Sickle cell disease

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 (HbS polymerisation inhibitor)^[1]	Hemoglobin oxygen-affinity modulator	1500 mg PO daily	≥4 years per local label	Improves haemoglobin and reduces transfusion need; available access varies; does not replace hydroxyurea
Crizanlizumab (P-selectin inhibitor)^[1]	Anti-P-selectin monoclonal antibody	5 mg/kg IV at 0, 2 weeks then every 4 weeks	≥16 years	Reduces vaso-occlusive crises in those with frequent crises; access and cost considerations; recent regulatory review (post-marketing data)
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 (HbS polymerisation inhibitor)^[1]

Hemoglobin oxygen-affinity modulator

Adult: 1500 mg PO daily
Paediatric: ≥4 years per local label

Improves haemoglobin and reduces transfusion need; available access varies; does not replace hydroxyurea

Crizanlizumab (P-selectin inhibitor)^[1]

Anti-P-selectin monoclonal antibody

Adult: 5 mg/kg IV at 0, 2 weeks then every 4 weeks
Paediatric: ≥16 years

Reduces vaso-occlusive crises in those with frequent crises; access and cost considerations; recent regulatory review (post-marketing data)

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)