Chapter 142: Sickle Cell Disease In Children

INTRODUCTION AND PATHOPHYSIOLOGY

Sickle cell disease is a spectrum of blood disorders of which sickle cell anemia (SCA) is the most serious. SCA is found primarily in children of African, Arab, or Mediterranean descent. It is caused by a single amino acid substitution in the sixth position of the β-globulin chain of normal adult hemoglobin (HbA), which creates the abnormal sickle hemoglobin (HbS). The HbS chain found in patients with SCA creates a hydrophobic region of the hemoglobin tetramer when it is deoxygenated.¹ In this state, noncovalent polymerization of the hemoglobin molecules creates chains that distort the shape of the membrane, causing the characteristic sickle appearance. The altered red blood cell shape and its associated rigidity and decreased deformability cause sickle cells to impede blood flow. This is responsible for most of the clinical manifestations of SCA through two primary mechanisms: hemolytic anemia and vaso-occlusion with subsequent ischemia-reperfusion injury. Interruption of blood flow created by the abnormal cells leads to poor tissue perfusion, acidosis, and hypoxia, which cause further sickling. The need to reverse these conditions is central to the management of SCA-related complications.

Children homozygous for this genetic abnormality have two genetic copies of the HbS mutation and are described as having classic hemoglobin SS (HbSS) disease, whereas heterozygotes for HbS with a second β-globulin chain that is normal (HbA) are considered to have sickle cell trait. These patients have enough HbA to prevent polymerization of the hemoglobin chains and subsequently avoid the more severe complications of the disease. Other patients may be heterozygous for HbS coupled with a second hemoglobin abnormality such as HbC, HbO, or β-thalassemia. Although some of these combinations can cause the severe pathology of SCA, patients with HbSC and the 90% of HbS/β-thalassemia patients with some normal β chains have fewer ischemic and infectious complications than patients with HbSS.

Because fetal hemoglobin (HbF) is unaffected by these genetic mutations, symptoms of SCA do not appear until HbF is replaced by the abnormal HbA. HbF predominates until 4 months of age, after which it rapidly declines, reaching baseline low levels just before 1 year of age. One of the first organs affected by the emerging sickle cells is the spleen. Recurrent splenic infarcts lead to a gradual decline in splenic function between 4 and 12 months of age, resulting in susceptibility to serious infections with encapsulated bacteria.

In the United States, all neonates are screened for SCA using highly sensitive and specific tests, so the diagnosis is rarely made in the ED. The clinical manifestations and potential complications of SCA, however, include symptoms that overlap considerably with diseases not related to SCA. Therefore, the diagnostic portion of this chapter is organized in a symptom-based fashion, and the treatment portion is grouped by disease physiology.

SICKLE CELL ANEMIA SYMPTOMS

EXTREMITY PAIN

Vaso-occlusive crises causing severe extremity pain are ...