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
• fetal hemoglobin
• SNPs
• fat embolism
• oxygen saturation
• lung
• transfusion

Article highlights

• Acute chest syndrome can be caused by infarction and thromboembolism. Severity ranges from very mild to fatal.

• Predicting severity is difficult, but radiographic and laboratory studies with careful assessment of the trajectory of oxygen saturation are helpful

• Treatment, predicated on severity includes transfusion, antibiotics and cooperation among hematologists, pulmonologists, and at times, critical care specialists.

• HbF levels and the coexistent α-thalassemia affect the incidence of acute chest syndrome. Genetic variants that are directly related to the incidence of acute chest syndrome have been difficult to replicate.

Declaration of interest

E Klings receives research support from Bayer, Novartis, FORMA Therapeutics and United Therapeutics. She is a consultant for Bluebird Bio and CSL Behring for sickle cell disease related clinical trials (no conflict with the present work). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.