Sickle cell disease (SCD) is an inherited chronic disease found primarily in those of African, Middle Eastern, Indian, or Mediterranean ancestry. SCD is characterized by a defect in the hemoglobin molecule, which normally consists of two pairs of α and β globin. A single amino acid substitution (valine for glutamine) on the β-globin gene results in sickle hemoglobin (Hb S). The mutation that causes the amino acid substitution is inherited as an autosomal recessive trait. Patients with sickle cell trait have one abnormal β-globin gene (heterozygous HbAS), whereas those with SCD have 2 abnormal β-globin genes (homozygous HbSS). During states of biologic stress (eg, low O2 state, infection, dehydration, pregnancy, cold exposure, trauma) the Hb S polymerizes, resulting in deformation (sickling) of the red blood cell (RBC). This sickled RBC has reduced ability to pass through small blood vessels, resulting in vasoocclusion, hemolysis, and end-organ damage. Premature destruction of the sickled RBC results in a shorter than normal life span of the cell.
Two million people in the United States have sickle cell trait, and 70,000 have sickle cell disease. Although survival has improved dramatically recently, life expectancy of patients with SCD is shorter than average, now just greater than 50 years.
Most patients with SCD present to the emergency department (ED) with either a painful vasoocclusive crisis or sequela from vaso-occlusion, some of which may be life-threatening. It is the role of the emergency physician to not only control pain but also diagnose and treat potential life threats. Acute sickle cell emergencies can be divided into several classifications: acute pain crisis, acute chest syndrome, infection, neurologic, splenic sequestration, aplastic crisis, hemolytic anemia, and priapism.
Vaso-occlusive pain crises account for approximately 90% of ED visits. Severe back and extremity pain results from micro-infarction of the bones and joints. Abdominal pain crises result from ischemia to the mesentery, spleen, and liver.
Acute chest syndrome is the most common cause of death in patients with SCD. Although it is more common in children, it is more severe in adults. Acute chest syndrome is characterized by fever, chest pain, respiratory symptoms, hypoxia, and an infiltrate seen on chest x-ray (CXR). It is a result of pulmonary ischemia and infarction. Acute chest is frequently a complication of pneumonia. Chlamydia and Mycoplasma are the 2 most common organisms, but viruses, Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae are all potential causes.
Patients with SCD are at increased risk of infection as a result of the loss of splenic function secondary to recurrent splenic infarcts. Children as young as 6 months of age may be functionally asplenic, and most patients with SCD are by the age of 5 or 6 years. This makes them more vulnerable to infections with encapsulated organisms such as S. pneumoniae and H. influenzae.S. aureus, Escherichia coli, and Salmonella typhimurium are also common pathogens. Bone, pulmonary, and central nervous system (CNS) infections are common and must be considered in any febrile patient with SCD.
Patients with SCD are at increased risk for cerebrovascular accident (CVA), ischemic and hemorrhagic, as well as subarachnoid hemorrhage. Approximately 10% of patients will have a CVA by the age of 20 years. Vasoocclusion, as well as endothelial damage, are believed to play a role in development of CVA.
The abnormal sickled cells become trapped in the spleen (splenic sequestration), leading to a rapid decrease in steady state hemoglobin and an enlarged spleen. A rapid decrease in hemoglobin can lead to hemodynamic instability and altered mental status. Splenic sequestration is a serious complication seen more commonly in children than adults and carries a significant morbidity and mortality potential.
Aplastic crisis arises when bone marrow production of RBCs stops or falls below the rate of destruction. Aplastic crisis is also associated with reticulocytopenia. Aplastic crisis in patients with SCD has been linked to infection with parvovirus as well as folic acid deficiency.
Chronic hemolysis is a problem for all patients with SCD due to the deformed RBC. Hemoglobin levels range from 6–9 g/dL. Patients will also have an increased reticulocyte count due to increase RBC destruction. Under stress (eg, infection), hemolysis rates may increase and patients my have a decrease in hemoglobin from their baseline.
Priapism, a painful failure of penile detumescence secondary to corpus cavernosum obstruction by sickled cells, has a bimodal peak (5–13 years and 21–29 years of age). Prolonged priapism can lead to impotence due to fibrosis and vascular damage.
