• What is the approach to managing pain episodes in sickle cell disease?
In sickle cell disease, vaso-occlusive pain events can be common, often beginning in early childhood.17 This disease complication accounts for 95% of all adult sickle cell disease hospitalizations.72 There is a great deal of variability in pain symptoms between individuals, and within individuals at various times in their lives:73 30% have no pain events, 50% have occasional events, and 20% have monthly or more frequent events that require hospitalization.74 The frequency and severity of pain events are modulated by HbF levels, β-thalassemia status, genotypes, therapies like hydroxyurea, or in rare cases, chronic transfusion therapy.23 Personal factors, such as psychosocial stressors, also contribute to the frequency of pain events.75 Pain event triggers include exposure to cold water, windy or cold weather, temperature changes, and extreme temperatures.76–79 Patient age also contributes to pain event frequency. Many patients see an increase in pain event frequency in their late 20s, and a marked decrease in their 40s.23,73 More than 3 pain events per year is associated with reduced life expectancy.23
Acute management of pain episodes involves nonsteroidal anti-inflammatory drugs, oral opioids, and when hospitalization is required, intravenous opioids, often delivered via patient-controlled analgesia (PCA) pumps.79 As sickle cell disease patients become teenagers and young adults, some experience an increased frequency of pain episodes, with fewer pain-free days, or a failure to return to baseline before the next pain crisis occurs.80,81 This is characteristic of emerging chronic pain.82 Chronic pain is a significant problem in adult patients with sickle cell disease, with up to 85% reporting pain on most days.72,80 The development of chronic pain may be reduced by early and aggressive treatment of acute pain events, as well as use of hydroxyurea to reduce the number of pain events. Many adult sickle cell patients with chronic pain are treated with daily opioids.20 Given the significant side effects of chronic opioid use—sedation, respiratory depression, itching, nausea, and impairment of function and quality of life—non-opioid therapies are under investigation.83 Many chronic pain patients have symptoms of neuropathic pain, and may benefit from neuropathic agents like gabapentin, both to reduce opioid use and to more effectively treat chronic neuropathic pain, which is known to respond poorly to opioids.84–86
• Is the patient’s peripheral blood smear consistent with a diagnosis of sickle cell trait?
Several target cells are visible, which is not typical of sickle cell trait, but may be seen in HbSC or thalassemia. The finding of an intracellular crystal is pathognomonic for HbSC or HbCC. HbC polymerizes in high oxygen conditions, opposite of HbS, which polymerizes in low oxygen conditions.9
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The patient’s family history is significant for a sister who died at age 3 from sickle cell–related complications, and a sister with sickle cell trait who had a cholecystectomy for gallstones at age 22. His father died at age 38 due to unknown causes. The sickle cell trait status of his parents is unknown. His mother is alive, and has hypertension.
• Is the medical history of this patient’s family members consistent with sickle cell trait?
It is unlikely that sickle cell trait would result in early death in childhood, or in gallstones at age 22. Gallstones in early adulthood is a common presentation for HbSC patients not diagnosed by newborn screening.87 Any hemolytic condition can lead to the formation of hemoglobin-containing pigmented gallstones, biliary sludge, and obstruction of the gallbladder. In the presence of right-sided abdominal pain, a serum bilirubin level of more than 4 mg/dL should lead to measurement of direct bilirubin; if greater than 10% of total, imaging of the gallbladder should be obtained. In sickle cell disease, 30% of patients will have gallstones by 18 years of age. The low hemolysis/high viscosity phenotype patients are typically older at diagnosis. Co-inheritance of Gilbert syndrome and sickle cell disease is not uncommon, and can result in formation of gallstones at a young age; Gilbert syndrome alone typically results in gallstones in mid-life.88