What is the management and treatment of sickle cell disease?

Management and Treatment of Sickle Cell Disease

Sickle cell disease requires a comprehensive management strategy centered on disease-modifying therapy with hydroxyurea as first-line treatment, aggressive management of acute pain crises with opioids and multimodal analgesia, prevention of complications through hydration and infection control, and consideration of curative hematopoietic stem cell transplantation in severe cases.

Disease-Modifying Therapies

• Hydroxyurea remains the first-line disease-modifying therapy for most individuals with SCD, increasing fetal hemoglobin production and reducing red blood cell sickling 1, 2, 3
• Three additional FDA-approved therapies serve as adjunctive or second-line agents: L-glutamine (reduced hospitalizations by 33% and mean length of stay from 11 to 7 days), crizanlizumab (reduced pain crises from 2.98 to 1.63 per year), and voxelotor (increased hemoglobin by ≥1 g/dL in 51% vs 7% with placebo) 1
• Hematopoietic stem cell transplant is the only curative therapy, with best results in children with matched sibling donors, though limited by donor availability 1

Acute Pain Crisis Management

Immediate Analgesic Approach

• Patient-controlled analgesia (PCA) with opioids is the cornerstone for moderate to severe pain, showing superior outcomes with lower overall morphine consumption compared to continuous infusion 4, 5
• Acetaminophen should be used as an adjunct to opioid therapy, not as monotherapy, since sickle cell pain crises typically require opioid analgesics for adequate control 4
• Nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids are the mainstay of pain treatment 3
• Baseline analgesic use must be documented and long-acting opioid medications continued throughout the peri-operative or crisis period 6, 5
• Pain should be reassessed regularly using validated pain scales appropriate for age, with documentation before and after each analgesic dose 4

Critical Pitfall to Avoid

• Opioid dependency is rare in sickle cell disease patients; opioid sensitivity is more common 6. Patients are not more likely to develop addiction to pain medications than the general population 1, so adequate opioid dosing should not be withheld due to unfounded addiction concerns

Supportive Care Measures

Hydration Management

• Aggressive hydration is mandatory as sickle cell patients have impaired urinary concentrating ability and dehydrate easily 4, 5
• Oral hydration is preferred when possible, with clear fluids encouraged up to 1-2 hours before any procedure 6
• Intravenous fluids should be administered if oral intake is inadequate, with meticulous fluid management and accurate measurement of losses 4, 5
• 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
• Fluid balance must be monitored continuously to prevent both dehydration and overhydration 5

Oxygen Therapy

• Baseline oxygen saturation must be documented pre-crisis and monitored continuously 6, 4
• Do not give continuous oxygen therapy unless necessary—oxygen should only be administered to keep SpO2 above baseline or 96% (whichever is higher) 6, 4, 5
• Oxygen administration should be reserved for hypoxic patients, not given routinely 7
• Continuous oxygen monitoring is required until saturation is maintained at baseline in room air 6, 5

Temperature Management

• Patients must be kept normothermic as hypothermia leads to shivering and peripheral stasis, which increases sickling 6, 5
• Active warming measures should be employed if needed 5
• A temperature spike ≥38.0°C may be an early sign of sickling or infection and requires blood cultures and prompt antibiotic initiation 4, 8

Infection Prevention and Management

• Vigorous antibiotic therapy is essential as infections are the leading cause of morbidity and mortality in sickle cell disease 7
• Antibiotic prophylaxis should be administered according to protocols, as patients with SCD are more susceptible to infections 5
• Blood cultures must be obtained and antibiotics initiated promptly if fever develops or signs of sepsis appear 4, 8

Complication-Specific Management

Acute Chest Syndrome

• Early mobilization, physiotherapy, and incentive spirometry every 2 hours (or blowing bubbles for young children) should be promoted after moderate or major surgery 6
• Bronchodilator therapy should be considered for patients with history of small airways obstruction, asthma, or acute chest syndrome 6
• Continuous positive airway pressure, high-flow nasal oxygen therapy, or nasopharyngeal prong airway may be useful 6

Priapism

• Immediate notification of the hematology team is required when priapism occurs, as this represents an emergency 5
• Men receiving regional anesthesia require regular examination as they may not notice priapism due to altered sensation 5
• There should be a low threshold for admission to high-dependency or intensive care units for prolonged or recurrent priapism 5

Abdominal Pain

• Abdominal pain requires careful evaluation to distinguish vaso-occlusive crisis from surgical emergencies, acute chest syndrome, or splenic/hepatic sequestration, which may require different management approaches 4

Dysmenorrhea

• Painful events appear more common around menstruation; education about distinguishing dysmenorrhea from generalized sickle cell pain is essential 8
• Initiate ibuprofen 400 mg every 4 hours starting at earliest onset of menstrual pain 8
• If inadequately controlled with ibuprofen alone, add PCA for moderate to severe pain if vaso-occlusive crisis develops 8

Thromboprophylaxis

• All post-pubertal patients should receive thromboprophylaxis as they have increased risk of deep vein thrombosis, with additional precautions for patients with risk factors such as immobility 5
• Early mobilization should be encouraged when appropriate to prevent thrombotic complications 5

Transfusion Therapy

• Blood transfusion should be given only when really indicated, not routinely 7
• Transfusions are used to improve oxygen delivery in specific circumstances 2

Multidisciplinary Care Coordination

• Hematology consultation is essential for all pediatric sickle cell patients presenting with acute pain crisis, as multidisciplinary care improves outcomes 4
• The pain team should be notified in advance for patients undergoing major surgery, particularly with history of opioid tolerance 6
• Consider admission to high-dependency or intensive care if pain is refractory to treatment, if complications develop, or if signs of acute chest syndrome, stroke, or sepsis appear 4

Additional Therapeutic Modalities

• Cognitive therapies, local pain control, muscle relaxants, and nonpharmacologic approaches serve as adjuncts to pharmacologic management 9, 3
• Healthy lifestyle habits and good behavioral and mental health are important for preventing and coping with sickle cell disease pain 3