A 47-year-old female with newly diagnosed acute myeloid leukaemia presents with the following blood results:

Parameter

Patient Value

Adult Normal Range

Haemoglobin

89 g/L*

120 – 160

White Cell Count

110.0 x 109/L*

4.0 – 11.0

Platelet count

32 x 109/L*

150 – 350

Blast cells

104 x 109/L

a) What specific issues might you anticipate as a result of the white cell count, and what clinical problems might these cause?

What management strategies would you employ to prevent or treat these issues?                                                                                               (60% marks)

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College answer

1.    Leukostasis/Hyperviscosity syndrome: white cell plugs in the microvasculature.
Most commonly affects lungs (dyspnoea, hypoxia, CXR infiltrates) and brain (visual changes, headache, dizziness, tinnitus, confusion progressing to coma)
Can also affect Heart (ischaemia, failure), kidney (AKI), liver/bowel ischaemia.

2.    Tumour lysis syndrome- either spontaneous or in response to chemotherapy
Electrolyte abnormalities including hyperkalaemia, hyperphosphataemia and hypocalcaemia. Can cause arrhythmias, seizures and sudden death.

3.    Artifactually low PaO2 on ABG due to metabolically active blasts which continue to utilise O2 in the test tube (SpO2 more reliable)

Management:
Keep hydrated
Start allopurinol or rasburicase to prevent TLS
Monitor FBC. Avoid RBC transfusion if possible (increases viscosity)
If there is a delay or contraindication to starting chemotherapy immediately, consider leukapheresis if symptomatic of hyper-viscosity.
For ABGs – sample transported on ice, analyse immediately. Monitor SpO2.
 

Examiners Comments:

When asked for a specific number of responses (e.g. 'three causes of') please supply this number of responses. Extra responses will not gain extra marks. If there are more causes, then list the most likely. Many candidates did not appear to pay attention to the mark allocation and gave insufficient detail in sections of the question worth the most marks.

Discussion

As a table, this answer makes more sense:

specific issues might you anticipate Leukostasis Tumour lysis syndrome
What clinical problems might these cause?
  • Severe headaches
  • A fluctuating conscious state
  • Stroke, seizures, coma (usually, venous cerebral infarction)
  • Constitutional symptoms: fatigue, malaise, lethargy
  • Haemorrhagic symptoms:  gingival or mucosal bleeding, or epistaxis.
  • Blurred vision due to central retinal vein occlusion
  • Headaches due to increased intracranial pressure (due to venous occlusion)
  • Fundoscopy reveals dilated, tortuous retinal veins, as well as flame-shaped haemorrhages.
  • Renal failure
  • Aggravated heart failure (more difficult to pump the viscous blood)
  • Priapism
  • Biochemical abnormalities due to TLS:
    • Hyperuricemia
    • Hyperphosphatemia
    • Hyperkalemia
    • Hypocalcemia
  • And as the result of these,
    • Tetany (due to hypocalcemia)
    • Confusion
    • Decreased level of consciousness
    • Hypotension
    • Atrial arrhythmias
    • Acute phosphate nephropathy
Management
  • Epiric hydroxyurea
  • Targeted chemotherapy
  • Leukopheresis
  • Phlebotomy and transfusion of red cells and plasma ("poor man's leukapheresis")
  • Dexamethasone
  • Vigorous IV fluid infusion
  • Aim for a urine output of 150-300ml/hr (i.e. 2-4ml/kg/hr).
  • Alkalinise the urine
  • Cease nephrotoxins
  • Allopurinol or febuxostat
  • Recombinant urate oxidase (rasburicase)
  • Haemodialysis if everything goes pear-shaped

Strictly speaking, this patient has hyperleukocytosis rather than leukostasis. Ganzel et al (2012) define it as any WCC in excess of 100,000, admitting that this is a fairly arbitrary cut-off. Leukostasis per se is a clinical manifestation of hyperleukocytosis, characterised by vascular occlusion and tissue hypoxia. It is seen with high WCCs, but usually quite a lot higher than this one (usually 400,000-1,000,000).

One last interesting feature is the need to refrigerate the ABGs. An excess of highly metabolically active blasts in the blood sample gives rise to "leukocyte larceny", where the hungry cells metabolise all the gases while you wait for the ABG machine to self-calibrate. The result is a spurious hypoxia and hypoglycaemia.

References

References

Porcu, Pierluigi, et al. "Hyperleukocytic leukemias and leukostasis: a review of pathophysiology, clinical presentation and management.Leukemia & lymphoma 39.1-2 (2000): 1-18.

Ganzel, Chezi, et al. "Hyperleukocytosis, leukostasis and leukapheresis: practice management." Blood reviews 26.3 (2012): 117-122.

Tiu, Ramon V., et al. "Tumor lysis syndrome." Seminars in thrombosis and hemostasis. Vol. 33. No. 4. New York: Stratton Intercontinental Medical Book Corporation, c1974-, 2007.

Howard, Scott C., Deborah P. Jones, and Ching-Hon Pui. "The tumor lysis syndrome." New England Journal of Medicine 364.19 (2011): 1844-1854.

Cairo, Mitchell S., and Michael Bishop. "Tumour lysis syndrome: new therapeutic strategies and classification." British journal of haematology 127.1 (2004): 3-11.

Gartrell, Kevin, and W. Rosenstrauch. "Hypoxaemia in patients with hyperleukocytosis: true or spurious, and clinical implications." Leukemia research 17.11 (1993): 915-919.