Chapter 84. Sickle Cell Anemia in Children

Sickle cell emergencies in children include vasoocclusive crises, hematologic crises, and infections. All children with sickle cell anemia (SCA) presenting with fever, pain, respiratory distress, or a change in neurologic function require a rapid and thorough ED evaluation.

Vasoocclusive sickle episodes are due to intravascular sickling, which leads to tissue ischemia and infarction. Bones, soft tissue, viscera, and the central nervous system (CNS) may be affected. Pain may be the only symptom.

Clinical Features

Pain crises are the most common SCA related presentation to the ED, and typically affect the long bones and back. They can be triggered by stress, extremes of cold, dehydration, hypoxia, or infection, but most often occur without a specific cause. In an individual patient, recurrent pain crises tend to be similar in location and quality to previous episodes. Although, typically, there are no physical findings, pain, local tenderness, swelling, and warmth may occur. Low-grade temperature elevations can occur, but true fever is rare. Infants and toddlers can present initially with dactylitis, a swelling of hands or feet, and low-grade temperature caused by ischemia and infarction of the bone marrow.

Diagnosis and Differential

Differentiating between infection and vasoocclusive crisis can be difficult, particularly since infection can precipitate a pain crisis. Fever, limited range of motion of a joint, and pain that differs in location or quality from previous crises should raise concern for an infection. Pain crises can be associated with leukocytosis; however, a left shift is suspicious for infection. Sedimentation rates are unreliable markers for infections in SCA patients due to anemia. All pain crises represent ischemia, but bony infarcts present with severe, difficult to control pain, significant tenderness, and leukocytosis. Patients with bony infarcts are at risk of fat embolism.

Pain localized to the hip or inguinal area worsening with weight-bearing may be due to avascular necrosis of the femoral head, which may demonstrate flattening and collapse of the femoral head on plain radiograph.

Abdominal pain resulting from vasoocclusive crises is common and is typically abrupt in onset, and poorly localized. Tenderness and guarding may be present on examination, but not rebound or rigidity. If not typical of a pain crisis, non-SCD related causes need to be considered (eg, appendicitis), as well as SCA-related cholelithiasis/cholecystitis (gallstones can occur as early as 2 years of age), intrahepatic cholestasis (sudden right upper quadrant pain and tenderness, jaundice, anorexia, hepatomegaly, and sometimes fever), splenic sequestration, or hepatic sequestration (anemia and hepatomegaly). Laboratories, ultrasound, and CT scan may be necessary to differentiate among these etiologies.

Emergency Department Care and Disposition

Pain management must be individualized, using previously effective regimens as a guide.

1. Mild pain

   1. Oral hydration

   2. Oral NSAIDS (10 milligrams/kilogram ibuprofen)

   3. Oral narcotics (0.2 milligram/kilogram hydrocodone)

2. Moderate to severe pain

   1. IV hydration (D5½NS at 1.5 X the age-appropriate maintenance rate),

   2. Oral or IV NSAIDS (0.5 milligram/kilogram ketorolac)

   3. IV narcotics (0.1 to 0.15 milligram/kilogram morphine or 0.015 milligram/ kilogram hydromorphone) every 15 to 30 min until pain control is achieved

3. Packed red blood cell (PRBC) transfusion for a significant drop in hemoglobin or Hgb < 5 grams/dL.

4. Admission is warranted for poor pain control or inadequate oral fluid intake. Children who have presented repeatedly for the same pain crisis also should be considered for admission.

5. Children discharged from the ED should continue analgesics at home on a scheduled basis with PCP or hematology follow-up the next day.

Acute chest syndrome is believed to represent a combination of pneumonia, pulmonary infarction, and pulmonary emboli from necrotic bone marrow. It is a leading cause of death in all patients with SCA, but especially those older than 10 years.

Clinical Features

Acute chest syndrome should be considered in all patients with SCA who present with complaints of chest pain, especially when associated with tachypnea, dyspnea, cough, or other symptoms of respiratory distress. Significant hypoxia and rapid deterioration to respiratory failure can occur.

Diagnosis and Differential

Chest radiographs should be obtained but may be normal during the first hours to days. The diagnosis is made in the setting of a new infiltrate on chest radiograph in the setting of chest pain and respiratory symptoms. Both pneumonia and acute chest syndrome typically cause leukocytosis. Thrombocytopenia may accompany a severe crisis. Sputum and blood cultures are rarely positive. Pneumonia is most commonly due to atypical bacteria (chlamydia, mycoplasma), but can represent community acquired pathogens (Streptococcus pneumoniae) as well.

Emergency Department Care and Disposition

Because deterioration can be rapid, close monitoring is required, typically in the ICU.

1. Initial stabilization: oxygen, hydration (see Pain Crisis), analgesia (see Pain Crisis)

2. Antibiotics: macrolide (eg, azithromycin 10 milligrams/kilogram PO or IV) and third generation cephalosporin (eg, 50 milligrams/kilogram/d ceftriaxone or cefotaxime IV)

3. Simple PRBC transfusion (5 mL/kg for pretransfusion Hgb of 4 to 6 grams/dL, 10 mL/kg for pretransfusion Hgb of > 6 grams/dL) should be considered in children with severe anemia or significant hypoxia (Pao2 < 70 mm Hg or oxygen saturation > 10% decrease from baseline). If the patient has a pretransfusion Hgb ≥ 10 grams/dL, exchange transfusion must be used in lieu of simple transfusion to prevent further sludging.

4. All children with suspected acute chest syndrome should be admitted to the hospital.

Clinical Features

Acute stroke should be considered in any patient with SCA who presents with sudden onset headache or neurologic changes, including hemiparesis, seizures, speech defects, visual disturbances, transient ischemic attacks, vertigo, cranial nerve palsies, paresthesias, altered mental status or coma. Children with SCA are at significantly higher risk of acute ischemic stroke than unaffected children.

Diagnosis and Differential

Because of the challenges in diagnosing acute ischemic stroke (eg, limited availability of MRI, CT negative in acute setting), providers may need to initiate treatment based exclusively on clinical suspicion. If clinical history is appropriate for a subarachnoid hemorrhage, workup should proceed as for a patient without SCA. Acute chest crisis, sudden severe anemia, and meningitis can cause neurologic symptoms, and appropriate tests should be sent to investigate these possibilities in the appropriate clinical setting.

Emergency Department Care and Disposition

Suspected CNS vasoocclusion necessitates immediate stabilization and careful monitoring. Urgent exchange transfusion should be initiated with the goal of <30% HbS (usually 1 to 2 blood volumes). As in any ischemic stroke, temperature, glucose, and oxygenation should be monitored and controlled. Alteplase has no role in the management of SCA related ischemic stroke in children. Intracranial hemorrhage should be managed in conjunction with a neurosurgeon. All children with suspected stroke should be admitted to the pediatric intensive care unit.

Clinical Features and Diagnosis

Priapism, a painful sustained erection in the absence of sexual stimulation, occurs when sickled cells accumulate in the corpora cavernosa. It can affect any male with SCA regardless of age, and severe prolonged attacks can cause impotence. Typically, the patient has an edematous and tender penis, with difficulty urinating.

Emergency Department Care and Disposition

Patients with priapism should receive IV hydration with D5½NS at 1.5 to 2 times maintenance and appropriate analgesia. As in non-SCA priapism, needle aspiration of the corpora cavernosa and administration of a vasoconstrictor (eg, 1:1,000,000 epinephrine solution) may be required. Patients failing this may require transfusion or exchange transfusion (see Acute Chest Crisis for transfusion guidelines). Management and admission decisions should be made promptly in consultation with urology and pediatric hematology.

Clinical Features and Diagnosis

Intrasplenic trapping of red cells primarily affects children under 5 years of age, but can occur in older patients with SCA. Often preceded by a viral syndrome, splenic sequestration presents with sudden onset left upper quadrant pain; pallor and lethargy; tender splenomegaly; and progresses to hypotension, shock, and death. A CBC shows profound anemia (hemoglobin < 6 grams/dL, or > 3 grams/dL lower than the patient's baseline level). Minor episodes can occur with insidious onset of abdominal pain, slowly progressive splenomegaly, and a more minor fall in hemoglobin level (generally the hemoglobin level remains > 6 grams/dL).

Patients may have accompanying mild neutropenia or thrombocytopenia. Less commonly, sequestration can occur in the liver. Clinical features include an enlarged and tender liver with associated hyperbilirubinemia, severe anemia, and elevated reticulocyte count. Cardiovascular collapse is rare in this condition.

Emergency Department Care and Disposition

PRBC transfusion and admission is required for major episodes. Occasionally, children with minor episodes can be observed, and discharged with close follow-up with a hematologist.

Potentially life-threatening aplastic episodes are precipitated primarily by viral infections (typically parvovirus B19), and present with gradual onset of pallor, dyspnea, and fatigue. The CBC shows an unusually low hemaglobin and reticulocyte count, with normal white blood cell and platelet counts. Recovery is spontaneous within 1 to 2 weeks, and patients can typically be temporized with PRBC transfusion in the ED (with close outpatient follow-up) or inpatient setting. Rapid transfusion in severe anemia can precipitate heart failure, so small volumes (3 to 5 mL/kg) given over 3 to 4 hours should be used in severely anemic patients (Hgb ≤ 6 grams/dL).

Bacterial and viral infections in children with SCA can precipitate rapid hemolysis, with sudden-onset of jaundice and pallor. A CBC shows hemoglobin level decreased from baseline, with markedly increased reticulocytosis. Specific therapy is rarely required, though transfusion may be helpful in symptomatic patients. Care should be directed toward treating the underlying infection. Close follow-up to monitor hemoglobin level and reticulocyte count should be arranged if discharged from the ED.

Clinical Features

Poor splenic function renders children with SCA particularly susceptible to bacterial infections, particularly in early childhood.

Diagnosis and Differential

The NIH recommends a CBC, urinalysis, blood, urine, and throat cultures, pulse-oximetry, and a chest radiograph in all febrile children with SCA. A lumbar puncture is indicated only for clinical suspicion of meningitis. Risk factors for sepsis in children with SCA include temperature > 40°C, WBC > 30,000 or < 5000 cells/mm3, platelet count < 100,000/mm3, Hgb < 5 grams/dL, ill appearance, and history of pneumococcal sepsis.

Emergency Department Care and Disposition

Children meeting any high-risk feature (above in Diagnosis) should receive a parenteral antibiotic with activity against Streptococcus pneumoniae and H influenzae (eg, ceftriaxone 50 milligrams/kilogram IV or IM) as soon as possible. Vancomycin should be added if the patient is at high risk for penicillin-resistant pneumococcal infection. Septic shock must be managed aggressively with early goal-directed therapy. Patients over 6 to 12 months of age without high-risk criteria who have reliable next day follow-up can be discharged following a parenteral dose of ceftriaxone pending culture results.

Sickle cell trait is the carrier state of SCA (heterozygous). These patients are typically asymptomatic, though baseline microscopic hematuria may exist, and experience sickling only in the presence of extreme hypoxia or high altitude. Sickle cell-hemoglobin C disease is a heterozygous condition characterized by mild to moderate anemia and fewer complications. However, splenomegaly can persist to adulthood, and these patients remain at risk for sequestration crises. Sickle cell β-thalassemia disease is a heterozygous condition with variable severity and symptoms.