Pseudohyperkalemia: a clinical study

Raised plasma/serum potassium (hyperkalemia), which is widely defined as potassium >5.0-5.3 mmol/L, is a common electrolyte disturbance with many possible causes, including renal failure, acidosis, aldosterone deficiency and tissue damage. Severe hyperkalemia is a potentially life-threatening condition that demands urgent (potassium-lowering) treatment. 

Faced with an unexplained increased potassium result, clinicians must give due consideration to the possibility that the result is spurious and not an accurate reflection of in vivo extracellular potassium concentration. The term pseudohyperkalemia is used to describe falsely raised serum or plasma potassium. 

It is obviously important that cases of pseudohyperkalemia are identified in order that inappropriate potassium-lowering treatment is not administered. Also, it must be noted that plasma/serum result within the normal range does not exclude the possibility of a falsely raised value; the patient may in fact be hypokalemic.

There are a number of causes of pseudohyperkalemia, but no matter what the cause, the potential for pseudohyperkalemia derives from the physiological marked disparity between intracellular fluid (ICF) and extracellular fluid (ECF) potassium concentration: ECF K⁺ ∼4 mmol/L, ICF K⁺ ∼150 mmol/L. This determines that relatively slight loss of potassium from blood cells (erythrocytes, leucocytes platelets) to plasma during or after blood is sampled can have marked effect on measured serum/plasma potassium. 

In vitro hemolysis due to poor sampling/handling technique and delay in separating plasma/serum from the whole-blood sample are probably the most common causes of pseudohyperkalemia but there are others, including extreme leukocytosis (massive increase in white cell count) and extreme thrombocytosis (massive increase in platelet count). Extreme leukocytosis and thrombosis are most commonly evident in patients suffering hematological malignancy. These two causes of pseudohyperkalemia (extreme leukocytosis and extreme thrombocytosis) are the focus of this recently published clinical study.

The principal aim of the study was to determine the white cell and platelet count thresholds at which patients are at high risk of pseudohyperkalemia. Investigators interrogated laboratory records generated during a 4-year period (2011-2016) at two laboratory sites. 

They extracted all serum and plasma potassium results derived from patients who had white cell count and platelet count determined within 24 hours and whole-blood potassium measured on blood gas analyzer within 2 hours of serum/plasma sampling. A total of 10,929 sets of results were extracted for analysis. Pseudohyperkalemia was defined by the authors as serum or plasma potassium >1.0 mEq/L (>1.0 mmol/L) than that obtained by whole-blood potassium analysis. 

Differences between whole-blood potassium and serum or plasma potassium were compared as functions of platelet or leucocyte count. Linear regression analysis revealed that difference between serum and whole-blood potassium increases as platelet count increases (approximately 0.05 mEq/L per 100x10⁹/L increase in platelet count). By contrast, difference between plasma and whole-blood potassium was shown to be unaffected by rise in platelet count. 

These data suggest that pseudohyperkalemia due to thrombocytosis does not occur if plasma samples are used, but can occur if serum samples are used. Around 14 % of serum samples with platelet count > 500x10⁹/L had potassium >1.0 mEq/L when compared with whole-blood potassium. On the basis of these and other data the authors propose a platelet threshold of >500x10⁹/L to indicate high risk of pseudohyperkalemia for serum samples. 

Linear regression analysis revealed that difference between serum and whole-blood potassium increases slightly with increasing white blood cell count (0.2 mEq/L for every 100x10⁹/L increase in white cell count). Difference between plasma and whole-blood potassium was more significantly affected by increasing white cell count (0.6 mEq/L increase for every 100x10⁹/L increase in white cell count). These data suggest that risk of pseudohyperkalemia due to extreme leukocytosis is greater for plasma samples than serum samples. 

Despite this, around 25 % of both serum and plasma samples that had white cell counts greater than 50x10⁹/L showed evidence of pseudohyperkalemia (i.e. serum/plasm value >1.0 mEq/L higher than whole-blood potassium). On the basis of these and other data the authors propose a white cell count of >50x10⁹/L to indicate high risk of pseudohyperkalemia for both serum and plasma samples. 

The authors recommend that all patients found to have a white cell count >50x10⁹/L or a platelet count >100x10⁹/L should be considered at risk of pseudohyperkalemia and in such cases potassium should be assessed by determining whole-blood potassium from a sample collected into a blood gas syringe. 

The authors demonstrate that direct communication of this advice to clinical staff when cases of high-risk pseudohyperkalemia are identified is more effective in avoiding inappropriate potassium-lowering treatment than including the advice on laboratory reports.