Red Flags
- Acute chest syndrome (chest pain + new infiltrate + hypoxia or fever) — admit; oxygen, antibiotics, transfusion (simple or exchange), bronchodilators[1]
- Acute ischaemic stroke or TIA — emergency exchange transfusion to HbS <30%; CT/MRI; secondary prevention with chronic transfusion[1]
- Splenic sequestration (rapid splenomegaly + falling Hb) — emergency transfusion; consider splenectomy after recovery in recurrent cases[1]
- Aplastic crisis (acute Hb fall with reticulocytopenia) — investigate parvovirus B19; transfusion until reticulocyte recovery[1]
First-line treatment
Interventions
- Hydroxyurea for all eligible HbSS / HbS-β0[1]Children ≥9 months and all adults with HbSS or HbS-β0 thalassemia regardless of severity; titrate from 15–20 mg/kg/day to 35 mg/kg/day or maximum tolerated dose; counsel about teratogenicity and contraception
- Universal infection prevention[1]Penicillin V prophylaxis (children ≤5 years); meningococcal, pneumococcal, Hib vaccination; influenza annually; HBV; aggressive antibiotic for febrile illness — empirical cover of pneumococcus
- Pain crisis management[1]Aggressive multimodal analgesia including IV opioid early; do not under-treat; warmth, hydration, oxygen if hypoxaemic; outpatient pathways for selected; check for triggers
- Stroke primary prevention with chronic transfusion or hydroxyurea[1]Children with abnormal TCD: chronic transfusion to keep HbS <30% (STOP); transition to hydroxyurea after 1+ year of normalised TCD per TWiTCH; magnetic resonance angiography for vasculopathy assessment
- Curative therapies[1]Allogeneic haematopoietic stem cell transplant for severe disease and matched sibling donor; gene therapy (lovotibeglogene autotemcel, exagamglogene autotemcel/Casgevy) for selected severe disease
First-line drug therapy
| Drug | Class | Adult | Paediatric | Notes |
|---|---|---|---|---|
| Hydroxyurea (hydroxycarbamide)[1] | Ribonucleotide reductase inhibitor / fetal Hb inducer | Start 15–20 mg/kg/day PO; titrate every 8 weeks to 35 mg/kg/day or to MTD by FBC; monitor for cytopenia | Children ≥9 months: same weight-based dosing | Disease-modifying — reduces vaso-occlusive crises, ACS, transfusion need, and mortality; teratogenicity — strict contraception; reversible cytopenia and hyperpigmentation |
| Penicillin V prophylaxis (children)[1] | Beta-lactam antibiotic | Not applicable | <2 years: 125 mg PO BD; 2–5 years: 250 mg PO BD; longer if asplenia | Universal in HbSS children ≤5 years; reduces pneumococcal sepsis mortality; alternative azithromycin in penicillin allergy; pair with vaccinations |
| Voxelotor — FDA withdrawal safety alert | Hemoglobin oxygen-affinity modulator | FDA advises health care professionals to stop prescribing voxelotor. Do not use historical dose schedules as current treatment. [2] | FDA’s withdrawal alert applies to the medicine, including its former paediatric uses. Arrange clinician-directed alternative treatment. [2] | FDA advised clinicians to stop prescribing Oxbryta (voxelotor) on 26 September 2024 after safety findings and manufacturer withdrawal. Patients should contact their treating clinician about stopping and selecting another treatment. Do not use the former dosing regimens as current treatment. [2] |
| Crizanlizumab (P-selectin inhibitor) | Anti-P-selectin monoclonal antibody | 5 mg/kg IV at 0, 2 weeks then every 4 weeks | ≥16 years | The European Union revoked crizanlizumab authorization in 2023 after the STAND study did not confirm clinical benefit. Its efficacy and availability must not be presented without this qualification. This EU decision does not establish current authorization in other jurisdictions; review the relevant regulator and current label before any use. [3] |
| L-glutamine[1] | Conditional amino acid | 5–15 g PO BD by weight | ≥5 years | Adjunctive reduction in pain crises and ACS; modest effect; combine with hydroxyurea |
Hydroxyurea (hydroxycarbamide)[1]
Ribonucleotide reductase inhibitor / fetal Hb inducer
- Adult
- Start 15–20 mg/kg/day PO; titrate every 8 weeks to 35 mg/kg/day or to MTD by FBC; monitor for cytopenia
- Paediatric
- Children ≥9 months: same weight-based dosing
Disease-modifying — reduces vaso-occlusive crises, ACS, transfusion need, and mortality; teratogenicity — strict contraception; reversible cytopenia and hyperpigmentation
Penicillin V prophylaxis (children)[1]
Beta-lactam antibiotic
- Adult
- Not applicable
- Paediatric
- <2 years: 125 mg PO BD; 2–5 years: 250 mg PO BD; longer if asplenia
Universal in HbSS children ≤5 years; reduces pneumococcal sepsis mortality; alternative azithromycin in penicillin allergy; pair with vaccinations
Voxelotor — FDA withdrawal safety alert
Hemoglobin oxygen-affinity modulator
- Adult
- FDA advises health care professionals to stop prescribing voxelotor. Do not use historical dose schedules as current treatment. [2]
- Paediatric
- FDA’s withdrawal alert applies to the medicine, including its former paediatric uses. Arrange clinician-directed alternative treatment. [2]
FDA advised clinicians to stop prescribing Oxbryta (voxelotor) on 26 September 2024 after safety findings and manufacturer withdrawal. Patients should contact their treating clinician about stopping and selecting another treatment. Do not use the former dosing regimens as current treatment. [2]
Crizanlizumab (P-selectin inhibitor)
Anti-P-selectin monoclonal antibody
- Adult
- 5 mg/kg IV at 0, 2 weeks then every 4 weeks
- Paediatric
- ≥16 years
The European Union revoked crizanlizumab authorization in 2023 after the STAND study did not confirm clinical benefit. Its efficacy and availability must not be presented without this qualification. This EU decision does not establish current authorization in other jurisdictions; review the relevant regulator and current label before any use. [3]
L-glutamine[1]
Conditional amino acid
- Adult
- 5–15 g PO BD by weight
- Paediatric
- ≥5 years
Adjunctive reduction in pain crises and ACS; modest effect; combine with hydroxyurea
Safety-net
- Take hydroxyurea every day — even when feeling well — and attend FBC monitoring; missed doses reduce protection[1]
- Fever ≥38.5°C — same-day medical review with empirical antibiotic; sepsis risk is elevated in functional asplenia[1]
- Stay well hydrated, avoid dehydration, extreme cold, alcohol, and high altitude — all can trigger crises; carry medical alert documentation[1]
Referral criteria
- Acute chest syndrome, ischaemic stroke, splenic sequestration, aplastic crisisEmergency department; haematology and transfusion service[1]
- All confirmed SCDHaematology service for hydroxyurea initiation, surveillance, immunisation[1]
- Severe disease eligible for transplant or gene therapyTertiary haematology / BMT centre[1]
- Pregnancy with SCDJoint haematology and obstetric clinic; high-risk pregnancy pathway[1]
Clinical summary
Diagnosis, disease-modifying therapy, complication-specific management, and transfusion support for adults and children with sickle cell disease.
References
- 1.ASH 2020 Guidelines for Sickle Cell Disease — Cardiopulmonary, Stroke, Pain, Transfusion (multiple modules); ICMR/MoHFW National Sickle Cell Anaemia Elimination Mission (2020)
- 2.FDA Oxbryta (voxelotor) withdrawal safety alert, 26 September 2024. Official regulatory safety communication (2024)
- 3.EMA: Revocation of authorisation for Adakveo (crizanlizumab), 3 August 2023. Official regulatory safety communication (2023)