Management of Sickle Cell Anemia
Hydroxyurea is the cornerstone disease-modifying therapy for patients with sickle cell anemia and should be initiated in most patients, with L-glutamine, crizanlizumab, or voxelotor added as adjunctive therapy for those with inadequate response. 1, 2
Disease-Modifying Therapy
Hydroxyurea remains first-line standard therapy for most patients with sickle cell disease, as it increases fetal hemoglobin (HbF) levels, reduces red blood cell sickling, and improves overall outcomes. 1, 2 Patients with high HbF levels (>8%) tend to have milder disease with fewer symptoms. 1 Critically, baseline hydroxyurea therapy must be maintained during acute crises and perioperative periods—never discontinue it during these vulnerable times. 1
Adjunctive FDA-Approved Therapies
When hydroxyurea alone is insufficient, three additional FDA-approved agents provide complementary mechanisms:
L-glutamine (FDA-approved for patients ≥5 years) reduces acute complications by decreasing oxidative stress, with clinical trials demonstrating a 33% reduction in hospitalization rates and mean length of stay reduced from 11 to 7 days compared to placebo. 3, 2
Crizanlizumab reduces vaso-occlusive pain crises from 2.98 to 1.63 per year compared with placebo by inhibiting P-selectin-mediated cell adhesion. 2, 4
Voxelotor prevents hemoglobin polymerization and increased hemoglobin by at least 1 g/dL in 51% of patients versus 7% with placebo. 2, 4
Management of Acute Vaso-Occlusive Crisis
Pain Control
Patient-controlled analgesia (PCA) with opioids is the preferred approach for moderate to severe pain, with scheduled around-the-clock dosing rather than "as needed" administration. 5, 6 Long-acting opioid medications must be continued if the patient is already taking them for chronic pain management. 5 Pain should be reassessed regularly using validated pain scales. 5
Hydration Strategy
Aggressive intravenous hydration is crucial because patients with sickle cell anemia have impaired urinary concentrating ability and become dehydrated easily. 5, 1 The specific approach depends on crisis severity:
- Oral fluids for mild crises 1
- IV hydration at maintenance rates for moderate crises 1
- Aggressive IV hydration with careful monitoring for severe crises 1
Critical pitfall: Avoid aggressive diuresis even if volume overload develops, as volume depletion induces sickling. 1 Use 5% dextrose solution or 5% dextrose in 25% normal saline rather than normal saline alone, as the haemoglobinopathy causes hyposthenuria with reduced ability to excrete sodium load. 7
Oxygen Therapy
Baseline oxygen saturation must be documented and monitored continuously. 5 Administer supplemental oxygen to maintain SpO2 above baseline or ≥96% (whichever is higher) to prevent hypoxemia-triggered hemoglobin polymerization. 5, 1 Oxygen should be reserved for hypoxic patients rather than given routinely. 7
Temperature Management
Maintain normothermia actively, as hypothermia leads to shivering and peripheral stasis, increasing sickling. 5 Regular temperature monitoring is essential because fever may signal sickling or infection. 5 If temperature reaches ≥38.0°C, obtain blood cultures immediately and start empiric broad-spectrum antibiotics promptly due to high infection risk from intestinal ischemia, bacterial translocation, and hyposplenism. 5, 1, 6
Monitoring for Life-Threatening Complications
Acute chest syndrome occurs in >50% of hospitalized patients with vaso-occlusive crisis and is defined by new respiratory symptoms plus new pulmonary infiltrates on chest X-ray. 5 Continuous SpO2 monitoring is mandatory, especially with opioid administration. 6 Implement chest physiotherapy and incentive spirometry every 2 hours after moderate or major crises. 5
Stroke occurs in up to 10% of children with sickle cell disease. 5 Any acute neurologic symptom other than transient mild headache requires urgent evaluation, including hemiparesis, aphasia, seizures, severe headache, cranial nerve palsy, stupor, or coma. 5
Splenic sequestration presents with rapidly enlarging spleen and hemoglobin decrease >2 g/dL below baseline, with potential rapid progression to shock and death. 5
Thromboprophylaxis
All post-pubertal patients must receive thromboprophylaxis as they have increased risk of deep vein thrombosis. 5 Early mobilization should be encouraged to prevent thromboembolic complications. 5
Transfusion Therapy
When transfusion is indicated, target hemoglobin of 100 g/L. 1 Blood must be HbS-negative, Rh and Kell antigen matched, with extended phenotype matching (C/c, E/e, Jka/Jkb, Fya/Fyb, S/s) to prevent alloimmunization. 1 If suspected hyperhemolysis occurs, avoid additional transfusions unless life-threatening anemia exists, as further transfusion may worsen hemolysis. 1
Perioperative Management
Surgery should ideally be performed at centers with experience in sickle cell disease care, with specialist hematology involvement throughout. 8, 1 Avoid routine surgery if the patient is febrile or having an active painful crisis. 8, 6
Key perioperative principles include:
- Schedule patients early on the operating list to avoid prolonged starvation 8
- Avoid factors that precipitate sickling: dehydration, hypoxia, acidosis, hypothermia, and pain 8
- Maintain a low threshold for admission to high dependency or intensive care, as the majority of complications occur postoperatively 8, 1
- Notify the acute pain team in advance for patients undergoing major surgery, particularly those with chronic pain history 8, 5
Critical Medications to Avoid
Never use phosphodiesterase-5 inhibitors (sildenafil, tadalafil) as they increase hospitalization risk for vaso-occlusive crisis. 1 Use vasopressors with extreme caution if needed, as norepinephrine and epinephrine impair mucosal perfusion and could worsen ischemia. 1 Do not use low-dose dopamine for any indication, including renal protection. 1
Curative Therapy
Hematopoietic stem cell transplant is the only curative therapy, but it is limited by donor availability, with best results seen in children with a matched sibling donor. 2 This should be considered standard care for severe disease when a matched sibling donor is available. 2
Prognosis
With optimal multidisciplinary care in specialist hematology clinics, survival up to the 7th decade can be expected. 1 Nearly all children with sickle cell disease survive to adulthood in the US, though average life expectancy remains 20 years less than the general population. 1, 2