Overview of the pulmonary complications of sickle cell disease
- Elizabeth S Klings, MD
Elizabeth S Klings, MD
- Associate Professor of Medicine
- Boston University School of Medicine
- Harrison W Farber, MD
Harrison W Farber, MD
- Professor of Medicine
- Boston University School of Medicine
- Section Editors
- Stanley L Schrier, MD
Stanley L Schrier, MD
- Editor-in-Chief — Hematology
- Section Editor — Myeloproliferative Disorders; Red Blood Cell Disorders
- Professor of Medicine
- Stanford University School of Medicine
- Jess Mandel, MD
Jess Mandel, MD
- Section Editor — Pulmonary Vascular Disease
- Professor of Medicine
- University of California, San Diego
Sickle cell disease (SCD) encompasses a group of hemoglobinopathies characterized by amino acid substitutions in the beta globin chain. The most frequently occurring form of SCD is caused by homozygous presence of hemoglobin S (HbSS). Hemoglobin S results from the substitution of a valine for glutamic acid as the sixth amino acid of the beta globin chain. The resulting hemoglobin tetramer (alpha2/betaS2) is poorly soluble when deoxygenated. Other forms of SCD include HbSC disease, in which an individual is a compound heterozygote for the sickle mutation and hemoglobin C (created by substitution of lysine for glutamic acid as the sixth amino acid), and sickle hemoglobin-beta thalassemia0 or + in which one beta chain allele has the HbS mutation and the other has a beta thalassemia mutation with reduced or absent production of the beta chain.
Deoxygenated sickle hemoglobin polymerizes into sheets of elongated rope-like fibers, causing a marked decrease in red cell deformability and distortion of the cell into the classic crescent or sickle shape (picture 1), the primary pathophysiologic event responsible for vaso-occlusive complications (picture 1) . Vaso-occlusive phenomena and hemolysis are the clinical hallmarks of SCD and result in recurrent painful episodes (previously called sickle cell crisis) and a variety of serious organ system complications that can lead to life-long disabilities and premature death. However, hemoglobin polymerization alone does not account for the full pathophysiology of SCD. Subsequent changes in red cell membrane structure and function, disordered cell volume control, and increased adherence to vascular endothelium also play an important role [1-3]. (See "Sickle hemoglobin polymer: Structure and functional properties" and "Mechanisms of vaso-occlusion in sickle cell disease".)
Chronic pulmonary complications are common in patients with SCD and contribute to morbidity and mortality [4-6]. These complications represent a broad group of disorders involving a spectrum of cell types and pathophysiologic processes and include:
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