Acute chest syndrome of sickle cell disease: genetics, risk factors, prognosis, and management

Abstract

Introduction: Sickle cell disease, one of the world's most prevalent Mendelian disorders, is a chronic hemolytic anemia punctuated by acute vasoocclusive events. Both hemolysis and vasoocclusion lead to irreversible organ damage and failure. Among the many sub-phenotypes of sickle cell disease is the acute chest syndrome (ACS) characterized by combinations of chest pain, cough, dyspnea, fever, abnormal lung examination, leukocytosis, hypoxia, and new radiographic opacities. ACS is a major cause of morbidity and mortality.

Area covered: We briefly review the diagnosis, epidemiology, etiology, and current treatments for ACS and focus on understanding and estimating the risks for developing this complication, how prognosis and outcomes might be improved, and the genetic elements that might impact the risk of ACS.

Expert opinion: The clinical heterogeneity of ACS has hindered our understanding of risk stratification. Lacking controlled clinical trials, most treatment is based on expert opinion. Fetal hemoglobin levels and coexistent α-thalassemia affect the incidence of ACS; other genetic associations are tenuous. Transfusions, whose use not innocuous, should be targeted to the severity and likelihood of ACS progression. Stable, non-hypoxic patients with favorable hematologic and radiographic findings usually do not need transfusion; severe progressive ACS is best managed with exchange transfusion.

Keywords: Hydroxyurea; SNPs; fat embolism; fetal hemoglobin; lung; oxygen saturation; transfusion.