Author:
Buchanan George R.,DeBaun Michael R.,Quinn Charles T.,Steinberg Martin H.
Abstract
Abstract
Much progress has been made during the past several decades in gaining understanding about the natural history of sickle cell disease and management approaches aimed at treating or even preventing certain disease complications. The characterization of the human genome now offers the opportunity to understand relationships regarding how gene polymorphisms as well as how environmental factors affect the sickle cell disease phenotype, i.e., the individual patient’s overall clinical severity as well as their specific organ function. This chapter explores some of these recent advances in knowledge.
In Section I, Dr. Michael DeBaun characterizes the problem of silent stroke in sickle cell disease, comparing and contrasting its clinical and neuroimaging features with overt stroke. Combined, these events affect virtually 40% of children with sickle cell anemia. New understanding of risk factors, associated clinical findings, and imaging technologies are impacting substantially on treatment options. The appreciable cognitive dysfunction and other sequelae of silent infarct demand more effective treatments and ultimate prevention.
In Section II, Dr. Charles Quinn addresses the conundrum of why some patients with sickle cell disease do well whereas others fare poorly. Some risk factors have been known for years, based upon careful study of hundreds of patients by the Cooperative Study for Sickle Cell Disease and investigators studying the Jamaican newborn cohort. Other prognostic measures have only recently been defined. Dr. Quinn devotes special attention to stroke and chest syndrome as organ-related complications but also describes attempts to measure overall disease severity and to predict survival. Recently, investigators have attempted to predict factors responsible for early mortality in children and following onset of pulmonary hypertension in adults.
In Section III, Dr. Martin Steinberg reviews pharmacologic approaches to sickle cell disease and the rationale for their use. In addition to the inhibition of hemoglobin S polymerization, newer targets have been defined during the past one to two decades. These include the erythrocyte membrane, changes in the red cell intracellular content (especially loss of water), endothelial injury, and free radical production. Hydroxyurea treatment attracted the greatest interest, but many uncertainties remain about its long-term benefits and toxicities. Newer “anti-sickling” agents such as decitabine and short-chain fatty acids also receive attention. Prevention of red cell dehydration, “anti-endothelial” therapy, and marshaling the potentially beneficial effects of nitric oxide are other new and exciting approaches.
Publisher
American Society of Hematology
Reference66 articles.
1. Armstrong FD, Thompson RJ, Jr., Wang W, et al. Cognitive functioning and brain magnetic resonance imaging in children with sickle cell disease. Neuropsychology Committee of the Cooperative Study of Sickle Cell Disease. Pediatrics. 1996;97:864–870.
2. Craft S, Schatz J, Glauser TA, Lee B, DeBaun MR. Neuropsychologic effects of stroke in children with sickle cell anemia. J Pediatr. 1993;123:712–717.
3. Miller ST, Macklin EA, Pegelow CH, et al. Silent infarction as a risk factor for overt stroke in children with sickle cell anemia: a report from the Cooperative Study of Sickle Cell Disease. 2001;139(3):385–390.
4. Pegelow CH, Macklin EA, Moser FG, et al. Longitudinal changes in brain magnetic resonance imaging findings in children with sickle cell disease. Blood. 2002;99:3014–3018.
5. Schatz J, Brown RT, Pascual JM, Hsu L, DeBaun MR. Poor school and cognitive functioning with silent cerebral infarcts and sickle cell disease. Neurology. 2001;56:1109–1111.
Cited by
66 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献