Sickle cell disease

Acute Chest Syndrome

• Hgb S = valine replaces glutamic acid in 6th position of beta chain (E6V)

  • Alters shape of cells in certain environments

  • Hemolysis from brittle RBC’s

• Vascular occlusion caused by sickled cells

• Hgb SS 0.2% American blacks

• Hemoglobin electrophoresis:

  • A homozygous patient will have hemoglobin SS (HbSS, 80-90%), hemoglobin F (HbF, 2-20%), and hemoglobin A2 (HbA2, 2-4%).

  • A carrier patient will have HbSS (35-40%) and hemoglobin A (HbA, 60-65%).

  • The test is not accurate in a patient who has recently received blood transfusions.

Sickle cell trait

• Heterozygous expression of sickle hemoglobin

• Affects ~10% Black Americans

• Hgb S: 35-45% (versus 80-95% in Hgb SS)

• Clinically benign (usually)

• Splenic infarct w/severe hypoxia

• Hyposthenuria

• Gross hematuria

• Occasional sudden death

• Genetic counseling

Clinical

Labs

• Hgb: usually 5-9 g/dL

• Peripheral smear: sickle cells, target cells, Howell-Jolly bodies

• Retic count: 5-15%

• Leukocytosis & thrombocytosis

• ESR: lowered (cells don’t rouleaux)

• if abd pain: do LFTs (chronic hemolysis may explain increased indirect hyperbili)

• consider type and crossmatch

Imaging

• Chest radiography

  • Perform in patients with respiratory symptoms.

  • Radiographic findings may initially be normal in patients with acute chest syndrome.

• Bone radiography

  • Perform in patients with localized bone tenderness.

  • Do not differentiate between osteomyelitis and bone infarction in the early stages. Radiographic signs of osteomyelitis may not appear for 8-10 days.

  • A view of the vertebral column shows typical fish-mouth appearance of vertebrae in patients with sickle cell anemia. This is due to expansion of the bone marrow.

• Ultrasonography

  • Use in patients with abdominal pain to rule out cholecystitis or an ectopic pregnancy.

  • Assess liver and spleen size.

  • Cholelithiasis may occur because gallstones form as a result of chronic hemolytic anemia. Ultrasound is diagnostic. If symptomatic, cholecystectomy is indicated.

• Head CT or MRI is used in cases of neurologic crisis.

• Bone scans can aid in early differentiation of bone infarction and osteomyelitis.

Diagnosis

• Hgb electrophoresis (newborn screen): Quantifies different Hgb fractions

• Sickle cell prep: Hgb added to buffer w/reducing agent; Turbid ppt forms if >15% Hgb S present

ED management

• Administer oral hydration if the patient is having a mild episode, is not vomiting, and can tolerate oral fluids.

• Administer IV fluids (at least 3-4 L normal saline solution [NSS]). Ensure accurate intake-output measurements by inserting a Foley catheter. Take care not to overload the patient.

• While considering the severity of pain and the patient's past response, follow consistent protocols to relieve the patient's pain.

• Oxygen supplementation is only beneficial if patient has hypoxia. Intubation and mechanical ventilation may be required in patients in whom cerebrovascular accidents have occurred.

• Simple blood transfusion is indicated in patients in aplastic crisis and acute sequestration crisis.

• Exchange blood transfusions are indicated in cases of cerebrovascular accidents and acute chest syndrome. They are performed occasionally in patients with acute sequestration crisis or in cases of priapism that do not resolve after adequate hydration and analgesia (ie  Priapism).

• Exchange transfusion consists of replacing the patient's RBCs by normal donor RBCs, decreasing HbS to less than 30%.

• In case of priapism that does not resolve after 6 hours of hydration and analgesia, consult a urologist for aspiration of corpus cavernosum or shunting.

  
   

Management

• Prevent & treat infections

  • Immunize!!! (esp. Hib, Pneumococcus)

  • PCN prophylaxis until age 6yo

  • Bring to medical attention for T> 38.5

• Refer to Sickle cell center

  • Anticipatory guidance re: splenic

  • sequestration & exam

  • Pain management

• Maintain hydration/oxygenation

• Hydroxyurea/Butyrate: Hydroxyurea is a purine analog that stimulates fetal Hgb production, however it can cause leucocytopenia and thrombocytopenia. Causes RBC macrocytosis, which can be monitored to evaluated compliance. Goal MCV is 110-125. It does not prevent stroke. It is used to decrease the number of vaso-occlusive crises, but does not prevent them completely. Do NOT use in pregnancy. With hydroxyurea, mortality is decreased in 50% of adults.

• Folate supplementation

• ? BMT

Med notes

• Folic acid should be prescribed to those who are not already taking it.

• Discharge patient on oral analgesics for a week. Up to 2 doses of narcotics can be administered in ED over a period of 4-6 hours.

• Oral drugs for mild pain include acetaminophen, ibuprofen, aspirin, and codeine. If pain is moderate, oxycodone or methadone can be administered.

• Administer parenteral drugs for severe pain. Morphine is the drug of choice, but meperidine with promethazine can be used.

• Antibiotics are indicated when an infection is suspected, when body temperature is higher than 38 degrees Celsius, or when a patient has localized bone tenderness. Fever in children is strongly suggestive of infection. It has been found that signs of infection are more accurate in children than in adults.

• Common infections include pneumonia, bronchitis, pyelonephritis, cystitis, osteomyelitis, meningitis, and sepsis. Recommended parenteral antibiotics include cephalosporins (eg, ceftriaxone, cefuroxime).

• If the patient is discharged home, oral antibiotics (eg, Augmentin, Ceclor) are useful. If the patient has localized bone tenderness, seek antibiotic coverage for S typhimurium and S aureus.

Patient Education

• Teach patients to seek medical care in certain situations, including the following:

  • Persistent fever (>38.3°C)

  • Chest pain, shortness of breath, nausea, and vomiting

  • Abdominal pain with nausea and vomiting

  • Persistent headache not experienced previously

• Patients should avoid the following:

  • Alcohol

  • Nonprescribed prescription drugs

  • Cigarettes, marijuana, and cocaine

  • Seeking help in multiple institutions

& pregnancy

• Sickle cell disease and pregnancy

• Patients who are pregnant and have sickle cell disease are at increased risk for crisis, toxemia, pyelonephritis, thrombophlebitis, and spontaneous abortion compared to the general population.

• Prophylactic transfusion with special concern for folic acid replacement have been shown to decrease the incidence of vasoocclusive crisis during pregnancy.

• In the past, pregnancy was strongly discouraged, and tubal ligation often was performed.
   

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CHLA Board Review 2005