstream, as needed. People with severe forms of the disease also may receive FVIII prophylactically, or as preventive measure, to maintain clotting factor levels in their blood sufficiently high at all times. Such preventive measures help type A patients to avoid spontaneous bleeds.
Also known as Christmas disease, from the first person to be diagnosed with this disorder type, hemophilia B stems from mutations in the F9 gene. Such mutations result in the lack of clotting factor IX, known as FIX.
Type B is similar to hemophilia A, in that F9 also is found on the X chromosome, making males more susceptible to the disease than females. Yet, hemophilia B is approximately four times less common than hemophilia A.
Like hemophilia A, hemophilia B also can be divided into three categories of severity (mild, moderate, and severe), based on FIX activity levels following the same percentage intervals.
Treatment for hemophilia B usually involves supplying FIX to patients prophylactically on a regular basis to prevent bleeds, or on an on-demand basis to treat bleeding episodes.
Missing or defective factor XI or FXI causes hemophilia C, also known as Rosenthal syndrome.
FXI assists in clotting by helping produce thrombin, a protein that converts fibrinogen — a soluble protein present in blood plasma — to fibrin. Fibrin traps small cell fragments called platelets, holding them together to keep a blood clot in place.
Unlike other types of hemophilia, the F11 gene encoding FXI is not located on the X chromosome, but on chromosome 4. For this reason, hemophilia C affects males and females equally, as both men and women inherit two copies of this chromosome.
Usually the disease is inherited in an autosomal recessive manner, meaning that a person must inherit two defective gene copies to develop the condition. However, in some cases, it also may be inherited in an autosomal dominant way, meaning that a single faulty copy of the gene is sufficient to trigger its onset.
In rare cases, this type of hemophilia also can be acquired instead of being inherited. In these cases, hemophilia C is normally associated with an underlying disorder, such as lupus.
While hemophilia A and B affect ethnic groups equally, hemophilia C is more commonly seen in Ashkenazi Jews, where it has an estimated incidence of 8%.
Bleeds in this type of hemophilia tend to be milder and symptoms are not always related to FXI levels. Spontaneous and internal joint bleeds, which are common in other forms of hemophilia, usually do not occur in people with type C.
Treatment might consist of antifibrinolytics, such as aprotinin, which prevent blood clots from dissolving by slowing the breakdown of fibrin. Other treatments include fresh frozen plasma, or concentrated FXI. This last treatment, however, remains unavailable in the U.S.
In rare instances, the immune system fails to recognize a clotting factor — usually FVIII — as a molecule that is part of the body. When that happens, the immune system starts producing antibodies that attack it as though it were a virus or other harmful foreign molecule, resulting in acquired hemophilia.
Although it usually affects the same clotting factor as hemophilia A, the bleeding patterns differ markedly between the two conditions. Why exactly this happens, however, is still not fully understood.
Bleeding in acquired hemophilia usually occurs just below the skin (subcutaneous bleeds), in the muscles (hematomas or bruises), and in the gastrointestinal tract. Joint bleeds are uncommon in acquired hemophilia, in contrast with hemophilia A. Bleeding often is severe in this type of hemophilia, and frequently spontaneous, meaning that it happens without a clear cause.
Acquired hemophilia affects males and females equally. It occurs more frequently in the elderly and is rarely seen in children.
Evidence suggests that it often develops from some triggering event, such as an infection or an underlying medical condition. Nonetheless, such coexisting disorders have only been identified in approximately 50% of cases. Some of these underlying conditions include lupus, multiple sclerosis, Sjögren’s syndrome, and certain cancers.
Because of its rarity and the small number of case studies describing it, treatment for acquired hemophilia tends to be highly tailored to the individual patient. Treatment aims to stop and control bleeding, as well as prevent the immune system from producing self-reactive antibodies against FVIII or other clotting factors.
Last updated: July 22, 2021
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