37 year old female presents to your Emergency Department complaining of shortness of breath and bilateral thigh pain after vomiting for one week.
It’s a busy day in the department, so whilst a bed is being organised the nursing staff have obtained IV access and taken the following venous blood gas…
- Moderate metabolic acidosis:
- HCO3 16, BE -10.
- Partially compensated with a pH 7.24
- Exp pCO2 = (1.5x 16) + 8 = 24 + 8 = 32.
- Actual = 39 (Likely due to VQ mismatch).
- High anion gap (Cl = 91)
- 135 – (91+16) = 28
- Delta ratio
- = (28-12)/(24-16)
- = 16/8
- = 2 ∴pure HAGMA
- Severely elevated lactate: 9.8 mmol/L !!
- DDx: sepsis, tissue ischaemia, medications…
- Moderately elevated serum creatinine
- Mild anaemia
- Mild hyperglycaemia
- Mildly low ionised calcium
The gas shows a high anion gap metabolic acidosis, specifically a lactic acidosis. This is likely driven by a Type 1 lactic acidosis due to tissue hypoxia and anaemia. Persistent vomiting is more likely to produce a metabolic alkalosis so this is not the driving force of this blood gas.
She is hypotensive at 90/60 mmHg and she is taken to the resuscitation bay where you meet her.
She rapidly states that she has heterozygous sickle cell disease.
Are all heterozygous patterns less severe? No!
This lady was HbS/β0 thalassaemia compound heterozygous and of similar clinical severity to HbSS disease (see the table below for more detail).
Are all heterozygous patterns less severe?
She has had non-bilious vomiting for the past 5 days which she puts down to a viral gastroenteritis that she caught from her daughter. During this time she has likely fallen behind in hydration as she didn’t seek help until she “couldn’t bear the pain.” Today, she started to have breathing difficulties.
She describes a mild headache plus bilateral deep burning pain in her thighs. She is on hydroxyurea, denies pregnancy and states she has had all her vaccinations.
- A. Patent & protected.
- B. Tachypnoeic to 32 breaths per minute. SpO2 93% on 15L via non-rebreather mask.
- C. Tachycardic (HR 121/min, sinus), Blood pressure 102/82 after an initial fluid bolus. Peripherally shut down and cool to touch. Dry mucosa.
- D. GCS15, PEARL, no focal neurology.
- E. Temperature 35.3*C. Appears lethargic++.
- Abdomen soft with a mildly enlarged liver
- No splenomegaly to suggest aplastic crisis.
- No warmth in the leg joints to suggest sceptic joint or soft-tissue infection.
What conditions specific to sickle disease would account for her symptoms?
SICKLE CELL CRISIS
Acute chest syndrome.
The exact pathogenesis of acute chest syndrome (ACS) is unclear and is probably multifactorial. It is essentially an ARDS-subtype and clinically diagnosed with pulmonary alveolar consolidation.
- Pulmonary infection:
54% of patients admitted for ACS will have an infectious agent identified. Community acquired pathogens are most common. Despite increased risk of encapsulated bacteria due to functional hyposplenism these are isolated in only 10% of patients.
- Fat emboli:
80% are involved with vasoocclusive (VO) crisis and this lends itself to the theory that fat emboli with secondary ARDs may be the underlying pathology. Studies show 44% of patients that underwent a bronchoscopy during an ACS crisis had lipid-laden alveolar macrophages.
Acute haemolysis coexists with a rise in LDH and dropping Hb. Mice models have shown that heme is necessary and sufficient to induce ACS.
- Pulmonary infarction/PE:
Given the prothrombotic state that sickle-cell patients are in during an acute crisis, they are susceptible to PE and lung parenchymal infarction. Literature suggests that PE is under diagnosed in this population despite the incidence actually being higher.
Vasoocclusive crisis (bony crisis).
“Sickling” causes microvascular entrapment of erythrocytes and leukocytes which lead to ischaemia. This leads to a subsequent inflammatory reaction that worsens the environment and encourages further sickling. The end product is necrosis that is felt as pain.
In this specific patient:
These patients are at risk of overwhelming sepsis. They have hypo/asplenism; so are vulnerable to encapsulated bacteria. She presented hypotensive & has an elevated lactate and should therefore receive empiric broad-spectrum antibiotics.
- Cerebrovascular events:
She had a mild headache but no focal neurological deficit. Ischaemic stroke was considered but the headache was thought to be due to skull bone vasoocclusive symptoms.
- Multi organ failure:
She had already developed an acute kidney injury and ARDS. During her admission she had deranged LFTs that normalised during her stay.
- Septic arthritis:
On inspection the legs were bone pain. Sickle cell patients (more common in paediatric patients) are at higher risk of sceptic arthritis.
- Aim to maintain saturations >97%.
- The peripheral pulse oximetry probe is unreliable and an ABG on room air should guide treatment (this also helps prognosticate for ACS/ARDS).
- Intravenous fluid:
- Traditionally 1.5x maintenance fluid is required.
- Pain crises are very painful and usually patients have tried opioids and escalating pain management regimens prior to attending hospital.
- Morphine PCA (or equivalent) is usually required.
- Infection is a leading cause of ACS.
- In this case we gave intravenous ceftriaxone.
- Biochemistry (Electrolytes, LFTs, CMP, βHCG)
- Group & hold
- Haemolytic screen, HbF
- Infectious screen including Parvovirus B12, EBV/CMV & blood cultures
- Arterial blood gas (preferably on room air)
In severe ACS/VO occlusive crisis after initial ED stabilisation the definitive treatments is plasma exchange. Essentially it aims to minimise the HbS load to <30% ( this number is institution dependent and some say <20%).
…..this patient had 8 units of PRBC and responded really well both clinically and biochemically. Her HbS went from 47% to 20%
This lady was Caucasian and presented with a sickle crisis most likely from dehydration secondary to her week of vomiting. She had a heterozygous phenotype that may have given some people false reassurance of her severity subtype. She got exchanged 8 units within 3 hours of presentation due to early involvement of Haematology and Intensive Care. This lady needed significant amounts of analgesia (at home prior to her presentation and in the Emergency Department). From a practical standpoint she had multiple antibodies in her blood and this made accessing suitable blood one of her rate limiting factors.
ACS carries a high risk of respiratory failure with 13% of patients requiring mechanical ventilation and a mortality rate of 9%. It is associated with prolonged hospitalisation and decreased overall prognosis. It remains the most common cause of death for this patient population. Ultimately, sickle cell disease is a terminal illness and these patients can get unwell quickly.
Fortunately this lady spent 48 hours in the ICU needing only the initial plasma exchange. She spent further time on the general ward in hospital and had a CTPA that showed a sub-segmental PE and was discharged with ongoing outpatient Haematology followup.
- Wasil, J (2011) Epidemiology of sickle cell disease in Saudi Arabia. Annals of Saudi Medicine 33(3):289-293.
- Novelli, E., Huynh, C., Gladwin, M.,Moore, C., Rangi, M(2012). Pulmonary Embolisation in Sickle Cell Disease: A case-control Study. Journal of Thrombosis Haemostasis. May 10(5):760-7663.
- Gladwin, M., Vinchinsky, E (2008) Pulmonary complications of Sickle Cell Disease. NEJM 2008: 359:2254-2265.
- EM: RAP: July 2017- Jonathan’s story. Dr Jessica Mason www.emrap.org.au
- Gladwin, M., Vichinsky, E (2008) Pulmonary complications of Sickle cell Disease. NJEM 359:2254-65
- Golman & Schafter. Goldman’s Cecil Medicine 24th edition. Ch166 Sickle cell disease and other haemoglobinopathies.
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- Novelli, E., Gladwin, M (2016) Crises in sickle cell disease. Chest 149(4):1082-1093
- Yawn, B., Buchanan, G., Afenyi-Annan, A (2014). Management of Sickle Disease. Summary of the 2014 Evidence-Based Report by Expert Panel Members JAMA 2014; 312(10):1033-1048
Author: Courtney Peros
Web editing: Chris Partyka