Martin H. Steinberg, MD
Steinberg MH. Sickle Cell Disease. Ann Intern Med. 2011;155:ITC3-1. doi: 10.7326/0003-4819-155-5-201109060-01003
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Published: Ann Intern Med. 2011;155(5):ITC3-1.
Sickle cell disease is a Mendelian genetic disorder caused by several common genotypes (see the Box: Common Genotypes of Sickle Cell Disease). Sickle cell trait is clinically benign and should not be considered a disease.
HbA is the major normal adult hemoglobin.
Many other compound heterozygotes have been described. Most are rare, and only a few have a clinical phenotype.
A single point mutation in the β-hemoglobin gene (HBB) is responsible for the synthesis of sickle hemoglobin (HbS, α2βS2). At least 50% HbS is present in all genotypes of sickle cell disease. Polymerization of deoxy sickle hemoglobin injures the sickle erythrocyte. Damaged sickle cells die prematurely, mainly by being caught in the reticuloendothelial system, but some hemolyze intravascularly. Sickle erythrocytes occlude blood vessels of all sizes. The complex pathophysiology resulting from sickle vasoocclusion and hemolytic anemia includes, at a minimum, abnormal erythrocyte volume regulation, impaired nitric oxide bioavailability, reperfusion injury, inflammation and oxidant damage, abnormal intercellular interactions, endothelial injury, and leukocyte and platelet activation. In sickle cell trait, HbS levels are 40% or less of total hemoglobin. As a result, in normoxic conditions these cells do not deform when they are deoxygenated, except in the renal medulla where pH and oxygen levels are low and the solute concentration is high (see below).
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Hematology/Oncology, Red Cell Disorders.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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