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INTRODUCTION

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The red blood cell is a vehicle that utilizes hemoglobin to facilitate the delivery of oxygen to vital organs or tissue. Hemoglobin is a tetrameric protein composed of two α- and two β-molecules. Hemoglobinopathies are a result of various types of mutation within either the α or β genes. This mutation affects transcription, translation, and ultimately protein formation. The mutated globin proteins lead to the lack of production, deletion, or dysfunctional hemoglobin subunits.

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SICKLE CELL DISEASE

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Sickle cell disease (SCD), or hemoglobin S (HbS), is the most common inherited hemoglobinopathy. The genetic mutation occurs at the sixth amino acid position of the β-chain. Glutamic acid, a negatively charged amino acid, is substituted for valine, a nonpolar amino acid. The loss of a negative charge group produces radical change, compromising the integrity of the hemoglobin structure causing instability and rapid degradation. In a low oxygen environment, HbS polymerizes, becomes insoluble, and forms a precipitate. Furthermore, the accelerated hemoglobin breakdown causes extensive cell membrane damage and dehydration. As a result, the shape of the red cell morphs to the characteristic “sickle” appearance. The second consequence of sickling causes a widespread vascular inflammation. The instability of the HbS releases iron into the circulation causing direct oxidative cell membrane damage locally and systemically. The circulating iron binds to endogenous nitric oxide (NO), thus consuming free nitric oxide and impairing normal physiologic transport of nitric oxide by erythrocytes. This chronic hemolysis will lead to a chronic state of NO deficiency and inflammatory vasculopathy.

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The clinical features of SCD are one of evolving organ damage. It can affect multiple different organs suffering early organ dysfunction and death (Table 100-1). Pulmonary and neurologic diseases are the leading causes of morbidity and mortality but chronic renal failure can be an additional contributing factor. Pain crises or vasoocclusive crises are noted in lumbar spine, abdomen, femoral shaft, and knee in the majority of the cases. Acute chest syndrome (ACS) is defined as new pulmonary infiltrates involving at least one complete lung segment. Ultimately, ACS will lead to chronic progressive lung damage. It may start as airway hyperreactivity to fibrosis and progressive restrictive defect. Stoke in SCD can be due to hemorrhage due to chronic damaged and weakened arteries, whereas infarction is secondary to intimal hyperplasia and progressive occlusion of large and small arteries. Nephropathies include papillary necrosis and glomerular disease. As a result, these potential organs damage can lead to devastating complications and debilitation.

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Table Graphic Jump Location
TABLE 100-1Clinical Features of Sickle Cell Anemia

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