A Tour around Haemophilia

In the second century AD, rabbinical rulings exempted Jewish boys from circumcision if two previous brothers had died of bleeding after the procedure. Despite this apparent early knowledge of an inherited bleeding disorder, haemophilia was not described in detail until 1803. This, and many other interesting facts about the history of the condition, can be found at the Oxford Haemophilia Centre web site. Did you know, for example, that within living memory (just) the range of treatments has included peanut flour, snake venom and bromide extract of egg white?

The term haemophilia describes a group of disorders in which the deficiency of a blood clotting factor leads to prolonged bleeding. A reduced amount of Factor VIII causes Haemophilia A (classical haemophilia), while a deficiency of Factor IX causes Haemophilia B, or Christmas disease. Only blood tests can differentiate between the two. Their severity is related to the degree of deficiency of clotting factor. When mild (levels 5 - 25% of normal) or moderate (levels 2 - 5% of normal), bleeding episodes are usually related to surgery, or injury such as a knock or deep cut. However, severe haemophilia (levels less than 2% of normal) is characterised by frequent and spontaneous bleeding into joints and muscles, which can be disabling. The online booklet Introduction to Haemophilia, published by The Haemophilia Society, provides some very good basic information. Rest assured, diagnostic methods have improved somewhat over the past two millennia!

Even for those whose knowledge of genetics does not extend beyond Gregor Mendel and peas, this booklet gives a clear explanation of the way in which haemophilia is inherited. The defective gene is recessive and carried on the X chromosome, so that males are affected by the condition and females are carriers - in their case the dominant normal X chromosome causes clotting factor to be produced. However, in about a third of female carriers bleeding problems may occur following tooth extractions, surgery or severe accidents.

Should you be an expert in this field, the splendidly named HAMSTeRS site - look out for the logo! - provides a resource for research into Haemophilia A. For detailed information about the structure and function of the Factor VIII gene, and mutations affecting it, the review entitled The Molecular Pathology of Haemophilia A presents a very comprehensive picture. There is a similar site for Haemophilia B, but it is essentially a database of mutations which have been discovered in the Factor IX gene.

Bleeding episodes are treated by intravenous injection of the missing clotting factor in the form of cryoprecipitate. This should be given as promptly as possible to minimise the period of incapacity and avoid permanent damage to joints and muscles. Often a single injection is sufficient to control the bleed. Nowadays most people with severe haemophilia carry cryoprecipitate around and treat themselves at home or at work, minimising the disruption caused by the condition. An alternative to this 'on-demand' therapy, pioneered in Scandinavia, is the prophylactic injection of Factor VIII or IX two or three times a week to prevent bleeding episodes. If this is carried out from an early age the risk of joint damage is greatly reduced. More information is again available on the Oxford Haemophilia Centre site.

Clotting factors may be derived from porcine plasma or pooled human plasma, or produced synthetically by recombinant technology. Many haemophiliacs contracted hepatitis C and HIV from human plasma in the early 1980s, but since the introduction of heat treatment and other virucidal techniques in 1985 no instance of viral transmission has been recorded.

Future treatment may well revolve around gene therapy - to see what is happening in this field, expressed in clear layman's language, check the archives at Kelley Communications. One particularly useful article is The Hope and Hype of Hemophilia Gene Therapy. However, if you want to keep up with all aspects of haemophilia research, a more comprehensive source is Hemophilia Reports, which is published six times a year.

To digress, haemophilia has often been termed the Royal Disease. Queen Victoria's eighth child Prince Leopold was a victim and two of her daughters, Alice and Beatrice, were carriers. The condition was transmitted through them to several European royal families including the Russian Tsars. It is widely accepted that the severe strain imposed on the Russian royal family by the young Tsarevich Alexei's haemophilia enabled Rasputin to gain influence over the Empress Alexandra - an important precipitating factor in the Russian Revolution and the murder of the entire Romanov family by Lenin's Bolshevik guards in July 1918.

An alternative explanation which challenges conventional wisdom has been put forward by Mars, Venus and Hemophilia. Although written in a light-hearted vein, it contains some penetrating insights which could boost understanding between partners.

However, the prospects for a youngster with haemophilia today are excellent. Apart from avoiding sports such as rugby and boxing, he can look forward to a normal education in an ordinary school and regular employment, even fatherhood. A survey of almost 1,000 patients published in the Annals of Internal Medicine concluded that when viral infection with HIV and Hepatitis C is excluded, the life expectancy of haemophiliacs now almost equals that of the general male population. Considering that 50 years ago these patients were frequently disabled by joint bleeds in their teens, and were unlikely to survive much beyond 30, this represents a very significant advance.

This tour was submitted by Derrick Garwood, freelance medical writer.

If you have any comments on this article, please email Derrick.

The details presented here were accurate at the time of publication, but remember that information on the Web has a tendency to change without notice!

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