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Sickle cell disease (SCD) is an autosomal recessive genetic condition that alters the shape and function of the hemoglobin molecule in red blood cells. While the overall survival rate among children with SCD has improved in recent years, pediatric rates of hospitalization, ED use, and mortality from complications of SCD remain high. Among patients ages 18 and older, hospital admission and ED usage are even greater—and the median age at death of people with SCD is considerably lower than that of the general population. Nurses who care for patients with SCD have an opportunity to improve health outcomes and quality of life for these patients by recognizing the major SCD-associated complications and providing patients and their caregivers with appropriate educational information. The authors discuss the genetic, hematologic, and clinical features of SCD and describe the major associated health complications. In addition, they review the nursing implications of each complication and provide online links to resources for clinicians, patients, and caregivers.