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The history of hemophilia

When was hemophilia first recognized?

Hemophilia was recognized, though not named, in ancient times.The Talmud, a collection of Jewish Rabbinical writings from the 2nd century AD, stated that male babies did not have to be circumcised if two brothers had already died from the procedure.

The Arab physician Albucasis, who lived in the 12th century, wrote of a family whose males died of bleeding after minor injuries.

Then, in 1803, a Philadelphia physician named Dr. John Conrad Otto wrote an account of 'a hemorrhagic disposition existing in certain families'. He recognized that the condition was hereditary and 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 appears in a description of the condition written by Hopff at the University of Zurich in 1828.

Why is hemophilia called The Royal Disease?

Hemophilia has often been called The Royal Disease. This is because Queen Victoria, Queen of England from 1837 to 1901, was a carrier. Her eighth child, Leopold, had hemophilia and suffered from frequent hemorrhages. These were reported in the British Medical Journal in 1868. Leopold died of a brain hemorrhage at the age of 31, but not before he had children. His daughter, Alice, was a carrier and her son, Viscount Trematon, also died of a brain hemorrhage in 1928.

Even more important to history was the existence of hemophilia in the Russian Royal Family. Two of Queen Victoria's daughters, Alice and Beatrice, were also carriers of hemophilia. They passed the disease on to the Spanish, German and Russian Royal Families.

Alexandra, Queen Victoria's granddaughter, married Nicholas, the Tsar of Russia in the early 1900's. Alexandra, the Tsarina, was a carrier of hemophilia and her first son, the Tsarevich Alexei, a hemophiliac. Nicholas and Alexandra were pre-occupied by the health problems of their son at a time when Russia was in turmoil. The monk Rasputin gained great influence in the Russian court, partly because he was the only one able to help the young Tsarevich. He used hypnosis to relieve Alexei's pain. The use of hypnosis not only relieved pain, but may have also helped slow or stop the boy's hemorrhages. The illness of the heir to the Tsar's throne, the strain it placed on the Royal Family, and the power wielded by the mad monk Rasputin were all factors leading to the Russian Revolution of 1917.

What is the history of hemophilia in the 20th century?

In the 20th century doctors looked for the cause of hemophilia. Until then, they had believed that the blood vessels of hemophiliacs were simply more fragile. In the 1930s doctors looked at defective platelets as the likely cause. Then, in 1937, Patek and Taylor, two doctors at Harvard, found they could correct the clotting problem by adding a substance which came from the plasma in blood. This was called anti-hemophilic globulin. In 1944, Pavlosky, a doctor from Buenos Aires, Argentina, did a lab test which showed that blood from one hemophiliac could correct the clotting problem in a second hemophiliac and vice-versa. He had stumbled upon two hemophiliacs each with a deficiency in different proteins - factor VIII and factor IX. This led to the recognition in 1952 of hemophilia A and hemophilia B as two distinct diseases.

In the 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 named the coagulation cascade.

In the 1950s and early 1960s, hemophiliacs were treated with whole blood or fresh plasma. Unfortunately, there wasn't enough of the factor VIII or IX proteins in these blood products to stop serious internal bleeding. Most people with severe hemophilia and some people with mild or moderate hemophilia died in childhood or early adulthood. The most common causes of death were bleeding in vital organs, especially the brain, and bleeding after minor surgery or after an injury.

Those who survived were usually 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 most painful diseases known to medicine. Then, in the 1960s, cryoprecipitate was discovered by Dr. Judith Pool. Dr. Pool found that the sludge that sunk to the bottom of thawing plasma was rich in factor VIII. For the first time, enough factor VIII clotting factor could be infused to control serious bleeding. Even surgery became possible.

Then, later in the 1960s and early 1970s, concentrates containing factor VIII and IX began to be available. These freeze-dried powdered concentrates could be kept at home and used as needed. They revolutionized hemophilia care. Hemophiliacs were now independent of hospitals. They could travel, hold steady jobs and hope to lead normal lives. Tragically, these same blood products carried blood-borne viruses like hepatitis C and HIV. Many hemophiliacs were infected.

In the 1990s, modern treatment, using safer factor concentrates, again improved the outlook. (See Table 1.) Most children born with hemophilia in Canada today can look forward to long, healthy, active and productive lives.

Unfortunately, only 25% of the world's hemophiliacs enjoy this level of care. The ones who do not have access to modern hemophilia care face the same fate as Queen Victoria's offspring in the 1800s - a life of pain and crippling, and an early death.

Table 1: The History of Clotting Factors in Canada

GenerationProductIntroduction in Canada
1.Fresh whole blood 1947
2.
Cryoprecipitate (factor VIII) 1965
3.
Factor VIII concentrate (lyophilized, unheated) 1968
4.
Factor VIII concentrate (lyophilized, dry heat-treated)

Factor IX concentrate (lyophilized, dry heat-treated)
1985

1985
5.
Factor VIII concentrate (enhanced viral inactivation: vapour heat, solvent detergent treatment)1987
6.
High purity factor VIII concentrate (Monoclonal antibody purified)

purity factor IX
1987

1991
7.
Genetically engineered (recombinant) factor VIII concentrate

Genetically engineered (recombinant) factor IX concentrate
1993

1998