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Sickle Cell Disease and Acute Chest Syndrome: Mechanisms and Pathogenenesis

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Hematologic Abnormalities and Acute Lung Syndromes

Part of the book series: Respiratory Medicine ((RM))

Abstract

Acute chest syndrome (ACS) is the major lung complication and leading cause of death in sickle cell disease (SCD). It is characterized by a rapid disease onset, pulmonary infiltration, hypoxemia, and several other clinical indications. Postmortem ACS lungs are characterized by histological evidence of alveolar capillary barrier disruption, fat emboli, and alveolar wall necrosis. Ischemia-reperfusion injury activation of invariant natural killer T lymphocytes is thought to heighten baseline pulmonary inflammation in SCD that may prime the lung for ACS development. Multiple factors, including hypoxia, infection, infarction, thrombosis, and fat emboli that are implicated in ACS pathogenesis are also associated with acute hemolysis. ACS is typically preceded by acute intravascular hemolysis, and the magnitude of anemia is linked to the severity of the lung injury. The heme hypothesis posits that the lung injury in ACS is caused by acute inflammation directly involving extracellular heme, a prototypical erythroid DAMP molecule released by hemolysis. In support of this model, the infusion of purified heme triggers a lethal acute lung injury in transgenic SCD mice that exhibit many of the characteristics of severe ACS. Additional experimental data indicate heme-induced ACS may involve vaso-occlusion and the release of neutrophil extracellular traps in the lung. Clinically, the risk of patients developing ACS is influenced by steady-state plasma concentrations of heme, and by polymorphisms in the gene encoding heme oxygenase-1, the rate-limiting heme degradation enzyme. Extracellular heme is therefore an ideal converging axis in the pathogenesis of ACS.

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Acknowledgements

The authors are supported by research funding from the National Heart, Lung and Blood Institute (Award Number: HL106192, HL106192S1, and U01HL117721). The authors thank Sonia Mckoy for comments and proofreading that helped to improve this book chapter.

Authorship

Contribution: OA, AOA, ADA, SG, and SFOA prepared, wrote, and edited the chapter.

Conflict of Interest

The authors OA, AOA, ADA, SG, and SFOA declare that no conflict of interest exists.

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Authors and Affiliations

  1. Department of Pediatrics, Emory University, Atlanta, GA, USA

    Olufolake Adetoro Adisa MD

  2. Division of Hematology/Oncology, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    Amma Owusu-Ansah MD, MBBS & Samit Ghosh PhD

  3. Department of Pathology, University of Ghana Medical School and Korle Bu Teaching Hospital, University of Ghana, Accra, Ghana

    Afua Darkwah Abrahams MBChB, FWACP & Solomon Fiifi Ofori-Acquah PhD

  4. Center for Translational and International Hematology, Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA

    Solomon Fiifi Ofori-Acquah PhD

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  1. Olufolake Adetoro Adisa MD
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Correspondence to Solomon Fiifi Ofori-Acquah PhD .

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  1. Division of Pulmonary, Allergy, and Critical Care Medicine Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

    Janet S. Lee

  2. Division of Pulmonary, Allergy, and Critical Care Medicine Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

    Michael P. Donahoe

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Adisa, O.A., Owusu-Ansah, A., Abrahams, A.D., Ghosh, S., Ofori-Acquah, S.F. (2017). Sickle Cell Disease and Acute Chest Syndrome: Mechanisms and Pathogenenesis. In: Lee, J., Donahoe, M. (eds) Hematologic Abnormalities and Acute Lung Syndromes. Respiratory Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-41912-1_3

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  • DOI: https://doi.org/10.1007/978-3-319-41912-1_3

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