What is the management plan for sickle cell disease?

Management of Sickle Cell Disease

Sickle cell disease requires a comprehensive management strategy centered on disease-modifying therapy with hydroxyurea as first-line treatment, aggressive prevention of complications through prophylactic measures, and meticulous management of acute crises with rapid pain control, hydration, and oxygenation. 1, 2

Disease-Modifying Therapy

Hydroxyurea - First-Line Treatment

• Hydroxyurea is 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 or recurrent acute chest syndrome. 2
• Offer hydroxyurea to infants, children, and adolescents without regard to symptom presence (moderate strength recommendation). 2
• Hydroxyurea increases fetal hemoglobin production and reduces red blood cell sickling, remaining the cornerstone of disease-modifying therapy. 3, 4

Additional Disease-Modifying Agents

• L-glutamine reduces hospitalization rates by 33% and mean length of stay from 11 to 7 days compared with placebo, and is FDA-approved for patients 5 years or older. 3, 5
• Crizanlizumab reduces pain crises from 2.98 to 1.63 per year compared with placebo, serving as an adjunctive or second-line agent. 3
• Voxelotor increases hemoglobin by at least 1 g/dL in 51% of patients versus 7% with placebo. 3

Curative Therapy

• Hematopoietic stem cell transplant is the only curative therapy, with best results in children with a matched sibling donor, though limited by donor availability. 3, 5

Preventive Care and Screening

Infection Prevention

• Daily oral prophylactic penicillin is strongly recommended up to age 5 years to prevent septicemia and meningitis from encapsulated bacteria, particularly Streptococcus pneumoniae. 2, 6
• Administer antibiotic prophylaxis according to surgical protocols and maintain high suspicion for infection. 1
• Any fever ≥38.0°C (100.4°F) requires immediate blood cultures and prompt empiric broad-spectrum antibiotics (ceftriaxone preferred) before culture results return. 6

Stroke Prevention

• Annual transcranial Doppler examinations are strongly recommended from ages 2 to 16 years in those with sickle cell anemia. 2
• Children under 17 years should have transcranial Doppler results available from within the previous 12 months before elective procedures. 1
• Long-term transfusion therapy is strongly recommended to prevent stroke in children with abnormal transcranial Doppler velocity (≥200 cm/s). 2

Transfusion Management

• Preoperative transfusion to increase hemoglobin to 10 g/dL is strongly recommended, with sickle hemoglobin maintained below 30% during long-term therapy. 2
• Assess iron overload regularly and begin iron chelation therapy when indicated. 2
• Avoid unnecessary transfusion to reduce allo-immunization risk. 7

Management of Acute Vaso-Occlusive Crisis

Pain Management

• Rapid initiation of opioids is strongly recommended for severe pain, using scheduled around-the-clock dosing or patient-controlled analgesia (PCA) rather than "as needed" dosing. 1, 2
• Document baseline analgesic use and continue long-acting opioids if already prescribed for chronic pain. 1
• Reassess pain regularly using validated pain scales. 1
• Notify the acute pain team in advance for patients with chronic pain history undergoing major surgery. 7, 8

Hydration

• Aggressive hydration is crucial—oral hydration is preferred when possible, but administer intravenous fluids if oral intake is inadequate. 1
• Maintain meticulous fluid management with accurate measurement and replacement of losses, carefully monitoring fluid balance to prevent overhydration. 1

Oxygenation

• Document baseline oxygen saturation and administer oxygen therapy to keep SpO2 above baseline or 96% (whichever is higher). 1, 8
• Continue oxygen monitoring until saturation is maintained at baseline in room air. 1, 8
• Pre-oxygenate before any procedures requiring sedation or general anesthesia. 1, 8
• Avoiding hypoxia is crucial as it precipitates sickling. 1

Temperature Management

• Keep patients normothermic as hypothermia leads to shivering and peripheral stasis, increasing sickling. 1, 8
• Use active warming measures including increased ambient temperature, warmed fluids, and avoiding unnecessary exposure. 8
• Monitor temperature regularly as fever may indicate early sickling or infection. 1, 8

Respiratory Care

• Use incentive spirometry every 2 hours after moderate or major crises (strong recommendation). 1, 2
• Encourage early mobilization and chest physiotherapy. 1, 8
• Consider bronchodilator therapy for patients with history of small airways obstruction, asthma, or acute chest syndrome. 1, 8

Thromboprophylaxis

• All post-pubertal patients should receive thromboprophylaxis due to increased deep vein thrombosis risk. 1, 8

Management of Chronic Complications

Avascular Necrosis

• Use analgesics and physical therapy for treatment (strong recommendation). 2

Nephropathy

• Use angiotensin-converting enzyme inhibitor therapy for microalbuminuria in adults (strong recommendation). 2

Retinopathy

• Refer children and adults with proliferative sickle cell retinopathy to expert specialists for consideration of laser photocoagulation. 2

Pulmonary Hypertension

• Perform echocardiography to evaluate signs of pulmonary hypertension and refer to specialists. 2

Peri-Operative Management

Pre-Operative Planning

• Screen all at-risk patients for hemoglobinopathy before surgery, avoiding unnecessary repeat screening. 7, 8
• Review patients in pre-assessment clinic with input from a nominated lead hematologist who determines the transfusion plan. 7, 8
• Schedule patients early on the operating list to avoid prolonged starvation and prevent last-minute cancellations, particularly if transfusion was given. 7, 8
• Avoid routine surgery if the patient is febrile or having a painful crisis. 7, 1

Intra-Operative Care

• Maintain meticulous care to avoid factors precipitating sickling: dehydration, hypoxia, acidosis, hypothermia, and pain. 7
• Pre-oxygenate before induction, avoid hypotension, use controlled ventilation for good oxygenation and normocarbia. 8
• Maintain normothermia through active warming measures. 8

Post-Operative Care

• Most complications occur postoperatively—maintain a low threshold for admission to high dependency or intensive care. 7, 1, 8
• Continue oxygen therapy for 24 hours or until patient can mobilize freely. 8
• Daily assessment by hematologist after moderate or major surgery. 8
• Maintain high index of suspicion for sickle complications (acute chest syndrome, pain, acute renal insufficiency, stroke), sepsis, and venous thromboembolism. 7

Life-Threatening Complications Requiring Urgent Evaluation

Acute Chest Syndrome

• Occurs in >50% of hospitalized patients with vaso-occlusive crisis, defined by new respiratory symptoms plus new pulmonary infiltrates on chest X-ray. 1
• Can develop rapidly and may require intensive care management with exchange transfusion. 1, 8

Stroke

• Any acute neurologic symptom other than transient mild headache requires urgent evaluation, including hemiparesis, aphasia, seizures, severe headache, cranial nerve palsy, stupor, or coma. 1
• Occurs in up to 10% of children with sickle cell disease. 1

Splenic Sequestration

• Characterized by rapidly enlarging spleen with hemoglobin decrease >2 g/dL below baseline, with potential rapid progression to shock and death. 1
• Requires careful transfusion to avoid acute overtransfusion. 1

Sepsis

• Patients with hyposplenism are particularly vulnerable to gram-negative sepsis including urinary tract infection, biliary sepsis, and non-typhi salmonella infection. 1
• Start antibiotics promptly if temperature reaches ≥38.0°C or signs of sepsis present. 1, 6

Multidisciplinary Care Structure

• Establish local departmental guidance for peri-operative management developed in partnership with hematology. 7
• Designate a nominated lead haematologist (or paediatrician/paediatric haematologist for children) for surgical cases. 7
• Ensure clear communication of sickle cell diagnosis at all stages of the patient pathway across all teams: haematology, anaesthesia, transfusion laboratory, waiting list coordinators, pre-assessment, and ward nursing staff. 7
• Work in partnership with patients and families, keeping them informed of clinical decisions at all times. 7, 1
• Planned surgery should ideally occur at centers with experience in sickle cell care and exchange transfusion capability. 7, 1