What is the management of sickle cell disease?

Management of Sickle Cell Disease

Hydroxyurea is the first-line disease-modifying therapy for sickle cell disease (SCD) and should be offered to all eligible patients to reduce pain crises, hospitalizations, and acute complications. 1, 2

Disease Overview

Sickle cell disease is a hereditary blood disorder characterized by:

• Production of abnormal hemoglobin S causing red blood cells to become sickle-shaped
• Vaso-occlusive crises leading to tissue ischemia and pain
• Chronic hemolytic anemia
• Progressive multiorgan damage
• Increased mortality (life expectancy approximately 20 years less than general population) 1

Comprehensive Management Approach

Disease-Modifying Therapies

1. Hydroxyurea (Hydroxycarbamide)

   • Mechanism: Increases fetal hemoglobin production, reduces red cell sickling 3, 1
   • Benefits: Reduces frequency of pain crises, hospitalizations, acute chest syndrome, and blood transfusion requirements 4, 2
   • Dosing: Requires adjustment in renal impairment (reduce dose when creatinine clearance <60 mL/min) 3
   • Monitoring: Regular blood counts to assess response and toxicity

2. Other FDA-approved therapies (as adjunctive or second-line agents) 1:

   • L-glutamine: Reduces hospitalization rates and length of stay
   • Crizanlizumab: Reduces pain crisis frequency
   • Voxelotor: Increases hemoglobin levels

3. Curative therapy:

   • Hematopoietic stem cell transplantation - most effective with matched sibling donors, primarily offered to children with severe disease 1

Management of Acute Complications

1. Pain Crisis Management:

   • Prompt analgesia following a tiered approach 5, 6:
     • Mild pain: Acetaminophen, NSAIDs
     • Moderate-severe pain: Opioids (morphine 5-10 mg IV/SC or oxycodone 5-15 mg oral)
   • Adequate hydration with 5% dextrose or 5% dextrose in 0.25% normal saline (avoid normal saline due to hyposthenuria) 7
   • Avoid factors that precipitate sickling: dehydration, hypoxia, acidosis, hypothermia 5

2. Acute Chest Syndrome:

   • Oxygen therapy for hypoxemia
   • Broad-spectrum antibiotics
   • Consider blood transfusion
   • Low threshold for admission to intensive care 5

3. Stroke Management:

   • Immediate medical attention
   • Exchange transfusion to reduce HbS percentage
   • Secondary prevention with chronic transfusion program or hydroxyurea 2

4. Infection Management:

   • Prompt and aggressive antibiotic therapy (patients are at increased risk of sepsis) 5, 7
   • Low threshold for hospital admission

Perioperative Management

1. Preoperative Assessment:

   • Review by anesthesia and hematology teams 5
   • Consider preoperative transfusion based on surgical risk and patient's baseline
   • Schedule early on operating list to avoid prolonged fasting 5

2. Intraoperative Care:

   • Maintain normothermia, adequate hydration, oxygenation
   • Avoid acidosis and hypotension 5

3. Postoperative Care:

   • Aggressive pain management
   • Early mobilization
   • Deep vein thrombosis prophylaxis
   • Low threshold for high dependency or intensive care admission 5

Preventive Care

1. Infection Prevention:

   • Vaccination (including pneumococcal, meningococcal, Haemophilus influenzae type b)
   • Penicillin prophylaxis in children

2. Stroke Prevention:

   • Regular transcranial Doppler screening in children
   • Chronic transfusion or hydroxyurea for those at high risk 2

3. Patient Education:

   • Recognition of fever, respiratory symptoms, worsening pain as emergencies
   • Importance of hydration and avoiding temperature extremes
   • Medication adherence, especially with hydroxyurea 6

Common Pitfalls and Caveats

1. Underutilization of hydroxyurea: Many patients are never offered this therapy despite proven benefits. The most common reason for not using hydroxyurea is that it was never offered to patients (40.9%) 4

2. Pain management misconceptions: SCD patients are not more likely to develop addiction to pain medications than the general population despite requiring frequent opioid analgesia 1

3. Transfusion overuse: Blood transfusions should be used judiciously to avoid alloimmunization 5

4. Delayed recognition of acute chest syndrome: This life-threatening complication requires prompt intervention and has high postoperative risk 5

5. Inadequate perioperative planning: Last-minute cancellations should be avoided, particularly if the patient has received blood transfusion in preparation for surgery 5

By implementing this comprehensive approach to SCD management, clinicians can help reduce complications, improve quality of life, and potentially extend survival for patients with this challenging condition.