Dr Marjon Cnossen (45) has been a pediatric hematologist at Sophia Erasmus MC children’s hospital in Rotterdam since 2008.

What’s your connection with sickle cell disease?

I’m the main medical practitioner of a group of about 150 children with sickle cell anemia aged up to 18. We’re part of the sickle cell centre of Erasmus MC Rotterdam. The adult outpatient clinic is across the road. I think we see about 100 children on a regular basis. Some of them we only see sporadically and, in my opinion, not enough because sometimes, people also miss their appointments.

What ethnic groups does the sickle cell population represent in Rotterdam and surroundings?

We see a lot of African people from the Congo, Angola and Guinea, as well as many people from Cape Verde and the Antilles. Asian and Arab people with compound sickle cell anemia are also seen regularly. The population is different than, say, in Amsterdam, where they tend to see many more people of Ghanaian and Surinamese origin.

Is there a difference in medical issues between these different groups?

In order to understand the difference, you need to know some of the background of the disease. Every human has 23 pairs of chromosomes, so for each chromosome, there’s another. If you have sickle cell disease, you have a sickle cell change on both chromosomes that contain the property of sickle cell anemia. This affects how your hemoglobin is produced. Hemoglobin is a part of the red blood cell that ensures oxygen is bound and, therefore, transported through the body. If you’re a carrier of sickle cell anemia , one of these chromosomes that contain the property of sickle cell anemia has changed. That doesn’t mean you’re ill, because part of your hemoglobin production still performs well. You can, however, pass on the disease to your children. The most common sickle cell change is the S-change, if you have these on both of your chromosomes, you have HbSS sickle cell anemia, which is a typical African disease. In the compound forms, you have an S-change on one of your chromosomes and on the other, you have a β change, for example (HbSβ-thalassemia sickle cell anemia) or a C change (HbSC sickle cell anemia). In Rotterdam, we see relatively lots of HbSS, as well as a lot of HbSβ sickle cell anemia due to the origins of the population of Rotterdam. Ghanaian people, who are seen more often in Amsterdam, tend to have HbSC sickle cell anemia. The course of disease for the different types of sickle cell anemia is broadly the same.

How do the diagnostics work?

A major improvement has been seen since the introduction of the heel prick test in 2007. This has made it possible to diagnose sickle cell disease among infants soon after birth. Newborn patients are now brought to our outpatient clinic before the age of 2 months. In the past, you only saw a child when it went through its first sickle cell crisis or had a serious infection. We were, in fact, playing catch-up all the time. Fortunately, things are much better now. We can now guide the children and inform the parents before any symptoms manifest themselves. They know how to recognise a sickle cell crisis, that it’s important to give antibiotics every day and why and they know who to contact if things aren’t going well.

Are you still missing out on patients?

Sickle cell anemia is common in families who live on the fringes of our society. This can be for social-economic reasons, because of a language barrier, because people don’t have transport or because they can’t read properly. It still happens that parents, despite all the information, don’t understand that we need to see them at the outpatient clinic at least every six months. Not only is this important for the patient, but also for his or her brothers and sisters, especially if they were born before 2007 because we want to determine whether they too have sickle cell anemia. This is one of the reasons why we’re still dealing with late diagnoses of the disease. Children born after 2007 can also be missed because they were born outside the Netherlands and came to this country later on. It’s also important that parents know that they are carriers of the disease and that they are at risk of having more children affected by sickle cell anemia. We, therefore, work closely together with the clinical geneticist or heredity physician in our hospital. We even have joint consultation hours every week.

Does early detection provide a better perspective?

I think it does but it is, in fact, too early to say. In a study that has been running for four and a half years now, we are monitoring all children who have been diagnosed by means of the heel prick test. We check whether symptoms and complications of the disease are manifesting themselves at this stage, but also whether there are certain risk factors that can trigger problems and what the quality of life is. One of the important complications that we want to have a closer look at in this group is neurological symptomatology, in other words, do symptoms of sickle cell disease also manifest themselves in the brain. We run an MRI scan twice at a young age. This is because sickle cell disease can cause small cerebral infarctions. Although the patient doesn’t show any external symptoms, they may well be present and influence the school performance.

How do you convince parents to come when a child doesn’t show any symptoms?

That’s difficult for some parents, but I try to motivate them to see the importance of outpatient visits and to administer medication (including daily antibiotics), even though there are no symptoms at that moment. Research tells us that patients who don’t have sickle cell crises can still get organ damage. I try to explain to the parents and children that it’s important to continue to be monitored so that we can intervene early if there are indications that the organs, such as the kidneys, the heart and the brain, function less well. This allows us to start the patient on certain medication that provides additional protection against complications (Hydroxyurea) or we can decide to give regular blood transfusions. Practice shows that children can sometimes become very ill if they don’t take their daily antibiotics. This is such a shame because the serious infection could have been prevented.

What do you do to promote therapy compliance?

We want to conduct research in Rotterdam in the coming years, particularly on how you can promote therapy compliance, in other words, how you can encourage patients and parents to take the prescribed medication and to show up for their appointments with the (pediatric) hematologist, cardiologist, clinical neurophysiologist (for brain research) and ophthalmologist. I think it’s important to explain a lot about the disease so that people understand why the medicines or visits to all these specialists are important. With that, as a doctor, you have to apply an open approach when enquiring about the medication and the successful administration thereof. Truth be told, it’s a pretty hard regime, day in and day out, at least twice a day. I’m convinced that a better understanding of the disease will lead to fewer sickle cell crises because if you drink a lot, take effective pain relief and fever-reducing drugs, keep warm and take antibiotics, you can often prevent worse in an oncoming crisis.

Can a child’s fitness be protected through treatment?

We can’t guarantee that. Symptoms differ from patient to patient. Hydroxyurea, a medicine that we prescribe when the sickle cell disease causes a lot of complaints, is very effective. We can help many children with this. It causes the production of red blood cells in the bone marrow to be suppressed. As a result, the bone marrow creates red blood cells with fetal hemoglobin (HbF) instead of sickle cell hemoglobin (HbSS). As the fetal hemoglobin volume increases, the volume of sickle cell hemoglobin decreases. Most children on this drug show fewer crises, often higher hemoglobin levels and less fatigue, as well as fewer complications. Many children under our care take Hydroxyurea for a prolonged period of time. Much of the time it’s so effective that even the administering of the drug isn’t a problem. Anyway, I’m rambling ...

Do you take a lot of time for your patients?

During consultation hours, I’m practically always behind schedule. In addition to all the information we provide, all patients are given an extensive blood test each year. Of course, we examine the patient’s hemoglobin and blood degradation levels and the performance of the organs in relation to the effect of the medication. We also take a single blood sample for DNA research, to test for possible red cell enzyme deficiencies and to determine the blood group and any antibodies against blood groups. Twice a year, we try to perform a transcranial Doppler examination of the brain, a cardiological check-up once a year and an eye-test once every two years. Patient care is extremely labour-intensive in this disease, but you also get a lot in return. We see a number of patients in combination with a pediatrician in a nearby hospital: they are seen by us twice a year and the peripheral pediatrician sees them twice during the intervening period as well. This is often very valuable in the case of acute admissions. These are very pleasant partnerships. I do also like to work in the outpatient clinic: they are a special group of patients.

What else is difficult in terms of treating sickle cell disease?

It’s what I said earlier, the serious complications that we’re confronted with sometimes. The strict therapy loyalty is another topic that’s close to my heart. I understand that it’s very difficult to stick to the drug regime and show up at all appointments, it’s just that want to see all patients doing well. We want to support them in this as much as possible and will, therefore, investigate how we can do this best.

Do you talk to young people about their future?

I know that this is something on the minds of many young people, although I don’t think it’s discussed enough in the consultation rooms. If you continue to ask questions, they do open up eventually. Especially when dealing with children you know.

Do you support young people in their choice of education, work and perspective?

That’s where the social worker comes in but it’s for adults. Unfortunately, we still don’t have a social worker in our sickle cell team here at the Sophia Children’s Hospital. That is why we often work with pediatricians in nearby hospitals, who often do have a social worker on their teams. We want to recruit someone within the team with this expertise in the near future. Although we will be reinforced with a sickle cell nurse next year, much to our excitement. This is a major step forward in the provision of care for sickle cell patients at the Sophia Children’s Hospital.