The earliest reference to the condition known as haemophilia came from ancient Jewish texts about two thousand years ago, which described the death of male children from excessive bleeding after circumcision. Males could be exempt from the tradition of circumcision if they had two brothers who had previously died from bleeding as a result of the procedure. By the Fifth Century AD, haemophilia was recognised as an inherited disease affecting mostly males.
Abulcasis (c.936-1013), considered to be the father of modern surgery, was an Arabian physician, pharmacist and surgeon who lived in Spain during the middle Ages. He was born in the town of Al-Zahra, near Cordova, and was the first physician to provide a clear written description of the disease. He described a family in which males died after what appeared to be minor injuries. His account of the family showed quite clearly that he recognised the hereditary nature of the disease.

Although descriptions of familial bleeding appear in ancient writings, it was John Conrad Otto (1774-1844) who was credited with the first modern description of the disease which he brought to the attention of physicians in the United States and Europe.
Dr. Otto came from a family of physicians and was born near Woodbury, New Jersey. He graduated from the University in Pennsylvania and began practising medicine in Philadelphia, eventually becoming attending physician at the Pennsylvania Hospital in 1813. In 1803 his article on haemophilia was published in Medical Repository, considered to be America’s first scientific journal. Dr. Otto studied the descendants of a New Hampshire woman to develop a clinical description of fatal bleeding, twenty-five years before the word 'haemophilia' was first used.

'About seventy or eighty years ago a woman by the name of Smitt transmitted the following idiosyncrasy to her descendants. If the least scratch is made on the skin of some of them, as mortal a hemorrhagy will eventually ensue as if the largest wound is inflicted… It is a surprising circumstance that the males only are subject to this strange affection, and that all of them are not liable to it. lthough the females are exempt, they are still capable of transmitting it to their male children.

The persons subject to this hemorrhagic disposition are remarkably healthy, and, when indisposed, they do not differ in their complaints, except in this particular, from their neighbors. No age is exempt, nor does any one appear to be particularly liable to it.'

In the nineteenth century, most physicians did not understand the 'mechanism' of haemophilia. They believed that it was caused by a defect in the structure of the blood vessels. It was not until the 1950s that the biochemical basis of haemophelia was determined and it was even later before the coagulation cascade was fully understood.

The most well known early case of the disease gives it the nickname 'The Royal Disease'. The presence of the condition among members of many European royal families during the 19th and 20th centuries originated with Queen Victoria, a spontaneous carrier whose descendants introduced the disorder to the royal houses of Russia, Germany and Spain.
Queen Victoria (1819-1901) married her first cousin, Prince Albert in 1840; they had nine children, five girls and four boys. Haemophilia did not appear in the family until her eighth child was born, Prince Leopold, Duke of Albany. Although the Queen’s ancestors did not appear to have haemophilia, some experts believe that there were cases in her male ancestors, but they were never diagnosed because they died so young or died before the disease was recognised. The general view, however, appears to be that the condition appeared as a random mutation in the genes of Victoria or her father, who then passed the affected gene on to her.
Because of his severe haemorrhages, Prince Leopold was unable to lead an active life either as a child or an adult and was kept under strict surveillance. Despite this, he died at the age of 31 from intracerebral bleeding after a fall.
Two of Victoria’s daughters (Alice and Beatrice) were carriers. Beatrice married Prince Henry, Duke of Battenburg, they had four children, two sons with haemophilia and one daughter, Eugenie, who was a carrier and subsequently introduced the disease into the Spanish Royal Family when she married King Alfonso XIII. Of their seven children, two boys are known to have suffered from haemophilia.
Alice married the Duke of Hesse, three of their sons had the disease and two of their daughters were carriers (Irene and Alexandra).
Irene married her first cousin, Prince Henry of Prussia; they had two sons with haemophilia, thus introducing the disease into the German Royal Family.
Alexandra married Russia’s last Czar, Nicholas II, they had four daughters before their long-awaited heir to the Russian throne was born, Alexis - he was affected with very severe haemophilia. The bleeding into his joints was crippling; he spent many weeks in bed and was forced to wear an iron brace. Alexis’ parents employed the monk Rasputin to help heal their son and the deteriorating state of affairs in Russia was partly blamed on the influence Rasputin had over the royal family, causing public unrest which eventually lead to the Bolshevik Revolution. Alexis did not die from haemophilia, but was executed with the rest of his family at the age of fourteen.
Queen Victoria’s reign is known as 'the Victorian Era', a time of progress and dramatic social, scientific, religious and artistic change. Although Victoria will be remembered for this period of world history, she will also be associated forever with haemophilia because it spread through the royal families of Europe from her descendants.

Dr. Judith Graham Poole

Dr. Judith Graham Poole (1919-1975) and her associates developed a process for freezing and thawing plasma to obtain cryoprecipitate; a factor-rich substance considered a breakthrough in the treatment of haemophilia.
Dr. Poole spent more than twenty years of her career studying blood coagulation and haemophilia and her first publication on the subject appeared in 1954. In the mid-1960s, she and her team published a paper entitled “High-potency antihaemophilic factor concentrates prepared from cryoglobulin precipitate”. The paper was published in the journal Nature in 1964 and a similar article appeared in the New England Journal of Medicine in 1965. From these articles, the medical community was introduced to the benefits and preparation of cryoprecipitate.

In the past plasma, carried the risk of transmitting blood-borne diseases, for example hepatitis and AIDS. In the early 1980s, sixty percent of people with haemophilia treated with plasma concentrates were infected with HIV, but today such risks have virtually been eliminated by the use of screened and processed blood.

Gene Therapy
In the 1980’s, haemophilia made the headlines as one the first human disorders in which the responsible gene was identified and cloned.

Acknowledgements:
Bleeding Disorders Information Centre/Hemophilia A
Haemophilia History and Advances in Therapy
Hemophelia by Teddi Softley, Ph.D.

History of Haemophilia