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Overview of Sickle Cell Anemia Pathophysiology

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Sickle Cell Anemia

Abstract

Sickle cell disease, caused by a mutation in the β-hemoglobin gene, is a Mendelian disorder with a very diverse phenotype. The primary cause of disease pathophysiology is the deoxygenation-induced polymerization of the mutant sickle hemoglobin. This ultimately leads to vasoocclusion by damaged sickle erythrocytes that interact with the endothelium and other blood cells, and the hemolysis of sickle cells within and outside of the vasculature. Treatment can target these separate but interconnected pathophysiologic pathways of sickle vasoocclusion and hemolytic anemia but targeting effectively a single limb or aspect of pathophysiology might have unintended consequences and increase the chance of complications closely associated with the other pathophysiologic pathway. The prime approach to treatment would be to effectively increase the level of the antisickling fetal hemoglobin in most sickle erythrocytes thereby thwarting all downstream effects of this primary pathophysiologic event.

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  1. Department of Medicine, Pediatrics, Pathology and Laboratory Medicine, Boston University School of Medicine, 72 E. Concord St., Boston, MA, 02118, USA

    Martin H. Steinberg M.D.

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  1. Centro de Hematologia e Hemoterapia, Unicamp, Campinas, São Paulo, Brazil

    Fernando Ferreira Costa

  2. Centro de Hematologia e Hemoterapia, Unicamp, Campinas, São Paulo, Brazil

    Nicola Conran

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Steinberg, M.H. (2016). Overview of Sickle Cell Anemia Pathophysiology. In: Costa, F., Conran, N. (eds) Sickle Cell Anemia. Springer, Cham. https://doi.org/10.1007/978-3-319-06713-1_3

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