SICKLE CELL DISEASE

Symptoms and signs

• Severe pain (usually in extremities, back or abdomen)
• Dehydration
• Enlarged liver or spleen
• Bone pain
• Low grade fever (<38°C) even in absence of infection

History

• Is pain similar to that of a sickle cell crisis or is it different in any way?
• Analgesia already taken for current episode?
• Any precipitating factors – infections, dehydration, stress?
• Any complicating factors:
• shortness of breath/cough/chest pain
• headache/neurological symptoms
• abdominal pain/priapism
• features to indicate infection
• assess features of other non sickle related presentations
• Previous episodes and complications
• Use age-appropriate pain score

Examination

• Look for:
• tachycardia
• tachypnoea
• hypo and hypertension
• fever
• dehydration
• SpO₂ on air and on oxygen (target oxygen saturation 95%)
• chest signs
• hepatosplenomegaly
• If neurological symptoms, full neurological findings

Investigations

• Presence of sickle cells in blood film does not correlate with clinical events
• FBC and reticulocyte count
• check whether Hb and reticulocyte count similar to patient’s baseline
• worsening anaemia and low reticulocyte count may indicate virus (parvovirus) – induced bone marrow aplasia
• Group and save
• in new patients, obtain full red cell phenotype
• U&E, LFT
• If fever or relevant symptoms or signs, septic screen
• Only if infection or acute chest syndrome suspected (see below), CXR
• Painful bones need not normally be X-rayed

Analgesia

• Select pain assessment tool (PAT)
• Administer first dose of analgesia within 30 min of presentation to emergency department
• Ensure drug, dose and administration route are suitable for severity of pain and age of patient
• Refer to patient’s individual care plan if available
• Offer a bolus of strong opioid to all patients presenting with:
• severe pain
• moderate pain not relieved by analgesia already taken

Non-opioid analgesia

• Not all patients require opioid analgesia although many do
• If no contraindications, offer the following regularly:
• paracetamol 1 g oral 6-hrly
• if well hydrated and eGFR ≥30 mL/min, naproxen 250 mg oral 6-hrly or ibuprofen 400 mg oral 8-hrly
• dihydrocodeine 30–60 mg oral 4–6 hrly (max 240 mg in 24 hr)
• Review doses in presence of renal impairment
• Do not use pethidine for treating pain in an acute sickle cell episode 

Opioids in opioid naïve patients

• If weight ≤50 kg, morphine 2.5 mg SC up to every 2 hr
• If weight >50 kg, morphine 5 mg SC up to every 2 hr

Opioids in patients using opiates/opioids regularly

• May require higher doses
• e.g. morphine 5–10 mg SC up to every 2 hr or equivalent dose of diamorphine or other alternatives
• if patient prefers and usually uses IV morphine, give morphine 0.1 – 0.15 mg/kg IV (maximum 10 mg) over 5 min
• pethidine is no longer recommended for sickle vaso-occlusive pain

Monitoring

• Reassess response in approximately 15–30 min after the completion of the IV infusion, or 30–60 min after SC injection
• consider repeating/increasing dosage according to efficacy
• do not adjust the dose of morphine before the expected time of peak onset of pain relief (i.e. 20 min for IV dosing)
• Assess pain every 30 min until satisfactory relief then monitor at least every 4 hr using an age-appropriate pain assessment tool
• if patient has severe pain on reassessment, offer second bolus dose of a strong opioid
• If repeated bolus doses of a strong opioid are needed within 2 hr
• consider admission to a surgical ward for patient-controlled analgesia – see Patient-controlled analgesia guideline in the Surgical guidelines
• Monitor patients receiving at least hourly for presence of adverse effects
• including respiratory depression (sedation score, respiratory rate) – see Opioids: monitoring and dose adjustment guideline in the Surgical guidelines

Itch and nausea

• Non-sedating antihistamines for itch
• Ondansetron for nausea 

Fluid replacement

• Replace fluid orally if possible
• Venous access often difficult in patients with SCD:
• reserve for situations where oral intake inadequate or inappropriate (e.g. vomiting)
• If unable to give orally, glucose (4%) and sodium chloride (0.18%) 1 L by IV infusion over 3 hr
• then follow IV fluid maintenance guideline
• NEVER add potassium chloride to infusion bags
• Avoid using veins in ankles/feet for venous access
• cannulation carries high risk of leg ulceration
• Avoid central lines as they carry high complication rate

Blood transfusion

• Indications for blood transfusion in sickle cell disease are very specific
• discuss all cases with haematologist

Oxygen therapy

• If SpO₂ <94%, give oxygen. See Oxygen therapy in acutely hypoxaemic patients guideline
• Carry out a full assessment of the reason for hypoxia
• opiate-induced respiratory suppression
• severe chest infection
• chest syndrome (see below)
• If SpO₂ cannot be maintained >94%, discuss with critical care team and haematology team

Antimicrobials

• Continue prophylactic antimicrobials as recommended by patient’s haematologist
• see BNF if not already on prophylaxis
• If evidence of infection, give antimicrobials
• see appropriate guideline for type of infection

Thromboprophylaxis

• Unless contraindicated, give thromboprophylaxis
• see Prophylaxis against venous thromboembolism guideline

• Painful crises usually last about 1 week
• Once pain controlled, reassess analgesic regimen daily and taper dosage gradually
• change to oral morphine (1 mg SC diamorphine = 3 mg oral morphine)
• If Hb falls below 50 g/L, especially if reticulocyte count decreased, consider blood transfusion
• discuss with haematologist

• Respiratory rate hourly after opioid started for evidence of respiratory suppression
• Pulse oximetry
• Fluid balance
• U&E for dilutional hyponatraemia
• Consider PAT to record pain response to analgesia

• Discuss with haematologist

Acute chest syndrome

• Acute life-threatening complication of sickle cell disease
• breathlessness, hypoxia, fever and new onset pulmonary infiltrates in CXR
• Discuss urgently with haematologist

Priapism

• Painful prolonged erection with/without prior sexual stimulus
• This is an emergency
• involve urologist early as penile aspiration/irrigation may be necessary
• in some instances shunt procedures are needed

Stroke

• More common in children
• Ischaemic stroke is more common in children
• Haemorrhagic stroke is more common in adults

Investigations

• Emergency CT scan of head to confirm whether ischaemic or haemorrhagic
• MRI scan of brain to delineate area of ischaemia/haemorrhage
• Carotid Doppler ultrasound scan
• Urgent review by neurologist and haematologist for exchange transfusion to reduce HbS <30%

Splenic sequestration

• More common in infants and children
• Often associated with sepsis
• Clinical features:
• rapidly enlarging, painful spleen
• anaemia – may present with shock
• fall in Hb of 20 g/L from baseline

Management

• Resuscitate and treat shock
• Emergency (top-up) transfusion: to baseline Hb
• Broad spectrum antimicrobials to cover pneumococcus and haemophilus

Hepatic sequestration

• Acute tender hepatomegaly and anaemia
• manage with a top-up transfusion to baseline Hb

Gallstone complications

• Common in this patient population
• manage as any other patient

Aplastic crisis

• Transient arrest of erythropoiesis
• Abrupt reduction in haemoglobin concentration
• Associated with human parvovirus B19, streptococci, salmonella, streptococci, and Epstein-Barr virus infections
• Emergency (top-up) transfusion: to baseline Hb
• Reticulocytes typically reappear within 2–14 days

Osteomyelitis

• Increased incidence in SCD from infection of infarcted bone
• Usually due to salmonella or other gram-negative organisms, such as Escherichia coli but also Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus
• Clinical presentation is often similar to a VOC frequently plus:
• a prolonged duration of fever and pain
• swelling and pain that is localised to a single site
• Discuss management with haematologist and orthopaedic surgeon
• surgical drainage or sequestrectomy may be required

Other infections

• Infection is a major cause of morbidity and mortality in SCD
• Therapy of specific infections varies with the clinical setting
• see relevant guideline for suspected source of infection

General principles

• All patients should carry a transfusion card with details:
• ABO group, extended red cell phenotype, Rh phenotype and
• existence of any red cell alloantibodies (current and historic)
• Transfusion history is important, particularly if care is in a different hospital
• liase with transfusion laboratory at primary hospital to get transfusion history
• Advise transfusion laboratory/blood bank that transfusion is for a patient with SCD
• Discuss with haematology to determine if simple top-up or exchange transfusion needed
• Determine post-transfusion target Hb and HbSS
• Record and document transfusion triggers and indications
• Monitor closely both during and after completion of transfusion for
• immune haemolytic transfusion reaction (IHTR)
• delayed haemolytic transfusion reaction (DHTR) and
• hyper haemolysis
• All patients should have annual viral screening for Hepatitis B, C and HIV 1 and 2

Venous access

• Simple top-up transfusion: single peripheral venous cannula
• Manual exchange transfusion: 2 separate large bore venous access
• one for transfusion and inlet port (wide bore needle grey/orange) and
• another for venesection (vascath: femoral/central neck line)
• Automated red cell exchange: femoral line/vascath – double lumen
• Long-term transfusion programme: consider a port-a-cath

Top-up transfusion

Indications

• Severe anaemia (Hb <50 g/L) owing to:
• hepatic or splenic sequestration
• red cell aplasia or haemolysis
• Severe anaemia when decrease in Hb >20% from baseline in a symptomatic patient (heart failure, dyspnoea, hypotension and marked fatigue)
• Transfuse to baseline Hb (patient’s Hb in steady state)
• Consider when exchange transfusion indicated and starting Hb <50 g/L.
• Discuss with haematologist

Exchange transfusion

Indications

• Severe chest syndrome
• New ischaemic stroke
• Multi-organ failure
• Consider in priapism
• Do not initiate exchange transfusion before discussing with haematologist

Targets

• To reduce HbS to <30%
• To maintain Hb <100 g/L
• note: haematocrit of donor blood is approximately double that of patient
• To maintain steady blood volume throughout procedure

Venous access

• Ideally, identify 2 ports for venous access; 1 for venesection, the other for transfusion
• in emergency, consider a central line, or arterial line (e.g. on ITU)
• Perform exchange transfusion isovolaemically (equal quantities in and out)
• Ensure patient well hydrated before exchange
• prehydrate with sodium chloride 0.9% 500 mL as first 500 mL of blood is being removed
• then give sodium chloride 0.9% 500 mL concurrently
• do not remove blood until venous access for transfusion is secure
• continue to administer IV fluids between transfusions at standard rate of 3 L/m²/24 hr
• See Blood and blood products guidelines

Method

• Usually requires at least 2 exchanges, each of 4 units venesected and 4 units transfused
• Venesect 500 mL of blood and simultaneously infuse 500 mL sodium chloride 0.9% at same speed as the bleeding
• As second 500 mL (and subsequent units) venesected, transfuse first unit of blood over 1–2 hr
• Venesect 500 mL and replace with blood and sodium chloride 0.9% five more times
• discuss in advance with haematologist
• Check interim Hct and Hb
• A simple top-up transfusion may be required following isovolaemic exchange transfusion
• Post-RBC exchange – FBC and Hct 

• Discharge home when pain controlled by oral medication
• Provide 3–4 days’ supply of analgesia
• Do not prescribe parenteral opioids TTO
• Provide patient or carer with information on the continuing management of the current episode including how to:
• obtain specialist support
• additional medication
• manage any potential side effects of treatment