Clinlab Navigator

Pseudohyperkalemia and Reverse Pseudohyperkalemia

Chemistry instruments in the core laboratory measure potassium using an indirect ion-selective electrochemical method that selectively allow potassium ions to interact with the electrode. A commonly used type of ion-selective membrane for potassium is a polyvinyl chloride membrane incorporated with valinomycin. Blood-gas analyzers use direct ion-selective electrodes to measure whole blood potassium concentrations.

A number of preanalytical factors can cause spurious elevation of potassium concentration in specimens. Examples include prolonged tourniquet time, excessive fist clenching, traumatic venipuncture, excess suction while drawing blood with a syringe, vigorous mixing, and delay of more than 2 hours in centrifugation. Familial pseudohyperkalemia is a rare, autosomal dominant cause of pseudohyperkalemia due to leakage of potassium across the red blood cell membrane when the specimen is stored at room temperature.

There are two defined clinical entities that cause spurious hyperkalemia: pseudohyperkalemia and reverse pseudohyperkalemia. Pseudohyperkalemia is an in vitro phenomenon in which potassium concentration is falsely elevated in serum but normal in plasma. Reverse hyperkalemia is just the opposite: potassium concentration is elevated in plasma and normal in serum.

Pseudohyperkalemia is defined as elevation in measured potassium concentration due to leakage of potassium out of cells either during or after drawing of blood. Pseudohyperkalemia should be suspected whenever hyperkalemia coexists with thrombocytosis. Platelet counts usually exceed 500,000/uL. Serum potassium levels rise by approximately 0.15 mEq/L for every 100,000/uL elevation in platelet count. Pseudohyperkalemia is caused by potassium release from activated platelets during clot formation in serum. For this reason, measurement of heparinized whole blood and plasma yield results that are representative of the true physiologic state of the patient, whereas serum gives falsely elevated results. Clinical decisions should be based on plasma or whole blood potassium measurements.

Reverse pseudohyperkalemia is an in vitro phenomenon in which plasma potassium concentration rises higher than serum potassium concentration, usually due to extreme leukocytosis. Leukemic leukocytes are more fragile than normal leukocytes, leading to in vitro lysis during centrifugation of plasma specimens and elevating potassium concentrations. In serum specimens, the formation of a fibrin clot is hypothesized to entrap and stabilize tumor cells during centrifugation. In these cases, buffy coat may be seen above the plasma gel, which is not observable on the serum gel. Reverse pseudohyperkalemia may be exacerbated by specimen transport through pneumatic tubes, which causes additional mechanical disruption of leukemic leukocytes. Whole blood can be used as an alternative specimen in cases of reverse pseudohyperkalemia.


  1. Talent Theparee; Robert C. Benirschke Hong-Kee Lee,
  1. Mansoor S, Holtzman NG, Emadi A. Reverse pseudohyperkalemia: an important clinical entity in chronic lymphocytic leukemia. Case Rep Hematol. 2015;2015:930379.
  2. Asirvatham JR, Moses V, Bjornson L. Errors in potassium measurement: a laboratory perspective for the clinician. N Am J Med Sci. 2013;5(4):255–259.
  3. Sevastos N, Theodossiades G, Archimandritis AJ. Pseudohyperkalemia in serum: a new insight into an old phenomenon. Clin Med Res. 2008;6(1):30–32.
  4. Avelar T. Reverse pseudohyperkalemia in a patient with chronic lymphocytic leukemia. Perm J. 2014;18(4):e150-e152.
  5. 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.
  6. Lee HK, Brough TJ, Curtis MB, Polito FA, Yeo KTJ. Pseudohyperkalemia—is serum or whole blood a better specimen type than plasma? Clin Chim Acta. 2008;396(1–2):95–96.
  7. Meng QH, Krahn J. Reverse pseudohyperkalemia in heparin plasma samples from a patient with chronic lymphocytic leukemia. Clin Biochem. 2011;44(8–9):728–730.
  8. Abraham B, Fakhar I, Tikaria A, et al. Reverse pseudohyperkalemia in a leukemic patient. Clin Chem. 2008;54(2):449–451.
  9. Dickinson H, Webb NJA, Chaloner C, Wynn RF, Bonney DK. Pseudohyperkalaemia associated with leukaemic cell lysis during pneumatic tube transport of blood samples. Pediatr Nephrol. 2012;27(6):1029–1031.
  10. Garwicz D, Karlman M. Early recognition of reverse pseudohyperkalemia in heparin plasma samples during leukemic hyperleukocytosis can prevent iatrogenic hypokalemia. Clin Biochem. 2012;45(18):1700–1702.
AddThis Social Bookmark Button