What is the historical background of hemophilia A?

Updated: Jan 14, 2019
  • Author: Douglass A Drelich, MD; Chief Editor: Srikanth Nagalla, MBBS, MS, FACP  more...
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Answer

Hemophilia is one of the oldest described genetic diseases. An inherited bleeding disorder in males was recognized in Talmudic records of the second century.

The modern history of hemophilia began in 1803 with the description of hemophilic kindred by John Otto, followed by the first review of hemophilia by Nasse in 1820. Wright demonstrated evidence of laboratory defects in blood clotting in 1893; however, FVIII was not identified until 1937, when Patek and Taylor isolated a clotting factor from the blood, which they called antihemophilic factor (AHF).

A bioassay of FVIII was introduced in 1950. Although the intimate relationship between FVIII and von Willebrand factor (vWF) is now known, it was not appreciated at the time. In 1953, decreased FVIII levels in patients with vWF deficiency was first described. Further research by Nilson and coworkers indicated the interaction between these 2 clotting factors.

In 1952, hemophilia B was described and was named Christmas disease after the surname of the first patient who was examined in detail. The differentiation of hemophilia B from hemophilia A followed the observation that mixing plasma from a patient with "true hemophilia" with plasma from a patient with Christmas disease corrected the clotting time. Hemophilia A makes up approximately 80% of hemophilia cases.

In the early 1960s, cryoprecipitate (the precipitate from fresh frozen plasma that has been thawed and centrifuged) became the first concentrate available for the treatment of patients with hemophilia. In the 1970s, lyophilized (ie, freeze-dried) intermediate-purity concentrates were obtained from large pools of blood donors. The introduction of concentrated lyophilized products that are easy to store and transport dramatically improved the quality of life of patients with hemophilia and facilitated their preparation for surgery and home care.

Unfortunately, the large size of the donor pool—as many as 20,000 donors may contribute to a single lot of plasma-derived FVIII concentrate—heightened the risk of viral contamination of commercial FVIII concentrates. By the mid-1980s, most patients with severe hemophilia had been exposed to hepatitis A, hepatitis B, and hepatitis C viruses and human immunodeficiency virus (HIV).

Viricidal treatment of plasma-derived FVIII concentrates has been effective in eliminating new HIV transmissions and virtually eliminating hepatitis B and hepatitis C exposures. The introduction of recombinant FVIII concentrate, and the gradual elimination of albumin from the production process used for these products, has virtually eliminated the risk of viral exposure.


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