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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
CASE REPORT  
Year : 2017  |  Volume : 28  |  Issue : 2  |  Page : 410-414
Pseudohyperkalemia: Look before you treat


Department of Nephrology and Hypertension, Ochsner Hospital System, New Orleans, Louisiana, USA

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Date of Web Publication23-Mar-2017
 

   Abstract 

Pseudohyperkalemia is defined as a reported rise in serum potassium concentration along with a normal effective plasma potassium concentration. We present a case report of a 57-year-old gentleman with a history of chronic lymphocytic leukemia, who presented with an elevation in serum potassium along with a normal plasma potassium concentration. Through an exploration of the literature, we demonstrate that pseudohyperkalemia is an important phenomenon to watch for as it may sometimes lead to unnecessary and potentially dangerous treatment.

How to cite this article:
De Rosales AR, Siripala DS, Bodana S, Ahmed F, Kumbala DR. Pseudohyperkalemia: Look before you treat. Saudi J Kidney Dis Transpl 2017;28:410-4

How to cite this URL:
De Rosales AR, Siripala DS, Bodana S, Ahmed F, Kumbala DR. Pseudohyperkalemia: Look before you treat. Saudi J Kidney Dis Transpl [serial online] 2017 [cited 2019 Apr 24];28:410-4. Available from: http://www.sjkdt.org/text.asp?2017/28/2/410/202773

   Introduction Top


Pseudohyperkalemia was first reported in 1955.[1] Pseudohyperkalemia is defined as a reported rise in serum potassium concentration with normal effective plasma potassium concentration. During the last decade, pseudohyperkalemia has been defined as a serum potassium concentration exceeding that of plasma by more than 0.4 mmol/L.[1],[2] The effective serum potassium level is not accurately reported in the results of the chemistry panel. The etiology is multifactorial. Pseudohyperkalemia may result from potassium leakage from platelets during the clotting process with thrombocytosis. Fukasawa et al[3] showed that even normal activated platelet counts can cause pseudohyperkalemia. Potassium is also released after hemolysis of cellular components of blood, such as during transport to the laboratory. Pseudohyperkalemia can also occur by mechanical release of potassium from cells during phlebotomy or specimen processing. The entity of pseudohyperkalemia is rare and not well appreciated. This case report emphasizes early recognition of pseudohyperkalemia in a patient with very elevated potassium and white blood cell (WBC), who had normal clinical and electrocardiogram (EKG) findings.


   Case Report Top


A 57-year old African-American gentleman, who had been diagnosed with chronic lymphocytic leukemia (CLL) nearly one year prior, was admitted to the university hospital for induction chemotherapy. He was asymptomatic at the time of admission, with a negative review of systems. His laboratory tests at the time of admission showed an elevated potassium level of 8.4 mEq/L (normal range 3.5–5.0 mEq/L) with normal renal function and no other electrolyte abnormality. The patient received treatment with calcium gluconate and insulin and dextrose, which reduced the potassium to 7.2 mEq/L. Subsequently, nephrology was consulted for the management of his hyperkalemia.

His medical history was positive for CLL, previously diagnosed on submandibular lymph node biopsy, hypertension, and dyslipidemia. His medications included amlodipine and hydrochlorothiazide. He denied any over the counter medication use. The patient was not on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. He denied any major surgery in the past. He had no known drug allergies. Social history was negative for any recent tobacco, alcohol, illicit, or intravenous drug usage. He was a prisoner. His family history was negative for any malignancy or kidney diseases. His sexual history was negative for same-sex contacts or multiple partners.

Physical examination including the vitals was unremarkable. The urine output was more than 100 mL/h.

Laboratory investigations showed a normal basic metabolic panel, except for the elevated potassium. He had normal phosphorus and uric acid levels and normal urinalysis. His complete blood count was significant for an elevated WBC count of 136 K/μL (normal range 3.90–12.70 K/μL) with normal red cell and platelet indices. EKG was unremarkable for signs of hyperkalemia such as peaked T-waves. Subsequently, a point-of-care plasma potassium level done with a point-of-care blood gas machine was drawn at the bedside to rule out pseudohyperkalemia. Plasma potassium was 4.5 mEq/ L, which was 1 mEq/L lower than the serum potassium obtained in the basic metabolic panel at the same time. A diagnosis of pseudohyperkalemia due to cancerous leukocytosis and the fragility of the WBCs was made, and the patient did not receive any further antihyperkalemic treatment.

This case report emphasizes early recognition and diagnosis of pseudohyperkalemia and prevention of unnecessary and potentially dangerous treatment. The dangers of erroneously treating pseudohyperkalemia include an inappropriate decrease in actual serum potassium levels, which may lead to arrhythmias and other adverse cardiovascular complications.

Whole blood potassium determination, done using a blood gas machine, will verify the correct diagnosis.


   Discussion Top


Hyperkalemia is a life-threatening electrolyte abnormality. Early recognition and treatment is crucial to achieve good outcomes. Typical clinical manifestations of hyperkalemia are cardiovascular and neurologic, and these usually occur when serum potassium levels are more than 7.0 mEq/L. Serum potassium levels >8.0 mEq/L are almost invariably associated with EKG changes.[4] The most catastrophic manifestation of hyperkalemia is hyperexcitability of cardiac tissues, which may lead to various cardiac arrhythmias such as ventricular fibrillation, second- and third-degree heart block, and even asystole. Neurologic manifestations include generalized weakness, muscle cramps, paresthesias, and tetany. In addition, hyperkalemia can present with an acute neuro-muscular paralysis characterized by slowed nerve conduction velocities and nerve conduction block.[5] It is important to obtain an EKG in any patient with profound hyperkalemia as this will guide the management strategy. Typical early EKG manifestations of hyperkalemia are peaked T-waves and shortened QT interval, followed by loss of P waves, widening and slurring of the QRS complexes, sine-wave appearance, ventricular fibrillation, or asystole.[6]

EKG changes may not always be readily apparent with true hyperkalemia. A retrospective study by Montague et al reported poor correlation of the severity of EKG changes with the serum potassium concentration.[7]

Furthermore, Szerlip et al reported two cases of severe hyperkalemia (greater than 9.0 mEq/L) in which the EKGs did not reveal the expected manifestations.[8] EKG manifestations of hyperkalemia may be detrimentally affected by other factors such as hyponatremia, hypocalcemia, acidosis, and the speed of the rise in potassium.[9] In a study by Aslam et al, 74 end-stage renal disease (ESRD) patients were stratified into four groups with potassium levels in the range of 4.4–>5.5. Among the four groups, there was no statistically significant difference in T-wave amplitude or T-wave to R-wave ratio. The study investigators did find that that an elevated serum calcium concentration was associated with low T-wave amplitude and a cardioprotective effect.[10] Cases of extremely elevated potassium levels and unremarkable EKG findings generally occur in patients with chronic renal failure due to the slow rise in serum potassium.[4],[8] This is especially true in ESRD patients who may develop a certain cardiac tolerance to hyperkalemia. EKG results must be interpreted with caution when managing an ESRD patient with hyperkalemia.

On the other hand, early recognition of pseudohyperkalemia is important to prevent unnecessary treatment that may lead to dangerous hypokalemia and cardiac arrhythmias. Pseudohyperkalemia may be masked if effective serum potassium is low.

Pseudohyperkalemia is multifactorial in etiology and is due to potassium movement out of the cells either during or after the blood specimen has been drawn. In other words, pseudohyperkalemia can occur at the point of blood collection or during the time of transport and storage before laboratory evaluation.

Potential causes of pseudohyperkalemia at the time of blood collection include repeated fist clenching,[11] traumatic venipuncture using a small gauge needle,[12] and hemolysis from mechanical trauma during venipuncture causing the release of potassium from red cells. For instance, Wiederkehr and Moe found that in a study of eight healthy volunteers comparing blood samples obtained with and without a tourniquet, plasma potassium was 0.2 mEq/L higher in blood samples drawn following tourniquet use than in free-flowing blood samples.[13]

Causes of pseudohyperkalemia occurring at the time of transport and storage include the use of vacuum tubes, pneumatic tube transportation, prolonged incubation, and recentrifugation after storage in gel separator tubes causing cell lysis.[14],[15],[16],[17] Guiheneuf et al present two leukemia cases with pronounced leukocytosis who each showed a profound elevation in serum potassium when the specimens were transported through pneumatic tube, but who showed a normal serum potassium when the specimens were transported through pedestrian.[18]

Temperature may also be a factor in the development of pseudohyperkalemia. Delayed processing of the sample or placing the sample on ice for a prolonged period can lead to pseudohyperkalemia.[12],[19] Sinclair et al also noted that ambient temperature may influence the development of pseudohyperkalemia. They looked at samples drawn in the summer months and winter months. The investigators found that colder ambient temperatures are more likely to artificially elevate the serum potassium versus warmer ones. It is possible that the colder ambient temperatures may lead to leakage of potassium from blood cells, which may lead to the phenomenon of pseudohyperkalemia.[20]

Ruddy et al presented a case of a 49-year-old postsplenectomy patient who developed thrombocytosis and concurrently developed a rise in serum potassium. The serum potassium was 5.9 mEq/L whereas the plasma potassium concentration was 3.9 mEq/L.[21] Caution is advised when interpreting serum potassium levels in postsplenectomy patients as these patients are predisposed to thrombocytosis and therefore pseudohyperkalemia. Precautions that can be taken include simultaneous measurement of plasma and serum potassium concentrations, avoiding use of vacuum tubes, and avoiding prolonged incubation of the blood sample.

It is important to differentiate pseudohyperkalemia from reverse pseudohyperkalemia. In pseudohyperkalemia, serum potassium is falsely elevated, and plasma potassium is within normal limits. In reverse pseudohyperkalemia, serum potassium is within normal range, and plasma potassium is falsely elevated. A possible cause is the use of heparin as an anticoagulant in the plasma collection tube as opposed to using the point-of-care arterial blood gas machine. The heparin in the plasma collection tube causes damage to the cell membrane during processing and centrifugation in the context of fragile cells of hematologic malignancy.[2]

For instance, Avelar noted a case of reverse pseudohyperkalemia in a patient with CLL. The patient had a WBC of 206 K/μL and a plasma potassium of 8.4 mEq/L without evidence of acute kidney injury. The repeat plasma potassium was 8.1 mEq/L. However, the patient did not have any EKG change consistent with hyperkalemia. He received antihyperkalemic treatment, but the plasma potassium continued to remain elevated at 8.1 mEq/L. The patient was started on hemodialysis due to refractory hyperkalemia. During the dialysis treatment, the clinicians rechecked the plasma potassium and serum potassium. While the plasma potassium was 7.9 mEq/L, the serum potassium was only 4.4 mEq/L.[22] Moreover, hemodialysis was discontinued. This case serves to illustrate the point that reverse pseudohyperkalemia can occur in patients with a pronounced leukocytosis and with the use of heparinized plasma collection tubes. In addition, the case demonstrates the importance of recognizing reverse pseudohyperkalemia to avoid unnecessary and potentially dangerous treatment.

Using gel tubes may also cause reverse pseudohyperkalemia. For example, Jowitt et al compared plasma potassium concentrations from blood collected in gel and nongel tubes. The investigators collected blood samples from nine hematology patients and found that the plasma potassium concentration was 0.3 mmol/L higher in samples collected in gel tubes versus those collected in nongel tubes.[23] This indicates that the use of a gel tube is more likely to lead to the phenomenon of reverse pseudohyperkalemia as well as pseudohyperkalemia. It is also advisable to avoid tubes with gel separators in patients with leukemia or other forms of leukocytosis as those patients already have an increased likelihood of reverse pseudohyperkalemia.

Familial pseudohyperkalemia is a rare genetic syndrome caused by RBC fragility and abnormal leakage of potassium at low temperatures during storage and laboratory evaluation, due to several autosomal dominant heterozygous missense mutations in the ABC B6 transporter.[24],[25]

It is important to differentiate between true hyperkalemia and pseudohyperkalemia to prevent unnecessary and potentially deadly treatment. If there is suspicion for pseudohyperkalemia or reverse pseudohyperkalemia, simultaneous measurement of serum and plasma potassium concentrations should be done. To prevent laboratory error, a point-of-care blood gas analyzer should be utilized.

Conflict of interest:

None declared.

 
   References Top

1.
Hartmann RC, Auditore JV, Jackson DP. Studies on thrombocytosis. I. Hyperkalemia due to release of potassium from platelets during coagulation. J Clin Invest 1958;37:699-707.  Back to cited text no. 1
    
2.
Singh PJ, Zawada ET, Santella RN. A case of ‘reverse’ pseudohyperkalemia. Miner Electrolyte Metab 1997;23:58-61.  Back to cited text no. 2
    
3.
Fukasawa H, Furuya R, Kato A, et al. Pseudohyperkalemia occurring in a patient with chronic renal failure and polycythemia vera without severe leukocytosis or thrombocytosis. Clin Nephrol 2002;58:451-4.  Back to cited text no. 3
    
4.
Martinez-Vea A, Bardaji A, Garcia C, Oliver JA. Severe hyperkalemia with minimal electrocardiographic manifestations: a report of seven cases. J Electrocardiol 1999;32:45-9.  Back to cited text no. 4
    
5.
Naik KR, Saroja AO, Khanpet MS. Reversible electrophysiological abnormalities in acute secondary hyperkalemic paralysis. Ann Indian Acad Neurol 2012;15:339-43.  Back to cited text no. 5
[PUBMED]  [Full text]  
6.
Dreifus LS, Pick A. A clinical correlative study of the electrocardiogram in electrolyte imbalance. Circulation 1956;14:815-25.  Back to cited text no. 6
    
7.
Montague BT, Oullette JR, Buller GK. Retrospective review of the frequency of ECG changes in hyperkalemia. Clin J Am Soc Nephrol 2008;3:324-30.  Back to cited text no. 7
    
8.
Szerlip HM, Weiss J, Singer I. Profound hyperkalemia without electrocardiographic manifestation. Am J Kidney Dis 1986;7:461-5.  Back to cited text no. 8
    
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10.
Aslam S, Friedman EA, Ifudu O. Electrocardiography is unreliable in detecting potentially lethal hyperkalaemia in haemodialysis patients. Nephrol Dial Transplant 2002;17:1639-42.  Back to cited text no. 10
    
11.
Don BR, Sebastian A, Cheitlin M, Christiansen M, Schambelan M. Pseudohyperkalemia caused by fist clenching during phlebotomy. N Engl J Med 1990;322:1290-2.  Back to cited text no. 11
    
12.
Verresen L, Lins RL, Neels H, De Broe ME. Effects of needle size and storage temperature on measurements of serum potassium. Clin Chem 1986;32:698-9.  Back to cited text no. 12
    
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Wiederkehr MR, Moe OW. Factitious hyperkalemia. Am J Kidney Dis 2000;36:1049-53.  Back to cited text no. 13
    
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Colussi G. Pseudohyperkalemia in leukemias. Am J Kidney Dis 2006;47:373.  Back to cited text no. 14
    
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Chawla NR, Shapiro J, Sham RL. Pneumatic tube “pseudo tumor lysis syndrome” in chronic lymphocytic leukemia. Am J Hematol 2009; 84:613-4.  Back to cited text no. 15
    
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Colussi G, Cipriani D. Pseudohyperkalemia in extreme leukocytosis. Am J Nephrol 1995;15: 450-2.  Back to cited text no. 16
    
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Kellerman PS, Thornbery JM. Pseudohyperkalemia due to pneumatic tube transport in a leukemic patient. Am J Kidney Dis 2005;46: 746-8.  Back to cited text no. 17
    
18.
Guiheneuf R, Vuillaume I, Mangalaboyi J, et al. Pneumatic transport is critical for leukaemic patients with major leukocytosis: what precautions to measure lactate dehydrogenase, potassium and aspartate aminotransferase? Ann Clin Biochem 2010;47(Pt 1):94-6.  Back to cited text no. 18
    
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Johnston JD, Hawthorne SW. How to minimise factitious hyperkalaemia in blood samples from general practice. BMJ 1997; 314:1200-1.  Back to cited text no. 19
    
20.
Sinclair D, Briston P, Young R, Pepin N. Seasonal pseudohyperkalaemia. J Clin Pathol 2003;56:385-8.  Back to cited text no. 20
    
21.
Ruddy KJ, Wu D, Brown JR. Pseudohyperkalemia in chronic lymphocytic leukemia. J Clin Oncol 2008;26:2781-2.  Back to cited text no. 21
    
22.
Avelar T. Reverse pseudohyperkalemia in a patient with chronic lymphocytic leukemia. Perm J 2014;18:e150-2.  Back to cited text no. 22
    
23.
Jowitt S, Longlands MG, Probert DE. Variation in plasma potassium when using collection tubes containing gel separators. Clin Chem 1996;42(8 Pt 1):1300.  Back to cited text no. 23
    
24.
Sugimoto T, Kume S, Osawa N, Nakazawa J, Koya D, Kashiwagi A. Familial pseudohyperkalemia: a rare cause of hyperkalemia. Intern Med 2005;44:875-8.  Back to cited text no. 24
    
25.
Andolfo I, Alper SL, Delaunay J, et al. Missense mutations in the ABCB6 transporter cause dominant familial pseudohyperkalemia. Am J Hematol 2013;88:66-72.  Back to cited text no. 25
    

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Correspondence Address:
Ana Rivera De Rosales
Department of Nephrology and Hypertension, Ochsner Hospital System, New Orleans, Louisiana
USA
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DOI: 10.4103/1319-2442.202773

PMID: 28352030

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