Sickle cell disease (SCD)—an inherited hemoglobinopathy characterized by erythrocytes that assume a rigid sickle shape under relatively hypoxic conditions—is more prevalent in people who themselves or whose forebearers came from tropical or subtropical sub-Saharan regions with current or previously endemic malaria.

In utero, at the end of the first trimester, erythrocytes contain hemoglobin (Hb)F (α₂γ₂), which, like HbA (α₂β₂) and HbA₂ (α₂δ₂), is composed of four protein (globin) molecules, each binding one of four hematoporphyrin rings. The P₅₀ of HbF is 19 mm Hg (compared with the P₅₀ of HbA of 26.8 mm Hg), that is, HbF has a higher affinity for O₂, which is necessary for the fetus to extract O₂ from the placenta and the maternal erythrocytes. Within 6 months of birth, HbF is replaced by adult Hb (HbA), except in individuals with hemoglobinopathies, of which there are close to 300 variants. In people with SCD, the amino acid valine is substituted for glutamic acid in the β-globulin chain. In the United States, approximately 1 in 500 African American children and 2 in 36,000 Hispanic American children have SCD. These children may initially have normal Hb values but, over time, develop anemia (sickle cell anemia [SCA]).

People with SCA, also referred to as HbSS because they have homozygosity for the gene encoding the β chain of hemoglobin (mutant S), develop sickling of erythrocytes in small arterioles at O₂ tensions of 40 to 45 mm Hg (the P₅₀ of HbS is approximately 49 mm Hg). However, although hypoxia may cause these cells to “sickle,” the process is far more complex, involving erythrocyte-endothelial cell interactions, viscosity of the blood, and probably cytokines released locally as part of a systemic inflammatory response. Patients with sickle cell trait, also called HbAS because of the heterozygosity for the mutation, can develop sickling of erythrocytes at O₂ tensions of 20 to 25 mm Hg. Other, rarer forms of SCD—such as sickle cell–hemoglobin C disease (HbSC), sickle cell–hemoglobin D disease (HbSD), sickle cell β-plus-thalassemia (HbS/β⁺), and sickle cell β-zero-thalassemia (HbS/β⁰)—are compound heterozygous states in which the affected individual has only one copy of the mutation that causes HbS and one copy of another abnormal hemoglobin allele. These cells can also “sickle,” but people with these heterozygous conditions tend to have higher Hb levels (approximately 10 g/dL) than do people with HbSS.

Although the term sickle cell crisis is commonly used, in reality, a variety of crises are subsumed under this term, including vaso-occlusive, splenic sequestration, aplastic, and hemolytic crises. Patients with SCA have increased perioperative morbidity and mortality rates, as compared with the general population, likely due to vaso-occlusion from sickled erythrocytes, resulting in acute tissue injury and chronic organ damage (Table 206-1). People with SCA also undergo more operations and at an earlier age; the most commonly performed surgical procedures are cholecystectomy (due to an increased rate of formation of pigmented gallstones and cholelithiasis in this population), splenectomy (because of splenic sequestration and splenic pooling), and hip arthroplasty (related to the 50% rate of osteonecrosis in the femoral head among individuals with SCA who are 35 years of age and older). In addition, postoperative hospital length of stay is typically longer in this population.

Table 206-1

Effects of Vaso-occlusive Insults from Sickled Erythrocytes on Organ Systems in Patients with Sickle Cell Disease

System	Effect	Cause	Finding(s)
Cardiac	Cardiomegaly Hyperdynamic circulation	Long-term increased cardiac output and gradual occlusion of pulmonary vascular bed	Full pulses Murmurs
Pulmonary	↓ Total lung capacity ↓ Vital capacity ↑ Risk of contracting pneumococcal pneumonia	In patients with SCD, mismatch and pulmonary sickling add to their likelihood of developing pulmonary infarction and infection perioperatively. When compared with the general population, these patients have a 10-fold higher risk of serious perioperative pulmonary complications.	Resting SaO2 70-90 mm Hg
Renal	Papillary necrosis and nephrotic syndrome	The relatively hypoxic, hypertonic, and acidotic environment in the medulla leads to sickling of RBCs with consequent vaso-occlusion, resulting in decreased renal medullary blood flow. Hematuria, which often occurs in patients with sickle cell nephropathy, increases venous pressure, further worsening the ischemia of the renal medulla and predisposing the patient to further RBC sickling.	Large dilute urine volume
Hepatic	Cirrhosis, hepatitis, hepatic sequestration, hepatosplenomegaly, and cholelithiasis Hemosiderosis Hemochromatosis	Both the vascular complications from the sickling process itself and the fact that patients with SCD have often received multiple transfusions increase their risk for developing viral hepatitis, iron overload, and (combined with the effects of chronic hemolysis) pigmented gallstones.	A combination of the following findings, depending on the hepatic cause: fever, pain, jaundice, elevated AST/ALT, cutaneous leukocytoclastic vasculitis, essential mixed cryoglobulinemia with purpura, arthralgias, glomerulonephritis, and peripheral neuropathy, positive PCR assay for viral RNA, elevated serum ferritin, Kupffer cell hyperplasia with erythrophagocytosis, sinusoidal distention with aggregates of sickled erythrocytes, and fine fibrosis in the space of Disse

AST/ALT, Aspartate transaminase/alanine transaminase; PCR, polymerase chain reaction; RBCs, red blood cells; SCD, sickle cell disease; , ventilation-perfusion.

Women with SCA are more likely to experience complications during pregnancy. Fifty-four percent of pregnancies in women with SCD result in a live birth, with the average gestational age at delivery being 34 weeks.