Sickle Cell Disease

Published on 06/06/2015 by admin

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53 Sickle Cell Disease

More than 100,000 Americans are affected with sickle cell disease (SCD), making it one of the most prevalent genetic disorders in the United States. The majority of affected individuals are of African or Mediterranean descent; this is related in part to the “natural selection” process because being a carrier of sickle hemoglobin (Hb) confers some resistance to malarial infection and a resultant survival advantage. The carrier rate among African Americans is approximately 8% (one in 12). Individuals with SCD can exhibit significant morbidity and mortality related to chronic hemolysis. Each year in the United States, an average of 75,000 hospitalizations are attributable to SCD, costing approximately $475 million. Neonatal screening, confirmatory diagnostic testing, family education, and routine comprehensive care of patients with SCD are imperative in reducing the morbidity and mortality of this lifelong disease.

Etiology and Pathogenesis

SCD is a group of inherited hemoglobinopathies associated with hemolytic anemia and vaso-occlusive complications. All forms of SCD are inherited in an autosomal recessive fashion and are the result of mutations in the two β-globin genes. β-Globin is one of the major components of adult Hb and is part of a group of genes involved in oxygen transport. Two β-globin chains combine with two α-globin chains to form the predominant Hb found in human adults, HbA. In HbS, an amino acid substitution from glutamic acid to valine ultimately leads to the polymerization of HbS molecules, causing the “sickling” effect (Figure 53-1)

The most common form of SCD is homozygous SS. Other variants of SCD are the result of compound heterozygotes for HbS and other β-globin variants, including SC as well as Sβ+ thalassemia and Sβ0 thalassemia. All individuals who are homozygous or compound heterozygous for HbS exhibit some clinical manifestations of SCD. Symptoms usually appear by the first 6 months of life when fetal Hb dissipates, but there may be late presentations as well. There is considerable variability in clinical severity, which is related to genotype (Table 53-1). Patients with SS have the most severe clinical phenotype followed by individuals with Sβ0 thalassemia. Those with SC and Sβ+ thalassemia tend to have milder clinical phenotypes.

Whereas SCD was once seen as a disease in which morbidity and mortality were directly related to vascular occlusion by red blood cell (RBC) sickling alone, it is now evident that chronic hemolysis secondary to endothelial dysfunction and vasculopathy plays a significant role in morbidity. Researchers have found that the release of Hb and arginase from hemolyzed RBCs leads to nitric oxide (NO) bioavailability, thereby resulting in increased oxidative stress and accelerated intravascular hemolysis. SCD confers a state of NO resistance, and animal studies have provided evidence that a reduction in NO is associated with vasoconstriction, decreased blood flow, platelet activation, and end-organ injury.

Management and Therapy

Acute Complications

Vaso-occlusive Episodes

Patients with acute pain require prompt evaluation and treatment. At initial presentation, it is important to determine the cause of pain based on location and patient presentation because pain is not always related to SCD (Table 53-2). Assessment of pain should include age- and developmentally appropriate tools. Uncomplicated pain crises can be managed at home. Nonpharmacologic measures to help manage pain symptoms can be extremely helpful and include a heating pad or hot packs, massage, and play activities. Pharmacologic management of vaso-occlusive episodes (VOEs) includes a combination of nonsteroidal antiinflammatory drugs (NSAIDs such as ibuprofen or ketorolac) and oral or IV analgesics (Tylenol, codeine, morphine, hydromorphone) (Table 53-3). It is important to adjust therapy according to the degree of pain (i.e., switching from oral to IV formulations) and to order medications to be given at scheduled intervals.

Table 53-2 Differential Diagnosis and Further Evaluation of Pain

Location of Pain Other Conditions to Consider Additional Studies to Consider
Head or face

Neck or throat

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