Spurious Lab Values in Patients with Leukocytosis

Abstract

Physiological derangements such as hypoxemia and hyperkalemia are medical emergencies that warrant prompt interventions to prevent further patient clinical deterioration. However, in patients with myeloproliferative diseases or malignancies that result in extreme leukocytosis, hypoxemia and hyperkalemia demonstrated in lab results could be deceiving due to in-vitro reactions and may not reflect actual patient condition. Clinicians have to be familiar with these phenomena so as to not cause harm by treating these spurious lab values.

Background

Myeloproliferative conditions and certain malignancies are characterized by an overproduction of white blood cells, most of which are in the form of blast or immature cells. The excessive amount of white blood cells have many clinical implications. They can increase blood viscosity and lead to hyperviscosity syndromes with neurological and pulmonary symptoms.¹ However, the markedly increased white blood cell count also has in-vitro implications that can cause clinical mismanagement if the provider is not familiar with these conditions.

Case Example

A female patient in her late 70s with previous medical history of chronic myeloid leukemia being followed expectantly due to intolerance of chemotherapy, presented to her local Emergency Department due to several days of dyspnea and fever. Chest x-ray was suspicious for pneumonia and a complete blood count shows anemia, thrombocytopenia and leukocytosis with white blood cell count of 800,000/mcL. The patient was admitted to the hospital and was treated with supplemental oxygen and empiric antimicrobials. While boarding in the Emergency Department, patient’s respiratory condition deteriorated rapidly and ultimately required endotracheal intubation. While waiting for an Intensive Care Unit bed, post-intubation labs were obtained. The patient’s arterial blood gas (ABG) was significant for hypoxemia with arterial partial oxygen pressure of 45 mmHg (Normal 80 – 100 mmHg). Despite the hypoxemia demonstrated by the ABG, the patient’s pulse oximeter showed 100% oxygen saturation. In addition to the abnormal ABG result, the patient’s basic metabolic panel (BMP) revealed a serum potassium level of 9 meq/dL. An electrocardiogram (EKG) was performed and it did not show expected EKG changes in the setting of hyperkalemia. The patient also did not have conditions such as renal failure, acidosis which would have placed her at risk for hyperkalemia. Both the ABG and the BMP were repeated due to the clinical inconsistencies but the repeated results were similar. The treating provider was baffled at these seemingly inexplicable laboratory results that do not fit the patient’s clinical status. However, both laboratory abnormalities are well documented phenomena seen in patients with severe leukocytosis.

Leukocyte Larceny

Leukocyte larceny is a term first coined in 1979 in by Hess et al. describing the condition of pseudo-hypoxemia due to leukocytosis.² The hypoxemia results from the high metabolic demand of the in-vitro white blood cells. In a normal person’s complete blood panel, the in-vitro red blood cells are not oxygen consuming. But the white blood cells and the platelets are metabolically active and consumes oxygen at a high rate. White blood cells typically are 45 times more metabolically active than platelets in oxygen consumption. Despite being much more metabolically active than platelets, white blood cell count in a normal person is significantly less than their platelet count, which offsets the high metabolic demand. However, a patient with leukocytosis due to myeloproliferative disorders or malignancy, this balance is broken and the overwhelming number of white blood cells will consume large amount of oxygen in-vitro.³ Moreover, leukocytes resulting from malignancy are often riddled with immature blast cells which are even more metabolically active than mature white blood cells. Hess et al. noted in their original study that the level of pseudo-hypoxemia is directly correlated with the number of white blood cells and the duration of process time for the blood sample.² This is logical since the long period of idle time for the blood sample to be processed, the more amount of oxygen would be consumed by the proliferated white blood cells in-vitro. While the sampled blood may demonstrate hypoxemia, the patient’s serum oxygen level is likely much higher, reflected by the higher pulse-oximetry reading.³ This discrepancy between the lab value and the bedside monitor may create confusion for the clinicians who are not familiar with the phenomenon of leukocyte larceny. As a result, there may be a delay of weaning the patient from high fractionated supplemental oxygen, superoxide damage and unnecessary repeated ABGs.

Spurious Hyperkalemia

In the case example, the patient’s serum potassium level was also noted to be dangerously high without associated EKG changes expected with such significant metabolic derangement. This clinical presentation is due to a phenomenon known as spurious hyperkalemia or also known as pseudohyperkalemia. It is a term used to describe falsely high level of potassium in the in-vitro serum due to movement of potassium ions from intracellular space to the extracellular environment during or after blood drawing.⁴ Spurious or pseudohyperkalemia has been reported in patients with erythrocytosis, leukocytosis or thrombocytosis. This is due to one of several scenarios. In patients with myeloproliferative disorders or malignancy, the high white blood cell count contain large amount of immature or fragile cells, which are prone to be damaged and subsequently lyse either during the blood draw process, during the transport of blood sample through pneumatic tubes to lab, during prolonged storage, or during the centrifuge process.⁵ With the lysing of the white blood cells, the intracellular potassium now have leaked into the extracellular environment and result in a potassium reading.⁵ It has also been thought that during the in-vitro clotting process, the fragile white blood cells lyse and leak potassium out of the cell and create a falsely high potassium reading. Moreover, heparin additives in the sampling tube may lead to heparin-induced membrane damage of the white blood cells and resulting in leakage of potassium in vitro and significantly alter the result. The number of heparin units in the blood tube directly correlated with the level of false results.⁶

Potential Solutions

In cases where patient has myeloproliferative conditions or malignancy, to minimize the effect of leukocyte larceny, a potential solution is to minimize the time from sample collection to processing, thus diminishing the time of oxygen consumption by the white blood cells.¹ Decreasing the temperature of the blood sample with ice may potentially slow the oxygen consumption by oxygen as well. Finally, the addition of potassium cyanide or sodium fluoride can inhibit the oxygen uptake by white blood cells.² However, neither of these additives are widely available therefore may not be feasible for many institutions. In the setting of extreme leukocytosis, bedside pulse oximetry may be the most accurate measurement of the patient’s actual oxygen saturation status.³

To prevent pseudohyperkalemia, it has been suggested to collect whole blood samples with lithium heparin balanced syringes and run the sample on blood gas analyzers or point of care testing machines without the use of centrifuge. This may produce more accurate potassium concentration readings. However, there have been conflicting evidence to the utility of this method. Other solutions include avoiding the use of pneumatic tubes to deliver the blood sample, careful handling of the sample to avoid mechanical cell destruction and intracellular potassium release.^6,7

Conclusion

Recognizing these unique laboratory presentations in the setting of leukocytosis is important for the provider to make proper clinical diagnosis and management plan. The inability to differentiate between true physiological derangement and spurious lab results can be harmful to the patient. Not recognizing leukocyte larceny can prevent the timely weaning of patient from the ventilator.¹ The inability to differentiate true hyperkalemia and pseudohyperkalemia has been reported to result in iatrogenic hypokalemia due to unnecessary treatment.⁷ Providers must be vigilant and understand these unique phenomenon in these special patient population with myeloproliferative disorders or malignancy.