What are the treatment options for a patient with sickle cell anemia?

Treatment Options for Sickle Cell Disease

Hydroxyurea remains the first-line disease-modifying therapy for most patients with sickle cell disease, with strong recommendations for use in adults experiencing 3 or more severe vaso-occlusive crises annually and moderate strength recommendations for offering it to all infants, children, and adolescents regardless of symptom severity. 1

Disease-Modifying Therapies

Hydroxyurea (First-Line)

• Strongly recommended for adults with 3 or more severe vaso-occlusive crises during any 12-month period, with pain or chronic anemia interfering with daily activities, or with severe/recurrent acute chest syndrome 1
• Moderately recommended for all pediatric patients (infants, children, and adolescents) without regard to symptom presence 1
• Mechanism: Increases fetal hemoglobin levels and reduces red blood cell sickling 2
• Remains the standard first-line therapy despite newer agents being available 2

L-Glutamine (Adjunctive/Second-Line)

• FDA-approved for patients 5 years and older to reduce acute complications of sickle cell disease 3
• Dosing based on body weight: 5g twice daily (<30kg), 10g twice daily (30-65kg), 15g twice daily (>65kg) 3
• Clinical trial data showed reduction in median sickle cell crises from 4 to 3 per year, reduced hospitalizations, and 25% reduction in average cumulative crisis count over 48 weeks 3
• Reduced hospitalization rates by 33% and mean length of stay from 11 to 7 days compared with placebo 2
• Can be used in combination with hydroxyurea 3

Crizanlizumab (Adjunctive/Second-Line)

• Reduced pain crises from 2.98 to 1.63 per year compared with placebo 2
• Approved as adjunctive therapy since 2017 2

Voxelotor (Adjunctive/Second-Line)

• Increased hemoglobin by at least 1 g/dL in 51% of patients versus 7% with placebo 2
• Approved as second-line agent since 2017 2

Preventive Care Strategies

Infection Prevention

• Daily oral prophylactic penicillin strongly recommended up to age 5 years due to functional hyposplenism and risk of overwhelming sepsis from encapsulated organisms 1, 4
• Additional pneumococcal and meningococcal vaccines beyond standard schedule 4
• Immediate empiric broad-spectrum antibiotics if temperature ≥38.0°C without waiting for culture results, as fatal sepsis can develop within hours 5, 4

Stroke Prevention

• Annual transcranial Doppler examinations strongly recommended from ages 2 to 16 years in children with sickle cell anemia 1
• Long-term transfusion therapy strongly recommended for children with abnormal transcranial Doppler velocity (≥200 cm/s) to prevent stroke 1
• All children and young people aged <17 years should undergo regular transcranial Doppler screening, with results available before elective surgery 4

Management of Acute Complications

Vaso-Occlusive Crisis

• Rapid initiation of opioids strongly recommended for severe pain, with patient-controlled analgesia (PCA) showing superior outcomes and lower overall morphine consumption compared to continuous infusion 5, 1
• Continue baseline long-acting opioids if already prescribed for chronic pain management 5
• Add NSAIDs or acetaminophen as adjunctive therapy, not monotherapy 5
• Use 5% dextrose solution or 5% dextrose in 25% normal saline for hydration, not normal saline alone, because patients have hyposthenuria with reduced sodium excretion capacity 5, 6
• Maintain SpO2 above baseline or 96% (whichever is higher) with oxygen therapy 5, 4
• Incentive spirometry strongly recommended for patients hospitalized with vaso-occlusive crisis 1

Acute Chest Syndrome

• Life-threatening complication requiring urgent evaluation with chest radiograph 5, 4
• Early mobilization, chest physiotherapy, and incentive spirometry every 2 hours (or blowing bubbles for young children) 4
• Consider bronchodilator therapy for patients with history of small airways obstruction, asthma, or previous acute chest syndrome 4
• May require exchange transfusion in severe cases 7

Stroke

• Any acute neurologic symptom other than transient mild headache requires urgent evaluation 4
• Initial evaluation includes CBC, reticulocyte count, blood type and crossmatch, and noncontrast CT or MRI to exclude hemorrhage 4
• Acute treatment may include partial exchange transfusion or erythrocytapheresis to reduce HbS to <30% and raise hemoglobin to 10 g/dL 4

Priapism

• Treated as painful event with hydration and analgesia at home if <4 hours duration 4
• Urgent medical attention required if lasting ≥4 hours when irreversible tissue damage may occur 4
• Exchange blood transfusion may be used for severe cases 7

Transfusion Therapy

Indications for Acute Transfusion

• Limited indications: acute hemolytic crisis, aplastic crisis, or sequestration crisis 7
• Transient aplastic crisis (typically parvovirus B19-related) with substantially decreased reticulocyte count to <1% 4
• Acute splenic sequestration crisis with massive splenomegaly, acute anemia (Hb drop 10-30 g/L), and hypovolemic shock 4
• Not indicated for routine painful vaso-occlusive crises treated with hydration and analgesia 7

Chronic Transfusion Protocols

• Implemented for stroke prevention or high cerebral blood flow on ultrasound studies 7
• Moderate strength recommendation to maintain sickle hemoglobin levels <30% prior to next transfusion during long-term therapy 1

Perioperative Transfusion

• Preoperative transfusion strongly recommended to increase hemoglobin to 10 g/dL before surgery 1
• Transfused blood should be HbS negative, Rh and Kell antigen matched 7
• Strong recommendation to assess iron overload with moderate strength recommendation to begin chelation therapy when indicated 1

Chronic Complication Management

Avascular Necrosis

• Analgesics and physical therapy strongly recommended for treatment 1
• Common in hips and shoulders 4

Nephropathy

• Angiotensin-converting enzyme inhibitor therapy strongly recommended for microalbuminuria in adults 1
• All patients develop hyposthenuria (inability to concentrate urine) 4

Retinopathy

• Referral to expert specialists strongly recommended for proliferative sickle cell retinopathy for consideration of laser photocoagulation 1
• Especially common in HbSC disease 4

Pulmonary Hypertension

• Echocardiography strongly recommended to evaluate signs of pulmonary hypertension 1
• More frequent in adults but may present during childhood 4

Curative Therapy

Hematopoietic Stem Cell Transplant

• Only curative therapy available but limited by donor availability 2
• Best results seen in children with matched sibling donor 2
• Now considered standard care for severe disease with appropriate donor 2

Critical Care Considerations

Multidisciplinary Management

• Patients should be managed in clinical networks with annual specialist review 4
• Nominated lead haematologist (or paediatrician for children) required when undergoing surgery 4
• Daily assessment by haematologist after moderate or major surgery 4

Common Pitfalls to Avoid

• Never delay antibiotics while waiting for culture results in febrile patients—functional hyposplenism creates risk of overwhelming sepsis within hours 5
• Avoid normal saline alone for hydration; use dextrose-containing solutions due to impaired sodium excretion 5, 6
• Do not give iron supplementation unless iron deficiency is biochemically proven, due to risk of lifetime iron overload from repeated transfusions 4
• Avoid hypothermia perioperatively as this leads to shivering, peripheral stasis, and increased sickling 4
• Maintain normothermia actively using warming measures in all clinical settings 5

Thromboprophylaxis

• Strongly recommended for all peri- and post-pubertal patients due to increased deep vein thrombosis risk 4
• Early mobilization should be encouraged 4