Sickle Cell Disease Management Guidelines-3

Clinical Guideline
SICKLE CELL DISEASE MANAGEMENT GUIDELINES

SETTING Bristol Royal Hospital for Children
FOR STAFF All clinical staff involved in the management of patients with sickle cell disorders
PATIENTS Sickle cell disorders include those genetic conditions in which sickle cell crises
may occur, e.g. HbSS, HbSC disorder, Sickle/beta thalassaemia. This does not
include sickle cell trait. The majority of newly diagnosed patients are infants
diagnosed as a result of the neonatal screening programme. Patients are well
known to the paediatric haematology team and are seen at regular intervals in
the haematology clinic held in Oncology Day Beds on Tuesday afternoons.
GUIDANCE
Written March 2010,

Updated October 2017
Authors: Dr Michelle Cummins

Dr Ruth Mixer
CNS Anna Farrell
CNS Caroline Roberts
Dr Rosanna Ghinai
Version 3 Oct 17 - Review Oct 2020 Author(s) M Cummins, R Mixer, A Farrell, C Roberts, R Ghinai Page 1 of 37
Extended until October 2022
Contents
Contents 2
Introduction 4
Paediatric Haematology Team 4
Admission Procedure 5
Initial Assessment 5
Conditions requiring immediate admission 5
Algorithm for initial assessment and management 6
Sickle Cell Crisis: Investigations 6

1. Routine (all patients) 7
2. Additional Investigations (selected patients) 7
3. Newly presenting patients 8
Management of Acute Painful Crisis 9

1. General 9
2. Pain relief 9
3. Other drugs 11
4. Fluids 12
5. Oxygen 12
6. Antibiotic policy 12
Management of Specific Sickling Problems 14

1. Acute Chest Syndrome 14
2. Acute Sequestration 15
3. Abdominal Crisis 16
4. Aplastic Crisis 17
5. Stroke 18
6. Priapism 19
7. Infection including osteomyelitis 20
8. Haematuria 21
9. Biliary Tract 22
10. Ophthalmic 22
Discharge from ward 23
Red Cell Transfusions 24

1. General Principles 24
2. Pre Transfusion Investigations 24
3. Top Up Transfusions 24
4. Exchange Transfusions 25
5. Elective Transfusions 28
Management of Surgery in patients with Sickle Cell Disease 29
1. Preoperative sickle screening 29
2. Dental Hospital procedure 31
3. Preoperative Management Plan 31
4. Preoperative Transfusion 32
5. Perioperative Management 33
Appendices
1. Flow chart for management of acute painful crisis 34
2. Practical points of manual exchange transfusion 35
3. Key references 37
Introduction
Sickle cell disorders include those genetic conditions in which sickle cell crises may occur, e.g.
HbSS, HbSC disorder, Sickle/beta thalassaemia. This does not include sickle cell trait. The
majority of newly diagnosed patients are infants diagnosed as a result of the neonatal screening
programme. Patients are well known to the paediatric haematology team and are seen at regular
intervals in the haematology clinic held in Oncology Day Beds on Tuesday afternoons.
Paediatric Haematology Team
Dr Michelle Cummins Consultant Paediatric 07770643638

Haematologist Ext 28911
Dr John Moppett Consultant Paediatric 07770643638
Dr Oliver Tunstall Consultant Paediatric 07770643638
Dr Rachel Dommett Consultant Paediatric 07974144974
Haematology/TYA
Dr Emma Phillips Consultant Paediatric 07968440889
Haematologist
Mrs Helen Gile Paediatric Haem Sec Ext 28752
Paed Haem SpR 8.30-1700 Mon-Fri Bleep 3495
Paed Haem/Onc On Call 1700-2300 Mon-Fri Bleep 2406
8.30-2300 weekend
Anna Farrell Paed Haem CNS Ext 28721
anna.farrell@uhbristol.nhs.uk (Mon-Thurs) Mobile 07747004996
Caroline Roberts Paed Haem CNS Ext 28721
Caroline.roberts@uhbristol.nhs.uk (Tues -Fri) Mobile 07920545620
Nicole Paterson Adult sickle cell CNS Ext 22774
Other Useful Numbers
Pain Team Pain Team CNS Bleep 3974

SpR Anaesthetist Bleep 2937
Oncology Day Beds Ext 28145/28522

Apheresis Ex 21092
Haematology Lab Ext 22708
Transfusion Lab Ext 22579
Admission Procedure
Parents contacting ODB or the Haematology CNS / SpR with a child with symptoms of a sickle cell
crisis are directed to A&E and are seen directly by the Paediatric Haematology SpR on arrival
(bleep 3495). Patients self-presenting to A&E are usually assessed first by the A&E paediatrician
and referred to Paediatric Haematology if admission for crisis is required. Children presenting
overnight (23.00-08.30) are assessed by the hospital night team. If in doubt, do not hesitate to
contact the paediatric haematology team promptly for advice. There is 24 hour haematology/
oncology consultant cover available via switchboard. The case notes of children with sickle cell
disease are mainly kept in the clinical records room in ODB. Please inform the haematology team
of any patients:
1) Admitted overnight
2) Discharged from A&E without the need for referral
If there is no indication for admission, following discussion with the haematology team a child can
be discharged from A&E with:
 Oral analgesia, Penicillin V and Folic acid
 Instructions to stay well hydrated
 Antibiotics if there is evidence of infection not requiring admission e.g. simple ear infection
Liaise with the haematology team (via email to the haematology CNS team) so that appropriate
follow up can be arranged on ODB
Initial Assessment:
Most presentations are with pain and require a simple approach; however, more complex/
life threatening issues (esp. chest crisis) must be excluded.
In babies, watch out for dactylitis, pneumococcal sepsis (have they been successfully
receiving prophylactic Penicillin V?) and splenomegaly.
*PLEASE FOLLOW ALGORITHM OVERLEAF (PAGE 6)*
1) If in pain, the site and intensity should be recorded using pain score tool
2) Note any analgesia already taken
3) Check complete set of observations including O2 saturations in air
4) Analgesia should be administered within 20 minutes of arrival
Reassess pain at least every 30 minutes
5) LMX4 should be placed on all patients (avoid lower limbs for cannulation)
Call the paediatric haematology team immediately if there is:

 Agonising pain (i.e. requiring parenteral opiate analgesia)
 Increased pallor, breathlessness, exhaustion
 Pyrexia > 38 oC, tachycardia or tachypnoea, hypotension
 Chest symptoms/signs: tachypnoea, hypoxia, signs of lung consolidation; pain
 Abdominal pain or distension, diarrhoea, vomiting, dehydration
 Headache, drowsiness, CVA, TIA or any abnormal CNS signs
 Priapism
Algorithm for initial assessment of a child with sickle cell disease
Check diagnosis (HbSC/HbSS/HbSβ0thal) – access clinic letters (medication, transfused, antibodies?)

↓
Obs: RR, work of breathing, Sa02 in air (give O2 if hypoxic p.14-15 and keep rechecking – also CXR, ABG,
consider NIV)
HR, BP, temperature (resuscitate in sepsis and as needed) – recheck Sa02 repeatedly
↓
Call haematology CNS in hours, registrar until 10pm, consultant 24h if concerns p.4-5
↓
Any pain (site, severity)? Give urgent analgesia p.9-11 and see below
↓
Ensure all patients are well hydrated p.12 (oral/ IV – site cannula with bloods)
↓
Bloods: Hb (compare with baseline), retics, UEs, LFTs, CRP, G+S (HbS% esp. if regularly transfused)
Additional bloods if patient not known to BRHC p.8
Any fever, neurological impairment, hepatosplenomegaly, chest features, pallor?

Fever may be due to sickling but treat for infection (full septic screen, antibiotics p.12-13, 20-21)
Neurological impairment may be seen with severe illness/ opioids but consider TIA/stroke p.18
Hepato/splenomegaly may be due to sequestration (check Hb compared with usual) p.15-16
Chest symptoms/signs require urgent and ongoing attention re acute chest syndrome (ACS) p.14
Pallor suggests severe anaemia incl. aplastic crisis – discuss transfusion with haematologist p.17
Site of pain may point to underlying syndrome (please discuss with haematology urgently):
Abdominal pain p.15-17

May or may not appear related to sickle cell disease (constipation, gastroenteritis, UTI, cholecystitis,
pancreatitis, appendicitis, Parvovirus B19, peptic ulcer) but all can lead to sickling complications:
 Mesenteric syndrome p.17: sickling mimics peritonitis, ileus; acute chest syndrome develops
 Splenic/hepatic sequestration: p.15-16: Hb <50g/L (or >20g/L fall), seen especially in babies
 Aplastic crisis p.17: Parvovirus B19 causes Hb <40g/L with reticulocytopenia for ~7-10 days
 Acute intrahepatic cholestasis: deranged LFTs; may progress to liver failure, bleeding, death
Limb pain p.9-11

Give analgesia, hydrate (oxygen not beneficial in simple pain crisis)
Check for dactylitis in babies (examine hands and feet for swelling and tenderness)
Consider osteomyelitis p.20 and necrosis (discuss imaging/ aspiration with orthopaedic team)
Chest symptoms and signs p.14-15

 Chest crises are not usually painful: establish site and source of chest pain if present (chest wall/ pleuritic
etc.)
 Chest crisis may develop from chest pain/ any other crisis so vigilance (incl. overnight) is crucial
o any respiratory compromise should be discussed with the haematology consultant on call
immediately
 Main concern is acute chest syndrome i.e. fever and new consolidation/ pulmonary infiltrate on CXR +/-
cough/ wheeze/ breathlessness. Give oxygen aiming for Sa02 100%; ABG if Sa02 <90% in air. Try
Optiflow, careful hydration and simple transfusion if early in crisis; exchange if evolving
 Also need to treat cause of chest crisis (fluid overload, infection, opioids, hypoventilation, PE)
Other presentations
Priapism p.19
Haematuria p.21
Ophthalmic p.22
Jaundice p.22 (also consider haemolysis including delayed haemolytic transfusion reaction)
Sickle Cell Crisis: Investigations
1. Routine Investigations (all cases)

Blood Tests
FBC/retics
Group and save
Urea& electrolytes, Creatinine, LFTs
CRP
Blood cultures (if any symptoms/signs of infection)
HbS % (esp. if on regular transfusion programme)
Microbiological screen
Urine dipstick & MSU culture
Other cultures as indicated (See below)
Other tests
Pulse oximetry (SaO2) on air
Chest x-ray if indicated (ie symptoms/signs)
2. Additional Investigations (according to clinical picture)
Test Indication
Arterial Blood Gases If O2 sats in air < 90%
Serum amylase Abdominal symptoms/signs

Abdominal X Ray Symptoms suggestive of
Abdominal ultrasound cholecystitis/ biliary obstruction
Screen stool for Yersinia. Patients on iron chelation

Serum for Yersinia antibodies (desferrioxamine, deferiprone,
exjade) with diarrhoea/abdominal
pain (STOP CHELATOR)
Parvovirus IgM/IgG serology Fall in Hb with low retics
(clotted)
Parvovirus PCR (EDTA)
CT scan of head See stroke and other CNS
complications
Xrays of painful joints/ limbs Generally not helpful. See page
26 regarding osteomyelitis
ECG If possible arrhythmia or cardiac
pain
Throat, nose, sputum, stool, As clinically indicated
wound, CSF cultures etc.
Viral & atypical pneumonia
serology to store
3. New patients not previously known to this hospital
All routine investigations plus additional blood tests
 Hb, HPLC, including % HbF

 Full red cell phenotype: Rh, Kell, MNS+U, Fya+b, Jka+b
 History of red cell antibodies, including from previous centres
 G6PD
 Ferritin
 Hepatitis B and C serology, HIV, CMV IgG, Parvovirus B19 serology
 Clotted sample to virology to store
Management of Acute Painful Crisis
There are no specific or curative treatments. Management is supportive, with the aim of treatment
to break the vicious cycle of sickling → hypoxia and acidosis → more sickling.
1. General management
 Pain relief
 Give reassurance that the patient’s pain will be relieved as soon as possible
 Massage and distraction techniques may help some children
 Keep warm and establish a position of maximum comfort
 Establish IV access as soon as possible
 Hydrate
 Identify and treat infection
 Regular observations and reassessment
2. Pain Relief
Pain in SCD is due to vaso-occlusion and may be severe. Most patients attend A&E
after trying unsuccessfully to relieve their pain at home using simple analgesics.
Medical and nursing staff often under-estimate the severity of pain and deal with it
inadequately. Severity may be difficult to assess but if in doubt it is better to over-
estimate the intensity and reduce analgesia afterwards. Inadequate analgesia will
precipitate a vicious cycle, resulting in increased fear, anxiety and more pain.
Aim to FULLY control pain as soon as possible after the child has been assessed. This should be
within 30 minutes of arrival within the department.
 Triage category 2; inform Paediatric Haematology SpR and CNS as soon as possible
 Assess the site, severity and duration of pain. Use analgesic ladder (overleaf – page 10)
and flow chart (Appendix 1 – page 35) to guide analgesia, and a pain score tool to monitor
effectiveness of pain relief. ALL children admitted must have analgesia prescribed to take
at regular intervals: a prn basis is not recommended.
Please refer to related Trust Guidelines
 Paediatric Pain Service: Acute Pain Management (includes section on Sickle)
 Intranasal Diamorphine
Analgesic Ladder
Paracetamol/ Ibuprofen (if not already administered)
↓
Tramadol + Paracetamol + Ibuprofen
Morphine (oral or intravenous) + Paracetamol + Ibuprofen
Severe Pain
The drug of choice is MORPHINE, given either orally or if not possible (vomiting, refusal, severe
pain) intravenously.
If pain is severe, whilst establishing intravenous access give intranasal diamorphine. Once the
patient is comfortable, oral morphine should be administered or IV access should be obtained for
further pain management
Diamorphine has a number of properties which render it desirable as an analgesic agent for
administration via the transmucosal route
 Rapidly and well absorbed across the nasal mucosa

 High aqueous solubility allows administration in a small volume
 Low irritancy
 Potency twice that of Morphine with similar duration of action
Morphine may be given by the oral or intravenous route (bolus dose or infusion).
Patient controlled analgesia/nurse controlled analgesia (PCA/NCA) can only be started by a

member of the pain team or the on call anaesthetist. If they are not available promptly, then it may
be necessary to commence on a morphine infusion.
The decision to use a PCA (background with boluses) will depend upon prompt availability of pain
team staff, pain severity and child’s previous experience and understanding. In practice they are
useful in very severe sickle pain as they allow more effective titration of morphine according to
pain. Older children who have experience of PCA often prefer having some control over the
delivery of pain relief. The background infusion can be removed as the child improves.
All patients receiving intravenous morphine require routine monitoring as described in

the Trust guideline, Acute Pain Management. Some children may require additional
monitoring, as indicated by their clinical needs
Moderate Pain
Moderate pain may respond to Tramadol.
3. Other Drugs
All children admitted with pain should have the following prescribed on transfer to the ward:
Regular Ibuprofen, Oral
Regular Paracetamol, Oral
Regular Movicol, Oral (for opiate induced constipation, unless abdominal signs)
PRN Naloxone, IV – required for all patients receiving iv morphine
PRN Chlorpheniramine, Oral or IV (for opioid induced itch)
PRN Ondansetron, Oral or IV (nausea & vomiting)
PRN Metoclopramide, Oral, IM or IV slow bolus (nausea & vomiting)
Regular Penicillin V, Oral (not whilst on other antibiotics but remember to restart) – lifelong for
prevention of pneumococcal infection in sickle cell disease (hyposplenic)
For child 1-11 months 62.5mg twice daily
For child 1-4 years 125mg twice daily
For child 5-17 years 250mg twice daily
Regular Folic acid, Oral (Elixir 2.5mg/5ml, Tablets 5mg)

For child 1 month to 3 years 2.5mg once daily
For child >3 years 5mg once daily
Version 2 Jan 17 - Review Jan 2020 Author(s) M Cummins, R Mixer, A Farrell, C Roberts, R Ghinai Page 11 of 37

4. Fluids
Children with sickle cell disease have reduced renal concentrating ability.
Continued fluid loss without adequate replacement causes reduction in plasma volume, increased
blood viscosity and aggravation of sickling.
Intravenous Fluids
 Use in all children with severe pain, abdominal symptoms and inadequate oral intake
 Hyper-hydration (150% of normal maintenance) should be commenced on admission and
reviewed daily (if concerned re possible acute chest syndrome, give normal maintenance)
 Correct fluid deficit if dehydrated
 Monitor fluid balance carefully with input/output charts and weights
 Reduce and stop IV fluids as soon as patient is pain free and taking adequate oral fluid
Oral Fluids
 In the less ill child who is able to drink the required amount, hydration can be given orally
 Consider fluids via nasogastric tube if the patient is unable to tolerate oral fluids and venous
access is poor.
5. Oxygen
 Oxygen is of no benefit in simple limb pain.

 Monitor O2 saturations in any patient with respiratory symptoms/signs and those on opiates
 If SaO2 < 95 %, give oxygen by face mask
 If SaO2 < 90 %, exclude opiate induced respiratory depression and check arterial blood gas
6. Antibiotic Policy
Infection is a common precipitating factor of painful or other types of sickle crises. Functional
hyposplenism occurs, irrespective of spleen size, resulting in an increased susceptibility to
infection, in particular with encapsulated organisms such as Pneumococcus, Haemophilus
influenzae and Salmonella – all of which can cause life-threatening sepsis. Vaccination and
prophylactic penicillin has decreased the incidence of pneumococcal sepsis but it remains a major
cause of death in young children with sickle cell disease.
It is important to remember that a low grade fever often accompanies a painful crisis even in the
absence of infection. Antibiotics are therefore NOT routinely indicated.
 Look for a clinical focus of infection (blood, lungs, bones, biliary, meninges, urinary or
gastrointestinal tract etc.) and investigate appropriately. If no obvious focus, collect blood,
urine, stool and swabs for bacteriology (+/- virology) before starting antibiotic as follows:

 Any child with a high fever (>38˚C), a sequestration syndrome (lung, splenic, hepatic) or who
is clinically unwell, should receive IV Ceftriaxone.
 If there are chest signs, or an abnormal CXR, add oral Clarithromycin
 If there is abdominal pain, cholecystitis or suspected mesenteric syndrome, add IV

Metronidazole to Ceftriaxone
 Patients on Desferroxamine/ Deferiprone/ Deferasirox who have diarrhoea should be started

on Ciprofloxacin and these drugs stopped, due to risk of Yersinia infection. Stool samples
should be sent for testing.
 For confirmed Salmonella osteomyelitis, first line therapy is high dose IV Ciprofloxacin,
pending sensitivities and discussion with microbiology
 If symptoms/ signs of focal infection are present (e.g. tonsillitis, UTI) consult the hospital
antibiotic policy for drug of choice.
 Stop prophylactic penicillin if additional antibiotics cover Pneumococcus
 All other patients should continue prophylactic Penicillin V. They should be reviewed
regularly. If pain and fever do not settle within 24-48 hours, use of broad spectrum antibiotics
should be considered. If in doubt, it is better to give broad spectrum intravenous antibiotics,
particularly in children under the age of 5 years.

Management of Specific Sickling Problems
1. Acute Chest Syndrome (ACS)

Acute sickle chest syndrome is likely to be multifactorial in origin, with infection, sickle cell
sequestration within the lungs and possibly fat embolism all resulting in similar clinical patterns.
Regular observations, careful opiate administration, pulse oximetry and arterial blood gas
sampling when oxygen saturations below 90% are recorded in air, are important in recognition of
this complication.
Symptoms
• May present as abdominal pain or develop during a painful vaso-occlusive limb crisis
• Dyspnoea
• Cough is a late symptom
• Occasionally other pain (chest wall, pleuritic, thoracic spine)
Signs
• High fever, tachypnoea, tachycardia
• Any child developing respiratory compromise should be discussed with the haematology
consultant on call immediately for consideration of exchange transfusion
• Signs of lung consolidation, usually bilateral, generally starting at the bases, but may be
unilateral and impossible to distinguish from infection
• Bronchial breathing may be very striking. Physical signs often precede x-ray changes
Differential diagnosis
Sickle lung and pneumonia are clinically and radiologically indistinguishable. However,
consolidation in the upper and/ or middle lobes, without basal changes, is suggestive of chest
infection rather than sickle chest syndrome. Bilateral disease is most likely due to sickling, but
atypical pneumonia should be considered. Pleuritic pain may also be due to spinal/ rib/ sternal
infarction, or from sub-diaphragmatic inflammation.
Investigations
• Arterial blood gases (ABG) if SaO2 < 90% in air
• Chest x-ray
• HbS%
• Blood, throat, sputum cultures; respiratory infection serology (Mycoplasma, Legionella, viral)
• Group & Save, ensure sickle negative red cells (ABO, Rh, K matched, antigen negative for
any known antibodies, ideally <7-10 days old) are available for transfusion; if diagnosis of
ACS clear, x-match for exchange transfusion (contact Transfusion Laboratory – ext 22579)
Management
Inform attending consultant paediatric haematologist and PICU consultant

a. Transfer all deteriorating patients (increasing oxygen requirement, work of breathing) to PICU
for ventilatory support and exchange transfusion (see pages 25-29)

b. Oxygenation - Options include high flow (15l/min) face mask oxygen, optiflow (consider early
to prevent deterioration), CPAP, ventilation. The latter 2 options require transfer to PICU. A
worsening chest x-ray, rapid fall in O2 saturations or persistent fever are all indications for
exchange transfusion.
Emergency exchange transfusion is usually an automated procedure performed by on call

apheresis team from Bristol Haematology and Oncology Centre (BHOC; Bristol Royal
Infirmary). Most patients require adequate venous access i.e. a vascath, and are electively
ventilated on PICU to achieve this. Usually give 40ml/kg packed RBCs for exchange in paeds.
A simple top-up transfusion can be a good temporising measure and may be sufficient in
milder cases. Consider this first if Pa02 <9kPa in room air, mild and early presentation - target
Hb 100-110g/L to prevent deterioration. If severe ACS or failure to respond to simple
transfusion or Hb >90g/L already then need to exchange.
c. Intravenous fluids (normal maintenance in ACS) and careful input/ output chart
d. Antibiotics: IV Ceftriaxone and oral Clarithromycin bd
e. Analgesia as required
f. Chest physiotherapy, with bubble pep or incentive spirometry hourly
g. Bronchodilators: may be useful for those patients with known airways disease but should not
be used routinely
Check HbS % post procedure, aim HbS% < 30 %
2. Acute Sequestration
SPLENIC SEQUESTRATION: Splenic sequestration is more common in infants and young

children (< 3 years old) and may be recurrent. It may be precipitated by fever, dehydration or
hypoxia. Rapid sequestration leads to sudden anaemia and can result in death from hypoxic
cardiac failure.
Symptoms
 Abdominal pain
 Abdominal distension
 Possibly sudden collapse
Signs
 Pallor
 Rapidly enlarging spleen (may or may not be painful)
 Shock (tachycardia, hypotension, tachypnoea)
 +/- Fever due to associated sepsis
Investigations
 FBC & retics (raised in sequestration but absent in aplastic crisis)
 U&E, LFTs
 Blood cultures & other infection screen, as clinically indicated
 Parvovirus B19 serology (differential diagnosis is aplastic crisis)
 Cross match

Cautious transfusion of small RBC volumes is now recommended to raise Hb level to steady
state – often reverses the process and corrects hypovolaemia and anaemia. Avoid Hb
>80g/L due to risk of hyperviscosity when sequestered RBCs return to circulation
Management
a. Give high flow oxygen
b. Establish IV access and give fluids to resuscitate and maintain adequate perfusion pressure
(caution as may cause cardiac decompensation), whilst waiting for blood
c. Emergency red cell transfusion. In extremis use uncross-matched, O neg blood
d. Broad spectrum antibiotics e.g. Ceftriaxone (vs Pneumococcus and Haemophilus)
e. Before discharge, teach parents to recognise the symptoms and to detect an increase in
spleen size
f. Consider transfusion regimen or splenectomy if recurrent
HEPATIC SEQUESTRATION: Less common than splenic sequestration and usually

less severe
Symptoms
 Right upper quadrant pain
 Abdominal distension
Signs
 Pallor
 Enlarging tender liver
 Increasing jaundice
 Collapse/ shock less common than with splenic sequestration
 +/- fever
Investigations
 Bilirubin may be very high
 Exclude gallstones by ultrasound
 Blood culture and other infection screens as appropriate
Management
a. Urgent top up or exchange transfusion. Cautious transfusion of small RBC volumes is now
recommended to raise Hb level to steady state – often reverses the process and corrects
hypovolaemia and anaemia. Avoid Hb >80g/L due to risk of hyperviscosity when sequestered
RBCs return to circulation
b. IV Ceftriaxone
3. Abdominal Crisis and Mesenteric Syndrome

ABDOMINAL CRISIS
Insidious onset with non-specific abdominal pain, anorexia and abdominal distension.
Constipation may often co-exist, especially if opiates have been used as analgesia. In an
abdominal crisis, bowel sounds are diminished, and there is often generalised abdominal
tenderness; rebound tenderness absent. The abdomen is not rigid and moves on respiration.
Vomiting and diarrhoea are uncommon.

MESENTERIC SYNDROME
Mesenteric syndrome (sickling and sequestration in the vascular bed then liver and lungs) is
said to exist when there is an established ileus with vomiting, a silent distended abdomen, and
distended bowel loops with fluid levels on abdominal x-ray. Some hepatic enlargement is
common, and it is often associated with bilateral basal lung consolidation (early ACS).
Differential Diagnosis
Consider other common causes of surgical abdomen: acute appendicitis, pancreatitis,
cholecystitis, biliary colic, splenic infarction. Well localised or rebound tenderness, board-like
rigidity or lack of movement on respiration are suggestive of these. Ultrasound may be helpful.
Investigations
 Oxygen saturation and chest x-ray
 Abdominal ultrasound and AXR, as indicated
 Serum amylase to exclude pancreatitis
Management
In addition to analgesia and fluids, as outlined before:

a. If there is vomiting, abdominal distension or absent bowel sounds, make NBM and
consider nasogastric suction.
b. Monitor abdominal girth, liver size, chest and SaO 2
c. Antibiotics: If patient is pyrexial/ unwell, first line is generally Ceftriaxone and Metronidazole. If
unusual features discuss with the infectious diseases team.
Severe mesenteric syndrome with impending ACS merits exchange transfusion
4. Aplastic Crisis
A temporary red cell aplasia caused by Parvovirus B19 can lead to a sudden severe worsening of
the patient’s anaemia. A viral prodromal illness may have occurred, but classical erythema
infectiosum (‘slapped cheek syndrome’) is uncommon and patients are often clinically well. The
main differential diagnosis is splenic sequestration, but in this retics are high and there is
abdominal pain and splenomegaly.
Diagnosis
 Hb > 20 g/L below steady state or rapidly falling Hb
 Reticulocytopenia
 Parvovirus IgM present
 Parvovirus PCR is positive
Management
 Crossmatch phenotyped blood (simple transfusion to steady state Hb is usually necessary to

maintain 02 carrying capacity of blood, particularly if no reticulocyte response - may need to
exchange if deterioration despite this) but should see spontaneous resumption of erythropoiesis
within 7-10 days of infection. Immunity to parvovirus appears to be lifelong.

5. Stroke
Stroke is a potentially devastating complication of sickle cell disease. In children, stroke is usually
due to vaso-occlusion of the cerebral vessels and infarction, rather than haemorrhage. The middle
cerebral artery territory is most commonly affected and untreated the majority will have a
recurrence. Predictive factors for stroke include those with a history of transient ischaemic attacks,
chest syndrome, hypertension, or those with a low Hb F and/or low total haemoglobin. The Stroke
Prevention Trial (STOP) showed that children with trans-cranial Doppler (TCD) velocities of
>200cm/sec are at increased risk, a risk that can be reduced by chronic blood transfusion therapy
to maintain HbS <30% in HbSS and HbS/beta0 thal. Whereas STOP2 trial found that stopping
transfusions meant reverting to abnormal TCDs and risk of stroke, TWiTCH trial showed that it is
safe to convert to Hydroxycarbamide after 1 year if no prior TIA or severe cerebral vasculopathy
as defined by MRA.
Minor symptoms can precede a major stroke. A transient ischaemic attack or stroke is
an indication for acute exchange transfusion to reduce HbS % to < 30 %, aiming for post
transfusion Hb of 100g/L to avoid high haematocrit and hyperviscosity which may worsen
neurological insult. This should be followed by regular transfusion to prevent recurrence.
SWiTCH trial showed transfusion to HbS<30% and iron chelation better than Hydroxycarbamide
and venesection for patients with iron overload and risk of stroke; SIT trial showed transfusion
benefit even post silent cerebral infarcts.
Investigations
 FBC, retics, U&E, LFTs, group and save
 Arrange urgent MRI brain and MRI angiogram. Discuss with on call neuroradiology. On call
MRI service is available and is the scan of choice. If not available urgently, a CT scan will
exclude haemorrhage but may not show evidence of infarction if performed too early. Young
children will require GA for MRI and on call anaesthetist should be contacted. Children > 3-4
years may tolerate scan with play therapy input
Management
a. Keep NBM in anticipation of general anaesthetic for MRI or line insertion

b. Neurological assessment, and regular monitoring of neurological status
c. If seizures occur, load with intravenous Phenytoin
d. Hydration
e. Crossmatch sickle negative, phenotypically matched blood (aim <7-10 days old)
If clinically unstable, exchange transfusion must be carried out urgently, preferably by

automated exchange which is quicker and allows greater control of the circulating volume.
This will require liaison between consultant paediatric haematologist, apheresis team and
anaesthetist for insertion of venous access. Alternatively a manual exchange is possible
but is labour intensive and is usually performed in 2 or 3 stages with an interval of 4-8
hours between each exchange; the aim is to achieve a HbS level below 30% within 2 days

f. If clinically stable, exchange transfusion should also be carried out urgently whenever possible;
the decision about the timing of exchange transfusion will need to be made for each individual
patient depending upon all considerations including availability of apheresis staff and ease of
venous access; such cases should always be discussed with the paediatric haematology
consultant on call.
6. Priapism
Priapism (a painful, persistent erection of the penis unrelated to sexual stimulation) can
occur in childhood. In sickle cell disease it is usually ischaemic ( or low-flow ) priapism
caused by veno-occlusive sickling in the corpus cavernosa erectile tissue. It often starts
at night in association with a full bladder. Untreated it can cause cumulative damage
and may result in impotence and for this reason requires prompt evaluation, and in the
case of fulminant priapism, emergency management.
Types of presentation
There are 2 main pictures
1. Fulminant (> 4 hours).

2. Stuttering (repeated painful erections lasting more than 30 minutes and < 4 hours)
Management
Acute/ fulminant priapism
a. Hydration intravenously
b. Reassure and keep child warm.
c. Opiate analgesia, +/- sedation
d. Catheterisation to empty bladder
e. Urgent Paediatric urology opinion
Ischaemic priapism requires intra-cavernous treatment in addition to conservative measures
above. The options are:
1. Intra-cavernous injection of sympathomimetic drugs such as phenylephrine.
Phenylephrine is diluted to a solution of 0.25mg/ml, and 0.25mg (1 ml) is injected directly into
one corpus cavernosum. Injections can be repeated every 5 minutes for an hour. Lower doses
and volumes should be used in smaller children. Patients should be monitored for
cardiovascular side effects: acute hypertension, tachycardia, reflex bradycardia.
2. Therapeutic aspiration and irrigation with dilute (1:1000000) epinephrine solution
Both of these require a consultant paediatric urologist and most likely GA. The longer acute
priapism has been present, the less likely these measures will be effective. For patients who fail
these measures, the following should be considered:

a. Epidural anaesthesia
b. Surgical intervention in the form of a shunt procedure. Pre-op transfusion may be indicated
– discuss with the paediatric haematology team
c. Exchange Transfusion: no good evidence although aiming HbS <30% may help. Outcome
is unpredictable and has been associated with onset of severe neurological complications
(ASPEN syndrome – association of SCA, priapism, exchange transfusion and neurology).
Stuttering Priapism
a. Increased oral fluids, with frequent emptying of bladder
b. Oral analgesia
c. A trial of oral Etilefrine in consultation with paediatric urology
The patient should attend A&E if an episode lasts > 2 hours
7. Infection
Osteomyelitis
The diagnosis of osteomyelitis in the context of sickle cell disease is often difficult, and relies on
factors such positive blood cultures, persistent local inflammation, unusual swelling, and/or pain.
Fevers may not be persistent. A high CRP may be helpful, but together with most of these other
features may also occur in uncomplicated vaso-occlusive crisis. Ultrasound and MRI may
occasionally be helpful, but often give ambiguous results. X-ray changes do not appear until
about 10 days after the onset of infection. Input from the orthopaedic team is valuable, and they
may recommend aspiration in order to try to identify organisms if fluid has been seen on
ultrasound. Fluid can be quite purulent even in patients with sterile infarcts.
Any recommendation to aspirate an affected joint or perform a bone biopsy must be
discussed with a consultant haematologist before proceeding (including the need for
transfusion pre-procedure).
Salmonella is the commonest organism in osteomyelitis in sickle cell patients, but Staphylococcus
and S. pneumoniae are also common. Advice on antibiotic choice and length of treatment should
be sought from microbiology and infectious diseases teams.
Pneumococcal and Haemophilus septicaemia
Overwhelming sepsis remains the major cause of death in children with sickle cell
disease, particularly in the developing world. Vaccination and compliance with
penicillin prophylaxis reduces but does not negate the risk.
Suspect in any clinically unwell sickle cell disease patient with pyrexia > 39 C

Investigations
 FBC, retics, U&E, LFTs, Coagulation screen, CRP
 Group and SaveSimple transfusion may be useful in improving anaemia, microvascular blood
flow, tissue oxygenation and overall condition (discuss with Paeds Haem first)
 Blood cultures
 Throat swab, Urine culture
 Venous blood gas
 LP if indicated
 CXR
Management
a. Establish IV access
b. Commence Intravenous antibiotics immediately. First line choice of antibiotic is as per
BRHC infection guidelines with CEFTRIAXONE 80 mg/kg once daily, which will cover both
Pneumococcus and Haemophilus and penetrate CSF. For severely ill children, add
Gentamicin. In children who have recently returned from abroad, where antibiotic
resistance may occur, add Vancomycin. Further discussion should take place with
microbiology
c. Fluid resuscitation if required
d. Monitor O2 saturations and give oxygen if < 95 %
Refer patients with an oxygen requirement or haemodynamic instability to PICU

Malaria
The sickle haemoglobin does not protect children with sickle cell disease from
malaria. Children with SCD and malaria may become severely unwell due to anaemia
from haemolysis. Any child returning from a malarious area with a fever must be
screened for malaria, even if chemoprophylaxis was taken
Investigations
 FBC, retics, U&E, LFTs, coagulation screen
 G&S (simple transfusion may help – discuss with the paediatric haematology team first)
 Blood cultures
 Thick and thin films x 3
 Malarial antigen test
 Check G6PD level
Management
Anti-malarials according to zone of infection and parasite identified. Discuss with the infectious
diseases team
8. Haematuria
Microscopic haematuria is common in sickle cell disease; macroscopic haematuria may be due to
urinary infection or papillary necrosis. Passing of renal papillae may cause renal colic and ureteric
blockage.

Investigation
 MSU for culture to exclude infection
 Ultrasound scan
9. Biliary Tract
Pigment gallstones due to ongoing haemolysis are common in sickle cell disease, occurring in at
least 30% of children. They are often asymptomatic but can precipitate painful abdominal crises.
They can also cause:
• Acute cholecystitis
• Chronic cholecystitis
• Biliary colic
• Obstruction of the common bile duct
• Acute pancreatitis
Investigations
 Abdominal ultrasound
 MRCP if evidence of common bile duct obstruction
Management
Acute episode of cholecystitis

a. Analgesia
b. Hydration
c. Antibiotics (discuss with ID team)
Recurrent cholecystitis is an indication for cholecystectomy
Common bile duct obstruction

Most stones will pass spontaneously and management is conservative with hydration, analgesia
and antibiotics. After one attack, refer for surgical opinion regarding elective cholecystectomy
Stones that do not pass need further investigation and management. Refer to surgical team/
gastroenterology
Magnetic resonance cholangiopancreatography (MRCP) will delineate number and location of

stones. Unresolving CBD obstruction may require ERCP and sphincterotomy or an open
procedure if ERCP not possible
10. Ophthalmic
The ocular complications due to sickle cell disease are uncommon in children; however retinal
vessel occlusion may begin in adolescence, in particular in children with HbSC disease. Thus
these children require annual ophthalmological assessment: referral should be made to Dr Cathy
Williams at the Bristol Eye Hospital

Management
Laser therapy is the treatment of choice for proliferative sickle retinopathy.
Vitreous haemorrhage and retinal detachment may occur. This is an indication for urgent
ophthalmology review: contact on call ophthalmology SpR via switchboard
Surgical treatment should not be undertaken without prior exchange transfusion.
Discharge from ward
 Ensure the patient has sufficient medication:

Antibiotics if completing a course
Prophylactic Penicillin V to restart when antibiotic course completed
Folic acid
Oral analgesia: paracetamol, ibuprofen and tramadol. Some patients may be discharged
home with short supply (5 days) of oramorph
 Plan a short-term review in Oncology Day Beds (Ext 8145/8522)

 Ensure that a haemoglobinopathy outpatient clinic appointment has been made. Liaise
with CNS or haematology secretary

Red Cell Transfusions
1. General Principles
• Blood transfusion should only be used for specific indications and as sparingly as possible.
• Avoid hyperviscosity by ensuring final haematocrit < 0.35.
• Give sickle negative, extended phenotype matched blood (incl. Rh C, D, E, Kell).
• Transfusion will NOT reduce severity or duration of uncomplicated painful crises.
2. Pre and post transfusion Investigations
For all transfusions in patients with sickle cell disease it is important to record the following
information before and after the procedure:
 FBC
• HbS % (or S+C in HbSC disease) – pre-transfusion only if previously transfused
• Antibody screen & crossmatch
• U&E, Cr, Ca, Phosphate
 LFTs
 Virology sample for storage
Ensure patient has been or is being vaccinated against hepatitis B. HIV and Hepatitis C antibody
status should be checked prior to embarking on regular transfusions.
3. Top Up Transfusions
Indication:
This is indicated if a patient with SCD drops their haemoglobin to a level causing/ risking clinical
compromise, including cardiac failure and hypovolaemic shock.
It is rarely necessary to transfuse if the Hb is >50g/L, or <20g/L below steady state, unless there is
reticulocytopenia associated with the falling Hb or clinical evidence that the fall in Hb will continue.
Top up transfusion may also be indicated in patients with moderately severe crises, where
exchange transfusion is not felt necessary.
These circumstances may arise with:

• Splenic sequestration
• Hepatic sequestration
• Acute chest syndrome
• Mesenteric syndrome
• Aplastic crises (parvovirus B19)
• Blood loss
• Haemolytic crises

Pre-operative blood transfusion may be indicated (see elective transfusions below, in keeping with
2016 BCSH guidance)
Blood transfusion before flying may also be considered.
Aims:
To improve oxygen carrying capacity
To dilute sickle cells and improve blood viscosity and flow
Raise Hb to patient’s steady state level.

Do not raise Hb > 100g/L or 10-20g/L above baseline (or Hct > 0.35) so as to avoid increasing
blood viscosity. Aim HbS <30%.
Practical Points:
Volume
Volume of blood to be transfused (ml) = (desired Hb – current Hb) x weight (kg) x K
K is a constant depending on the haematocrit of the blood to be transfused:

3.5 – packed red cells
4 – plasma reduced blood (SAG-M)
Rate
In severe anaemia, it is preferable to transfuse a maximum of 5ml/kg over 4 hours at one session
and repeat as necessary.
Blood products:
Usually packed red cells are used.
These should be sickle negative, ABO, Rh and Kell compatible, extended matched phenotype and
<7-10 days old.
4. Exchange Transfusion
Exchange transfusion is generally reserved for the treatment of life or organ-threatening crisis or
other major complications of SCD and should only be undertaken following assessment by the
responsible paediatric haematology consultant.
Indications:
• Severe acute chest syndrome

• Mesenteric syndrome
• New CVA
• Fulminant hepatic or multi organ failure
• Priapism unresponsive to therapy
Sometimes indicated:
• Pre-operatively (see page 32)

Aims:
To remove sickle cells, dilute those remaining and improve blood viscosity, flow AND oxygen
carrying capacity.
To avoid a rise in haematocrit and blood viscosity (final Hct < 0.35).
To reduce final HbS to < 30%.
To keep final Hb < 110 g/L (up to 120g/L permitted if HbS <30% confirmed)
To avoid changes in circulating blood volume throughout the exchange
METHODS
a. Automated
Modern cell separators e.g. COBE Spectra can perform automated red cell exchange.
This method, if available, is preferred to manual exchange – it is quicker and allows greater
control of circulating volume. The apheresis team is based at Bristol Haematology and Oncology
Centre (BHOC; Ward D701 of BRI) and is available including out of hours (please discuss with
consultant paediatric haematologist, who will liaise with apheresis team).
Good venous access is essential in order to maintain adequate flow rates, which are necessary
for the machine’s running. In most patients, particularly small children, a temporary vascath will be
inserted. For children already on PICU this will be facilitated by PICU staff. For children on general
wards, liaise with on call anaesthetist and theatre
Information required for apheresis team pre-exchange:
Patient details
 Sex
 Height
 Weight
 Pre Hb/ Hct
 Pre transfusion Hb S%
Hct of transfused blood

 0.65 for packed red cells (0.55-0.75)
Desired post Hct

 0.35 (to avoid hyperviscosity)
Desired % FCR (fraction of patient cells remaining)

 20%
Volume of blood to be exchanged is calculated by the machine but should equate to

1-1.5 x total blood volume (tbv = 80ml/kg), and the correct amount of cross matched blood
needs to be available at the start of the procedure. Packed red cells are used and should be
specially grouped (ABO compatible, Rh and Kell compatible – request extended matched
phenotype), and Hb S negative and aim <7-10days old. Ensure that the blood transfusion
laboratory is aware that the blood required is for exchange transfusion.

Blood needs to be warmed before transfusion. Do not use diuretics with the transfusion as this
may increase procedure risk by increasing blood viscosity.
During automated red cell exchange, patients may experience symptoms related to
hypocalcaemia (peri-oral paraesthesia, tetany etc.). These can generally be prevented by
administration of oral calcium supplements during the procedure. If symptoms occur they
can be relieved by administration of intravenous calcium gluconate (0.5ml/kg 10% calcium
gluconate).
Post Exchange Investigations
 FBC – For final Hb/ Hct. There may also be loss of platelets during these procedures,
which usually recover spontaneously
 Hb S% (or S + C in HbSC disease)
 Coagulation screen
 U&E, Cr, Ca, Phosphate
 LFTs
b. Manual
A manual exchange can be performed under certain circumstances such as unavailability of

apheresis staff or inability to obtain adequate access for automated exchange. However it is
labour intensive, time consuming and it is not usually possible to achieve the desired reduction in
Hb S% in one procedure. Wider fluctuations in blood volume than in automated exchanges can
occur. For these reasons, in critically unwell patients, it is always preferable to perform an
automated exchange in PICU if possible. See Appendix 2 (p. 35) for practical points.

5. Elective Transfusions
These may be used for patients with severe complications of sickle cell disease, in particular:
• Stroke & other CNS complications

• Chronic organ damage such as chronic renal failure or chronic lung disease
• Failure to thrive (when causes other than sickle cell disease have been excluded) or
delayed puberty
• Intractable or very frequent painful crises or chest crises – but only if Hydroxycarbamide
contraindicated/ failed
Aim to keep HbS level < 30%. This can be achieved by regular top-up transfusions (generally at 3
– 4 weekly intervals). Patients vary in the frequency and amount of blood required to suppress
HbS production. In children with HbSC disease it is usually necessary to start with an exchange
transfusion and in other children it may be necessary to intermittently exchange at times. There
are both advantages and disadvantages to performing regular exchange transfusions, which may
be more effective in reducing HbS% and complications of sickling and cause less iron
accumulation and less risk of hyperviscosity. However, they are associated with higher donor
exposure and require better venous access.
For top-up transfusions the volume of packed red cell required (ml) is:
(Hb desired in g/L – Hb current in g/L) x weight (kg) x 0.35
e.g. (100g/L – 70g/L) x 40kg x 0.35 = 30 x 40 x 0.35 = 420ml
The usual rate of transfusion is 5ml/kg/hour for elective transfusion
Post-transfusion, check FBC and HbS level
In some cases failure to get an adequate increment may be due to an enlarged spleen resulting in
hypersplenism and the K value should be increased to 4 or 5. If Hb is very low pre-transfusion,
consider increasing frequency of transfusion – if Hb is low post- transfusion, consider increasing
volume of blood transfused.
Additional Investigations
• HBsAg, level of anti-HBs Ab annually. Remember to state on the virology request form that
the patient has been vaccinated.
• HCV Ab and save serum annually
• HIV Ab (with parental/ guardian consent) at outset
• Serum ferritin
These children will require iron chelation therapy and appropriate monitoring performed to ensure
adequate and safe chelation (see Thalassaemia protocol).

Management of Surgery in patients with Sickle Cell Disease
1. Preoperative Sickle Screening

It is important to detect all patients with sickle cell disease and sickle cell trait before anaesthesia
in order to ensure that the necessity for pre-operative blood transfusion is considered and also
that the patient is kept well hydrated and oxygenated both during surgery and in a post-operative
period.
There is a wide range of ethnic groups in which haemoglobin S may occur – testing should be
performed on all patients who are not of northern European origin as below:
* Ethnic groups at risk of Haemoglobinopathy (NB Ethnic origin of BOTH

parents must be identified)
African
Caribbean
Mediterranean including North Africa, Italy, Greece, Cyprus, Turkey
Middle Eastern
Indian subcontinent and South East Asia
Investigations
Newborn screening for sickle cell disease introduced 2006 in UK but older children/ born outside
UK may not have been screened at birth so still important to check.
The admitting clinicians (paediatricians or surgeons) should ensure that verbal consent is
obtained for testing and that an appropriate explanation is given to parents.
The ethnic group should always be stated on the blood form.
Routine surgery – FBC, sickle solubility test and HPLC
Emergency surgery – FBC, Sickle solubility test, blood film, with HPLC to follow
Patients may have a normal haemoglobin especially those with haemoglobin SC disease and S
beta+ thalassaemia
Management
Children with newly identified sickle cell disease having elective surgery should be seen prior to
surgery in the paediatric haematology clinic. Those having emergency surgery should be seen on
the ward. Contact Haematology SpR or CNS.
It is safer to assume sickle cell disease if it is suspected and definitive diagnosis is not possible
pre-operatively.

Below is a suggested protocol for pre-anaesthetic testing for sickle cell disease
A protocol for pre-anaesthetic

testing for sickle cell disease
Assess urgency of
anaesthesia and surgery
Surgery is Surgery
non-urgent is urgent
Assess patient and Ascertain if patient

perform FBC, blood has clinical features
film, haemoglobin suggestive of sickle
electrophoresis or cell disease
HPLC and sickle
solubility test;
proceed to surgery
when investigations Clinical Clinical
Clinical Clinical
completed. Refer features features
features features
children with sickle absent present
absent present
cell disease
Perform sickle Perform sickle

solubility test, FBC solubility
solubilitytest
test and
and
and examine blood FBC and examine
FBC and examine
film if anaemic blood
blood film
film
No relevant No relevant Relevant clinical

clinical
No features,
relevant clinical features, features or blood
negative
clinical features, positive sickle film suggestive of
solubilitysolubility
negative test solubility test, sickle cell disease,
and normal Hb
test and normal normal Hb or positive sickle
Hb abnormal Hb and solubility test
film not indicative
of sickle cell
Regard patient as
Regard patient assickle
sickle
disease, consult
disease, consult
haematologist, avoid
haematologist, avoid
Regard patient as hypoxia, hypotension,
hypoxia, hypotension,
Regard patient sickle cell trait, hypothermia and
hypothermia or
dehydration
as normal avoid hypoxia dehydration

2. Preoperative Sickle cell screening of children at Dental Hospital
Please refer to specific guideline on DMS on Intranet. Children with known sickle cell disease
should not have dental surgery at the Dental Hospital. Arrangements should be made for dental
surgery to be performed at the Children’s Hospital.
3. Preoperative Management Plan

All children with SCD are at increased risk of sickle complications at the time of surgery. Certain
patients with sickle disease are at greater risk of perioperative complications. They include
patients with:
 severe sickle related problems such as chest crisis, CNS disease and frequent, painful
crises
 severe obstructive sleep apnoea
 planned management involving major surgery
The pre-operative management of patients with sickle cell disease therefore requires good
communication at all times between the surgeons, anaesthetists, haematologists, paediatricians
and nursing staff. It is essential that the paediatric haematology team be informed well in advance
so that they can help to formulate an appropriate management plan; they should have >2 weeks’
notice of elective surgery in case plans need to be made for top up or exchange transfusion. Try
to avoid scheduling anything more than minor procedures immediately before a weekend
 Ensure that the full red cell phenotype is known by the blood transfusion laboratory. In
all cases, there must be at least a group and save in the laboratory before theatre and
phenotyped blood (extended match) should be available before surgery. Multiple red
blood cell antibodies may be present as a result of repeated transfusions – the lab
needs 24 hours’ notice of requirements as compatible blood may need to come from
Filton or beyond.
 Ensure that the blood transfusion lab knows that the blood is for a patient with sickle cell
disease – request sickle negative, recently donated blood.
 Multiple red cell antibodies or risk of hyper-haemolysis mean that transfusion is not a
viable option for some children, when the haematology team may consider a prolonged
course of erythropoietin before surgery. Religious and cultural preferences may also
need to be negotiated, e.g. Jehovah’s Witness.
 There should be a plan documented in the notes by the paediatric haematology team
for perioperative management. If the patient is referred from another hospital in the
region, it is essential that there is discussion with the haematologists from that hospital
to ensure that the relevant past history is communicated and that there is a joint
perioperative management plan.
 Ensure that the anaesthetists are aware of the patient’s sickle cell status
 Ensure any special support e.g. PICU bed for CPAP has been organised.

4. Pre-operative transfusion
The optimal pre-operative transfusion policy in sickle cell disease is controversial but recent
BCSH guidelines (2017) simplify decision making to an extent.
This is largely due to the recent TAPS trial (Howard et al, Lancet 2016), which reported decreased
perioperative complications, especially chest crises, in patients who were transfused before low or
medium risk surgery.
Good perioperative management (optimising oxygenation, hydration and analgesia) are essential,
and the decision to transfuse before surgery still needs to be considered on an individual basis as
early as possible in discussion with the haematology team. However, the following are guidelines
for practice:
 For HbSS and HbSB0thalassaemia patients undergoing low risk surgery (e.g.
adenoidectomy, dental procedures, port or grommet insertion, D&C) or medium risk
surgery (e.g. abdominal, orthopaedic, tonsillectomy):
o If Hb <90g/l, raise Hb to around 100g/L through simple transfusion 2-10 days
beforehand
o If Hb >90g/L, do partial exchange transfusion 2-10 days beforehand
 For HbSS and HbSB0thalassaemia patients undergoing high risk surgery (e.g. eye/
neurosurgery, cardiac surgery, organ transplant, use of tourniquets or hypothermia):
o Perform exchange transfusion 2-10 days beforehand
 For HbSC patients undergoing medium risk surgery (e.g. abdominal, orthopaedic,
tonsillectomy) or high risk surgery (e.g. eye/ neurosurgery, cardiac surgery, organ
transplant, use of tourniquets or hypothermia):
o If Hb <90g/l, raise Hb to around 100g/L through simple transfusion 2-10 days
beforehand
o If Hb >90g/L, do partial exchange transfusion 2-10 days beforehand
 All others patients should be individually assessed, taking into account previous history
(including significant comorbidities) and risk/ length of surgical procedure. Transfusion is
more likely to be indicated if the chance of post-op chest infection or acute chest syndrome
is high.
Emergency surgery
All children with sickle cell disease requiring a general anaesthetic and surgery should be
discussed with the on call haematology team (including out of hours), who will review the patient
and produce a pre-operative plan.
In the emergency situation decisions will be based on the sickle genotype, phenotype, Hb level,
urgency and type of surgery, and baseline fitness of the child.
 Most patients with HbSS and HbSB0thalassaemia will have Hb <90g/L and can be
managed with top up transfusion if no undue delay to surgery. Exceptions are high risk
surgery and significant chronic disease (consider exchange).

 If delay threatens survival, surgery should be performed and blood transfusion (top up or
exchange) can be given intra-operatively or post operatively.
 If Hb >90g/L and surgery is low risk, it is acceptable to proceed to surgery with a plan to top
up or exchange transfuse during or after the operation if needed.
5. Perioperative Management
Ensure surgeons, anaesthetists, haematologists and nursing staff are aware of the patient and the
expected time of surgery. Admit the patient the day before to an inpatient bed
 Start IV fluids when oral fluids are stopped and continue until the patient is able to take oral
fluids freely
 Monitor SpO2 for 24 hours after surgery
 Give prophylactic antibiotics (antibiotic choice depends on type of surgery)
 Ensure adequate postoperative analgesia is prescribed
 For thoracic surgery and some abdominal and pelvic surgery, including splenectomy,
CPAP on PICU for a minimum of 24 hours after surgery is recommended. All other patients
should receive prophylactic post-operative chest physiotherapy, including incentive
spirometry
RELATED Paediatric Pain Management Guidelines

DOCUMENTS
QUERIES Contact Anna Farrell (Paed Haem CNS Mon-Thurs) or Caroline Roberts (Paed
Haem CNS Tues-Fri) on ext 28721

APPENDIX 1
Flow Chart for the Management of Painful Sickle Cell Crises
Mild Pain Moderate Pain Severe Pain

0–4 5–7 8 – 10
Paracetamol
Paracetamol
Ibuprofen
Ibuprofen Intranasal Diamorphine
Tramadol
LMX4
LMX4 Oramorph
(Omit any that they have
(Omit any that they have
had already)
had already) LMX4
Pain reduced Pain reduced Arrange

in 30 mins in 30 mins admission
yes no yes no
■ IV access
■Bloods (FBC & retics, G&S, U&Es,

LFTs)
■Reassess pain in 30 mins
Pain relieved: Oramorph 4 hourly
Ongoing pain: Morphine IV followed

by either:
Observe
for 2 hours Observe ■Oramorph regularly
for 2 hours
OR
■ Morphine IV infusion/PCA/NCA
Contact Pain team
■ Regular Paracetamol & Ibuprofen
■ Movicol
Home on
Paracetamol Home on ■ Antiemetics
& Ibuprofen Paracetamol
■Ensure folic acid and prophylactic
Ibuprofen &
Penicillin V continue.
Tramadol
■ IV fluids
Modified from pain flow chart from Guidelines for

The Management of Sickle Cell Disease, Birmingham
Children’s Hospital

APPENDIX 2
Practical points of manual exchange transfusion
Total Volume of blood to be exchanged = 1.5–2 x total blood volume (tbv =80ml/kg).
A single volume exchange will replace ~ 65% of the patient's cells; a double volume exchange will
replace ~85%.
It is usual that 3-4 exchanges will be necessary lasting approximately 3 hours each. Where
possible, leave a 4 - 8 hour break between exchanges. In the very sick patient, the procedure is a
continuous process. In these patients, particular attention should be paid to PaO2, core
temperature, U&E, Ca++, phosphate, platelets and clotting.
Preparation of the patient
Patients must be well hydrated prior to starting an exchange transfusion. Adequate explanation
must be given to the child and parents as to the indication for exchange and its potential risks and
benefits and this should be documented in the case-notes.
Venous access
Good venous access is essential:

 Two cannulae will allow venesection from one and transfusion through the other
 In patients with a port in situ, a cannula can be used for venesection and the port for
transfusion. Peripheral lines and port will need intermittent flushing with dilute heparin to maintain
patency
 In some patients a central venous line may be required – this can be used, with a three-way
tap, for the exchange transfusion
 An arterial line may be used for blood removal and a peripheral or central venous line for
transfusion
Procedure
Aim to exchange 0.5 blood volume in each exchange, over about 4 hours
For a 0.5 blood volume exchange, the volume of blood removed for each procedure should be:
40 x weight in kg = volume in ml (assuming total blood volume of 80 ml/ kg)
The aim is that this should be an isovolaemic procedure with frequent monitoring of blood
pressure, heart rate and oxygen saturations and temperature.
 It is important to ensure that the child is well hydrated between successive exchanges and that
the haemoglobin is regularly monitored and remains < 100 g/L until the final exchange
 For the first procedure, start by venesecting 25% of the above volume (ie 10 ml/kg) over
approx. 60 minutes in aliquots of 10 - 50 ml using a large syringe. Normal saline should be
concurrently infused at the same rate to maintain isovolaemia. If the child has haemoglobin of
less than 60 g/L or Hct < 0.2, replacement with blood rather than normal saline will be needed.

 If it is only possible to get a single venous line, use a three-way tap to remove an
aliquot of blood and then replace with the same volume (transfuse and venesect in
aliquots of 10-30ml).
 The venesected blood can be discarded into a venesection bag via a 3-way tap.
 Continue venesecting the remaining 75% of the volume (30 ml/kg) replacing with packed
red cells at the same rate instead of normal saline. Note that the haematocrit of transfused
packed cells (approximately 0.65) is higher than that of the venesected blood.
This process should take about 4 hours depending on the rate of flow of blood and the
clinical condition of the patient.
Where possible leave at least 4-6 hours between each exchange procedure. In critically ill
patients exchanges may need to be continuous.
Check FBC, HbS %, U&E, Cr, Calcium, and clotting at the end of each procedure.
Ensure that the Hb <100 g/L to reduce the risk of hyperviscosity.
Continue with 3 to 4 exchange procedures until the Hb S <30%.
NB For the second and subsequent exchange procedures, it may be necessary to use a ratio
of 50% saline: 50% blood (rather than 25:75) in order to prevent the Hb from rising too high.
This should be discussed with the paediatric haematology SpR or consultant when planning
the procedure. A top-up transfusion can be given at the end of the final exchange procedure to
give a final Hb of ~120 g/L.

APPENDIX 3
Key References
1. Howard J, Malfroy M, Llewelyn C, Choo L, Hodge R et al. The Transfusion Alternatives

Preoperatively in Sickle cell disease (TAPS) study: a randomized, controlled, multicentre
clinical trial. Lancet 2013; 381(9870): 930-8 [doi:10.1016/S0140-6736(12)61726-7]
2. Howard J, Hart N, Roberts-Harewood M, Cummins M et al, and on behalf of the BCSH

Committee. Guideline on the management of acute chest syndrome in sickle cell disease.
British Journal of Haematology 2015; 169(4): 492-505 [doi:10.1111/bjh.13348]
3. Davis B, Allard S, Qureshi A, Porter J et al, and on behalf of the BCSH Committee. Guidelines
on red cell transfusion in sickle cell disease. Part 1: principles and laboratory aspects. British
Journal of Haematology 2017; 176(2): 179-91 [doi: 10.1111/bjh.14346]
4. Davis B, Allard S, Qureshi A, Porter J et al, and on behalf of the BCSH Committee. Guidelines
on red cell transfusion in sickle cell disease. Part 2: indications for transfusion. British Journal
of Haematology 2017; 176(2): 192-209 [doi: 10.1111/bjh.14383]
5. Adams R, McKie V, Hsu L, Files B, Vichinsky E et al. Prevention of a first stroke (STOP) by
transfusions in children with sickle cell anaemia and abnormal results on transcranial Doppler
ultrasonography. New Engl J Med 1998; 339: 5-11 [doi: 10.1056/NEJM199807023390102]
6. Adams R, Brambilla D, Optimising primary stroke prevention in sickle cell anaemia (STOP2)
trial investigators. Discontinuing prophylactic transfusions used to prevent stroke in sickle cell
disease. New Engl J Med 2005; 352(26): 2769-78 [doi: 10.1056/NEJMoa050460]
7. Ware R, Helms R, for the SWiTCH Investigators. Stroke with transfusions changing to
Hydroxyurea (SWiTCH). Blood 2012; 119: 3925-32 [doi: 10.1182/blood-2011-11-392340]
8. Ware R, Davis B, Schultz W, Clark Brown R, Aygun B et al. Hydroxycarbamide versus chronic
transfusion for maintenance of transcranial Doppler flow velocities in children with sickle cell
anaemia – TCD with transfusions changing to Hydroxyurea (TWiTCH): a multicentre, open-
label, phase 3, non-inferiority trial. Lancet 2016; 387(10019): 661-70 [doi: 10.1016/S0140-
6736(15)01041-7]
9. Estcourt L, Fortin P, Trivella M, Hopewell S. Preoperative blood transfusions for sickle cell
disease (review). Cochrane Database of Systematic Reviews 2016; 4: CD003149 [doi:
10.1002/14651858.CD003149.pub3]
10. Howard J, Morley A, Westerdale N. Perioperative management of sickle cell disease in adults
(clinical guidance). Guys and St Thomas’ NHS Foundation Trust 2014; v4.0

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Clinical Guideline

SICKLE CELL DISEASE MANAGEMENT GUIDELINES

Written March 2010,

Authors: Dr Michelle Cummins

Sickle Cell Crisis: Investigations 6

Management of Acute Painful Crisis 9

Management of Specific Sickling Problems 14

Discharge from ward 23

Red Cell Transfusions 24

Paediatric Haematology Team

Dr Michelle Cummins Consultant Paediatric 07770643638

Other Useful Numbers

Pain Team Pain Team CNS Bleep 3974

Oncology Day Beds Ext 28145/28522

*PLEASE FOLLOW ALGORITHM OVERLEAF (PAGE 6)*

Call the paediatric haematology team immediately if there is:

Check diagnosis (HbSC/HbSS/HbSβ0thal) – access clinic letters (medication, transfused, antibodies?)

Any fever, neurological impairment, hepatosplenomegaly, chest features, pallor?

Abdominal pain p.15-17

Limb pain p.9-11

Chest symptoms and signs p.14-15

1. Routine Investigations (all cases)

2. Additional Investigations (according to clinical picture)

Serum amylase Abdominal symptoms/signs

Screen stool for Yersinia. Patients on iron chelation

 Hb, HPLC, including % HbF

Please refer to related Trust Guidelines

 Paediatric Pain Service: Acute Pain Management (includes section on Sickle)

Morphine (oral or intravenous) + Paracetamol + Ibuprofen

 Rapidly and well absorbed across the nasal mucosa

Patient controlled analgesia/nurse controlled analgesia (PCA/NCA) can only be started by a

All patients receiving intravenous morphine require routine monitoring as described in

Moderate pain may respond to Tramadol.

Regular Ibuprofen, Oral

Regular Paracetamol, Oral

PRN Naloxone, IV – required for all patients receiving iv morphine

PRN Chlorpheniramine, Oral or IV (for opioid induced itch)

PRN Ondansetron, Oral or IV (nausea & vomiting)

PRN Metoclopramide, Oral, IM or IV slow bolus (nausea & vomiting)

Regular Folic acid, Oral (Elixir 2.5mg/5ml, Tablets 5mg)

Extended until October 2022

 Oxygen is of no benefit in simple limb pain.

Extended until October 2022

 If there are chest signs, or an abnormal CXR, add oral Clarithromycin

 If there is abdominal pain, cholecystitis or suspected mesenteric syndrome, add IV

 Patients on Desferroxamine/ Deferiprone/ Deferasirox who have diarrhoea should be started

 Stop prophylactic penicillin if additional antibiotics cover Pneumococcus

Extended until October 2022

1. Acute Chest Syndrome (ACS)

Inform attending consultant paediatric haematologist and PICU consultant

Extended until October 2022

Emergency exchange transfusion is usually an automated procedure performed by on call

Check HbS % post procedure, aim HbS% < 30 %

SPLENIC SEQUESTRATION: Splenic sequestration is more common in infants and young

Extended until October 2022

HEPATIC SEQUESTRATION: Less common than splenic sequestration and usually

3. Abdominal Crisis and Mesenteric Syndrome

Extended until October 2022

PLEASE FOLLOW ALGORITHM OVERLEAF (PAGE 6)