Elevated potassium can quickly lead to fatal cardiac arrhythmias, muscle weakness or paralysis. Therefore accurate measurement of potassium is critical for patient management and laboratories often use potassium turnaround time as important quality indicator. One complicating factor is that elevated potassium can be caused by both physiological and pre-analytical issues. Elevated potassium due to pre-analytical factors that doesn’t truly reflect the patient’s electrolyte status is often termed pseudohyperkalemia. Distinguishing true hyperkalemia from pseudohyperkalemia is important for both laboratories and clinicians alike.
One of the most common causes of pseudohyperkalemia is hemolysis of red blood cells during collection. Fortunately, hemolysis of red blood cells is easily and routinely detected by chemistry platforms colorimetrically and results can be suspended or suppressed if hemolysis is detected. But what if pseudohyperkalemia is suspected in the absence of visible hemolysis?
Several other biochemical and environmental factors can contribute to pseudohyperkalemia including leukocytosis, thrombocytosis, temperature storage, collection, and possibly pressurized centrifugal forces. Beyond hemolysis, leukocytosis or elevated white blood cells, can be a possible cause of pseudohyperkalemia. Significant leukocytosis is seen in numerous disease states such as chronic lymphocytic leukemia (CLL). It is thought that WBC production in the setting of CLL may contribute to increased cellular fragility that is more prone to mechanical stress. This hypothesis is difficult to evaluate and attempts to quantitatively correlate WBC elevation with pseudohyperkalemia suggest the effect is multifactorial. Additionally the presence of heparin has been associated with increased fragility of WBCs which is often termed reverse pseudohyperkalemia.
Thrombocytosis, or elevated platelets, has also been associated with instances of pseudohyperkalemia. The cause of thrombocytosis can arise from many reasons but several case reports have highlighted elevated potassium post splenectomy. Both increased production of platelets or decreased removal can result in large elevations. During clot formation, fragile platelets may lyse releasing excess potassium. The exact conditions which result in pseudohyperkalemia are not well understood but much like leukocytosis, they are probably multifactorial. In addition to these two biochemical conditions, decreased temperature inhibits Na/K ATPase pumps present on red blood cells which result in leakage of potassium outside the cells. Additionally centrifugal forces and pneumatic tube system transport have all been documented as factors than may result in pseudohyperkalemia in the absence of red blood cell hemolysis.
Laboratories can develop strategies to identify and triage specimens with suspected pseudohyperkalemia. Several studies have tried to develop guidelines for differentiating affected versus unaffected specimens based on WBC and platelet elevations. Additionally, very active discussions on AACC’s Artery (see links below) have highlighted a variety of cutoffs and approaches used by other institutions. These measures include investigation of elevated potassium when WBC and platelets are elevated beyond a specific threshold, specific instructions on delivering specimens to the lab, and avoiding heparin anticoagulants in favor of serum separator tubes for certain patient populations. Despite their differences, most laboratorians agree that whole blood analysis of potassium is a viable confirmation of the true potassium value if pseudohyperkalemia is suspected.
- Sevastos N, Theodossiades G, Archimandritis AJ. Pseudohyperkalemia in Serum: A New Insight into an Old Phenomenon. Clin Med Res. 2008;6(1):30-32. doi:10.3121/cmr.2008.739
- Mansoor S, Holtzman NG, Emadi A. Reverse Pseudohyperkalemia: An Important Clinical Entity in Chronic Lymphocytic Leukemia. Case Rep Hematol. 2015;2015:930379. doi:10.1155/2015/930379
- Ranjitkar P, Greene DN, Baird GS, Hoofnagle AN, Mathias PC. Establishing evidence-based thresholds and laboratory practices to reduce inappropriate treatment of pseudohyperkalemia. Clin Biochem. 2017;50(12):663-669. doi:10.1016/j.clinbiochem.2017.03.007
- Ahmed R, Isaac AM. Postsplenectomy thrombocytosis and pseudohyperkalemia in trauma: a case report and review of literature. J Trauma. 2009;67(1):E17-19. doi:10.1097/01.ta.0000238653.55029.cd
- Katkish L, Rector T, Ishani A, Gupta P. Incidence and severity of pseudohyperkalemia in chronic lymphocytic leukemia: a longitudinal analysis. Leuk Lymphoma. 2016;57(8):1952-1955. doi:10.3109/10428194.2015.1117608