Hemophilia is a genetic bleeding disorder that prevents the blood from clotting normally. The main symptom is uncontrolled, often spontaneous bleeding. Internal bleeding into the joints can result in pain, swelling and, if left untreated, can cause permanent damage.

Hemophilia results from the deficiency of one more proteins known as blood clotting factors. There are 13 clotting proteins in the body, all of which contribute to the formation of a clot. The two main forms are hemophilia A (factor VIII deficiency) and hemophilia B (factor IX deficiency). Hemophilia occurs in 1 in 5,000 live male births, of these 80% are hemophilia A and 20% are hemophilia B. The worldwide incidence of hemophilia is estimated at more than 400,000 people. Approximately 70% of people around the world do not have access to treatment.

  • Currently, there is no cure for hemophilia. While treatment exists, it is costly and may require lifelong infusion of replacement clotting factor that is manufactured either from human plasma or using recombinant technology. Hemophilia occurs predominately in males. Women are carriers of the defective gene and may experience mild symptoms. In about one-third of cases there is no known family history of hemophilia. Instead, the disorder results from a spontaneous genetic mutation.
  •  Nearly 90% of Americans with severe hemophilia became infected with HIV in the 1980s when the nation’s blood supply was contaminated by blood pooled from people infected by HIV/AIDS. More than 50% of people with hemophilia infected with HIV have died. Since 1986, there have been no reported cases of HIV transmission through factor concentrates in the U.S. Current donor screening measures and improved viral inactivation methods have been integrated into the manufacturing process to dramatically improve the safety of these plasma-derived products.

Early History

References to excessive and unexplained bleeding have been made since antiquity. In the Talmud, a collection of Jewish Rabbinical writings from the 2nd century AD, it was written that male babies did not have to be circumcised if two brothers had already died from the procedure. In the 12th century AD, an Arabian physician from Cordoba named Albucasis wrote of males in a particular village, who had died of uncontrollable bleeding. Occasional references to bleeding can be found in the scientific literature of following centuries.

In the U.S., the transmission of hemophilia from mothers to sons was first described in the early 19th century. In 1803, the Philadelphia physician Dr. John Conrad Otto wrote an account of “a hemorrhagic disposition existing in certain families.” He recognized that a particular bleeding condition was hereditary and predominately affected males. He traced the disease back through three generations to a woman who had settled near Plymouth, New Hampshire in 1720. The word “hemophilia” first appeared in a description of a bleeding disorder condition at the University of Zurich in 1828.

Finding the Cause

In the 20th century doctors looked for the cause of excessive bleeding. Until then, they had believed that the blood vessels of people with hemophilia were simply more fragile.

1920s
von Willebrand disease, the most common hereditary bleeding disorder, was first recognized by the Finnish physician Erik von Willebrand in 1925. He published his first paper on the disease in 1926. In it, he presented the pedigree of a Scandinavian family from the island of Aland, reporting bleeding symptoms in 23 of 66 family members.

1930s
Doctors previously thought defective platelets were the likely cause of bleeding disorders. But in 1937, doctors at Harvard University found they could correct the clotting problem by adding platelet-free plasma. They called the substance “anti-hemophilic globulin.”

1940s
In 1944 Dr. Pavlosky from Buenos Aires, Argentina, did a lab test which showed that blood from a person with hemophilia could correct the clotting problem in a second person with hemophilia and vice-versa. He had stumbled upon two patients, each with a deficiency in different proteins – Factor VIII and Factor IX. This led to the eventual recognition of hemophilia A and hemophilia B as two distinct diseases. By the end of the decade people with hemophilia had a life expectancy of less than 30 years. Treatment was limited to icing joints where internal bleeding occurred and painful transfusions of whole blood.

1950s & 1960s
In the 1950s and early 1960s, hemophilia and other bleeding problems were still being treated with whole blood or fresh plasma. Unfortunately, there were not enough factor VIII or IX proteins in these treatments to stop serious internal bleeding. Many people with severe hemophilia, and some people with mild or moderate forms, died in childhood or early adulthood. The most common causes of death were bleeding in vital organs, especially the brain, and excessive bleeding after minor surgery or trauma. Those who survived were often crippled by the long-term effects of repeated hemorrhages into the joints. The pressure of massive bleeding into joints and muscles made hemophilia one of the more painful diseases.

By the mid-1960s the clotting factors were identified and named. An article in Nature in 1964 described the clotting process in detail. The interaction of the different factors in blood clotting was termed the “coagulation cascade.”

In 1965, Dr. Judith Graham Pool published a paper on cryoprecipitate. In a major breakthrough, Dr. Pool discovered that the precipitate left from thawing plasma was rich in factor VIII. She found that because cryoprecipitate contained a substantial amount of factor, it could be infused to control serious bleeding. Blood banks were able to produce and store the component, making emergency surgery and elective procedures for hemophilia patients more practicable. This advancement also ended the need for high-volume whole plasma transfusions for people with hemophilia.

1970s
By the 1970s, freeze-dried powdered concentrates containing factor VIII and IX became available. Factor concentrates revolutionized hemophilia care because they could be stored at home, making treatment easily accessible. People with hemophilia could now “self-infuse” factor products, drastically reducing the number of requisite hospital visits. Activities such as work and travel were now carried out with much greater ease, the benefits being increased convenience and independence.

1980s
Although hepatitis C was already present in the blood supply, by the early 1980s a new blood-borne disease would emerge. By the mid 1980s, it had become clear that HIV/AIDS could be transmitted though the use of blood and blood products, such as those used to treat hemophilia. Approximately half of the people with hemophilia in the U.S. would eventually become HIV-infected and thousands would die. The overwhelming impact of HIV on the hemophilia community would reverberate well into the next decade.

1990s to present
Treatment for hemophilia and other bleeding disorders advanced in the 1990s. The safety and efficacy of factor concentrates improved. Factor products became safer as tighter screening methods were implemented and advanced modes of viral inactivation were utilized. In addition, synthetic (not derived from plasma) factor products were manufactured using recombinant technologies. In 1992, the first recombinant factor VIII product was approved by the Food and Drug Administration (FDA). In 1997, the first factor IX product was granted FDA approval. Additional synthetic drugs such as desmopressin acetate (DDAVP) were also introduced to treat mild-to-moderate hemophilia A and von Willebrand disease.

By the mid 1990s prophylactic (a preventative treatment regimen) therapy in children with hemophilia became more common. Proponents argued that the implementation of prophylaxis would prevent the chronic bleeding episodes that typically characterized hemophilia. Since the advent of prophylaxis, children could look forward to a life of less pain, without the orthopedic damage associated with chronic bleeding. As a result, most children born with hemophilia in the U.S. today can look forward to long, healthy and active lives.

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