On Saturday, the 18th of June, 2011, a team of Science Students who have volunteered their time to research information on Sickle Cell Disease for the Sickle Cell Association of Ontario had the opportunity to interview Dr. Graham Serjeant. Dr. Graham Roger Serjeant is a British medical researcher who studied sickle-cell disease in Jamaica, setting up screening programmes and long-term cohort studies. He was Director of the MRC Epidemiology Research Unit at the University of the West Indies and remains chairman of the Sickle Cell Trust (Jamaica). He is author or co-author of three books and over 140 publications on sickle-cell disease. His work has addressed the variability of sickle-cell disease with special emphasis on developing low-cost models of management suitable to countries with large numbers of patients and limited resources.
Below is a transcript of their conversation.
Q: In which ways do you think the search for Sickle Cell Disease (SCD) treatment has taken a back seat to other chronic illnesses worldwide? Seeing as how SCD is a serious detriment to quality of life and productivity during a patient’s prime, why does the treatment of chronic diseases that occur much later in life take precedent?
This is a difficult question; you are saying that SCD takes a back seat compared to diabetes,
hypertension, which is true because funding and research depend on public perception of
health care needs. There is no doubt that SCD is grossly underestimated as there is a large
political and social component – that is gradually being rectified – but it is very difficult to
actually access the demand of different disease processes.
Q: How much money is spent on SCD on average?
In London, at an average teaching hospital, the cost for SCD care is 1000 pounds per day, and an average stay is for 10 days for a painful crisis. There are about 12,000-15,000 SCD patients currently known in the UK, but the issue is that these sort of economic arguments are facile – a large proportion of hospitalizations are due to a painful crisis, so care and costs for that should be evaluated more.
Q: What is the distribution of pain in painful crisis?
In a painful crisis, the bone close to the joint is affected, and multiple areas in the body can be affected at the same time.
Q: What is the pathology of a painful crisis?
Bone has a cortex on the outside and a medulla on the inside. So during a painful crisis, the medulla is affected, as this area of the bone houses the bone marrow (which is where red blood cells are made). Normal red blood cell survival in non-SCD patients is 120 days – in sickle cell disease the cells last 10-12 days, meaning the destruction of blood is 10 times faster – so the bone marrow is much more expanded, as it is so highly active. What happens in painful crisis is that bits of the bone marrow die suddenly. However, the death of bone marrow is not important. The problem is the inflammatory response in the bone marrow to remove dead tissue. You get white cells and fluid flowing into the area, pressure goes up and bones are very sensitive to intermedullary pressure. This causes a patient to have pain.
Q: Why do some patients get painful crisis, but not others?
There are some triggers: over-exertion, airplanes, or exposure to cold are some examples.
In Jamaica, 90% of patients say they get pain when they get cold or wet – taking a bath,
swimming, doing laundry, getting caught in the rain – cold exposure is a major cause, as is dehydration or overexertion. Whether it is due to dehydration or acidosis, we don’t know. Knowing this allows doctors to advise patients to get temperature control in their houses and avoid cold. For instance, in Jamaica, there is an area where they wake up in the morning at 6am and have a bath – they get cold and get pain. These patients are advised to make lifestyle changes and use warm water for their bath if they can, or to take a bath in the middle of the day when the water is warm. The point is that minor lifestyle changes can make a huge difference.
Q: What can patients do to deal with severe Canadian winters?
Patients should bundle up a lot to prevent pain. Some people who move to colder areas from
places like Jamaica, where it is warm, tend to move back because they think their health is
better when it is warm – however, you can live with SCD in cold temperatures if you are careful to avoid cold. Cold exposure is important, and we often ask patients about it. Bundling up is important, and these are simple changes in lifestyle; in our experience, there are many simple manoeuvres like this that have a profound effect.
Q: What is your opinion on the relationship between sickle cell trait and protection against malaria? This is a hotly debated issue.
Virtually everybody accepts that sickle cell trait confers some protection against malaria. That
window of protection depends on the pattern of malarial transmission – the “window” being
referred to is the loss of passively-acquired immunity by the mother and development of active immunity by the mother. During that window, if you have the trait, you are less likely to die from malaria, and you are more likely to survive. The survival advantage is conferred on the trait. Of course, if you have the disease, then you have no protection against malaria. If you already have SCD, malaria can be a major cause of death in sickle cell disease in the same environment – you don’t know if it is death due to malaria or a malaria-related complication.
Q: In your opinion, what contributed most to development of policies toward SCD in places, such as Britain, where treatment is quite advanced?
Pressure did; in Britain, there was a political idea that the government would ask people in
the public about what they thought was a priority for the NHS (National Health Service) to focus on for treatment. The Sickle Cell Society had a prominent effect, and so they brought attention to the disease, and hence policymakers responded. The prevalence of sickle cell disease is also different in various parts of the world; in Jamaica, 10% have the trait, and 1 in 300 births has sickle cell disease amongst the ethnic population, so there, it is more common. Therefore, in different areas, there is a different response. Where it is more prevalent, of course, the disease would have more attention, policies and funding.
Q: Over the course of your career, which events have had the highest impact on the
research, treatment and policy surrounding SCD?
I got interested in SCD because when I got to Jamaica in 1966, textbooks usually had a few
lines about this disease and usually stated that it was a disease that mostly affected one race
only, that few cases survived to childhood and that most people did not make it to adulthood. However, what I saw in my clinics was different – I saw older patients. I published about this disease, and we found 60 patients who were over 30 years old and had not seen the university hospital in 10 years. We asked why they had not come – some said they were busy, and some said that as they got older, they felt better, and they were working full-time. People said that this is not like the disease we know in the West of the world – there is huge bias built in from public perception of the disease. The oldest patient I know with SS disease was almost 88 when she passed away; hence, what interested me was how little was known about the disease, and I have been able to dispel certain myths through my work.
Q: What is the most important piece of information you can give to patients with SCD?
Well, that is a difficult question; one important piece of advice is that you have to find a good doctor who knows a lot about SCD – you have to make sure your management is excellent. Some patients do not have the type of care that they need; I have seen patients who look gray because of iron overload due to treatment, and this can also cause heart complications, and they can die, all due to inappropriate or excessive treatment. Therefore, you have to be careful about your treatment choices, be well informed and be with a doctor who you trust.
Q: Within the field of sickle cell research, what would you like to see get more attention?
Population screening should get more attention; everybody has focused on finding a treatment – but there will be no magic pill that is a permanent cure, as this is a very complicated disease. There have been major advances in therapy for the disease, of course, but they are often very complicated and unrealistic in terms of cost for society. The only long-term hope is prevention, to reduce the problem so that you have fewer patients to treat so that you can put resources into better treating fewer patients via dedicated sickle cell centers, where patients can get specialized care.
Q: What is your opinion about hydroxyurea treatment?
Many doctors say that hydroxyurea has changed the lives of many patients. However, some patients do not respond at all – it costs $1 per capsule, and an average of 3 capsules a day are required – there are toxic effects though, and dosage needs to be adjusted. We don’t know about long-term dangers, but no doubt it has had a substantial change in the US, but in the UK, it is used very little, since patients are very reluctant to take it. In Jamaica, there are not as many resources available, but there are other methods that could be used to deal with the painful crisis, as discussed before (make lifestyle changes). It is important to note also that people do not always die due to painful crisis; you can get better as you get older and have painful crises less often – this is empowering for people with painful crisis. Some continue to be admitted, of course, and in Jamaica, about 90% of the patients go to day care centers and go home in evening, so you don’t always have to be hospitalized. There are many ways to deal with painful crisis other than hydroxyurea.
Q: What are some myths about sickle cell disease that you have encountered in your practice/life?
One myth was that it is confined to people of African origin, and another myth was that you
can’t survive to adulthood with it. These can change with time, of course.
Q: What would you like the general public to know about sickle cell disease?
What you have to do is increase the level of awareness amongst the public. Many people here have not heard of it, whereas in other parts of the world, it is very well-known, so education is very important.
Q: What is the biggest limitation for you when treating patients with sickle cell disease?
Time is a huge limitation; what is important in sickle cell disease is having increased rapport
with patients. There is often not enough time to treat everything and everyone, and this is a
problem you often face as a doctor.
Q: What is the biggest limitation when doing research for sickle cell disease?
In my opinion, it is a limitation of ideas, not of money. Of course, grants are difficult to come by, but I think the biggest limitation is a lack of good ideas and a lack of dedication.
Interviewers: Dan Froimovitch, Supipi Kaluarachchi, Audrey Kapeleris, Atiqa Malik, Kristen McKenzie, Tyler Vaivada
Interview recorded and transcribed by: Atiqa Malik