Spurious hypokalaemia and hypophosphataemia due to extreme hyperleukocytosis in a patient with a haematological malignancy

Abstract

Serious hyperleukocytosis can strongly affect laboratory results of potassium, phosphate and arterial oxygen tension. A 40-year-old woman is presented with an acute myeloid leukaemia and a strongly elevated leukocyte count (310 × 10⁹/L). Apart from this hyperleukocytosis, initial blood tests showed hypokalaemia, hypophosphataemia and serious hypoxaemia without any corresponding complaints. Blood sampled and transported on ice or directly analysed showed no electrolyte abnormalities and hypoxaemia. The observed discrepancy in laboratory results is probably due to the metabolic activity of the leukocytes in vitro. Spurious laboratory results can be a reason for incorrect decisions concerning additional diagnostics and treatment. In conclusion, hyperleukocytosis can cause pseudohypokalaemia, pseudohypophosphataemia and pseudohypoxaemia, which can be prevented by correct sampling and immediate analysis.

Introduction

Patients with an acute leukaemia may present with an extreme high leukocyte count. This hyperleukocytosis can lead to false laboratory results when blood samples are not directly analysed and stored at room temperature. Pseudohypoxaemia is the most described phenomenon occurring in patients with hyperleukocytosis. ^1–8 In addition, pseudohypokalaemia is described as well in this group of patients. ^9,10 Also pseudohyperkalaemia can occur in patients with hyperleukocytosis, due to the in vitro release of potassium from leukocytes undergoing lysis during the clotting process. ¹¹ The following case illustrates the strong influence of extreme hyperleukocytosis on potassium, phosphate and oxygen results in routine laboratory evaluation.

Case report

A 40-year-old woman was admitted to the Department of Haematology at the University Medical Center Utrecht, because of a de novo acute myeloid leukaemia without maturation according to WHO classification. Laboratory examination showed an extreme high leukocyte count (310 × 10⁹/L) with 86% blast cells, very low potassium (1.6 mmol/L) and low phosphate (0.57 mmol/L) (Table 1). Surprisingly, the patient did not show any neurological symptoms like muscle weakness, muscle spasm or paresthesias despite the low potassium. A second blood sample was drawn and placed on ice and showed normal results of potassium and phosphate (Table 1). Apparently potassium and phosphate were spuriously decreased in the first sample, implying that suppletions of potassium and phosphate were unnecessary.

Table 1

Laboratory results

	Primary analyses	Analyses on ice	Reference values
Leukocytes (×109/L)	310	–	4.0–10.0
Blast cells (×109/L)	267	–	0
Haemoglobin (mmol/L)	3.7	–	7.4–9.6
Thrombocytes (×109/L)	109	–	150–450
Creatinine (μmol/L)	74	–	58–103
Sodium (mmol/L)	140	–	136–146
Potassium (mmol/L)	1.6	3.9	3.8–5.0
Magnesium (mmol/L)	0.68	–	0.70–1.00
Phosphate (mmol/L)	0.57	0.96	0.80–1.50
Chloride (mmol/L)	100	–	99–108
Bicarbonate (mmol/L)	29.3	–	23.0–29.0
Uric acid (mmol/L)	0.37	–	0.14–0.34
Alkaline phosphatase (U/L)	223	–	40–130
Gamma-GT (U/L)	261	–	15–45
Alanine transaminase (ALT) (U/L)	121	–	10–50
Lactate dehydrogenase (U/L)	7701	–	300–620

Treatment with hydroxycarbamide was started and allopurinol and hyperhydration were given to prevent tumour lysis syndrome. On the second day of treatment, leukocytes were not decreased and the patient became dyspnoeic. Chest X-ray showed diffuse infiltrative abnormalities, suspicious for leukostasis. The patient was admitted to the intensive care unit (ICU) for mechanical ventilation. After intubation, saturation measured by finger pulse oximetry was more than 95%, whereas blood gas analyses showed hypoxaemia (Table 2).

Table 2

Blood gas analyses

	After intubation	21:46 h	21:51 h	Reference values
pH	7.49	7.52	7.52	7.37–7.45
pCO2 (kPa)	4.39	4.12	4.12	4.65–5.99
pO2 (kPa)	5.59	6.92	5.72	9.98–13.3
Actual bicarbonate (mmol/L)	24.2	24.3	24.1	21–26
Base excess (mmol/L)	0.9	1.4	2.3	−3 to +3
O2 saturation (%)	85	96	87	96–100

Hereafter, a new blood gas sample was analysed directly on the ICU, in which a normal oxygen concentration was found. However, when the same blood sample was analysed six minutes later in the laboratory, it once more showed serious hypoxaemia (Table 2).

Discussion

Pseudohypoxaemia is the spurious reduction of oxygen in blood in vitro. ² The mechanism is oxygen consumption in the sample by leukocytes, reticulocytes and thrombocytes. ⁷ These cells preserve their metabolic activity after withdrawal from the bloodstream and continue to consume oxygen. Normally, this metabolic activity will not be detectable because of the relatively low amount of these cells. However, in cases of a hyperleukocytosis this phenomenon can cause decreased arterial oxygen tension in vitro. ⁸ Furthermore, leukaemic blasts have higher respiratory oxygen consumption compared with normal leukocytes. ⁵ This is due to an increased Na⁺-K⁺-ATPase activity, which leads to a higher oxygen consumption in the cell. ¹⁰ Therefore, pseudohypoxaemia is only described in patients with haematological malignancies. ⁶ Because of the in vitro nature of this phenomenon, oxygen saturation measured by finger pulse oximetry is not affected, ^4,8 making this a more reliable method to measure the concentration of oxygenation in patients with hyperleukocytosis.

Pseudohypokalaemia is the spurious reduction of potassium in blood. The mechanism of pseudohypokalaemia in patients with hyperleukocytosis is multifactorial. Firstly, leukaemic leukocytes have increased sodium permeability in comparison with normal leukocytes. This leads to an augmented Na⁺-K⁺-ATPase activity, which causes an elevated cellular potassium uptake, ⁹ in combination with the extreme leukocytosis in this patient this may lead to the observed hypokalaemia in vitro. Other factors that possibly stimulate the potassium uptake by leukocytes are: depletion of oxygen, clotting, decrease of temperature, exposition to glass or other surfaces and the release of tissue factors. ⁹

Pseudohypophosphataemia has never been described in patients with hyperleukocytosis. The mechanism for pseudohypophosphataemia in this case is unknown. The most plausible explanation for this observation is the high count of leukocytes and the increased metabolism of young leukaemic blast cells accompanied by the intracellular use of electrolytes. Transmembrane phosphate transport is regulated by a family of sodium-phosphate (NaPi) co-transporters, which are dependent on the activity of Na⁺-K⁺-ATPase. ^12–15 These proteins are widely expressed in human tissue and play an important role in phosphate homeostasis and cellular metabolism. ^12–15 Recently, a sodium-phosphate co-transporter has been described on a human leukaemic cell line. ¹⁶ We speculate that this co-transporter is involved in the spurious hypophosphataemia in this case report.

Pseudohypoxaemia and spurious electrolyte results have been described in patients with hyperleukocytosis caused by both lymphocytic and myeloid disorders. ^6–9 Therefore, presence of these phenomena seems to be related to the amount of leukocytes in the peripheral blood.

This case shows the influence of an extreme hyperleukocytosis on the content of oxygen, potassium and phosphate in vitro, which can lead to spurious laboratory results. Unawareness of this phenomenon can lead to unnecessary diagnostic procedures and/or incorrect treatment, and thereby unnecessary risks for the patient. Especially in case of pseudohypokalaemia the consequences can be very harmful, because unnecessary potassium suppletion may result in a, by this phenomenon masked, serious hyperkalaemia, for example in patients with reduced renal function. Hence, correct sampling and blood analyses are crucial in these patients. Laboratory results can only be interpreted after sampling the blood on ice or after immediate analyses of the blood sample. ^1–10 Hypoxaemia, hypokalaemia and hypophosphataemia in patients with hyperleukocytosis should therefore only have clinical consequences if the blood is sampled and analysed correctly.

DECLARATIONS

Competing interest: None.

Funding: None.

Ethical approval: None.

Guarantor: RP.

Contributorship: RP and SK wrote the paper. AH and MAS contributed in writing the paper.

Acknowledgements: None.