Sickle Cell Syndromes

Authors: Aekta Sharma, Jasmine Lee, Olu Adenugba / Editor: Liz Herrieven, Swagat Mishra / Codes: PAP4, HC8, HP1, SLO1, SLO3, SLO5 / Published: 16/11/2021

You’re in leafy Great Britain, and a young patient arrives in lots of pain. They ask for some morphine, because they have sickle cell, and you’re not really sure whether this is appropriate.  Keep reading to explore more about sickle cell! 

Sickle cell syndromes are hereditary haemoglobinopathies with homozygous sickle cell anaemia as the most common variant. In the UK over 12,500 people have sickle cell anaemia predominately individuals of African and East Mediterranean descent. A point mutation in the beta–globin chain results in substitution of glutamic acid by valine, therefore polymerisation of mutant Haemglobin S. This results in impaired erythrocyte morphology and survival. This is beautifully described by the Calgary Guide here.

Clinically this manifests with both haemolytic anaemia and microvascular vaso-occlusion leading to end organ injury and infarction. In the long term this results in progressive loss of organ function and chronic pain. However, in the ED the bulk of our interaction with SCD patients is in acute vaso-occlusive i.e painful crisis. This can be triggered by any event causing reduced oxygen tension e.g. hypoxia, infection, dehydration, hypothermia,  stress, pregnancy. (Members: Refresh your oxygen dissociation curve knowledge in our learning session here)

Vaso-occlusive crisis is a broad term describing all of the organs that can be occluded by the sickled cells. Cells can sickle anywhere – this includes joints, splenic sequestration crisis, acute chest syndrome (pulmonary vaso-occlusion), hepatic crisis and priapism. For most presentations, pain is the most common and serious presenting feature. For others, the sickling cells cause further complications.

Painful crisis

Acute painful crisis is the most common cause of presentation to hospital for patients with sickle Cell Disease. NICE guidelines state analgesia should be administered within 30 minutes of presentation, and RCEM state any adult patient in severe pain should get analgesia within 15minutes of arrival.

Across some Trusts, pain management plans will be personalised and uploaded onto a central system for ED doctors to access and follow. However, it can be tricky to manage a patient completely new to the hospital and studies have shown disparities in analgesia prescribing practices in this patient cohort. So how can we identify acute painful crisis and manage this effectively?

Most often these patients are experts at managing their own crises. SCD is often diagnosed in early childhood, so by the time they are an adult, they have had a lot of experience with different analgesia and regimes. Acute vaso-occlusive crisis are medical emergencies and as ED doctors we need to be confident to diagnose and treat this.

Key parts of the history:
– Precipitating factors e.g. fever, dehydration, temperature
– Location of pain  e.g. limbs, chest, back, abdomen
– Typicality of pain – is it their normal pain?
– Neurological symptoms- high risk of stroke
– Shortness of Breath – chest crisis life threatening

Investigations:

These depend on clinical judgement. Bloods, ECG, urinalysis, chest x-ray can all be useful but not always needed as they might not change management. You can check a reticulocyte count – but you know it’ll be high as they’re in crisis – it won’t change anything but is a good sign in sickle cell patients as it shows a responsive bone marrow. Generally, we only check bloods if patients get admitted, or their pain is atypical.
If you are suspicious of acute chest syndrome obtain spirometry if you are able to.

Management- Analgesia

Now we have completed our assessment and we are confident that our patient has acute painful crisis… what now?
Analgesia! This must be administered within 15 – 30 minutes of arrival to hospital and is your priority. It is more important than a cannula, or IV fluids, or a full assessment, and providing early analgesia reduces length of stay – as well as being humanitarian.

It has been well documented that painful crisis is often undertreated and multiple reasons exist for this including concerns around addiction or dependence, adverse side effects and lack of specific examination findings as well as patients looking comfortable. The recent report “No One Is Listening” describes the probable role of racial bias and is also worth a read.

Morphine is usually the first line for a strong opioid. Some patients may have diamorphine, oxycodone or fentanyl on their care plan. Often administered subcutaneously, guidelines vary but 5-10mg subcutaneously is a good option if no local protocol. Subcut analgesia is to be encouraged – it’s quick acting, less painful than IM, and can be provided more quickly than IV, particularly as many patients with SCD have difficult IV access because of repeated cannulations. In truth, most do not need IV access.

Usually give antiemetic and antihistamine alongside!

Avoid Entonox- this is usually given by paramedics en route to the hospital but prolonged use can reduce the production of red blood cells, and we’ve certainly had patients who have had sickle induced cord degeneration, and others who have become dependent. Also, nitrous is bad for the environment so we shouldn’t be using it.

Do not use Pethidine- this was commonly used in the 90s but now clearly stated in NICE guidelines to not use in SCD patients. It has a long half life and unfortunately its metabolite is a neuro-irritant which can reduce the seizure threshold.

Don’t forget to give the patient their normal oral analgesia if the timing is right.

More analgesia?

Reassess patients every 20-30 minutes and offer further boluses of strong opioid in the same dose until adequate pain relief has been achieved. How many boluses are too many boluses? As a rule of thumb offering three or more boluses of strong opioid is a good indicator that the ED will not be able to manage this patient’s pain alone. This patient will likely need admission for analgesia and consider using patient controlled analgesia (PCA).

In Summary:

– Provide strong opioids
– Clarify what the patient has already taken as often SCD patients have analgesia at home
– Refer to the patient’s individual care plan if available.
– If no care plan:    PO Paracetamol 1g QDS
PO Ibuprofen/Naproxen if no contraindications
SC Opioid

What else can we do for these patients?

Find any reversible causes and treat them. Think about infection, but the most common is dehydration- offer fluids orally or IV if they can’t tolerate oral.
Keep the patient warm.

Psychological input- consider offering breathing techniques and other non pharmacological techniques to help pain.

Bowel care – all these opiates can cause constipation – offer laxatives.
Watch out for complications including acute chest syndrome, osteomyelitis, bone infarction.

Exchange Transfusion may be done emergently in patients who have a severe crisis. Your haematology team will be able to advise. There’s a video guide available via twitter, or the patient blood management here.

“Special” Cases

Case 1 – A 36-year-old male presents to hospital with a two day history of worsening shortness of breath on exertion, feeling feverish and intermittent severe right sided chest pain. He has a past medical history of sickle cell disease. He takes folic acid regularly and recently recovered from a painful crisis involving his arms and legs.
On arrival to hospital his obs are RR 30, Sats of 93% on air, BP 130/65 HR 115 Temp 37.6.
On examination he is tachypnoeic, clinically dry and warm to touch, he is visibly uncomfortable. He has bilateral basal crackles on auscultation of the chest.
You request bloods, arterial blood gas and a CXR …

 


Case courtesy of Dr Andrew Ho, Radiopaedia.org. From the case rID: 30511

The patient is started on oxygen therapy, IV fluids and analgesia. His observations begin to improve with HR 98 BP 130/65 Temp 36.9 RR 25 Sats 95% on 1L but he is still complaining of pain. We suspect this patient has Acute Chest Syndrome in sickle cell disease

Is there anything else that might help this patient?
– Analgesia
– IV antibiotics- as per local guidelines (continue prophylactic penicillin)
– Adequate hydration – consider IV fluids
– Controlled oxygenation
– Consider blood transfusion
– Incentive Spirometry- repeated every two-three hours (plus more analgesia!)
– Haematology review
– ITU review

Acute Chest Syndrome

Acute Chest syndrome is one of the leading causes of mortality in patients with sickle cell disease. With improved recognition and medical management the mortality rates are improving. It is defined as an acute illness characterised by fever +/- respiratory symptoms accompanied by new pulmonary infiltrates on chest x-ray. It is a spectrum of disease from mild lower respiratory tract illness to ARDS.

  • Bacterial or viral infections are the most common cause especially in children! Patients with sickle cell disease must never be diagnosed with pneumonia as this cannot be differentiated clinically, biochemically or radiologically from ACS.
  • Hypoventilation-  A painful crisis affecting bony areas of the chest wall can result in hypoventilation and then basal atelectasis. This can perpetuate sickling in the pulmonary vasculature.
  • Fat Emboli- another common cause due to bone marrow infarction and circulating fat globules
  • Asthma- The patient will have corresponding signs and symptoms of an acute asthma exacerbation.

Patients with a pre-existing diagnosis will be at a higher risk of acute chest syndrome.

We must maintain a high index of suspicion in SCD patients with chest symptoms even in the presence of normal chest examination and x-ray. The chest examination is typically normal in children and often symptoms will precede chest x-ray changes

Investigations in sickle chest crisis will be thorough and include:

Blood tests including- full blood count to look for Hb and platelet fall, reticulocytes to confirm bone marrow function, biochemistry (urea, electrolytes, creatinine, liver function test) to look for infection and function, group and screen (sickle patients have special requirements for transfusion – discuss with your transfusion expert. In the UK, RBC for sickle Cell patients must be ordered from the National Blood Service which can delay transfusion times.
– Blood cultures
– Consider Arterial blood gas
– Infectious disease testing: The most common bacterial cause in adults is Chlamydia Pneumonia and in children mycoplasma pneumonia. Consider RSV screening in children – Send sputum/swabs for respiratory viral panel.

Management

Most hospitals who see sickle cell patients regularly will have a pathway as these patients can deteriorate rapidly and may require respiratory/ventilatory support. Early critical care intervention is advised.

1. Inform the on call haematology team & inform critical care team
2. Oxygen therapy to maintain Sats >95%
3. IV fluids- aim 3L IV fluids daily
4. Effective pain relief management
5. Incentive Spirometry +/- Chest physiotherapy
This should be offered to all sickle cell patients with chest pain. It has been shown to reduce the incidence of chest crisis from 42% to 5% in patients presenting with a painful crisis. Usually given every 2-3hours
6. Antimicrobials- Current guidelines state that all patients with chest crisis should be treated empirically for community acquired pneumonia plus cover for atypical organisms.
7. Blood Transfusion – Usually after advice from Haematology team and should be considered in patients with Pa02 <9.0 on room air +/- exchange transfusion in those with severe disease
8. Advanced respiratory support. Including non-invasive ventilation and invasive ventilation.

Case 2 – A young man with sickle cell disease attends with pain. He’s been reluctant to tell the triage nurse where and what the pain is. He eventually tells you he has a priapism.

Priapism is common in sickle cell patients. We’ve covered it on RCEMLearning already, but hospitals who see lots of patients with sickle cell will generally try drug therapy before aspiration. Have a look at this pathway. You may think priapism is a urological emergency, and generally you’d be right – but in patients with sickle priapism they’ll want the medics involved too.

Case 3 – A patient with sickle attends with a sore hip. His x-rays are normal. You consider salmonella osteomyelitis, which is eventually proven to be true. Sickle cell patients are more likely to have osteomyelitis but osteomyelitis is still extremely rare. X-rays and isotope scans in the early stages are not helpful. If considering performing an X-ray please discuss with senior colleague first. If there is a strong clinical suspicion of osteomyelitis (localised pain, swelling, high fever, systematically ill child), consider asking for an orthopaedic opinion. MRI or USS may be helpful in the first 24 hours if available.

Case 4 – A 15-year-old patient with sickle attends with a left sided hemi-paresis. You consider a stroke due to a vaso-occlusive crisis. He is urgently transferred to the specialist centre for exchange transfusion. Exchange transfusion is indicated for acute CVA, severe chest crisis, and life-threatening infection; the target HbS is <30% and PCV <0·35, two exchanges may be needed to achieve this.

Case 5 – A 12-year-old with sickle attends with fever. They deteriorate quickly. Remember… Children with SCD are hyposplenic and at risk of overwhelming sepsis, particularly from Streptococcus pneumoniae, Meningococcus, Salmonella spp, E.Coli and S.aureus. The risk of overwhelming pneumococcal sepsis is 600 times greater in the young child with SCD. Symptoms have a rapid onset and death can ensue within 2-3 hours.

Final points…

1. Sickle cell crisis can appear in many forms as sickling can occur in all organs. It often manifests with pain but be highly suspicious of any new neurological signs or symptoms
2. Don’t go easy with the analgesia! Follow the WHO ladder and remember these patients are often undertreated and face stigma for their analgesia needs. Hint- most patients have their tailored management plan!
3. Any adult or child with a fever and chest symptoms – look for acute chest syndrome and treat it if you’re convinced!
4. Consider blood tests in acute chest syndrome, concerns around organ failure and Sepsis (e.g shock, acute splenomegaly, jaundice).
5. Avoid Entonox, think opioids!

You can now complete our SBA on this topic. Please log in to access it.

You may also wish to complete the Not So Hip SAQ which covers the same topic.

8 Comments

  1. Irphan Yonis says:

    Outstanding info about SCD. We receive some cases of crisis. Well done.

  2. Mohammad Mutiuddin Sufyan says:

    Well written

  3. Dr. Nia Rhianwen Jones says:

    Useful summary thanks

  4. Olubusola says:

    Excellent resource

  5. Dr. RaviRaja Muddana says:

    Very detailed yet simple and catchy.Thanks.just read.

  6. Dr. Adeel Ahmad Chaudhary says:

    Very useful revision about a common ER presentation, thanks.

  7. Dr Sanaullah Chaudhry says:

    Nice review of SCD presenting to ED.

  8. Dr. Yusuf Dala Gali says:

    Quick and concise

Leave a Reply