What is the recommended treatment plan for a patient with sickle cell anaemia?

Treatment of Sickle Cell Anaemia

Hydroxyurea is the primary disease-modifying therapy and should be offered to all patients with HbSS or HbSβ0-thalassemia genotypes starting as early as 9 months of age. 1

First-Line Disease-Modifying Therapy

Hydroxyurea

• Hydroxyurea remains the cornerstone of treatment for sickle cell disease, working by increasing fetal hemoglobin levels and reducing red blood cell sickling through inhibition of ribonucleotide reductase. 2, 3
• Start hydroxyurea in infants at 9 months of age with HbSS or HbSβ0-thalassemia, regardless of symptom severity. 1
• For adults, hydroxyurea is strongly indicated when patients experience 3 or more severe vaso-occlusive crises in any 12-month period, when pain or chronic anemia interferes with daily activities, or with severe/recurrent acute chest syndrome. 4
• Monitor complete blood count every 1-3 months during treatment. 1
• In patients with renal impairment (creatinine clearance <60 mL/min), reduce the hydroxyurea dose by 50%. 2

Common pitfall: Many patients remain undertreated with hydroxyurea despite strong evidence for its benefit. The 2014 expert panel emphasized that both hydroxyurea and transfusion therapy are underutilized despite being strongly recommended. 4

Additional Disease-Modifying Therapies

L-Glutamine (Endari)

• Approved for patients 5 years and older to reduce pain events by decreasing oxidative stress in red blood cells. 1
• In clinical trials, L-glutamine reduced hospitalization rates by 33% and mean length of stay from 11 to 7 days compared with placebo. 3

Chronic Transfusion Therapy

• Strongly recommended for primary stroke prevention in children with abnormal transcranial Doppler velocity (≥200 cm/s). 4
• Indicated for secondary stroke prevention and recurrent acute chest syndrome unresponsive to hydroxyurea. 1, 5
• Either red cell exchange with isovolemic hemodilution or conventional red cell exchange may be used for chronic transfusion programs. 5
• Target hemoglobin levels around 100 g/L (10 g/dL) to avoid hyperviscosity, with HbS percentage maintained <30%. 6, 5

Blood Product Matching Requirements

• All transfusions must be HbS-negative and matched for Rh (C, E or C/c, E/e) and K antigens (strong recommendation). 5
• Extended matching for Jka/Jkb, Fya/Fyb, and S/s provides additional protection from alloimmunization. 5
• Obtain extended red cell antigen profile by genotype (preferred) or serology before the first transfusion whenever possible. 5
• Use blood <10 days old for simple transfusion and <8 days old for exchange transfusion. 6

Management of Specific Complications

Acute Vaso-Occlusive Crisis

• Rapid initiation of opioids for severe pain (strong recommendation). 4
• Use incentive spirometry in hospitalized patients to prevent acute chest syndrome. 4
• Blood transfusion is NOT indicated for uncomplicated pain crises—these are managed with hydration and analgesia. 7

Acute Chest Syndrome

• Automated or manual red cell exchange is preferred over simple transfusion for severe acute chest syndrome. 5
• Target HbS reduction to <30% (ideally <20%). 5
• Automated red cell exchange is preferred over manual exchange as it more rapidly reduces HbS levels. 5

Stroke Prevention

• Annual transcranial Doppler examinations from ages 2 to 16 years in children with sickle cell anemia (strong recommendation). 4
• Long-term transfusion therapy to prevent stroke in children with abnormal transcranial Doppler velocity ≥200 cm/s (strong recommendation). 4

Chronic Kidney Disease

• Combination therapy with hydroxyurea and erythropoiesis-stimulating agents is recommended for patients with worsening anemia associated with chronic kidney disease. 6, 1
• Target hemoglobin should not exceed 10 g/dL (hematocrit 30%) when using erythropoiesis-stimulating agents to reduce risk of vaso-occlusive complications, stroke, and venous thromboembolism. 6, 1
• Blood pressure goal of ≤130/80 mmHg for adults with sickle cell disease (strong recommendation). 6, 1

Pulmonary Hypertension

• Hydroxyurea is strongly recommended for patients with confirmed pulmonary hypertension. 1
• Consult with cardiologist, pulmonologist, or pulmonary hypertension expert when interpreting right-heart catheterization results. 6

Perioperative Management

• Preoperative transfusion is recommended for surgeries requiring general anesthesia lasting more than 1 hour. 5
• Target total hemoglobin >9 g/dL (or around 10 g/dL) before surgery. 6, 5
• For high-risk surgery or patients with significant comorbidity, exchange transfusion should be considered to reduce HbS% to <30%. 6
• For emergency surgery with hemoglobin ≥90 g/L and low surgical risk, proceed without delay and transfuse intra- or postoperatively if necessary. 6

Delayed Hemolytic Transfusion Reaction

• For patients with delayed hemolytic transfusion reaction and ongoing hyperhemolysis, immunosuppressive therapy is recommended over no treatment. 5
• Options include IVIg (0.4-1 g/kg/day for 3-5 days), high-dose steroids (methylprednisolone or prednisone 1-4 mg/kg/day), or rituximab (375 mg/m² repeated after 2 weeks). 5
• Avoid further transfusion unless life-threatening anemia with ongoing hemolysis is present, as additional transfusions may worsen hemolysis and potentially induce multiorgan failure and death. 5

Preventive Care

Infection Prevention

• Daily oral prophylactic penicillin V potassium starting at 2 months of age for all infants with HbSS and Sβ0-thalassemia, continuing up to age 5 years (strong recommendation). 1, 4

Iron Overload Monitoring

• Screen for iron overload by MRI for liver iron content rather than serial ferritin monitoring alone in patients receiving chronic transfusion therapy. 5
• Use validated R2, T2*, or R2* methods consistently over time. 5
• If ferritin <1000 ng/mL and patient receives chronic transfusion by red cell exchange with neutral or negative iron balance, MRI is likely not needed. 5

Curative Therapy

Hematopoietic Stem Cell Transplantation

• The only curative therapy currently available, but limited by donor availability. 3, 8
• Best results seen in children with matched sibling donors. 3
• Consider for severe disease, though less toxic conditioning regimens and alternative donor options are being evaluated to expand eligibility. 8

Important consideration: While sickle cell disease is characterized by acute and chronic pain, patients are not more likely to develop addiction to pain medications than the general population—this misconception should not limit appropriate pain management. 3