The following data refer to a 67-year-old male 8 days following initiation of treatment for acute leukaemia:
|Parameter||Patient Value||Normal Adult Range|
|Haemoglobin||102 g/L*||130 – 180|
|White Cell Count||111 x 109/L*||4 – 11|
|Platelets||21 x 109/L*||150 – 350|
|Blasts||100 x 109/L*||0|
|Sodium||136 mmol/L||136 – 145|
|Potassium||6.1 mmol/L*||3.5 – 5.0|
|Chloride||95 mmol/L*||98 – 106|
|Bicarbonate||17 mmol/L*||23 – 28|
|Urea||21.8 mmol/L*||2.9 – 7.1|
|Creatinine||209 μmol/L*||60 – 120|
|Calcium (corrected)||2.48 mmol/L||2.20 – 2.60|
|Phosphate||2.76 mmol/L*||0.80 – 1.45|
|Magnesium||0.81 mmol/L||0.60 – 1.10|
|Urate||0.84 mmol/L*||0.20 – 0.42|
|Total protein||59 g/L*||60 – 78|
|Albumin||27 g/L*||35 – 55|
|Bilirubin||9 μmol/L||< 20|
|Alkaline phosphatase (ALP)||587 U/L*||36 – 92|
|Alanine transferase (ALT)||42 U/L*||< 35|
|Gamma glutamyl transferase (GGT)||110 U/L*||< 30|
|Lactate dehydrogenase (LDH)||7157 U/L*||60 – 100|
a) Give the underlying cause of the above abnormalities and give your reasoning to explain these findings. (20% marks)
b) List the treatment options for this condition. (30% marks)
Tumour lysis syndrome
Renal impairment with hyperkalaemia, hyperphosphataemia, hyperuraecamia and increased LDH
Resuscitation – Adequate IV hydration
Treatment of hyperkalaemia – Calcium chloride, bicarbonate if ECG changes, dextrose- insulin, dialysis, resonium
Renal replacement therapy – metabolic acidosis, hyperkalaemia and hyperphosphataemia Allopurinol
Let us dissect the results systematically.
The abnormalities and their potential explanations are:
- Anaemia: from bone marrow suppression (leukaemia or chemotherapy)
- Leukocytosis (leukaemia)
- Thrombocytopenia: from bone marrow suppression (leukaemia or chemotherapy)
- High blast count (leukaemia)
- Hyperkalemia (tumour lysis syndrome)
- Acidosis (low bicarbonate); probably due to some combination of urate lactate and other retained non-volatile acids in renal failure
- High anion gap; (136 + 6.1) - (95 + 17) = 30.1
- Hyperuciaemia (tumour lysis syndrome)
- Hyperphosphataemia (tumour lysis syndrome; though surprisingly the calcium is normal)
- Hypoalbuminaemia (critical illness; it is a "negative acute phase reactant")
- Raised alkaline phosphatase is probably due to leukaemia itself (immature leukocytes have increased ALP levels, as per Masakazu et al, 2005). It is an isolated finding, with the other LFTs remaining relatively normal.
- Raised LDH (tumour lysis syndrome)
The patient also has a white cell count of 111. This gives rise the the supicion that the hyperkalemia may be "pseudohyperkalemia of malignancy". The presence of haematological malignancy generally means a high white cell count; these extra cells are immature blasts which are structurally unsound, being exempt from normal cellular quality control mechanisms. The very act of aspirating these fragile cells into a syringe or vacutainer may give rise to wholesale cellular destruction by shear stress. The result is a falsely elevated potassium level. Kintzel and Scott presented a case report of this (2012) where the potassium level was 9.8mmol/L in the badly lysed sample and 4.1 mmol/L in the heparinised tube.
The treatment options are:
- Adequate hydration: aim for a urine output of 150-300ml/hr (i.e. 2-4ml/kg/hr).
- Alkalinisation of urine using oral or IV bicarbonate
- Cessation of nephrotoxins.
- Electrolyte monitoring and intelligent electrolyte replacement
- Xanthine oxidase inhibitors (allopurinol or febuxostat)
- Recombinant urate oxidase to enhance clearance of urate: rasburicase, 0.15-0.20mg/kg for 5-7 days
- Haemodialysis is ultimately the most immediately effective solution for the whole host of metabolic abnormalities.
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Izumi, Masakazu, et al. "Increased serum alkaline phosphatase activity originating from neutrophilic leukocytes." Clinical chemistry 51.9 (2005): 1751-1752.