Sickle cell disease

Disclaimer These guidelines have been produced to guide clinical decision making for the medical, nursing and allied health staff of Perth Children’s Hospital. They are not strict protocols, and they do not replace the judgement of a senior clinician. Clinical common-sense should be applied at all times. These clinical guidelines should never be relied on as a substitute for proper assessment with respect to the particular circumstances of each case and the needs of each patient. Clinicians should also consider the local skill level available and their local area policies before following any guideline.  Read the full CAHS Emergency Department disclaimer

Aim

To guide PCH ED staff in the management of children presenting to the Emergency Department with sickle cell disease (SCD).

Background 

Sickle cell disease is caused by structurally abnormal haemoglobin (Hb S) that polymerises with shape change when deoxygenated, resulting in haemolysis and obstruction of blood flow.¹

There are 3 common types causing sickle disease, all of which are treated the same way:

• sickle cell anaemia (HbSS) is the most common
• sickle beta thalassaemia (HbSβ)
• sickle haemoglobin C (HbSC) disease

Acute crises may occur spontaneously, or may be precipitated by

• Infection
• Dehydration
• Hypoxia
• Sedatives, local anaesthetics and surgery

All patients develop functional asplenia and are therefore, at risk of infection, particularly by encapsulated organisms (e.g. pneumococcus, meningococcus, haemophilus)²

Key points

• Patients with sickle cell disease (SCD) may present with the following:
  • Vaso-occlusive crisis (painful crisis)
  • Fever – sepsis
  • Acute chest syndrome
  • Stroke
  • Priapism
  • Aplastic crisis
  • Acute splenic sequestration
  • Acute hepatobiliary disease

Many of these presentations need urgent treatment Discussion with Haematology Fellow / Consultant is mandatory

• Patients with sickle cell disease can also present with non-sickle related problems

Triage and admission guidelines

• Children and young adults known to have SCD who present with pain or an acute inter-current illness should receive a minimum ATS Category 3 (review within 30 minutes of presentation)
• Treatment should be undertaken with early ED Consultant or Senior Registrar consultation
• SCD patients with the following presentations must be referred for consideration of admission:
  • Significant pain not responsive to simple analgesia
  • Fever (>38°C) without clear focus or patients who are clearly unwell/systemic toxicity
  • Fever in a child with a central venous access device (CVAD) including infusaports
  • New neurologic signs or symptoms / concern for stroke
  • Splenic sequestration (see below)
  • Acute Chest Crisis (see below)
  • Priapism
  • SCD patients under 2 years with any acute problem should be strongly considered for admission.

General management

• A child with SCD presenting to ED with fever or pain should be assessed within 30 minutes of arrival. Consult on call Haematology Fellow / Consultant early.
• Do not wait for topical local anaesthetic for commencement of IV fluids or analgesia.

Vaso-occlusive crisis (VOC)

• Precipitated by dehydration, hypoxia or infection. Vaso-occlusion results in tissue ischaemia, with early management aiming to prevent infarction.²
• All episodes of pain should be treated initially as vaso-occlusive disease as per general management above.
• NB Chest pain may indicate an acute chest syndrome rather than as a vaso-occlusive episode if associated with respiratory symptoms.
• Common sites include bone (extremities, dactylitis or hand / foot syndrome, back), and abdomen.
• Bone pain (most common type of pain crisis) may or may not be accompanied by swelling, low-grade fever, redness, and warmth. It may be symmetrical, asymmetrical, or migratory.
• Dactylitis is a common presentation in infants and toddlers; back and abdominal pain are more common in older children.
• Abdominal pain is usually a simple VOC, but other diagnoses may present similarly (splenic sequestration, liver sequestration, constipation, appendicitis, pancreatitis, biliary colic and cholecystitis, urinary tract infection, pelvic inflammatory disease, etc.) and should be ruled out.
• Pain may be very severe and should receive urgent attention.
• Analgesia should be provided as per general management above.

Fever

Patients are at greater risk of invasive disease by encapsulated organisms due to functional asplenia.

Fever Management:

• Obtain appropriate cultures – blood, sputum, urine. Consider viral nasopharyngeal flocked swab (BioFire^® respiratory multiplex PCR).
• Commence IV antibiotics. Refer to Sepsis and Bacteraemia: Paediatric – (Clinical Scenario - Asplenia – Fever in an asplenic patient) - ChAMP guidelines.
• If giving ceftriaxone, monitor for haemolysis.
• Consider cover for atypical organisms (azithromycin) if significant respiratory component.
• Treat pain as per vaso-occlusive crisis.
• Consider and treat for acute chest syndrome if cough, hypoxia or dyspnoea is present.

Acute chest syndrome

• Acute Chest Syndrome (ACS) is defined as a new pulmonary infiltrate and ANY one of the following:
  • fever
  • tachypnoea
  • cough
  • hypoxia (oxygen saturation < 96%)
  • increased work of breathing
  • chest pain⁶
• Chest pain and hypoxaemia may be the only signs. There is significant overlap with pneumonia particularly in young children.⁶
• Chest pain should be treated as an acute chest syndrome and not simply as a vaso-occlusive crisis. Chest crisis can be a life threatening condition and patients can deteriorate rapidly.

Acute chest syndrome management

• Oxygen to keep oxygen saturation > 95% or for comfort
• Fluid management (see above) – over-hydration increases the risk of developing and exacerbating chest crisis⁴
•  Investigations including blood culture, BioFire^® respiratory multiplex PCR
• Analgesia - Emergency Department guideline
• Commence IV antibiotics – Ceftriaxone (monitor for haemolysis). Consider azithromycin if features of atypical organism.
• Chest X-ray – but this should not delay commencement of treatment
• Early referral to PCC for respiratory support if significant hypoxia or respiratory distress

Stroke

• Stroke in the SCD population is usually due to a cerebral vasculopathy caused by a combination of microvascular ischaemia-reperfusion injury and the hyperdynamic blood flow typical of patients with SCD.
• Untreated, up to 10% of children with HbSS disease will have a stroke by the age of 10 years with an incidence of 1.02% per year between 2 and 5 years.⁸
• Stroke can occur suddenly or as a complication of acute chest syndrome or aplastic crisis.

Stroke Management:

• Neuroimaging required to determine if haemorrhagic or ischaemic stroke.
• Discuss with Consultant Radiologist
• MRI is preferred.
• CT without contrast (risk of hyperviscosity) if timely MRI not available.
• Contact neurology for urgent referral.
• Exchange transfusion is indicated in the setting of acute stroke:
  • Discuss with on call Haematology Fellow/Consultant.
  • Arrange urgent red cell apheresis and exchange transfusion. 

Priapism

• Priapism is prolonged painful erection of the penis often starting in the early hours of the morning.
• May be intermittent or prolonged – common in adolescent years.
• Occurs in 2 forms:
  • Stuttering episodes which last 2-4 hours but are often recurrent and may precede a severe episode
  • Severe attack lasting longer than 4 hours and can result in cavernous fibrosis and impotence.⁹

Priapism management:

• Do not use ice
• Analgesia, oxygen, IV hydration
• Encourage emptying of bladder – may need catheterisation
• Simple measures e.g. moderate exercise, take a bath or shower
• Transfusion support is not recommended⁴– discuss with Haematology Fellow / Consultant

Priapism lasting more than 3 hours can result in ischaemia and is a urological emergency  Consult General Surgery (Urology) and on-call Haematology Fellow / Consultant urgently if > 3 hours

Aplastic crisis

• An acute illness with a decrease in haemoglobin without a reticulocyte response (usually <1%).
• Usually associated with acute infection including parvovirus.
• Presents with pallor +/- shock.

Aplastic crisis management:

• Fluid resuscitation – sodium chloride 0.9% 10 - 20 mL/kg if shocked
• Intravenous fluids and oral intake to a total of maintenance requirements
• Viral serology including parvovirus B19, Epstein-Barr Virus (EBV), Cytomegalovirus (CMV)
• Exclude splenic sequestration clinically
• Transfuse red blood cells if patient is symptomatic with anaemia or Hb < 50 g/L (do not increase Hb by > 30 g/L)
• IV antibiotics if febrile as per Sepsis and Bacteraemia: Paediatric - ChAMP guidelines.

Acute splenic sequestration

• Splenic sequestration is defined as a haemoglobin drop of at least 20 g/L below baseline level for that patient with an acutely enlarged spleen.⁶
  • Mild to moderate thrombocytopenia is often present.
  • Reticulocyte count is equal to or greater than patient's usual baseline.  
  • Consider co-existent aplastic crisis if reticulocyte count is low.

Acute splenic sequestration management

• Fluid resuscitation – sodium chloride 0.9% 10 - 20 mL/kg for hypovolaemia while waiting for blood.
• Initial transfusion to aim for Hb of 50-60 g/L initially to ameliorate shock / haemodynamic instability (do not increase > 30 g/L or higher than patient baseline)

Auto-transfusion will occur if haemoglobin is increased excessively or too quickly.This increases risk of stroke due to hyper-viscosity.

• IV antibiotics if febrile as per Sepsis and Bacteraemia: Paediatric - ChAMP guidelines

Acute Hepatobiliary complications

• Acute hepatic sequestration is defined by a sudden increase in liver size, associated with right upper-quadrant abdominal pain, and an acute decrease in Hb >20 g/L¹⁰
• Other acute hepatobiliary complications in SCD include development of gallstones due to chronic haemolysis, acute cholecystitis, and deranged LFTs.

Acute Hepatobiliary complications management

• Pain management
• Fluids
• Abdominal ultrasound for investigation of liver and biliary tree
• IV antibiotics as per Sepsis and Bacteraemia: Paediatric - ChAMP guidelines
• Transfusion if concerns of Hepatic sequestration.
• Consider viral screening for Hepatitis A, B and C, EBV, CMV, adenovirus

References

1. Piccin, A., Murphy, C., Eakins, et al. Insight into the complex pathophysiology of sickle cell anaemia and possible treatment. Eur J Haematol, 102(4), 319-330; 2019.
2. Novelli, E. M., & Gladwin, M. T. Crises in Sickle Cell disease. Chest, 149(4), 1082-1093; 2016.
3. Wang, C. J., Kavanagh, P. L., Little, A. A., Holliman, J. B., & Sprinz, P. G. (). Quality-of-Care Indicators for Children With Sickle Cell Disease. Pediatrics, 128, 484-493; 2011.
4. National Heart, Lung and Blood Institute. Evidence-Based Management of Sickle Cell Disease: Expert Panel Report. Bethesda: National Institutes of Health; 2014.
5. Davies P, Robertson S, Hegde S, Greenwood R, Massey E, Davis P. Calculating the required transfusion volume in children. Transfusion. 2007 Feb;47(2):212-6. doi: 10.1111/j.1537-2995.2007.01091.x.
6. Morrissey BJ, Bycroft TP, Almossawi O, Wilkey OB, Daniels JG. Incidence and Predictors of Bacterial infection in Febrile Children with Sickle Cell Disease. Hemoglobin. 2015;39(5):316-9. doi: 10.3109/03630269.2015.1065419.
7. Jain, S., N. Bakshi & L. Krishnamurti. Acute Chest Syndrome in Children with Sickle Cell Disease. Pediatric Allergy, Immunology, and Pulmonology, 30, 191-201; 2017.
8. Brewin, J. & J. Howard. Sickle cell disease: an update on management. Paediatrics and Child Health, 27, 506-510; 2017.
9. Donaldson, J. F., R. W. Rees & H. A. Steinbrecher. Priapism in children: a comprehensive review and clinical guideline. Journal of Pediatric Urology, 10, 11-24; 2014.
10. Slimane, A., M. Mariane de, B. Valentine, H. Claire, T. Melissa, B. Josephine, M. Elisabetta, G. Nicolas & L. Florence. Hepatobiliary Complications in Children with Sickle Cell Disease: A Retrospective Review of Medical Records from 616 Patients. Journal of clinical medicine, 8, 1481; 2019

Endorsed by:	Nurse, Co-director, Surgical Services	Date:	Mar 2023
		Review date:	Mar 2026

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