Role of point-of-care arterial blood potassium in diagnosing pseudohyperkalemia

Abstract

Hyperkalemia is a life-threatening emergency, but it needs to be differentiated from pseudohyperkalemia to avoid unnecessary treatment. We present a case of pseudohyperkalemia in a chronic lymphocytic leukemia patient with severe leukocytosis, highlighting the role of point-of-care potassium. Laboratory workup showed persistent hyperkalemia on analysis of venous blood samples even after treatment for hyperkalemia. Point-of-care potassium checks on whole arterial blood immediately after sampling were consistently in the normal range. Treatments for hyperkalemia were stopped to avoid life-threatening hypokalemia.

Pseudohyperkalemia is a false elevation of potassium on in vitro blood sampling analysis that is not representative of in vivo potassium. It was first described in 1955 by Hartmann and Mellinkoff when they noted significant elevation in serum potassium levels without any clinical signs or symptoms in patients with thrombocytosis.¹ The initial clue toward diagnosis comes from the absence of hyperkalemic electrocardiographic changes² and lack of response to treatment for hyperkalemia. We describe the role of point-of-care arterial blood potassium in pseudohyperkalemia patients.

CASE DESCRIPTION

A 65-year-old man presented to the emergency department with the chief complaints of fever, cough, and worsening shortness of breath for 1 week. Past medical history included chronic lymphocytic leukemia and asthma. He was on active surveillance for his leukemia. The patient had moderate respiratory distress and a blood oxygen saturation of 80% on room air. The blood pressure was 116/64 mm Hg; heart rate, 120 beats/min; and respiratory rate, 30 breaths/min. Chest imaging showed scattered patchy bilateral interstitial and ground-glass infiltrates and a dense consolidation with air bronchograms occupying most of the left lower lobe. He tested positive for severe acute respiratory syndrome–coronavirus 2. Arterial blood gas showed a pH of 7.51; partial pressure of carbon dioxide, 28 mm Hg; partial pressure of oxygen, 49 mm Hg; and bicarbonate, 22 mmol/L. He was placed on noninvasive ventilation, but his respiratory status declined, requiring endotracheal intubation and mechanical ventilation. The results of laboratory investigations are summarized in Table 1.

Table 1.

Laboratory values

Parameter (units)	Value
Potassium (mmol/L)	6.2
Sodium (mmol/L)	139
Creatinine (mg/dL)	0.7
Calcium (mg/dL)	8.8
Phosphate (mg/dL)	3.4
Uric acid (mg/dL)	5
Bicarbonate (mmol/L)	22
Blood glucose (mg/dL)	149
White blood cells (k/μL)	197
Hemoglobin (g/dL)	11
Platelets (k/μL)	202
pH	7.51
Partial pressure of carbon dioxide (mm Hg)	28
Partial pressure of oxygen (mm Hg)	49

An electrocardiogram showed sinus tachycardia without any ST segment, T wave, or conduction abnormalities. High-sensitivity troponins were in the normal range. The patient received calcium gluconate and regular insulin with dextrose for hyperkalemia. Repeat potassium 4 hours later was 6.7 mmol/L, and the patient received sodium zirconium cyclosilicate. Potassium levels remained in the range of 6 to 7 on repeat checks, even after multiple treatments. Arterial blood with a heparinized arterial blood gas syringe was obtained, and immediate point-of-care (POC) potassium was in the normal range, confirmed on repeat checks. The decrease in leukocyte counts also led to the normalization of potassium levels even on laboratory venous samples (Table 2). All treatments for hyperkalemia were stopped considering pseudohyperkalemia related to severe leukocytosis. The patient received treatment for coronavirus disease 2019 pneumonia and antibiotic therapy for concern of superimposed bacterial pneumonia. He was then weaned off of the ventilator. Daily arterial whole blood potassium checks remained in the normal range.

Table 2.

Comparison of point-of-care (POC) arterial and laboratory venous blood potassium analysis

Sample day	Sample time	Leukocyte count (k/µL)	Laboratory venous blood potassium (mmol/L)	POC arterial blood potassium (mmol/L)
Day 1	12:00	197	6.2	–
	16:24	212	6.7	–
	21:09	183	6.6	–
Day 2	05:54	158	5.7	–
	16:42	156	5.4	–
Day 3	05:22	261	6.6	–
	17:20	201	6.7	3.9
Day 4	04:52	118	5.1	3.5
Day 5	04:41	200	6.5	3.7
Day 6	04:44	104	5.5	3.7
Day 7	04:09	102	5.5	3.9
Day 8	05:00	60	4.1	3.5
Day 9	04:35	53	3.8	3.4

– indicates not checked.

DISCUSSION

Pseudohyperkalemia is usually caused by potassium release from mechanical cell lysis during or after blood collection. The mechanism of cell lysis could be related to venipuncture, tourniquet application, use of a vacutainer during blood collection, pneumatic tube transport, or centrifugation during the transport and preparation for running the test in the laboratory.³ A hemolyzed blood sample is a common cause that can easily be seen in the laboratory. Severe thrombocytosis or leukocytosis in hematologic disorders can also lead to pseudohyperkalemia.

Although the phenomenon was first described in patients with severe thrombocytosis, it has been observed with severe leukocytosis, which was first described in 1975 by Bellevue et al. The pseudohyperkalemia in leukemic patients results from the release of potassium from cell lysis due to the increased fragility of the leukocytes.⁴ This can occur due to negative pressure of the vacutainer, pneumatic tube transport, prolonged sample-to-analysis time, or centrifugation of the blood.⁵ The scarcity of the metabolic resources for the excessive leukocytes can cause impairment of the sodium-potassium adenosine triphosphate activity and can lead to cell lysis.⁶

We highlight the use of POC potassium in diagnosing pseudohyperkalemia. The use of arterial blood in heparinized arterial blood gas syringes with immediate POC analysis can prevent cell lysis and reflect true in vivo potassium levels. This occurs due to lack of tourniquet use with arterial sampling, no vacutainer use, absence of pneumatic tube transport, early analysis, and thus less chance of leukocyte destruction. This phenomenon has been described by Ruddy et al, who reported a discrepancy between arterial and venous potassium levels due to pseudohyperkalemia. In their case, the arterial blood was also sent to the laboratory for analysis immediately after collection to target the minimum sample-to-analysis time.⁷ It is important to look for other causes of hyperkalemia in these patients, as tumor lysis syndrome can also occur and lead to hyperkalemia. Renal insufficiency is another cause in these patients. The presence of normal levels of uric acid, calcium, phosphate, and creatinine ruled out these causes.