Sickle Cell Disease

Take home messages

• Sickle cell disease is an autosomal co-dominant congenital haemoglobinopathy
• The two main problems are vaso-occlusive crises and haemolysis
• Avoid hypoxia, pain, dehydration, hypothermia and acidosis if you're anaesthetising someone with sickle cell disease

Pathophysiology

As you'll remember immediately from medical school, haemoglobin has four polypeptide chains, each covalently bound to a haem moiety.

Within this haem moiety we find a porphyrin ring at the centre of which resides an iron atom in its ferrous state (Fe 2+)

• α subunits are encoded by chromosome 16
• β or non-α subunits are encoded by chromosome 11

What happens in sickle cell

Sickle cell is a congenital haemoglobinopathy as a result of a mutation on chromosome 11.

This produces HbS.

• Homozygotes are HbSS and have sickle cell disease
• Heterozygotes are HbAS and have sickle cell trait

The problems arise because HbS is prone to polymerising at low partial pressures of oxygen, forming structures called tactoids, which are far less cool than they sound.

This causes the red blood cell to lose its flexibility, making them stiff and fragile - hence they're said to 'sickle'.

HbAS can also sickle, but only at very low partial pressures of oxygen, which don't tend to occur in usual clinical practice, so sickle cell trait patients don't generally suffer from the same symptoms as HbSS.

Effects on the body

You might get asked about the systemic effects of sickle cell disease on the body, and as always it is best to break it down by organ system:

Pain crises

Apart from a patient with sickle cell disease (or trait) passing through your anaesthetic room for an unrelated operation, the other time you'll tend to find yourself in front of a patient with sickle cell as an anaesthetist is during an acute pain crisis.

These cruel repeated episodes of severe unrelenting pain can be triggered by a number of stresses including dehydration, pain, stress and even changes in altitude, and the ward team may well call upon the anaesthetists for help with specialist methods of pain control.

The priority of course is analgesia, but it is also crucial to ensure you're not missing something else that may be bubbling away in the background.

Is the pain normal for them during a crisis?

Sickle cell patients know their pain very well indeed, and can often predict when a crisis is going to take hold with remarkable accuracy.

The following scenarios should make you feel very differently:

• "I always get this pain in my back and lower abdomen, it lasts for a few hours and I usually need IV morphine to get on top of it"
• "She's complaining of abdominal pain but usually her pain is higher up in the back - this time seems different"

Sickle cell crisis is a great mimic, but it can also conceal other underlying diagnoses, which you need to be on the lookout for.

Remember an underlying pathology can also trigger a pain crisis. Just to make life easier for everyone involved.

If you're in any doubt, escalate your concerns and encourage investigation of possible underlying pathologies - we don't want to leave a 15 year old in crisis with a ruptured appendix now do we.

Pain control options

• Paracetamol
• Ibuprofen
• Oramorph
• Nasal fentanyl
• PCA or IV morphine
• MST once a baseline requirement is calculated

With regards to dosing, your trust will most likely have a pro-forma with the approved doses by weight or age for sickle cell patients, like this incredibly helpful one from Norfolk and Norwich University Hospitals that we found online.

Non-pharmacological

• Keep them warm
• Reassurance
• Parental presence
• Distraction

Paw patrol isn't going to reduce the pain of an acute sickle crisis but it's markedly more tolerable than staring at a blank wall.

Testing for it

The sickledex test is an easily performed bedside test which reveals the presence of HbS, but does not differentiate between the heterozygous (sickle cell trait) and the homozygous state.

How it affects your anaesthetic

What you'll notice in this section is that most of the management is exactly what you'd do for any other patient, but you just need to do it even better.

In the bad old days, perioperative mortality in unwell sickle cell patients hovered around 30-40%, but it's mercifully more like 1% now that we've figured out what we're supposed to do.

Oxygen

The most important feature is to avoid hypoxia. While this is important in all patients, it is especially crucial in order to avoid sickling in HbSS carriers.

Hypoxia is exceedingly poorly tolerated in these patients.

For those alveolar gas equation aficionados among you - slight hyperventilation can also increase arterial oxygen tensions if needed.

Hydration

Again - all patients need to be adequately hydrated - but hypovolaemia is bad news for those with shapeshifting erythrocytes.

Transfusion

Crossmatching is going to take longer in these patients, so make sure group and saves and crossmatching requests are done well in advance wherever possible.

You can also consider prophylactic transfusion to achieve two things:

• aim for an Hb >100
• try and replace as much of their sickly red cells with non-sickly ones

Clearly this carries all the requisite risks associated with elective blood transfusion and should probably be discussed on an individualised basis with haematology.

Fluid management

It is likely that a patient - particularly a child - in severe pain hasn't been drinking enough. Furthermore sickle cell patients often have an element of reduced nephron function already. This results in dehydration, increased blood viscosity and more sickling.

Oral fluids are always preferable, but if needed to avoid dehydration then IV replacement can be started. Choice of fluid varies between hospitals, but as long as it's vaguely balanced with some sugar and you're monitoring potassium then it doesn't matter too much.

For Adults:

• Encourage oral fluids where possible
• Aim for a total fluid intake of 70-90 ml/kg body weight over 24 hours as maintenance
• Hypovolaemia or clinical dehydration should be treated in addition to this
• Start a fluid balance chart
• It is very important to avoid fluid overload, as hypoxia from pulmonary oedema can be catastrophically bad
• Avoid central lines unless absolutely needed

It will not surprise you that viscous, sickly blood rather enjoys setting up camp on indwelling lines.

For a child for 24 hours:

• 100ml/kg for the first 10kg
• 50ml/kg for the next 10kg
• 20ml/kg thereafter

So a 19kg child would require 10x100 + 9x50 = 1450 ml over 24 hours.

Life threatening complications

The majority of the time, pain crises will require pain control and rehydration but not a whole lot more.

But you need to be on the lookout for the really bad stuff so you can spot and manage it in good time.

Useful Tweets and Resources

25-year-old, sickle cell disease, evolving CXRs. Day 1 looks clear, but what's next? Can you track the changes? #MedTwitter #MedEd #FOAMed https://t.co/nhCYooXctc pic.twitter.com/6OlxtX0hVC

— LITFL (@LITFLblog) January 5, 2024

References and Further Reading

Anaesthetic management of children with sickle cell disease

Sickle cell disease (SCD) is an inherited disorder with multisystem complications, often presenting in childhood.1 Anaesthetists are frequently involved throughout perioperative care, in the management of acute pain and acute complications.

BJA EducationSearch for articles by this author

Anaesthetic management of patients with sickle cell disease in obstetrics

Sickle cell disease (SCD) is the most commonly inherited haemoglobinopathy, with 15 000 affected individuals in the UK and 100–200 affected pregnancies annually.1,2 Sickle cell disease is not a benign condition in pregnancy, as highlighted in a recent UK Obstetric Surveillance System (UKOSS) study.3…

BJA EducationSearch for articles by this author

Haemoglobinopathy and sickle cell disease

Sickle cell disease (SCD), first described in the early twentieth century, is an inherited haemoglobinopathy resulting from a mutation on chromosome 11.1 The mutation causes an amino acid substitution on the β-globin subunit of normal adult haemoglobin A, resulting in the formation of haemoglobin S.…

Continuing Education in Anaesthesia, Critical Care and PainSearch for articles by this author

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