Haematology & Oncology

Sickle Cell Disease

An inherited haemoglobinopathy in which deoxygenated haemoglobin S polymerises, making red cells rigid and adhesive; vaso-occlusion causes ischaemic pain while haemolysis causes chronic anaemia and progressive organ damage.

In a nutshell

Sickle cell disease is chronic haemolysis punctuated by vaso-occlusive pain, in a patient whose spleen no longer works. Treat an acute painful episode as an emergency: give plan-matched analgesia within 30 minutes, then reassess every 30 minutes.

Classic presentation

A young adult with known HbSS presents with severe back and limb pain after a cold, wet weekend, on a background of jaundice and chronic anaemia.

Key points

Fetal haemoglobin blocks haemoglobin S (HbS) polymerisation, so infants are protected for their first few months, and hydroxycarbamide works by raising it.
CG143 gives no drug doses at all. It sets the timings and defers every dose to the BNF and the local protocol.
Moderate pain is a visual analogue score of 4 to 7 and severe pain is above 7. CG143 uses those bands to choose weak or strong opioid.
Acute chest syndrome can be triggered by fluid overload, opioid narcosis, hypoventilation or pulmonary embolism, so treating the pain badly can cause it.
The BNF records a possible association between morphine given during a vaso-occlusive crisis and acute chest syndrome, and advises watching for it.
CG143 dates from 2012, but NICE's 2023 exceptional surveillance found no reason to update any section of it, so it remains the current UK guideline.
Newborn blood spot screening identifies sickle cell disease in England, and affected babies are referred for specialist care by 3 months of age.

First-line investigation

FBC and reticulocyte count against the patient's steady state, plus a group and screen; add chest X-ray and blood gas if saturations are 94% or below on air.

Management

The first 30 minutes

Treat as an acute medical emergency. Offer analgesia within 30 minutes of arrival (CG143 recommendation 1.1.4). Do not wait for bloods, imaging or senior review.^4,7
Use the individual care plan and prior opioid exposure. If unavailable, an opioid-naive adult example is morphine 5 mg by slow IV injection, adjusted to response.^4,9
Untreated moderate pain: a weak opioid may suffice. Adult example: codeine 30 to 60 mg orally every 6 hours, adjusted for age and risk.^4,10,9
Record blood pressure, pulse, respiratory rate, temperature and saturations on air. Offer oxygen if saturations are 95% or below.⁴

Adjuncts and reassessment

Regular paracetamol 1 g every 6 hours (maximum 4 g daily) plus an NSAID unless contraindicated. Avoid NSAIDs in the third trimester of pregnancy.^4,11
With opioids, offer a regular laxative. Give an antiemetic or antipruritic only if needed; adult examples are lactulose, cyclizine and chlorphenamine.^4,12,13,14
Reassess pain every 30 minutes until controlled, then at least 4-hourly. Still severe: second strong-opioid bolus. Repeated boluses within 2 hours: patient-controlled analgesia.⁴
Sedation score and adverse-effect check hourly for the first 6 hours, then at least 4-hourly. Keep the patient warm and give fluids orally where possible.⁴

Acute chest syndrome and stroke

Acute chest syndrome is fever and/or respiratory symptoms with a new infiltrate on chest X-ray. It can appear at any point in the admission, not only at presentation.⁵
Arterial blood gas in adults if saturations are 94% or below on air. Give oxygen to hold saturations at 95% or above, or within 3% of baseline.⁵
Antibiotics with atypical cover: co-amoxiclav 1.2 g intravenously every 8 hours plus clarithromycin 500 mg twice daily; ceftriaxone 2 g intravenously once daily if penicillin-allergic.^5,15,16
Add incentive spirometry, and a bronchodilator if there is bronchospasm. Involve critical care early for non-invasive or invasive ventilation.⁵
Suspected acute ischaemic stroke: emergency exchange transfusion to HbS below 30%, alongside the hyperacute stroke pathway.⁸

Transfusion decisions

Acute chest syndrome with hypoxia (PaO2 below 9.0 kPa on air): simple top-up transfusion to a target haemoglobin of 100 to 110 g/L.⁸
Exchange transfusion for severe or progressive acute chest syndrome, failure to respond to top-up, or a haemoglobin already above 90 g/L.^8,5
Aplastic crisis and splenic sequestration: simple transfusion back to steady state only. Going above 80 g/L in sequestration risks hyperviscosity as the spleen releases cells.⁸
Uncomplicated painful crisis: no transfusion, unless haemoglobin falls more than 20 g/L below baseline or below 50 g/L, or an organ is threatened.⁸

Preventing the next episode

Phenoxymethylpenicillin 250 mg twice daily from age 5 and in adults, usually for life. Ages 1 to 4: 125 mg twice daily. Under 1 year: 62.5 mg twice daily.^17,6
Pneumococcal, meningococcal, Haemophilus influenzae type b and annual influenza vaccination, because the spleen no longer clears encapsulated organisms.^1,5
Folic acid 5 mg every 1 to 7 days, replacing what chronic haemolysis consumes.¹⁸
Hydroxycarbamide 15 mg/kg daily, titrated to 15 to 30 mg/kg daily (maximum 35 mg/kg), for recurrent painful episodes or recurrent acute chest syndrome.^19,5,8
On hydroxycarbamide, check FBC every 2 weeks for the first 2 months, then every 2 to 3 months. Avoid it if the estimated glomerular filtration rate is below 30 mL/minute/1.73 m2.¹⁹

Discharge and surveillance

Written discharge plan: stepping analgesia down, side effects to expect, how to reach the specialist team and how to obtain more medication.⁴
Return urgently for fever, chest symptoms, new neurological signs, sudden pallor, persistent priapism or uncontrolled pain.^4,3
Children with HbSS or HbS-beta-zero thalassaemia have annual transcranial Doppler ultrasound from age 2 to 16 years to find those at high stroke risk.^1,8
Chronic transfusion, stem cell transplant and exagamglogene autotemcel (NICE TA1044, managed access, aged 12 and over) are specialist-only decisions.^20,8

Exam traps

The 30-minute target runs from arrival at hospital, not from the doctor seeing the patient, and bloods or imaging are not a reason to delay.
Do not offer pethidine for an acute painful sickle cell episode. It is the one analgesic CG143 explicitly rules out (recommendation 1.1.11).
Do not use corticosteroids in an uncomplicated acute painful episode (CG143 recommendation 1.1.21).
An early normal chest X-ray does not exclude acute chest syndrome. Keep looking if the patient is hypoxic or has chest signs.
Falling haemoglobin with a high reticulocyte count is sequestration or haemolysis; with a low reticulocyte count it is aplastic crisis from parvovirus B19.
In sequestration, transfuse back to steady state only. Pushing haemoglobin above 80 g/L causes hyperviscosity when the sequestered cells re-enter the circulation.
Transfusion does not shorten an uncomplicated painful crisis and is not given for pain alone.
Annual transcranial Doppler screening is for children aged 2 to 16 with HbSS or HbS-beta-zero thalassaemia. It is not a routine adult test.

Illustrations

Sickled red cellColour-enhanced scanning electron micrograph showing a crescent-shaped sickled red cell alongside normal biconcave red cells.OpenStax College, Wikimedia Commons · CC-BY-3.0

HbS polymerisation on deoxygenationDiagram showing haemoglobin S polymerising into rigid rods when deoxygenated and distorting the red-cell membrane.PassFinals · original

Vaso-occlusion versus haemolysisDiagram mapping vaso-occlusion and premature red-cell destruction to their clinical consequences.PassFinals · original

Key sources

This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.