Leukaemia causing trouble

Labs and Lytes 039

Author: Dr Courtney Cini
Reviewers: Dr Craig Johnston, Dr Sarah Yong

A 36-year old male with a background of chronic myeloid leukaemia (CML), presented to the emergency department with fatigue, cough and abdominal pain in the setting of non- compliance to his CML medications.

This is his initial full blood count (FBC):

Haemoglobin (hb)67*(128-175 g/L)
White cell count (WCC)661(3.9-12.7 10^9/L)
Platelets238(150-397 10^9/L)
Haematocrit0.21(0.36-0.5 L/L)
Mean cell volume (MCV)88(80-97 fL)
Mean cell haemoglobin (MCH)26.7(28-34 pg)
Red cell count2.51(4-5.8 10^12L)
Neutrophils276(1.9-8 10^9/L)
Lymphocytes3.31(0.9-3.3 10^9/L)
Monocytes6.62(0.3-1.1 10^9/L)
Eosinophils:21.5(0.5 10^9/L)
Basophils:21.5(0.2 10^9/L)
*Corrected for over-linearity of WBC

Q1. Interpret the full blood count.

Key findings:

  • A WCC of 661 is indicative of profound leukocytosis. Neutrophils, monocytes, eosinophils and basophils are markedly elevated.
  • A normocytic and a mildlly hypochromic anaemia is also present.

Profound leukocytosis can result in multiple oncological emergencies, including leukostasis and disseminated intravascular coagulation (Schiffer, 2021). The mainstays of management of leukostasis are treatment of the underlying disease, hydration, and cytoreduction (e.g. leukophoresis). Note, these oncological emergencies will not be the focus of this Labs and Lytes post.

Q2. What other oncological emergency is this patient at high risk of developing?

This patient is at high risk of developing tumour lysis syndrome.

Tumour lysis syndrome most commonly occurs 12-72 hours post commencement of cytotoxic treatment in patients with a haematological malignancy (Nickson, 2020). However, it can also occur spontaneously in patients with a very high tumour burden (Larson and Ching-Hon Pui, 2022).

Q3. What is the pathophysiology of this other oncological emergency?

In tumour lysis syndrome, tumour cell lysis leads to the massive release of intracellular components, including nucleic acid, phosphate and potassium.

  • Nucleic acid in the blood stream is converted to uric acid, which in turn leads to hyperuricemia. This can subsequently cause acute urate nephropathy with acute kidney injury (Larson and Ching-Hon Pui, 2022).
  • Acute kidney injury can also result from precipitation of calcium phosphate salts in the renal tubules, which occurs when excess phosphate binds to calcium. This in turn results in secondary hypocalcaemia, which can lead to neuronal excitability and seizures, and hypophosphataemia,
  • Release of intracellular potassium combined with acute kidney injury predisposes the patient to hyperkalaemia.

Q4. What are the clinical manifestations?

The clinical manifestations of tumour lysis syndrome are directly related to the degree of acute kidney injury and electrolyte abnormalities (Cairo and Bishop, 2004):

  • Acute kidney injury can lead to peripheral oedema, oliguria and lethargy. Metabolically, it can lead to acidaemia, uraemia and electrolyte disequilibrium
  • Hyperphosphatemia can cause symptoms of nausea, vomiting, diarrhoea and seizures
  • Hypocalcaemia can lead to muscular, cardiovascular and/or neurological manifestations. Severe hypocalcaemia is one of the most critical clinical manifestations of TLS
    • Muscular features can include: muscle cramps, parasthesias and tetany
    • Cardiovascular features can include: cardiac arrhythmias, heart block and hypotension
    • Neurological complications include confusion, delirium and seizures
  • Hyperkalaemia can also cause non-specific symptoms such as nausea/vomiting and diarrhoea. It can also lead to neuromuscular and cardiac complications
    • Neuromuscular symptoms include muscle weakness, cramps and parasthesias
    • Cardiac complications include: cardiac arrhythmias and possible sudden cardiac death

Additionally, precipitation of calcium phosphate in the heart may lead to an arrhythmia (Larson and Ching-Hon Pui, 2022).

Q5. What is the diagnostic criteria that is used to diagnose the condition?

The Cairo-Bishop definition is commonly used to confirm a diagnosis of TLS (Coiffier et al, 2016):

Laboratory TLSClinical TLS
Two or more laboratory changes within 3 days before or 7 days after
commencing cytotoxic treatment:
Uric acid: >/= 0.476 mmol/L
Potassium: >/= 6 mmol/L
Phosphorus >/= 1.45 mmol/L
Calcium </= 1.75 mmol/L
Patient with laboratory TLS and at least one of:
Creatinine >/= 1.5 upper limit of normal (age > 12 years or age-adjusted)
Cardiac arrhythmia
Sudden death
Seizure

Q6. Outline the specific prophylactic management of this condition.

Aggressive hydration is the mainstay prophylaxis and treatment of TLS. It improves renal perfusion and glomerular filtration and therefore induces a high urine output state to reduce the chance of uric acid or calcium phosphate deposition in the tubules (Larson and Pui, 2022).

Other prophylactic therapies include hypouricemic agents such as allopurinol and rasburicase

  • Allopurinol is a xanthine oxidase inhibitor which inhibits the conversion of hypoxanthine and xanthine to uric acid and it is recommended for low to intermediate risk patients (Larson and Pui, 2022). Allopurinol dose for TLS prophylaxis is generally 300 mg daily (Baldini et. al, 2014). Xanthine concentration, in rare cases, could increase sufficiently to cause deposition in the urinary tract and subsequently lead to renal impairment (Allopurinol, 2018), which can be a limitation in its efficacy.
  • Rasburicase is a urate oxidase which catalyses the oxidation of uric acid to allantoin, a more water soluble compound. Rasburicase is reserved for patients who are intermediate to high risk (Larson and Pui, 2022). The recommended rasburicase dose is 0.15-0.2 mg/kg/day for 5-7 days with studies showing lower doses to be effective for TLS prevention (Philips et. al, 2018).

References

All case-based scenarios on INTENSIVE are fictional. They may include realistic non-identifiable clinical data and are derived from learning points taken from clinical practice. Clinical details are not those of any particular person; they are created to add educational value to the scenarios.

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