Reduce stroke risk in sickle cell anemia patients.
Dr. Orah S. Platt, professor of medicine at Harvard Medical School, Boston, and chief of the department of laboratory medicine at Children's Hospital Boston, said that as overall health of patients with sickle cell anemia (SS) improves and diagnostic techniques become more sensitive, physicians are seeing pediatric patients with an increasingly wide range of subtle and not-so-subtle brain injury.
It has been known for decades that SS patients are at increased risk for strokes and recurrent strokes. Red cell exchange and chronic maintenance transfusion have become established methods to manage acute stroke and prevent recurrence. Recently, the focus has shifted to primary stroke prevention, and the search for methods to detect patients at high risk of stroke is ongoing, Dr. Platt said.
In studying children with SS, Dr. Robert J. Adams and his colleagues from the Medical College of Georgia, Augusta, discovered that transcranial Doppler (TCD) ultrasonography can identify narrowed internal carotid or middle cerebral arteries in asymptomatic children and detect the high-flow blood pattern characteristic of patients at high risk for stroke. (See related story below.)
"They determined that children with rapid flow, over 200 cm/sec, were at an extremely high risk of developing stroke. Asymptomatic children with high TCD had more than an order of magnitude higher rate of stroke than the SS population in general," Dr. Platt said. When children such as these are preemptively treated with maintenance transfusion, 90% of strokes are prevented. In most studies, TCD outcomes revert to or toward normal, but unfortunately, the risk of stroke reappears once the transfusions are stopped.
Dr. Platt's recommendations for preventing stroke in children with SS are to first screen all children with SS between the ages of 2 and 16 years with TCD. If the initial study is normal, repeat the study annually. In the "conditional" range (170-199 cm/sec), TCD should be repeated every 6 months. If the reading is abnormal (greater than or equal to 200 cm/sec), a repeat study should be done to confirm it and then a maintenance transfusion treatment program should be started.
The blood should be matched for ABO, C, D, E, and Kell antigens, and timed and dosed to keep hemoglobin S (Hb S) less than or equal to 30%. One should be careful to monitor the patient for iron overload, she said.
"The impact of this approach has been amazing. It has been known for decades that SS is one of the major risk factors for stroke in children. The implementation of TCD screening and transfusion therapy has been so successful in California that the overall rate of stroke in SS children has declined since the publication of the SS data," Dr. Platt commented.
Transfusion has many benefits for SS patients, including reduction of strokes, silent infarcts, pain events, and acute chest syndrome, and improvement in growth. However, it is associated with some adverse effects such as iron overload, increased alloimmunization, and possible increased exposure to pathogens.
"We know that with improved chelation [to remove iron], this benefit-risk ratio will tip even more toward the benefits," Dr. Pratt said.
Alternatives to transfusion, such as hydroxyurea and bone marrow transplant, are under active study. Chronic administration of hydroxyurea shows promise for preventing primary and secondary stroke, although bone marrow transplant has as yet not proven to be superior to chronic blood transfusion.
Dr. Platt stressed the importance of assessing risk factors beyond high TCD scores. These include high blood pressure, the absence of alpha thalassemia, and the presence of moyamoya disease.
More recently, tests have become available that can help detect a high-risk genetic profile. Imaging studies have revealed that many SS patients develop "silent infarcts," a term used to describe unexplained bright objects on MRI scans.
Although patients with silent infarcts can have normal neurological exams, they often show deficits on neuropsychological tests. It has been shown that children with SS who have silent infarcts are at higher risk for stroke and that many neurologically normal patients with elevated TCD have them.
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|Title Annotation:||Clinical Rounds|
|Date:||Mar 1, 2007|
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