About This Page
This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
The Bottom Line
- Autosomal recessive: point mutation in beta-globin gene producing HbS. Homozygous HbSS = sickle cell anaemia (most severe); HbSC and HbS/beta-thal are milder variants
- Detected by UK newborn screening programme (heel-prick test). Haemoglobin electrophoresis is the confirmatory diagnostic test
- Acute painful (vaso-occlusive) crisis: medical emergency — aggressive analgesia within 30 minutes (NICE CG143), IV fluids, oxygen if hypoxic, avoid pethidine
- Acute chest syndrome: fever + new chest X-ray infiltrate + respiratory symptoms — most common cause of death. Treat with antibiotics, oxygen, transfusion, and consider exchange transfusion
- Long-term management: hydroxycarbamide (raises HbF, reduces crises), folic acid 5 mg daily, penicillin V prophylaxis, pneumococcal and influenza vaccination
Overview
Sickle cell disease (SCD) is an autosomal recessive haemoglobinopathy caused by a single amino acid substitution (glutamic acid → valine) at position 6 of the beta-globin chain, producing haemoglobin S (HbS). Under conditions of hypoxia, dehydration, acidosis, cold, or infection, HbS polymerises and causes red blood cells to adopt a rigid sickle shape. Sickled cells are fragile (chronic haemolysis) and obstruct small blood vessels (vaso-occlusion), causing tissue ischaemia and organ damage. The disease is lifelong with multi-system complications affecting virtually every organ.
Epidemiology
SCD predominantly affects people of African, African-Caribbean, Middle Eastern, and South Asian ancestry. There are an estimated 15,000 people with SCD in the UK, with approximately two-thirds living in London. It is the most common genetic condition detected by the UK newborn screening programme. Sickle cell trait (HbAS carriers) affects ~10% of Black African/Caribbean populations and confers partial protection against falciparum malaria, explaining its geographic prevalence. The median life expectancy in the UK has improved to approximately 60 years with modern care.
Clinical Features
Symptoms
Painful vaso-occlusive crises — severe bone pain (long bones, spine, pelvis), often triggered by cold, dehydration, infection
Chronic fatigue from baseline haemolytic anaemia (Hb typically 60–90 g/L)
Priapism — sustained painful erection; urological emergency
Chest pain, cough, fever, and hypoxia (acute chest syndrome)
Sudden severe headache or focal neurology (stroke — affects 10% of children with SCD)
Sudden severe anaemia with pallor and lethargy (splenic sequestration crisis — especially in children <5)
Abdominal pain (mesenteric vaso-occlusion, splenic sequestration, gallstones)
Signs
Pallor, jaundice (chronic haemolysis)
Splenomegaly in young children (auto-infarcts by age 5 in HbSS → functional asplenia)
Dactylitis — painful swollen hands/feet in infants (first presentation of SCD)
Leg ulcers (chronic, especially around malleoli)
Growth retardation and delayed puberty
Focal neurological signs (stroke)
Investigations
First-line
Newborn screening (heel-prick test)Part of UK newborn screening programme — detects SCD using haemoglobin electrophoresis/HPLC
FBCBaseline Hb typically 60–90 g/L; raised reticulocytes (chronic haemolysis); raised WCC (often elevated at baseline in SCD)
Haemoglobin electrophoresis / HPLCConfirmatory test: HbSS, HbSC, HbS/beta-thal patterns. HbS typically 80–95% in HbSS; HbF variable
Second-line
Blood filmSickle cells, target cells, Howell-Jolly bodies (functional asplenia), polychromasia (reticulocytosis)
LDH, bilirubin, reticulocytesBaseline haemolysis markers — important to know patient's steady-state values for comparison during crises
Group and save / crossmatchExtended phenotype matching essential — SCD patients develop alloantibodies frequently (~30%)
Specialist
Transcranial Doppler (TCD)Annual screening in children aged 2–16 years — identifies high cerebral blood flow velocity indicating stroke risk. Abnormal >200 cm/s → chronic transfusion programme
EchocardiogramScreening for pulmonary hypertension (tricuspid regurgitant jet velocity)
MRI brainIf stroke suspected or abnormal TCD — to detect cerebral infarction
Chest X-rayIn suspected acute chest syndrome — new pulmonary infiltrate
1
Acute vaso-occlusive crisis (NICE CG143)
- Treat as a MEDICAL EMERGENCY — analgesia within 30 minutes of presentation
- Strong opioid (morphine) for severe pain: IV or SC morphine, titrate to effect
- Paracetamol and NSAID (ibuprofen) alongside opioid — multimodal analgesia
- Do NOT offer pethidine (risk of seizures with metabolite norpethidine)
- IV fluids to correct dehydration; oxygen ONLY if SpO2 <94% (over-oxygenation is not beneficial)
- Reassess regularly — escalate if signs of acute chest syndrome, stroke, or sepsis
2
Acute chest syndrome
- New pulmonary infiltrate on CXR + respiratory symptoms (cough, dyspnoea, chest pain) ± fever
- Most common cause of death in SCD — treat aggressively
- Broad-spectrum antibiotics (include atypical cover — macrolide + cephalosporin)
- Oxygen, analgesia (chest wall pain impairs breathing)
- Simple top-up transfusion (target Hb 100 g/L) or exchange transfusion (target HbS <30%)
3
Long-term disease-modifying treatment
- Hydroxycarbamide (hydroxyurea): first-line disease-modifying agent — increases HbF production, reduces crisis frequency by ~50%, reduces acute chest syndrome and stroke risk
- Indications: ≥3 crises/year, recurrent acute chest syndrome, symptomatic anaemia, stroke prevention
- Monitor FBC regularly — dose-limiting toxicity is myelosuppression
- Folic acid 5 mg daily (increased demand from chronic haemolysis)
4
Infection prevention
- Penicillin V prophylaxis from diagnosis (lifelong in many centres) — functional asplenia increases encapsulated organism risk
- Vaccinations: pneumococcal (PCV13 + PPV23), Hib, meningococcal ACWY and B, annual influenza
- Low threshold for antibiotics in febrile patients — treat as potentially septic
5
Chronic transfusion programme
- Indicated for stroke prevention (abnormal TCD or previous stroke)
- Aim to keep HbS <30% with regular exchange transfusions
- Monitor for iron overload — iron chelation with deferasirox if ferritin >1000 µg/L
Complications
- Stroke: Affects ~10% of children — leading cause of morbidity. Both ischaemic and haemorrhagic. TCD screening + chronic transfusions have dramatically reduced incidence
- Acute chest syndrome: Leading cause of death — pulmonary vaso-occlusion ± infection ± fat embolism
- Splenic sequestration: Pooling of blood in spleen → acute severe anaemia and hypovolaemia. Emergency in children. Recurrent episodes → splenectomy
- Aplastic crisis: Parvovirus B19 infection causing temporary red cell aplasia — sudden drop in Hb with absent reticulocytes
- Avascular necrosis: Especially femoral head — chronic bone infarction
- Chronic kidney disease: Renal papillary necrosis, chronic sickle nephropathy
- Pulmonary hypertension: Chronic haemolysis → nitric oxide depletion → endothelial dysfunction
UKMLA Exam Tips
- 1Acute painful crisis: analgesia within 30 minutes, strong opioid for severe pain, NEVER pethidine (NICE CG143)
- 2Acute chest syndrome = new CXR infiltrate + respiratory symptoms — most common cause of death. Exchange transfusion may be needed
- 3Howell-Jolly bodies on blood film = functional asplenia = encapsulated organism risk = needs vaccination + penicillin
- 4Parvovirus B19 in SCD → aplastic crisis: sudden severe anaemia with LOW reticulocytes (different from haemolytic crisis)
- 5Hydroxycarbamide raises HbF — the single most effective disease-modifying drug, reduces crises by ~50%
- 6Dactylitis (hand-foot syndrome) in infants is often the FIRST presentation of SCD
- 7TCD screening annually in children: velocity >200 cm/s → chronic transfusion programme to prevent stroke
practicetest your knowledge on sickle cell diseaseApply what you've learnt with UKMLA-style questions from the iatroX Q-Bank — haematology and beyond.
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