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This bad blood
HAEMOPHILIA
This bad blood Peter M Green “
o how long have you had this bad blood?” I was asked as I registered with a new family doctor at the age of 13. I patiently explained that since haemophilia was an inherited disease, I had, of course, had it since birth; my mother was a carrier and her father also had the disease. That many doctors have never heard of Christmas disease (named after the patient who was first diagnosed with the distinct form of haemophilia), is surprising, but not uncommon. I had my first haemorrhage (into an ankle joint) before I could walk, and as childhood progressed, more of my joints succumbed to their first “bleed”. Every bleed into a joint was, at that time, untreatable and took its course, typically swelling up, reducing movement of the joint, and hindering mobility if in a leg joint, then gradually subsiding over 3 to 10 days. I missed a great deal of school because of my disease, and spent many days in hospital. Plasma infusions were frequently given to The author, aged 18 months, after taking a typical toddler's tumble help replenish the missing factor IX from my blood, the use of recombinant factors as products of choice although I was always doubtful that they had any effect. in 1996 to treat both haemophilia A (with F VIII) and Pain relief was limited, mostly to paracetamol, which haemophilia B (with F IX) as they are free of any possible couldn’t touch the pain of a severe joint bleed. Because my blood-borne viruses. However, only a minority actually father was in the armed forces, we moved about a lot, and receive it, since health services are deterred from providing lived for a while in Yemen, Germany, and Hong Kong. the best (and ultimately the cheapest) treatment available We were sent home early from all three of these countries because of cost. The message should be simple—spending because the authorities were worried about my health. more money now will save money later. However, there was very little in the way of treatment I have always been interested in what exactly causes the back then, even in the UK. The most dramatic oversymptoms of my haemophilia. I hoped that this knowledge reaction occurred in Germany; I was 7 and my milk teeth might allow me to explain to friends at school exactly why had started to fall out. I had profuse bleeding, which I seemed to break my arm so often (elbow bleeds were although very uncomfortable, was hardly life threatening. more comfortable with my arm in a sling, hence other Nevertheless, on two occasions, I was flown by emergency children assumed that I had broken my arm) and was light aircraft back to the Oxford Haemophilia Centre, UK, always wearing callipers on my leg. I knew that the basic for treatment. answer was that my body produced no factor IX, but I By the time I reached my teens, replacement treatment couldn’t explain why. Eventually, at school, I learnt the with plasma-derived factor IX concentrate was available, basics of genetics, and then became curious about what though only from Oxford. Consequently, I attended a DNA change had caused this fault in my factor IX gene. boarding school in Oxford so as to be near the centre, and The need to find out what this mutation was became more was able to treat myself with intravenous factor IX from relevant when I discovered, early on in my working life as the age of 16 (and have been doing so ever since). The use a geneticist, that my sister (who had a 50% chance of of replacement therapy has made a big difference to my inheriting the gene) wanted to be tested for her carrier life, as a bleed need no longer be so incapacitating, status; existing tests based on concentration of factor IX in particularly if treated at the earliest possible moment. the blood are often inconclusive. Researchers expected, Indeed, doctors soon realised that prophylactic treatment even before analysis of gene mutations had begun, that could prevent bleeds altogether, and I became one of the different families with haemophilia would harbour earliest patients on trial prophylaxis. Prevention of different mutations, since the family history of the disease bleeding avoids the permanent damage to the joints that rarely went back more than a few generations. This otherwise leads to crippling arthritis at an early age. heterogeneity of mutations could provide scientists Results of research have shown that such preventitive investigating the disease with important information, and measures are highly costeffective (repeated admissions to might also help in the development of diagnostic tests. For hospital are very expensive), and yet most patients with this reason, we established the confidential haemophilia B haemophilia in the world do not receive prophylaxis, even national database of mutations and, later, that for in developed countries, such as USA. haemophilia A (still under completion). The directors of the UK Haemophilia Centre endorsed
R A Green
S
Peter M Green is a lecturer in molecular genetics. Division of Medical and Molecular Genetics, GKT School of Medicine, Guy's Tower, London SE1 9RT, UK (P M Green [email protected]
The Lancet Supplement | 358 | December | 2001
MRCPath)
S34
For personal use. Only reproduce with permission from The Lancet Publishing Group.
This bad blood Peter M Green “
o how long have you had this bad blood?” I was asked as I registered with a new family doctor at the age of 13. I patiently explained that since haemophilia was an inherited disease, I had, of course, had it since birth; my mother was a carrier and her father also had the disease. That many doctors have never heard of Christmas disease (named after the patient who was first diagnosed with the distinct form of haemophilia), is surprising, but not uncommon. I had my first haemorrhage (into an ankle joint) before I could walk, and as childhood progressed, more of my joints succumbed to their first “bleed”. Every bleed into a joint was, at that time, untreatable and took its course, typically swelling up, reducing movement of the joint, and hindering mobility if in a leg joint, then gradually subsiding over 3 to 10 days. I missed a great deal of school because of my disease, and spent many days in hospital. Plasma infusions were frequently given to The author, aged 18 months, after taking a typical toddler's tumble help replenish the missing factor IX from my blood, the use of recombinant factors as products of choice although I was always doubtful that they had any effect. in 1996 to treat both haemophilia A (with F VIII) and Pain relief was limited, mostly to paracetamol, which haemophilia B (with F IX) as they are free of any possible couldn’t touch the pain of a severe joint bleed. Because my blood-borne viruses. However, only a minority actually father was in the armed forces, we moved about a lot, and receive it, since health services are deterred from providing lived for a while in Yemen, Germany, and Hong Kong. the best (and ultimately the cheapest) treatment available We were sent home early from all three of these countries because of cost. The message should be simple—spending because the authorities were worried about my health. more money now will save money later. However, there was very little in the way of treatment I have always been interested in what exactly causes the back then, even in the UK. The most dramatic oversymptoms of my haemophilia. I hoped that this knowledge reaction occurred in Germany; I was 7 and my milk teeth might allow me to explain to friends at school exactly why had started to fall out. I had profuse bleeding, which I seemed to break my arm so often (elbow bleeds were although very uncomfortable, was hardly life threatening. more comfortable with my arm in a sling, hence other Nevertheless, on two occasions, I was flown by emergency children assumed that I had broken my arm) and was light aircraft back to the Oxford Haemophilia Centre, UK, always wearing callipers on my leg. I knew that the basic for treatment. answer was that my body produced no factor IX, but I By the time I reached my teens, replacement treatment couldn’t explain why. Eventually, at school, I learnt the with plasma-derived factor IX concentrate was available, basics of genetics, and then became curious about what though only from Oxford. Consequently, I attended a DNA change had caused this fault in my factor IX gene. boarding school in Oxford so as to be near the centre, and The need to find out what this mutation was became more was able to treat myself with intravenous factor IX from relevant when I discovered, early on in my working life as the age of 16 (and have been doing so ever since). The use a geneticist, that my sister (who had a 50% chance of of replacement therapy has made a big difference to my inheriting the gene) wanted to be tested for her carrier life, as a bleed need no longer be so incapacitating, status; existing tests based on concentration of factor IX in particularly if treated at the earliest possible moment. the blood are often inconclusive. Researchers expected, Indeed, doctors soon realised that prophylactic treatment even before analysis of gene mutations had begun, that could prevent bleeds altogether, and I became one of the different families with haemophilia would harbour earliest patients on trial prophylaxis. Prevention of different mutations, since the family history of the disease bleeding avoids the permanent damage to the joints that rarely went back more than a few generations. This otherwise leads to crippling arthritis at an early age. heterogeneity of mutations could provide scientists Results of research have shown that such preventitive investigating the disease with important information, and measures are highly costeffective (repeated admissions to might also help in the development of diagnostic tests. For hospital are very expensive), and yet most patients with this reason, we established the confidential haemophilia B haemophilia in the world do not receive prophylaxis, even national database of mutations and, later, that for in developed countries, such as USA. haemophilia A (still under completion). The directors of the UK Haemophilia Centre endorsed
R A Green
S
Peter M Green is a lecturer in molecular genetics. Division of Medical and Molecular Genetics, GKT School of Medicine, Guy's Tower, London SE1 9RT, UK (P M Green [email protected]
The Lancet Supplement | 358 | December | 2001
MRCPath)
S34
For personal use. Only reproduce with permission from The Lancet Publishing Group.