About 100-thousand Americans have sickle cell disease – a genetic condition where the body's red blood cells are deformed, clogging up arteries, and causing pain, disability or major stroke, even in kids. Patients who suffer strokes often have regular blood transfusions to prevent a repeat attack. Researchers now say those transfusions can be crucial for many more young sickle cell patients, even those who are showing no outward signs of brain injury.
12-year old Alexis Haynes has come a long way. At age six, a sudden stroke put her in a coma for a full month.
"The doctors told us that she wouldn't be able to walk, she wouldn't be able to talk, she wouldn't remember us," Kelvin Haynes, Alexis' father told Ivanhoe.
Every six weeks, Alexis spends hours getting her blood transfused. New red blood cells replace her sickle-shaped ones. While Alexis' stroke was apparent, experts say one in three children with sickle cell suffer silent strokes.
"These are injury to parts of the brain that don't control speech, they don't control movement in an arm or a leg, so they typically go unnoticed," Michael Noetzel, M.D., and Pediatric Neurologist at Washington University School of Medicine, St. Louis, told Ivanhoe.
These kids have a higher risk of memory problems. Many have trouble at school. They're also at much higher risk for having a major stroke.
Dr. Noetzel studied one-hundred and 96 children age five and older, who had brain scans that showed evidence of silent strokes. For three years, 99 received monthly transfusions, the rest did not. Researchers found the transfusions reduced the risk of strokes of any kind by 58-percent.
"Now that we have an intervention at hand that could be helpful-there's no reason not to think about screening younger children," Dr. Noetzel explained.
Identifying kids at risk before any damage is done.
Risks from transfusions include infections, reactions to donated blood and buildup of iron in the bloodstream. Researchers are planning longer-term studies to see whether transfusions, in combination with other sickle cell treatment options -- like stem cell transplantation, can help prevent kids from losing cognitive function.
BACKGROUND: Sickle cell disease is an inherited blood disorder in which red blood cells contain an abnormal type of hemoglobin, hemoglobin S. When a red blood cell becomes sickle-shaped (crescent), they have a hard time passing through blood vessels; this in turn causes less blood flow to tissues in the body, which can become damaged. Lung tissue damage, pain episodes in the extremities and torso, and stroke can result from this lessened blood flow. Spleen damage, especially in children, can cause overwhelming susceptibility to bacterial infections. The most common types of sickle cell disease are Sickle Cell Anemia (SS) and Sickle-Hemoglobin C Disease (SC).
(Source: http://www.sicklecelldisease.org/index.cfm?page=about-scd)
TREATMENT: There is no cure for sickle cell disease. Early diagnosis of sickle cell disease can be maintained through vaccination against pneumococcus bacteria, folic acid supplements, or penicillin prophylaxis. Antibiotics, intravenous fluids and pain management can all be a part of a comprehensive program of care to manage complications and symptoms. For sickle cell anemia, bone marrow transplants are the closest treatment to a cure, however with very serious risks. Bone marrow treatment is aimed at symptom relief and avoiding major crises.
(Source: http://www.sicklecelldisease.org/index.cfm?page=about-scd, http://www.mayoclinic.org/diseases-conditions/sickle-cell-anemia/basics/treatment/con-20019348)
TREATING SIDE EFFECTS: Doctors can find out when a child has a high risk of stroke by using a special non-invasive ultrasound machine, called a transcranial Doppler (TCD). It can be used on children as young as two years of age to assess the probability of stroke, which can be lessened with blood transfusions. The TCD examines blood circulation within the brain with sound waves that reflect movement of blood cells within blood vessels. A radiologist will then calculate their speed. Blood transfusions replace the abnormal red blood cells, and reduce recurrent pain, but at the risk of developing an iron overload. Treatments are available to remove any excess iron from the body, in turn avoiding organ damage in areas such as the heart, liver pancreas, and other endocrine organs.
(Source: http://www.mayoclinic.org/diseases-conditions/sickle-cell-anemia/basics/treatment/con-20019348, http://www.ncbi.nlm.nih.gov/pubmed/9647873, https://my.clevelandclinic.org/health/diagnostics/hic-abdominal-renal-ultrasound/hic-ultrasonography-test-transcranial-doppler)
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Michael Noetzel, M.D., Pediatric Neurologist, Professor of Neurology and Pediatrics, Vice Chair in the Division of Pediatric and Developmental Neurology at Washington University talks about the risk of stroke in children with sickle cell disease.
Interview conducted by Ivanhoe Broadcast News in September 2014.
Can you describe what sickle cell disease is; who it affects and how it affects them?
Dr. Noetzel: Sickle cell disease is what we call hemoglobinopathy. A big long word that basically means the red cells that are circulating in your body don't work the way they should. In sickle cell disease it's because the cells themselves or a certain portion of them have an abnormal shape and are deformed and are sticky and they don't flow through blood vessels the way that they should. As a result you get clogging up of the blood vessels and a variety of medical problems. It's estimated that about a hundred thousand people in the United States have sickle cell disease. More importantly it affects about slightly under one out of every four hundred individuals who are African Americans in the United States. In terms of how it impacts on their lives, again there are a large number of problems that they can encounter; the one that I deal with most has to do with stroke or cognitive impairment as a result of a variety of different blood vessel problems in the brain. But I think if you talk to the kids even those that don't have stroke, a big problem is they have what are called pain crises. Again, just like the blood not flowing the way it should, getting sticking, blocking off arteries causing strokes in brain, in other organs it causes pain, in the bones, the lungs in particular. So there are a lot of hospitalizations with a lot of discomfort from the kids.
Is there a cure and is there a best treatment for this?
Dr. Noetzel: There are a variety of approaches. I think some people would say we're getting close to what we consider a cure, but the cure would be if you want getting rid of the abnormal gene that causes the sickling to the cells. Bone marrow transplant previously, now stem cell transplant is certainly a very viable option. Again sickle cell disease comes with a variety of degrees of severity. You have some people that fortunately can go through with minimal problems and other individuals that have major hospitalizations and unfortunately there's a certain mortality related to sickle cell disease. Trying to figure out kind of early on who is going to be really severe and would benefit very much from stem cell transplant and who is going to have a mild form is not something that we're capable of doing at this point. But certainly here at St. Louis Children's Hospital and at a lot of other places consideration of stem cell transplant is a very high priority.
Tell me a little bit about your study?
Dr. Noetzel: Maybe a little bit of background would be helpful. It's been well known for forty or fifty years that children, adolescents with sickle cell disease have a very high risk for stroke. Strokes that are clinically apparent to the patient and to their families. Their risk over if you want an average child without sickle cell disease is about two hundred times higher. But in addition to those strokes over the last maybe twenty years we've recognized that there is an even greater risk for children with sickle cell disease to have what are called silent infarcts or silent strokes and these are injury to parts of the brain that don't control speech, they don't control movement in an arm or a leg so they typically go unnoticed by the family, the patient and they may be impossible to detect even on a very detailed neurologic exam. Unfortunately for children with the silent infarcts, their risk of a whole variety of thinking problems is markedly increased. These children are at much higher risk not to do well in school, to fail grades, to have a lower IQ, for example than their brother and sister or another child with sickle cell disease without the infarcts. In addition to which it also because we know their blood vessels are having problems in the brain they're at much increased risk of having a major stroke, one that everybody is aware of. The problem has been with this recognition we really didn't have a way of acting on it, trying to figure out what the next step would be. So our study identified a large number of patients with sickle cell disease, no prior history of anything concerning for a stroke, a normal neurologic exam and none of the other risk factors basically for stroke but whose MRI scan demonstrated that they had in fact sustained a silent stroke. The the children, roughly about two hundred of them, where one group was treated with monthly transfusions with blood and the other received what we call routine care, frequent examinations evaluations and at the end of a three year period of time when we assessed the outcome in these two groups it was very clear that the children who had received the blood transfusions had far fewer clinical strokes or overt strokes. They had far fewer new silent infarcts and as a byproduct they also had far fewer hospitalizations and far fewer complaints of the painful crises that are so common for kids with sickle cell disease. The reason for this is if you can replace their sickled blood cells with normal blood cells then you're able to kind of reverse some of what we'd say are the pathways that create the injury both to the brain and cause pain in other organs.
Why the monthly transfusions, why that period of time?
Dr. Noetzel: If you go back and look at what we had learned in the past from kids with overt strokes, if you're child with sickle cell disease and you have a clinically apparent stroke the standard of care for the last ten or twelve years, probably longer than that is you get monthly blood transfusions. The reason for that is you want to keep the percentage of sickle cells in the body below a certain level. We just adopted what I'm going to say was standard of care but put it to use in a completely different sort of group. I might add children with sickle cell disease and silent infarcts there are about three times as many of those as there are with clinically apparent strokes. We had a much bigger population to deal with in terms of risk to the patients.
What is the percentage you said you had to keep it below a person certain percent what is that?
Dr. Noetzel: When you examine the blood, if you keep the number of sickle cells or what we call the hemoglobin S under thirty percent that seems to be protective for a variety of complications and in particular both in silent infarcts and clinically apparent strokes.
Did you see any changes from this study? What is the implication from the information that you guys have?
Dr. Noetzel: We're hoping it will be a major one. When we started on this quest to try and see if we could intervene we had to overcome individuals who were uncertain about whether these silent infarcts were really significant. In other words did they really predict challenges in a child's neurologic outcome. As studies came along we demonstrated that clearly was the case. But then the next kind of response was somewhat of a well, okay it may be important but it's not as important as it would be if we could actually do something, there was an intervention that made sense. I think we're now at the point that we would encourage clinicians taking care of kids with sickle cell disease, families of a child with sickle cell disease to start thinking about getting images of the brain, MRI scans because if you can identify a silent infarct we can now intervene and make their outcome better. Now in our study we did not treat children younger than the age of five because to get an MRI scan in children younger than that you have to sedate them and we didn't want to expose them to any risk. But I think now because we have an intervention at hand that could be helpful there's no reason not to think about screening younger children. It's very clear that a vast majority of these children are going to have their silent infarcts by the time they are five, six, seven and eight but it keeps increasing as they get older. By the time they are a teenager more than a third of them will have a silent infarct. We're now starting to explore what happens if we look at the MRI scans in a three-year-old and find something can we intervene.
Do you have specific statistics, you said with the monthly transfusions there were far fewer new silent strokes, and fewer hospitalizations.
Dr. Noetzel: I can tell you in terms of the overall goal was to look at what we call recurrence of stroke. That would be clinically overt stroke or a new or an enlarging silent stroke. We were able to reduce that about fifty-eight percent in the treatment group compared to the group were they got the observation. I don't have on hand the hospitalizations but I know that the number and the number of times the child have a painful crises was again statistically significantly lower.
Is there anything else that you think people need to know about your study and where this research could take you?
Dr. Noetzel: I would say a byproduct of the study is I think an acknowledgment now that the sickle cell community, parents and families and clinicians have embarked on a large number of studies over the last ten or fifteen years and I think they are to be congratulated on their willingness to participate. To look at what is a major health problem in the African American community and figure out what are the ways that we can encourage research so that we can come up with answers. It's a real tribute to you know the families that were willing to say yeah, I will come in every month with my child and get the blood transfusions because the transfusions themselves have a variety of health considerations in addition to just the, for lack of a better word, the inconvenience. The fact that they were able to partner with us at not only here at St. Louis but at multiple sites throughout the United States I think is a real tribute to them again as a group of healthcare minded families.
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