Patients with sickle cell disease (SCD) experience a number of complications that are likely to bring them to the emergency department (ED). Hemoglobin S (HbS) is a variant resulting from a single nucleotide mutation in the sixth codon of the β-globin gene leading to the substitution of hydrophobic valine for the normal hydrophilic glutamic acid. SCD occurs when an individual is homozygous for HbS or is a compound heterozygote for HbS and another interacting β-globin variant. The most common combination of hemoglobins leading to SCD are HbSS (sickle cell anemia), HbSC (hemoglobin SC) disease, and HbS-β thalassemia (either β⁰ or β⁺). Although there is wide variability in individual severity of illness, patients with HbSS or HbSβ⁰ (no hemoglobin A production) have the greatest severity of disease.^1,2 The other double heterozygous states, such as HbSC and HbSβ⁺ thalassemia, are typically less seriously affected.¹ Patients with HbS/HPFH (hereditary persistence of HbF) and HbS/HbE show mild to no symptoms.¹ Approximately 1 in 12 African Americans carry the allele, and 1 in 500 African Americans born has the disease. HbS also occurs in people of Mediterranean, South Asian, and Middle Eastern descent.¹

Patients with a single abnormal gene for HbS have sickle cell trait. The concentration of HbS is typically 40%, and the large percentage of normal hemoglobin allows the patients to remain asymptomatic except under the most severe hypoxic stress. Sickle trait should be considered a benign condition.¹

Acute vasoocclusive crisis (VOC) events (painful “crisis” events) are the most common complication of SCD and are the most frequent cause of ED visits.^1,3 Prompt pain control is a high priority.^3,4,5 Severe pain episodes result from the obstruction of blood flow in the microcirculation leading to tissue ischemia and microinfarction. Vasoocclusion and subsequent tissue hypoxia occur via a combination of sickle cell interactions with endothelial cells, obstruction from nondeformable sickled cells and heterocellular aggregates, release of inflammatory mediators and free radicals, ineffective nitric oxide (a vasodilator) binding/release, hemolysis, and reperfusion injury.¹

VOC most often presents initially as “dactylitis,” or hand–foot syndrome, between 6 to 18 months of age,^5,6 which is vasoocclusion in the marrow of the metacarpal or metatarsal bones (Fig. 105-1). Infants present with hand and foot swelling and tenderness, which may lead to refusal to walk and irritability. Dactylitis declines with age as hematopoiesis shifts to the long bones.

Older patients typically experience VOC in the extremities, back, or chest.^1,5 Pain events may be precipitated by dehydration, hypoxia, cold exposure, or infection. However, no instigating factor is identified in many instances. There is a great deal of individual variation in the number and severity of painful crises. Figure 105-2 outlines a suggested approach to the management of VOC acute pain in the ED.

As there is no diagnostic test or clinical finding that will identify patients in vasoocclusive crisis, the diagnosis is made clinically with a heavy reliance on history.^1,7 Patients with SCD and pain should be evaluated for other disease processes such as traumatic injuries, osteonecrosis, osteomyelitis, septic arthritis, and surgical abdominal problems.^2,7 The formation of gallstones due to chronic hemolysis may lead to cholecystitis or pancreatitis and abdominal pain.^1,5 A complete blood count (CBC) and reticulocyte count are indicated in every encounter with SCD patients. Typically, patients remain at baseline hemoglobin levels during a painful event. Hydration at maintenance rate should be initiated to correct and prevent dehydration. Overhydration may lead to acute chest syndrome and should be avoided.⁷ Oxygen has not been shown to be beneficial in the management of pain crises unless hypoxemia is present.

Pain relief is achieved with a variety of analgesics, depending on the severity of the crisis and what the patient has required in past crises. Oral agents such as acetaminophen, NSAIDs, and narcotic analgesics used separately or in combination are the mainstays of treatment for mild to moderate pain.^5,6 Usually, patients have unsuccessfully tried these therapies at home prior to presenting to the ED. Parenteral opioids (morphine, fentanyl, or hydromorphone), are often necessary for severe pain.^1,5 Intranasal fentanyl can be given initially to reduce the time to initial analgesia administration.^3,8,9 Pain should be assessed at least every 30 minutes using standardized pain scales. Anxiety about giving children narcotics leads to undertreatment of pain, which should be avoided.^4,5,7 Meperidine treatment is associated with the concern for its metabolite normeperidine, which has been linked to emotional/behavioral changes and seizures, especially in those with reduced renal function.¹

Analgesia should be provided at frequent regular time intervals to avoid breakthrough pain. Typically, ED patients are observed for 3 or 4 hours. EDs should consider the patient-controlled analgesia (PCA) option since patients will often require several doses of parenteral opioids.^1,7 If the patient remains comfortable without further need for parenteral opioid, he or she may be discharged with continued scheduled oral opioid and NSAID at home.¹ If adequate pain relief is not achieved, the patient is hospitalized for further parenteral analgesia. Hypoventilation as a result of opiate use may increase the risk of developing acute chest syndrome. Incentive spirometry should be encouraged in order to reduce this risk.⁵

Acute chest syndrome (AChS) is the presence of a new lobar or segmental pulmonary infiltrate in the presence of fever, respiratory symptoms, and/or chest pain (Fig. 105-3). Various causes may contribute to AChS including infection, pulmonary infarction due to vasoocclusion, and fat emboli from marrow infarction.^1,6 Chest pain from vasoocclusion (VOC) may cause splinting and hypoventilation, leading to the development of AChS in a patient who initially presents with a painful episode.¹ It is difficult to differentiate vasoocclusion from pneumonia in patients with AChS, since both etiologies cause similar manifestations. Infectious organisms associated with AChS include S. pneumoniae, Mycoplasma, or Chlamydia.^1,5 AChS may present with or rapidly progress to respiratory failure requiring mechanical ventilation.⁵