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Pseudohyperkalemia Due to Pneumatic Tube Transport in a Leukemic Patient
Abstract
Pseudohyperkalemia is an elevation in measured serum or plasma potassium levels caused by mechanical release of potassium from cells during phlebotomy or specimen processing. We describe a case of pseudohyperkalemia caused by mechanical disruption of white blood cells from a leukemic patient because of pneumatic tube transport of the specimen. This is the first description of pneumatic tube transport causing pseudohyperkalemia, and clinicians should be aware of this potential cause of false elevation of plasma potassium levels.
... For example, our hospital's PTT, delivering about 4,000 packages a day, can reach a linear speed of 17 mph with rapid accelerations and decelerations, as well as angular velocity changes with turns. Pneumatic transport of specimens with normal WBC counts did not affect the potassium measurement [10,11]. However, Kellerman, et al., described the first case of pseudohyperkalemia caused by pneumatic tube transport of blood specimens from a patient with extreme leukocytosis [11]. ...
... Pneumatic transport of specimens with normal WBC counts did not affect the potassium measurement [10,11]. However, Kellerman, et al., described the first case of pseudohyperkalemia caused by pneumatic tube transport of blood specimens from a patient with extreme leukocytosis [11]. The patient apparently had acute lymphocytic leukemia transformation originating from his prior mantle-cell non-Hodgkin lymphoma. ...
... Clotting did not play a role because all blood samples were heparinized. Prompt diagnosis of pseudohyperkalemia is critical to avoid iatrogenic hypokalemia from treatment (including emergency hemodialysis) for pseudohyperkalemia [5][6][7]11]. When significant leukocytosis, thrombocytosis, hyperproteinemia, or hyperlipidemia are present, whole blood potassium measurements should be utilized [13]. ...
Background
Pseudohyperkalemia is well known in acute or chronic lymphocytic leukemia, but it is very rare in acute myeloid leukemia (AML). The lab flagging system for leukocytosis to prevent pseudohyperkalemia may not work.
Case presentation
A 55 year-old white man with AML was sent to emergency department for transfusion due to severe anemia. Blood test showed severe leukocytosis and elevated potassium. Repeated blood test showed his potassium was even higher. Anti-hyperkalemic medical treatment was given. He was then diagnosed with pseudohyperkalema.
Investigation
I was repeatedly reassured that the lab’s manual flagging system for leukocytosis was the key in reaching the correct diagnosis. My persistent inquiries, however, revealed that the flagging system was not functioning in the care of this patient. It was clinicians’ suspicion of pseudohyperkalema that led to the correct diagnosis, although the clinicians’ recommendation of obtaining a heparinized plasma for test did not play a role because all blood samples were already heparinized. The cause of pseudohyperkalemia was pneumatic tube transport. After this incident, our laboratory is investigating the options of using the Laboratory Information System to automatically flag the results and Clinical Laboratory Scientists to make the chemistry team more aware of potentially erroneous potassium results due to pseudohyperkalemia.
Conclusions
Pseudohyperkalemia associated with leukocytosis still occurs. This is the first case of pneumatic tube transport causing pseudohyperkalemia associated with AML. When significant leukocytosis, thrombocytosis, hyperproteinemia, or hyperlipidemia is present, whole blood should be utilized for potassium measurements and walked to the lab instead of sent by pneumatic tube transport. Even in a lab with a manual flagging system, there is still room to improve by implementing an automatic flagging system.
... Furthermore, despite the patient being referred to distinct clinical departments, being treated by several specialists and having multiple consults, the factitious character of his hyperkalemia remained undiscovered up until the 15th day after the initial admission. This demonstrates well that factitious hyperkalemia is still widely unrecognized, and may have a burden on patient care [1,2]. Therefore, discussion of distinct mechanisms of factitious hyperkalemia, a summary of their frequencies and of their resolution is warranted. ...
... Again, no similar mechanical force applies to whole blood samples, where potassium measurement occurs directly with blood gas analyzers without previous centrifugation. According to previous reports, the major culprit of leukocytosis-associated factitious hyperkalemia is when Li-heparin anticoagulated plasma samples are transported by pneumatic tube transport [2,15,16]. Importantly however and consistently with their mechanical vulnerability, even if plasma samples are 'walked' to the laboratory, considerably more potassium may leak out of leukocytes upon centrifugation than from serum samples [16][17][18]. The reason for the increased mechanical vulnerability of the plasma samples is still unknown. ...
... Furthermore, concerning whole blood samples, venous sample are convenient and no arterial puncture is required [23] in contrast to earlier reports [24]. Concerning pneumatic transport, it may factitiously increase potassium concentration in serum and whole blood samples as well [25,26], while in other reports no similar effect was found [2,16]. This probably reflects differences between pneumatic transport systems of different institutions. ...
... On the other hand, aggressive treatment including renal dialysis may be unnecessarily commenced. 3 Therefore, clinicians should be aware of the conditions that may give rise to falsely elevated potassium levels. ...
... Conditions that induce in-vitro haemolysis include fist clenching during phlebotomy, drawing blood into an evacuated tube, use of smallgauge needles, use of tourniquets, cold storage, delay in sample processing, mechanical trauma during vigorous mixing, or hard centrifugation. 1,3 There is a rare genetic condition, familial pseudohyperkalaemia, which is an autosomal dominant disorder associated with excessive leakage of potassium across red cell membranes. 9 Pseudohyperkalaemia can also be the result of pre-existing pathological conditions resulting in cellular potassium leakage. ...
... The effect on potassium resulting from pneumatic tube transport is likely due to both WBC number and fragility. 3 Chawla et al 12 also reported a case of pseudohyperkalaemia due to mechanical disruption of leukocytes in a patient with chronic lymphocytic leukaemia and proposed to designate this phenomenon as pneumatic tube "pseudo tumour lysis syndrome". Ruddy et al 13 also reported a chronic lymphocytic leukaemia patient with venous potassium levels spuriously higher than arterial potassium levels. ...
Falsely elevated serum or plasma potassium level can be the result of mechanical injury to blood cells. We describe pseudohyperkalaemia caused by pneumatic tube transport of blood specimens from a patient with leukaemia. Clinicians should be aware of this possibility when interpreting the clinical significance of hyperkalaemia. In leukaemic patients, pneumatic tube transport of blood specimens for potassium analysis should be avoided.
... Leukocytosis/leukemia/polycythemia vera In 1966, Bronson et al. published the first description of leukocytosis as the cause of pseudohyperkalemia in serum samples as a result of potassium release during clotting processes [32]. A number of published case reports demonstrated pseudohyperkalemia ranging from 7.3 to over 10 mmol/L in both serum and heparin plasma samples from leukemia patients [33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48]. Some of these even received incorrect treatment prior to the identification of the biased potassium values (see case report 3). ...
... These studies hypothesize that increased membrane fragility of neoblastic white blood cells (WBCs) in these patients may lead to an increased risk of cell rupture, including leakage of intracellular potassium in both serum and plasma samples. This risk is increased by sample transportation via pneumatic tube systems (see case report 4) [3,35,36,38,43,44,47,49,[52][53][54] or during blood collection, where shear forces during the process may have a greater impact on fragile cells than normal ones. ...
Potassium is one of the most requested laboratory tests. Its level is carefully monitored and maintained in a narrow physiological range. Even slightly altered potassium values may severely impact the patient's health, which is why an accurate and reliable result is of such importance. Even if high-quality analytics are available, there are still numerous ways in which potassium measurements may be biased, all of which occur in the preanalytical phase of the total laboratory testing process. As these results do not reflect the patient's in-vivo status, such results are referred to as pseudo-hyper/hypokalemia or indeed pseudo-normokalemia, depending on the true potassium result. Our goal in this review is to present an in-depth analysis of preanalytical errors that may result in inaccurate potassium results. After reviewing existing evidence on this topic, we classified preanalytical errors impacting potassium results into 4 categories: 1) patient factors like high platelet, leukocytes, or erythrocyte counts; 2) the sample type 3) the blood collection procedure, including inappropriate equipment, patient preparation, sample contamination and others and 4) the tube processing. The latter two include sample transport and storage conditions of whole blood, plasma, or serum as well as sample separation and subsequent preanalytical processes. In particular, we discuss the contribution of hemolysis, as one of the most frequent preanalytical errors, to pseudo-hyperkalemia. We provide a practical flow chart and a tabular overview of all the discussed preanalytical errors including possible underlying mechanisms, indicators for detection, suggestions for corrective actions, and references to the according evidence. We thereby hope that this manuscript will serve as a resource in the prevention and investigation of potentially biased potassium results.
... The literature regarding reverse pseudohyperkalemia is limited to 13 case reports and case series [11][12][13][14][15][16][17][18][19][20][21][22]28] of patients with HMs, predominantly CLL. Among the reported cases, WBC counts have ranged between 206 and 545 Â 10 3 /mL with a median of 332 Â 10 3 /mL (Table 4). ...
... While the underlying mechanism for the development of reverse pseudohyperkalemia remains unknown, possible mechanisms involve collection tube heparin-induced WBC membrane damage and cell lysis [17], leukocyte-induced consumption of metabolic fuels with resultant inhibition of the sodium pump (Na þ /K þ -ATPase) and subsequent potassium release [15], lithium-induced Na þ /K þ -ATPase dysfunction and pneumatic transport causing mechanical disruption of the WBC membrane and/or activation of mechanoactivated cell membrane potassium channels [19,28]. Two case reports provide insights into potential mechanisms. ...
Background
Hyperkalemia is a potentially life-threatening electrolyte abnormality that often requires urgent treatment. Clinicians should distinguish true hyperkalemia from pseudohyperkalemia and reverse pseudohyperkalemia (RPK). RPK has exclusively been described in case reports of patients with hematologic malignancies (HMs) and extreme leukocytosis [white blood cell (WBC) count >200 × 103/mL].
Methods
This single-center retrospective study analyzed laboratory data from the Mount Sinai Data Warehouse between 1 January 2010 and 31 December 2016 for plasma potassium and serum potassium samples drawn within 1 h of each other, with plasma potassium ≥1 mEq/L of the serum potassium. Only plasma potassium ≥5 mEq/L were included. Samples that were documented to be hemolyzed or contaminated were excluded. Clinical history and laboratory data were collected from the identified cases.
Results
After applying the inclusion/exclusion criteria to 485 potential cases, the final cohort included 45 cases from 41 patients. There were 24 men and 17 women with a mean age of 52 years. The median plasma potassium was 6.1 mEq/L and serum potassium was 4.4 mEq/L. The median WBC count was 9.35 × 103/mL (interquartile range 6.5–19.7 × 103/mL). Only 44% of the samples had leukocytosis, defined as WBC >11 × 103/mL.
Seven patients had a HM and comprised 11 of the cases (24%) with a median WBC of 181.8 × 103µL. There was no difference in their plasma and serum potassium levels when compared with the total cohort, despite a higher median WBC count. Thirty-eight percent of the cases required medical management.
Conclusions
The literature on RPK is limited to case reports and series associated with extreme leukocytosis. This is the first study characterizing RPK predominantly associated with normal leukocyte counts. Further investigation is required to more precisely characterize factors associated with RPK and to elucidate RPK mechanisms.
... 15 When the potassium concentration is falsely elevated because of mechanical fragmentation of lymphocytes, both serum and plasma potassium are affected. [22][23][24] To avoid confusion, we suggest the terms "platelet-induced serum pseudohyperkalemia," "lymphocyteinduced plasma pseudohyperkalemia," and "shaken-lymphocyte pseudohyperkalemia." To exclude lymphocyte-induced plasma pseudohyperkalemia, serum potassium or whole blood potassium from a sample drawn in a blood gas syringe (which contains lower concentrations of heparin) should be measured; if shaken-lymphocyte pseudohyperkalemia is suspected, samples should be hand-carried to the laboratory. ...
... To exclude lymphocyte-induced plasma pseudohyperkalemia, serum potassium or whole blood potassium from a sample drawn in a blood gas syringe (which contains lower concentrations of heparin) should be measured; if shaken-lymphocyte pseudohyperkalemia is suspected, samples should be hand-carried to the laboratory. [22][23][24] The electrocardiogram in hyperkalemia Hyperkalemia decreases the transmembrane potassium gradient leading to increased potassium conductance, and this shortens the duration of the action potential. 25 As potassium rises to 5.5 to 6.5 mmol/l, peaked T-waves and a prolonged PR segment may be seen, advancing with higher levels of potassium to progressive widening of the QRS complex, fascicular and bundle branch blocks, a "sine-wave" appearance, and asystole. ...
Treatment options for hyperkalemia have not changed much since the introduction of the cation exchange resin, sodium polystyrene sulfonate (Kayexalate, Covis Pharmaceuticals, Cary, NC), over 50 years ago. Although clinicians of that era did not have ready access to hemodialysis or loop diuretics, the other tools that we use today - calcium, insulin, and bicarbonate - were well known to them. Currently recommended insulin regimens provide too little insulin to achieve blood levels with a maximal kalemic effect and too little glucose to avoid hypoglycemia. Short-acting insulins have theoretical advantages over regular insulin in patients with severe kidney disease. Although bicarbonate is no longer recommended for acute management, it may be useful in patients with metabolic acidosis or intact kidney function. Kayexalate is not effective as acute therapy, but a new randomized controlled trial suggests that it is effective when given more chronically. Gastrointestinal side effects and safety concerns about Kayexalate remain. New investigational potassium binders are likely to be approved in the coming year. Although there are some concerns about hypomagnesemia and positive calcium balance from patiromer, and sodium overload from ZS-9 (ZS Pharma, Coppell, TX), both agents have been shown to be effective and well tolerated when taken chronically. ZS-9 shows promise in the acute treatment of hyperkalemia and may make it possible to avoid or postpone the most effective therapy, emergency hemodialysis.
... 5,6 However, a case-control study by Kellerman et al showed no difference in plasma potassium levels when the phlebotomy with performed with a vacutainer versus a syringe, provided that the method of transporting the sample to the laboratory was similar. 7 In our case, vacutainers were used to collect the blood sample, but only transport by the pneumatic tube system resulted in the apparent rise in potassium. ...
... The case-control study by Kellerman et al, 7 additional case reports found in the literature, [12][13][14] and our case report indicate that pneumatic tube transport systems have been responsible for significantly elevated serial potassium results. It would appear that spurious results utilizing pneumatic tube transport systems are especially likely to occur in patients with severe leuko-or thrombocytosis. ...
Objective
To report a case of pseudohyperkalemia due to a pneumatic tube transport system.
Case Summary
A 75-year-old male presented to the emergency medicine department with chest pain and intermittent vision loss over the previous 2 days. Laboratory studies revealed a potassium value of 9.6 mEq/L and a white blood cell (WBC) count of 262 × 10⁹/L. An electrocardiogram did not reveal changes consistent with hyperkalemia. Emergent treatment for the hyperkalemia was instituted. Repeat plasma potassium values obtained after treatment for the hyperkalemia remained significantly elevated. It was eventually recognized that the hyperkalemia was due to the combination of undiagnosed leukemia causing a significantly elevated WBC count and transport of the patient's specimen to the laboratory via a pneumatic tube transport system. Manual transport of the specimen to the laboratory repeatedly revealed normal or hypokalemic values.
Discussion
Hyperkalemia is a potentially fatal electrolyte abnormality that must be differentiated from pseudohyperkalemia. Pseudohyperkalemia is defined as a spurious elevation of potassium levels usually due to mechanical trauma during venipuncture resulting in hemolysis and release of potassium from the cellular elements of blood. Pneumatic tube transport systems should be listed in the scientific literature as another potential cause of pseudohyperkalemia, especially in patients with high WBC and/or platelet counts.
Conclusion
Pharmacists and other health care providers should be aware of pneumatic tube transport systems potentially causing pseudohyperkalemia, because regular treatments for hyperkalemia for this problem may cause patient harm.
... [2,6] Cases of pseudohyperkalemia due to pneumatic tube transport/unpadded canisters have been reported, especially in disease states with fragile cell membranes such as leukemia. [9,10] Mechanical force during specimen processing such as vigorous mixing, excessive centrifugal force, prolonged fixed angle centrifugation or re-centrifugation of gel separator tubes also need to be considered. [2,6] ...
... Factitious hyperkalemia may be seen in WBC neoplasms due to increased membrane fragility and little reserve capacity for withstanding mechanical agitation or by leakage into the serum. [10] It is suspected that neoplastic WBC membranes (e.g., chronic lymphocytic leukemia) are more likely to be leaky or to be disrupted during pneumatic chute transport. Another factor is that at high-levels of leukocytosis, there is increased consumption (and thereby exhaustion) of metabolites that fuel the ATP pump. ...
Errors in potassium measurement can cause pseudohyperkalemia, where serum potassium is falsely elevated. Usually, these are recognized either by the laboratory or the clinician. However, the same factors that cause pseudohyperkalemia can mask hypokalemia by pushing measured values into the reference interval. These cases require a high-index of suspicion by the clinician as they cannot be easily identified in the laboratory. This article discusses the causes and mechanisms of spuriously elevated potassium, and current recommendations to minimize those factors. "Reverse" pseudohyperkalemia and the role of correction factors are also discussed. Relevant articles were identified by a literature search performed on PubMed using the terms "pseudohyperkalemia," "reverse pseudohyperkalemia," "factitious hyperkalemia," "spurious hyperkalemia," and "masked hypokalemia."
... 3,4 Other rarer causes of pseudohyperkalemia include thrombocytosis (release from platelets after clotting has occurred, thereby causing elevated serum potassium measurement) and severe leukocytosis (release during blood processing because of cell fragility). 5,6 True hyperkalemia may occur when potassium shifts or gets released outside of cells because of tissue injury or trauma, tumor lysis syndrome, insulin deficiency in diabetes, metabolic acidosis from inorganic acids, and to a lesser extent from severe respiratory acidosis. 7-10 True hyperkalemia may also occur when there is excess total body potassium, which is more likely to develop among individuals in whom there is malfunction of the major players in potassium homeostasis, namely CKD, heart failure, DKD, any combination of these, and the use of RAASi. ...
The last decade has seen tremendous advances in the prevention and treatment of recurrent hyperkalemia. In this narrative review, we aim to highlight contemporary data on key areas in the epidemiology and management of hyperkalemia. Focusing on drug-induced hyperkalemia (the implications of renin-angiotensin-aldosterone system inhibitors [RAASi] discontinuation and the role of mineralocorticoid receptor antagonists), newer concurrent therapies that modify potassium handling (sodium-glucose transporter 2 inhibitors [SGLT2i]), the introduction of new treatment agents (oral potassium binding agents), and the controversial role of dietary potassium restriction, we apply recent research findings and review the evidence in a case-based format.
... [24] PHK is usually induced by fist clenching pending phlebotomy or excessive tourniquet time, by hemolysis due to mechanical distension in the course of venipuncture, by some hematological diseases such as thrombocytosis and leukocytosis or during transportation. [25][26][27][28][29] Attention should be paid to tourniquet applications in the ED. A significant increase was detected in the serum potassium level between 0.05 mmol/L and 0.5 mmol/L through tourniquet administration in a previous study. ...
Hyperkalemia is a common, life-threatening medical situation in chronic renal disease patients in the emergency department (ED). Since hyperkalemia does not present with any specific symptom, it is difficult to diagnose clinically. Hyperkalemia causes broad and dramatic medical presentations including cardiac arrhythmia and sudden death. Hyperkalemia is generally determined through serum measurement in the laboratory. Treatment includes precautions to stabilize cardiac membranes, shift potassium from the extracellular to the intracellular, and increase potassium excretion. The present article discusses the management of hyperkalemia in the ED in the light of current evidence.
... It is different from the cryogenic superconducting maglev technology. High-temperature superconducting maglev technology uses liquid nitrogen cooling (-196 • C), improving the working temperature [22]. Strong superconductivity is the advantage of Japanese cryogenic superconducting maglev technology while the low working temperature is its disadvantage, and it is also not easy to maintain long-distance stability [23]. ...
Super-speed rail (SSR) is a kind of train design based on the theory of vacuum pipeline transportation, having the advantages of super speed, high safety, low energy consumption, low noise, no vibration and no pollution. SSR may be a new generation of trains after cars, ships, trains and aeroplanes. The SSR system includes two parts, namely vacuum pipe technology and magnetic levitation technology. Based on the definition of SSR, the present paper analyses the operation principle of SSR. According to distribution characteristics of SSR, the evaluation index system of SSR was set up. In analysing the main characteristics of SSR, this paper builds the evaluation model by improved value function. The application results validate the feasibility of the new method in comprehensive evaluation for SSR. It is consistent with the results of other methods. The result reveals that SSR is completely feasible from a theoretical point of view and it is impossible to build SSR in a short time from the application perspective. The evaluation results can reflect the actual situation. The comprehensive evaluation model is scientific and the process is simple.
... The measured serum potassium may denote the actual circulating value in patients with intravascular hemolysis. In patients with leukocytosis due to lymphoma or leukemia, spurious hyperkalemia has also been described after mechanical disruption of WBCs in the course of transporting the blood samples via pneumatic tube systems [6,7]. Repeated fist clenching during blood collection can raise the serum potassium level by more than 1-2 mmol/L in that forearm [8]. ...
Hyperkalemia is a common electrolyte disorder with potentially life-threatening consequences, including cardiac dysrhythmias. Pseudohyperkalemia must always be ruled out before implementing treatment for true hyperkalemia. Here, we present a case of a 63-year-old male with chronic lymphocytic leukemia (CLL) with a white blood cell count greater than 200 thousand/mm3 and persistently high serum potassium concentration as high as 8.4 mmol/L. A venous blood gas analysis was performed, which confirmed the patient's plasma potassium levels were within the normal range (3.7-4.4 mmol/L). In patients with CLL, due to the increased fragility of their white blood cells, mechanical stress such as centrifugation can lead to cell lysis resulting in pseudohyperkalemia. Our emphasis with clinicians is to familiarize themselves with these spurious laboratory values and prevent unnecessary invasive testing and treatment.
... For example, according to the literature pseudo hyperkalemia occurs due to PTS transportation of samples in leukemic patients. The underlying cause is that people with hematological or oncological diseases have abnormal blood cells that have increased susceptibility to hemolysis and destruction during PTS transport [29][30][31]. In addition, we did not use a data logger to measure temperature. ...
Objectives:
Academics are far from a consensus regarding the effects of pneumatic tube system (PTS) delivery on sample integrity and laboratory test results. As for the reasons for conflicting opinions, each PTS is uniquely designed, sample tubes and patient characteristics differ among studies. This study aims to validate the PTS utilized in Ankara City Hospital for routine chemistry, coagulation, and hematology tests by comparing samples delivered via PTS and porter.
Methods:
The study comprises 50 healthy volunteers. Blood samples were drawn into three biochemistry, two coagulation, and two hemogram tubes from each participant. Each of the duplicate samples was transferred to the emergency laboratory via Swiss log PTS (aka PTS-immediately) or by a porter. The last of the biochemistry tubes were delivered via the PTS, upon completion of coagulation of the blood (aka PTS-after). The results of the analysis in these groups were compared with multiple statistical analyses.
Results:
The study did not reveal any correlation between the PTS and serum hemolysis index. There were statistically significant differences in several biochemistry tests. However, none of them reached the clinical significance threshold. Basophil and large unidentified cell (LUC) tests had poor correlations (r=0.47 and r=0.60; respectively) and reached clinical significance threshold (the average percentages of bias, 10.2%, and 15.4%, respectively). The remainder of the hematology and coagulation parameters did not reach clinical significance level either.
Conclusions:
The modern PTS validated in this study is safe for sample transportation for routine chemistry, coagulation, and hematology tests frequently requested in healthy individuals except for basophil and LUC.
... The authors' observations are in line with several recent reports where pneumatic tube use was suspected as the cause of reverse pseudohyperkalemia. 4,5,7,8 During the authors' monitoring of the patient for TLS, comparison of repeat values for potassium showed a significant difference of about 2.7 mEq/L between samples transported manually and samples sent via pneumatic tube (Figure). Similar elevations of values have been described in other case reports. 1 Reverse pseudohyperkalemia is a phenomenon that should not be overlooked in the medical management of patients with CLL with leukocytosis, especially in asymptomatic chronic patients. ...
Treatment of reverse pseudohyperkalemia for a patient with chronic lymphocytic leukemia was complicated by falsely reported elevated potassium levels.
... Reverse pseudohyperkalemia is a phenomenon opposite to what has been described earlier for pseudohyperkalemia, i.e., plasma K + levels are higher than serum K + levels (differentials based on serum and plasma K + levels are summed in Table 2). It is commonly seen in patients with hematological malignancies, especially CLL [9,10]. The true underlying mechanism is unclear, however there are certain theories for the pathology behind this phenomenon based on the observations of the clinicians and the lab personnel. ...
... Aspirasi darah yang kuat sewaktu pengambilan darah, penggunaan vacutainer, goncangan yang keras dan pecahnya trombosit selama koagulasi (jika jumlah trombosit lebih dari 500 x 10 9 / L) dapat menyebabkan kerusakan sel. 8,9 Pada pasien dengan leukemia dan hiperleukositosis, leukosit memiliki kerapuhan abnormal dan hal ini dapat menyebabkan pelepasan kalium ketika terkena tekanan mekanik. Peningkatan kalium yang bermakna terjadi ketika jumlah leukosit melebihi 50 hingga 100 x10 9 /L, yang dapat terjadi pada keganasan hematologis dan infeksi berat. ...
Pseudohyperkalemia dan pseudohypokalemia mengacu pada peningkatan ataupun penurunan kadar kalium serum yang tidak sesuai dengan kondisi sistemik pasien yang sebenarnya. Ketika klinisi dihadapkan pada kasus-kasus hiperkalemia atau hipokalemia, pertanyaan pertama yang seharusnya muncul adalah apakah hasil tersebut sesuai dengan kondisi klinis pasien. Beberapa faktor dapat menyebabkan timbulnya pseudohyperkalemia ataupun pseudohypokalemia, di antaranya adalah hiperleukositosis yang sering muncul pada kasus-kasus keganasan hematologi. Hiperleukositosis sangat berpengaruh pada hasil pemeriksaan laboratorium seperti kalium, fosfat, dan tekanan oksigen arterial. Kami menyajikan dua kasus dengan hasil kalium serum yang palsu pada pasien leukemia myeloid dengan jumlah leukosit yang sangat tinggi. Satu sampel pemeriksaan darah awal dari satu pasien menunjukkan hipokalemia dan pasien lainnya menunjukkan hiperkalemia tanpa keluhan yang sesuai. Sampel darah berikutnya yang diambil dari pasien pertama segera diperiksa setelah dilakukan sentrifugasi, yang memperlihatkan hasil elektrolit yang normal. Ketidaksesuaian dari hasil laboratorium ini kemungkinan disebabkan oleh aktivitas metabolisme leukosit secara in vitro pada kasus-kasus hiperleukositosis. Hasil laboratorium yang tidak sesuai ini dapat menyebabkan pengambilan keputusan yang salah baik dalam hal penegakan diagnosis dan pemberian terapi. Penemuan mengenai ketidaksesuaian hasil elektrolit dengan kondisi klinis pasien pada keganasan hematologi yang disertai dengan hiperleukositosis dapat mencegah intervensi terapeutik yang tidak tepat. Ke-simpulannya, hiperleukositosis dapat menyebabkan pseudohyperkalemia dan pseudohypokalemia yang dapat dicegah dengan pengambilan sampel yang benar dan analisis serum atau plasma dengan segera setelah proses sentrifugasi.Â
... Similarly, elevated potassium levels have been described in leukocytosis as well. An artifactually elevated serum potassium level or spurious hyperkalemia was first described [38] with extreme leukocytosis (>600 Â 10 9 /L) and several case reports thereafter [39][40][41]. Katkish et al. [42] reviewed >300 patients with CLL listed in the tumor registry in the state of Minnesota between 1997 and 2014. The researchers found that the adjusted odds of a patient's potassium being elevated increased by 1.4 [95% confidence interval (CI) 1.2-1.5; ...
Chronic lymphocytic leukemia (CLL) is the most commonly diagnosed adult leukemia in the USA and Western Europe. Kidney disease can present in patients with CLL as a manifestation of the disease process such as acute kidney injury with infiltration or with a paraneoplastic glomerular disease or as a manifestation of extra renal obstruction and tumor lysis syndrome. In the current era of novel targeted therapies, kidney disease can also present as a complication of treatment. Tumor lysis syndrome associated with novel agents such as the B-cell lymphoma 2 inhibitor venetoclax and the monoclonal antibody obinutuzumab are important nephrotoxicities associated with these agents. Here we review the various forms of kidney diseases associated with CLL and its therapies.
... Potassium is now measured in plasma or in heparinized tubes, clotting is unlikely to be causal, but lysis of cells still can occur [1]. Use of vacuum tubes, pneumatic tube transportation, prolonged incubation, tourniquet use, and processing of specimens through centrifugation have all been implicated as causing lysis of cells and releasing serum potassium [4][5][6]. In patients with CLL, the leakage of potassium from elevated fragile white blood cells results in falsely elevated serum potassium. ...
Introduction
Hyperkalemia is a commonly encountered clinical problem. Pseudohyperkalemia is believed to be an in vitro phenomenon that does not reflect in vivo serum potassium and therefore should not be treated. Here, we present a case who unfortunately underwent unnecessary treatment because of failure to detect the common lab abnormality of pseudohyperkalemia.
Case Presentation
A 91-year-old female with a history of chronic lymphocytic leukemia presented to the emergency with nausea and vomiting 24 hours after her first chemotherapy with chlorambucil. Physical examination was overall unremarkable. She had a leukocytosis of 210 × 10³/µL with 96% lymphocytes along with chronic anemia with hemoglobin of 8.1 g/dL. Her initial sodium and potassium levels were normal. During the clinical course, her potassium progressively worsened and failed to improve despite standard medical treatment. Patient ultimately underwent dialysis.
Conclusions
Differentiating true hyperkalemia from pseudohyperkalemia is very important in selected group of patients to avoid unnecessary medications, higher level of care, and unnecessary procedure including dialysis. We want to emphasize the importance of simple yet profound knowledge of technique of blood draws and basic metabolic panel processing for every clinician in day-to-day practice.
... Presumably heparin induces lysis of fragile malign cells [3]. The 3-fold higher heparin concentration in flebotomy tubes as compared to blood gas syringes [3], pneumatic-transport [4] and longer contact times prior to centrifugation [5] may exacerbate the phenomenon. ...
Objectives
Arterial blood gas analysis (ABG) reflects a patient’s ventilatory,
acid-base and oxygenation status and provides
clinicians with information for patient assessment, therapeutic
decision-making and prognoses. In the ICU setting,
accurate and timely interpretation of ABG results
can be key to good clinical decision-making. Correct
interpretation however can be difficult and depends on
the judgment by experienced clinicians. At present, most
clinical laboratories only report numerical values, making
correct interpretations challenging, especially for less
experienced clinicians. In 2011 Park et al. published an
algorithm for the prompt and accurate interpretation
of ABG results. The aims of our study were to: (a) asses
inter-observer variability and accuracy in interpretation
of ABG results and (b) to clinically validate the published
modified algorithm for automated ABG interpretation.
Methods
The modified algorithm published in 2011 by Park et
al. uses pH, HCO3- an PaCO2 as inputs and interprets
ABG results into 13 acid-base statuses. One hundred
ABG results from ICU patients were randomly selected
and imported into an excel spreadsheet. All results were
measured by a RapidPoint 500 instrument (Siemens)
on arterial blood, drawn from 26 ICU patients. Four
experienced clinicians were asked to independently
interpret and classify these 100 ABG results into 13 acidbase
statuses. In addendum the specialist in laboratory
medicine also evaluated the ABG results. All results were
pooled later on. If results between clinicians agreed with
a minimum of 75% (3/4), this interpretation was used
as the clinical consensus. For ABG results with only
50% agreement (2/4), the evaluation by the specialist in
laboratory medicine was taken into account to obtain a
clinical consensus of 60% agreement (3/5). All results
with a lesser degree of agreement were discussed among
participants to withhold a clinical consensus.
Deviations from the clinical consensus were classified
as being minor (only the amount of compensation different
from the clinical consensus) or major (reported
normal for pathological or vice versa; wrong classification
of the origin of the acid-base problem i.e. metabolic
for respiratory or vice versa). Inter-observer variability
and accuracy in interpretation of ABG results were also
evaluated.
Results
For 98% of all results, consensus was found (41% 4/4;
36% 3/4; 21% 2 + 1/5). Two cases (49 and 87), were
discussed among all participants and eventually classified
as ‘Not Compensated Metabolic Alkalosis’ and
‘Compensated Respiratory Acidosis or Compensated
Metabolic Alkalosis or Normal’ respectively. Overall, the
evaluated algorithm showed an agreement of 88% (81.1–
94.9%; 95% CI) with the clinical consensus. Clinicians
showed an overall agreement of 79% (64–96%; 95% CI)
with the clinical consensus. The algorithm also did not
report any major discrepancies as did three out of four
clinicians
Conclusions
Interpretations by the algorithm showed to be equivalent
to those reported by the clinicians. The interpretations
by the algorithm can therefore help clinical practice for
all critical care providers. It should however only be used
as an aid to a full clinical assessment of a patient’s acidbase
status.
References
Park SH, An D, Chang YJ, et al. Development and validation
of an arterial blood gas analysis interpretation algorithm
for application in clinical laboratory services. Ann Clin
Biochem. 2011;48:130–135.
... Pseudohyperkalemia has also been linked to traumatic transport of blood samples in hospital pneumatic tube transport systems. [30][31][32] Whatever the cause, pseudohyperkalemia should be recognized as a spurious increase of potassium level and should not be treated, as it usually does not have the life-threatening consequences of true hyperkalemia. ...
Hyperkalemia is a common electrolyte disorder associated with life-threatening cardiac arrhythmias and increased mortality. Patients at greatest risk for hyperkalemia include those with diabetes and those with impaired renal function in whom a defect in the excretion of renal potassium may already exist. Hyperkalemia is likely to become more common clinically because angiotensin receptor blockers and angiotensin-converting enzyme inhibitors are increasingly being used in higher doses and are thought to confer cardiovascular and renal protection. Until recently, options for treating hyperkalemia were limited to the use of thiazide and loop diuretics and sodium polystyrene sulfonate. Newer options such as sodium zirconium cyclosilicate will allow for the safe and effective treatment of hyperkalemia while maintaining patients on prescribed renin-angiotensin-aldosterone system inhibitors.
... Mechanische Beeinflussung während des Transports der Blutprobe kann ebenfalls zu einer Freisetzung von Kalium und damit zu einer Pseudohyperkaliämie führen [18,30]. ...
Die akute Hyperkaliämie ist eine gefährliche und sofort zu behandelnde Elektrolytstörung. Durch Veränderungen im Membranpotenzial kann sie zu Herzrhythmusstörungen und Tod führen. Die auftretenden EKG-Veränderungen sind vielfältig und sollten schnell erkannt werden. Die Therapie besteht aus verschiedenen Stufen. Neben einer allfällig notwendigen Membranstabilisierung gilt es, Kalium in den Intrazellulärraum zu verschieben und danach aus dem Körper zu eliminieren. Eine gängige Methode zur Verschiebung des Kaliums in den Intrazellulärraum besteht aus der durchaus komplikationsträchtigen Verabreichung von Insulin-Glucose-Gemischen. Hier kommen im klinischen Alltag vielfältige Rezeptvariationen zur Anwendung, die im Hinblick auf das jeweilige Nutzen-Risiko-Verhältnis nicht immer ideal zu sein scheinen. Ein praxistaugliches und gut memorierbares Insulin-Glucose-Gemisch weist ein Verhältnis von 1 IE Insulin zu 4 g Glucose (1:4) auf. Die therapeutische Elimination aus dem Körper geschieht über eine gesteigerte Diurese oder die Anwendung von Nierenersatzverfahren. Ein besonderes Augenmerkt muss der engmaschigen Kontrolle des Kaliums und des Blutzuckerspiegels zukommen. Nach Überwindung der Akutsituation muss das Augenmerk auf der Therapie der zugrunde liegenden Störung und ggf. auf der Neueinstellung der Dauermedikation des Patienten liegen.
... 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. ...
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.
... In addition, potassium measured on heparinized whole blood samples may not be the best benchmark for true physiologic concentration of potassium because heparin has been shown to lyse leukocytes in vitro [27]. However, for practical purposes whole blood potassium is an appropriate comparison sample, as it undergoes less sample handling, which seemingly also reduces in vitro cell lysis [8,11,19,32]. Another limitation of our study is the inherently small sample size when estimating the impact of high platelet or white counts on magnitude of whole blood from serum/plasma potassium deviation. ...
Background:
Unrecognized pseudohyperkalemia (PHK), defined as an artificial increase in measured potassium concentration, due to thrombocytosis and leukocytosis can lead to inappropriate patient treatment. Understanding the laboratory and patient characteristics that increase risk of PHK is key to preventing diagnostic errors.
Methods:
Serum/plasma potassium results collected at 2 laboratories over 4years were selected based on blood cell counts collected within 24h and whole blood potassium concentrations determined within 2h of the serum/plasma sample. Differences between whole blood and serum or plasma potassium were compared as functions of platelet or leukocyte count, fit to linear models, and stratified based on leukemia diagnosis codes. Patients having a serum/plasma potassium concentration that was at least 1mEq/mL higher than the whole blood concentration were defined as having PHK. Based on this analysis, high-risk patients were prospectively identified and PHK risk was communicated to providers. Medication administration records were queried to compare rates of kayexalate use pre- and post-intervention.
Results:
Approximately 14% of serum samples with platelet counts >500×10(9)/L had a>1mEq/L increase relative to whole blood potassium. >25% of serum and plasma samples showed a>1mEq/L increase relative to whole blood potassium when leukocyte counts were >50×10(9)/L. Patients with chronic lymphocytic leukemia and high WBC count demonstrated the highest rates of PHK. The rate of kayexalate administration prior to confirmatory testing decreased from 37% to 16% after the laboratory started verbally communicating the possibility of PHK to treating providers.
Conclusions:
According to our data, a leukocyte count threshold for plasma samples of 50×10(9)/L is appropriate for indicating a high risk of PHK. Direct communication by the laboratory to the care team reduces inappropriate potassium lowering treatment in populations at high risk.
... เนื่ องจากความเร็ ว ของกระสวยบรรจุ ตั วอย่ าง (pod) ในท่ อลมเพิ ่ มขึ ้ นและลด ลงอย่ างรวดเร็ วเกิ ดแรงกระแทกกั บหลอดตั วอย่ างที ่ ไม่ มี ฉนวนกั นกระแทกทำ าให้ เม็ ดเลื อดแตกเพิ ่ มขึ ้ น (20) ทำ าให้ ระดั บ โพแทสเซี ยมในผู ้ ป่ วยกลุ ่ มนี ้ มี ค่ าเพิ ่ มขึ ้ นแบบเที ยมประมาณ 3-5 มิ ลลิ โมล/ลิ ตร (21) เมื ...
... It has been demonstrated previously that elevated potassium concentrations occur more frequently with the use of PST than the use of SST [8]. Furthermore, potassium concentration is thought to be increased by hemolysis during specimen transportation [15]. ...
To rapidly obtain outpatient results, we use plasma separation tubes (PST) for chemistry analysis. If lactate dehydrogenase measurement is required, serum separation tubes (SST) are used. There has been no evaluation of hemolysis with these tubes. We compared the hemolytic index (HI) obtained by using PST and SST and applied this for choosing appropriate tubes for clinical laboratories.
The HI of specimens obtained from outpatients visiting Asan Medical Center between July and December 2012 was analyzed. The HI was scored from 0 to 10 by using the Toshiba 200FR (Toshiba Medical Systems Co., Japan). HI was classified by sample tube type, and significant hemolysis was defined as a HI of 2 or more. For significant hemolysis cases, medical records were reviewed to identify the causes.
Among 171,519 specimens, significant hemolysis was observed in 0.66% of specimens (0.68% of PST specimens, 0.46% of SST specimens). The mean HI in PST was 0.18 (SD: 0.43) and that in SST was 0.14 (SD: 0.37). The proportion of significant hemolysis was significantly higher in PST than in SST (P=0.001). The cause of significant hemolysis was identified as chemotherapy and prosthetic valve in 48.1% of specimens. Complex sampling errors may have caused significant hemolysis in the remaining 51.9% of specimens.
The incidence of hemolysis was slightly higher for PST than SST, although both were <1%. PST are thought to be more useful than SST in outpatient testing because of rapid turnaround time, greater sample volume, and less risk of random errors due to fibrin strands.
... However, in rare cases, serum or plasma potassium elevation is factitious due to cell release within the sample tube. Causes of pseudohyperkalemia include errors during venipuncture that lead to hemolysis including sustained tourniquet application, use of thin needles, bad sample handling or systems of pneumatic tube transport 4 . Besides hemolysis, pseudohyperkalemia can be seen in polycytaemia as well as with WBC>100000/mm 3 or platelet count >1000000/ mm 3 , although there is a discrepancy concerning the role of white blood cell count 5,6 . ...
Hyperkalemia is a relative common and sometimes life threatening electorlyte disorder. Although its symptomatic treatment is relatively easy, since precise therapeutic algorithms are available, its differential diagnosis is more complicated. The present review aims to unfold the differential diagnosis of hypekalemia using a pathophysiological, albeit clinically useful, approach. The basic elements of potassium homeostasis are provided, the causes of hyperkalemia are categorized and analysed and finally the required for the diferrential diagnosis laboratory tests are mentioned.
... Pseudohyperkalemia is defined as an elevated serum potassium value (in vitro) in a patient with an in vivo potassium level within the reference limits. 1 A high index of suspicion is warranted when an elevated potassium value is found without any clinical manifestations, ECG changes or an obvious cause. ...
Hyperkaliaemia is a common finding in the hospital and outpatient setting. Often the cause can be identified easily. If the cause seems obscure, further investigation is warranted.
Pseudohyperkalemia (falsely elevated serum potassium) must be distinguished from true hyperkalemia to avoid unnecessary treatment. Some case reports suggest that pneumatic tube transportation may increase the risk of pseudohyperkalemia, but comprehensive research on the topic is lacking. Here, we aimed to assess the association between WBC levels, pneumatic tube transport, and pseudohyperkalemia prevalence.
We analyzed 1188 samples collected from 240 patients between 2019 and 2022. Samples with elevated WBC counts (≥ 100 × 103/μL) and potassium levels were included in this study. The method of specimen transportation was documented.
Pseudohyperkalemia was observed (7/390) in specimens transported using pneumatic tubes. No pseudohyperkalemia was identified with manually transported specimens (0/132). Every increase in WBC count by 100 × 103/μL in the specimens multiplied the odds ratio of pseudohyperkalemia by 3.75 when delivered with pneumatic tube. The prevalence of pseudohyperkalemia increased as WBC count increased, especially at WBC counts greater than 200 × 103/μL.
Pneumatic tube transport poses a risk for pseudohyperkalemia in patients with extreme leukocytosis. Physicians should anticipate odd potassium levels when interpreting blood test results. Redrawing of blood samples, manual specimen transportation, or point-of-care testing are suggested to prevent further misdiagnosis.
Background
Potassium is one of the most abundant cations in the human body. Increased plasma potassium concentration (hyperkalemia) is one of the most common electrolyte abnormalities in contemporary clinical practice. Moderate and severe hyperkalemia are potentially life-threatening conditions and constitute medical emergencies. Measured hyperkalemia may be true hyperkalemia or false hyperkalemia (pseudohyperkalemia). Pseudohyperkalemia is due to false elevation of measured potassium concentration in vitro and it is a fairly common source of preanalytical error of potassium determination in the clinical laboratory.
Objective
To review the general and recent concepts/mechanisms that underlie the phenomenon of pseudohyperkalemia in contemporary clinical practice.
Methods
An up-to-date review of available literature and selected references on the phenomenon of pseudohyperkalemia, its causes, variants, mechanisms, clinical implications, identification, management, and prevention.
Conclusion
Pseudohyperkalemia is a fairly common preanalytical error of potassium measurement in the clinical laboratory and a potential cause of misdiagnosis and unnecessary treatment of hyperkalemia. Exclusion of pseudohyperkalemia before the diagnosis of hyperkalemia (true hyperkalemia) is highly recommended.
Patients with newly diagnosed hematological malignancies often present with a considerable cellular burden, leading to complications including hyperkalemia. However, pseudohyperkalemia, arising from in vitro cell lysis, can pose challenges in clinical practice. Although pseudohyperkalemia is frequently reported in adult hematological malignancies, its occurrence in pediatric patients is underreported, and its incidence in this demographic remains unclear. We retrospectively reviewed the medical records of pediatric patients who received a new diagnosis of hematological malignancies from 2011 to 2022 at Taichung Veterans General Hospital. Hyperkalemia was defined by a serum or plasma potassium level exceeding 5.5 mEq/L. Pseudohyperkalemia was defined by 1) a potassium decrease of over 1 mEq/L in within 4 h without intervention or 2) the absence of electrocardiography changes indicative of hyperkalemia. Cases with apparent red blood cell hemolysis were excluded. A total of 157 pediatric patients with a new diagnosis of hematological malignancies were included, 14 of whom exhibited hyperkalemia. Among these 14 cases, 7 cases (4.5%) were of pseudohyperkalemia. This rate increased to 21.2% in patients with initial hyperleukocytosis. Pseudohyperkalemia was associated with a higher initial white blood cell count and lower serum sodium level. All episodes of pseudohyperkalemia occurred in the pediatric emergency department, where samples were obtained as plasma, whereas all true hyperkalemia cases were observed in the ordinary ward or intensive care unit, where samples were obtained as serum. Timely recognition of pseudohyperkalemia is crucial to avoiding unnecessary potassium-lowering interventions in pediatric patients with newly diagnosed hematological malignancies.
The term pseudohyperkalemia refers to a false elevation in serum potassium levels due to potassium release from cells in vitro. Falsely elevated potassium levels have been reported in patients with thrombocytosis, leukocytosis, and hematologic malignancies. This phenomenon has been particularly described in chronic lymphocytic leukemia (CLL). Leukocyte fragility, extremely high leukocyte counts, mechanical stress, higher cell membrane permeability related to an interaction with lithium heparin in plasma blood samples, and metabolite depletion due to a high leukocyte burden have been reported to contribute to pseudohyperkalemia in CLL. The prevalence of pseudohyperkalemia is up to 40%, particularly in the presence of a high leukocyte count (>50 × 109/L). The diagnosis of pseudohyperkalemia is often overlooked, which may result in unnecessary and potentially harmful treatment. The use of whole blood testing and point-of-care blood gas analysis, along with thorough clinical evaluation, may help differentiate between true and pseudohyperkalemic episodes.
Electrolyte and acid-base disorders are frequently encountered in patients with malignancy, either due to cancer itself or as a complication of its therapy. However, spurious electrolyte disorders can complicate the interpretation and management of these patients. There are several electrolytes that can be artifactually increased or decreased serum electrolyte values that do not correspond to their actual systemic levels, potentially resulting in extensive diagnostic investigations and therapeutic interventions. Examples of spurious derangements include pseudohyponatremia, pseudohypokalemia, pseudohyperkalemia, pseudohypophosphatemia, pseudohyperphosphatemia, and artifactual acid-base abnormalities. Correctly interpreting these artifactual laboratory abnormalities is imperative as it might avoid unnecessary and potentially harmful interventions for the cancer patient. It is also important that factors influencing these spurious results be recognized, and steps are taken to minimize them. We present a narrative review of commonly reported pseudo-electrolyte disorders and describe strategies to exclude erroneous interpretations of these laboratory values and avoid pitfalls. Awareness and recognition of spurious electrolyte and acid-base disorders can prevent unnecessary and harmful treatments.
Purpose of review:
Hypernatremia, hyperphosphatemia, hypocalcaemia, hyperkalaemia and hypermagnesemia are electrolytes disturbances that can arise in cancer patients in relation to unique causes that are related to the cancer itself or its treatment and can lead to delay or interruption of cancer therapy. This article summarizes these main causes, the proposed pathophysiology and the recommended management for these disturbances.
Recent findings:
There have been many cancer drugs approved in the field of oncology over the past several years and a subset of these drugs have been associated with electrolytes disturbances. This includes, for example, immune checkpoint inhibitor related hyperkalemia, fibroblast growth factor 23 inhibitor associated hyperphosphatemia and epidermal growth factor receptor inhibitor associated hypomagnesemia and hypocalcaemia.
Summary:
This article provides an updated review of certain electrolytes disturbance in cancer patients and allows clinicians to have a greater awareness and knowledge of these electrolyte abnormalities in efforts to early recognition and timely management.
Background:
Hyperkalemia is an electrolyte disorder requiring medical attention because it can cause cardiac arrhythmias. Pseudohyperkalemia is the phenomenon of an elevated potassium concentration that is present in the blood sample but not in the patient. Pseudohyperkalemia can be caused by hemolysis, leukocytosis, thrombocytosis, seasonal pseudohyperkalemia, potassium release from muscle cells due to fist clenching during venipuncture, and contamination due to blood withdrawal from an intravenous line over which potassium was administered. Rarer causes include EDTA contamination and familial pseudohyperkalemia.
Case description:
A 23-year old woman was admitted with ascites due to polycythemia vera and essential thrombocytosis for which hydroxycarbamide was started. The reported serum potassium concentrations were 6.1 and 6.8 mmol/l. The use of spironolactone was discontinued and she was treated with sodium polystyrene sulfonate and insulin-glucose infusion. The serum potassium concentration only decreased on the ninth day of admission, when the thrombocyte count was normalizing. A diagnosis of pseudohyperkalemia due to thrombocytosis was established.
Conclusion:
Knowledge of the causes of pseudohyperkalemia and interaction between the clinician and clinical chemist aids in the differentiation between true hyperkalemia and pseudohyperkalemia and may prevent unnecessary diagnostics and harmful treatment.
Tumor lysis syndrome (TLS) is a life-threatening condition that may occur in patients with lymphoma, leukemia, or cancers with high cellular burdens. Without appropriate treatment, electrolyte imbalances, namely hyperkalemia, hyperphosphatemia, and hypocalcemia, can be fatal in patients with TLS. In pseudohyperkalemia, concurrent hyperphosphatemia and hypocalcemia can render devising a treatment strategy challenging. We report an adolescent with T-lymphoblastic lymphoma who presented with pseudohyperkalemia but actual hyperphosphatemia and hypocalcemia, to highlight the importance of accurate clinical interpretations of laboratory data in patients with TLS.
Pseudohyperkalemia, a false elevation of potassium level in vitro, can be observed in chronic lymphocytic leukemia (CLL) patients due to fragility of leukocytes along with a high leukocyte count. This retrospective, observational study included all patients diagnosed with CLL at our hospital who had at least one leukocyte count ≥ 50.0 × 109/L during the years 2008–2018. All hyperkalemic episodes (including when leukocyte count was below 50.0 × 109/L) during this period were assessed. Pseudohyperkalemia was defined as when a normal potassium level was measured in a repeated blood test or when known risk factors and ECG changes typical of hyperkalemia were absent. Of the 119 episodes of hyperkalemia observed, 41.2% were considered as pseudohyperkalemia. Pseudohyperkalemia episodes were characterized by significantly higher leukocyte counts as well as higher potassium and LDH levels compared to true hyperkalemia. Pseudohyperkalemia was documented in medical charts only in a minority of cases (n = 4, 8.1%). Treatment was administered in 17 of 49 (34.7%) cases and caused significant hypokalemia in 6 of those cases. The incidence of pseudohyperkalemia in this study was rather high, suggesting that physicians should be more aware of this phenomenon in patients with CLL.
Résumé
Introduction
L’hyperkaliémie nécessite une prise en charge rapide, notamment symptomatique à visée cardio-protectrice. À côté des causes facilement évoquées telles l’insuffisance rénale, l’insuffisance surrénalienne, la lyse cellulaire ou les causes iatrogènes, celle d’une fausse ou pseudo-hyperkaliémie l’est moins et ne doit pas être oubliée.
Observations
Trois patients (1 homme, 2 femmes, âgés de 78, 84, 88 ans) pris en charge pour thrombocytose (entre 1306 et 2404 G/L) et hyperkaliémie non symptomatique (entre 6,1 et 7,7 mmol/L) sont rapportés. La kaliémie de contrôle sur tube hépariné était normale (entre 4,4 et 4,6 mmol/L). Il n’a donc pas été nécessaire d’instaurer de traitement spécifique à cette pseudo-hyperkaliémie.
Conclusion
L’association thrombocytose et hyperkaliémie non symptomatique doit faire évoquer le diagnostic de pseudo-hyperkaliémie et faire impérativement réaliser un contrôle de la kaliémie sur tube hépariné. La reconnaissance de ce diagnostic est importante afin de ne pas instaurer un traitement non nécessaire et potentiellement délétère.
Potassium abnormalities are associated with many aspects of cancer care. Whether because of the direct effects of malignancy, such as in spontaneous tumor lysis, or as a result of medication associated toxicities, both hyperkalemia and hypokalemia may complicate cancer treatment. Hypokalemia has long been associated with hematologic cancers via mechanisms, such as leukemic cell renin production and lysozymuria. Many anticancer agents are known to induce proximal tubular damage or full Fanconi syndrome leading to persistent hypokalemia and hypomagnesemia, among other abnormalities. Hyperkalemia may occur via alterations in glucose metabolism in hematopoietic stem cell transplant recipients, tumor lysis syndrome or chemotherapy-induced rhabdomyolysis. In addition to actual potassium changes in vivo, artefactual potassium abnormalities are often reported in patients with cancer. These may occur because of changes in the total number white blood cells and platelets, increased cell membrane fragility and particular processing techniques, such as pneumatic blood sample transport systems.
Objectives:
Investigate concomitant and spurious high potassium and low sodium results in heparinized plasma.
Methods:
Potassium and sodium values were measured from heparinized plasma and serum in a patient with B-cell non-Hodgkin lymphoma using both an automated chemistry analyzer (indirect ion selective electrode) and blood gas analyzer (direct ion selective electrode).
Results:
Potassium levels were significantly increased while sodium levels were significantly decreased in heparinized plasma compared to serum on several occasions.
Conclusions:
To our knowledge, concomitant reverse pseudohyperkalemia and pseudohyponatremia has not been reported previously. We postulate the discrepancy between plasma and serum sodium (pseudohyponatremia in plasma) may be unique to cases of reverse pseudohyperkalemia with extreme potassium elevations.
Introduction: For the last few decades, electrolyte determinations in plasma or serum are carried out by reliable potentiometric methods. In recent years, a marked technical evolution has taken place, where the clinical analysis of common analytes (e.g. electrolytes) is partly moving from centralised clinical core laboratories to near-patient point-of-care testing.
Methods: As the measuring principle used by point-of-care testing markedly differs from the one used in core laboratories, sodium results are not always interchangeable in critically ill patients due to the different sensitivity of the analytical methods for the electrolyte exclusion effect.
Results: This effect mainly occurs in patients with decreased plasma protein values. The observed differences in generated test results might significantly affect the judgment and the treatment of electrolyte disturbances. As technical solutions are not likely to occur in the near future, clinicians and laboratorians should be well aware of this growing problem. Mathematical correction of the sodium results for plasma protein concentration may resolve the problem to a certain extent.
Discussion: Although electrolyte determinations are generally very reliable, analytical interferences can occur for sodium rarely, mainly due to contamination by surfactants, benzalkonium in particular. For potassium, the major problem is hemolysis. To a lesser extent, leukocyte lysis and thrombocytopenia may also interfere. For chloride determination, the selectivity of the electrodes used is not ideal. Occasionally, false positive signals can be observed in presence of interfering ions (e.g. bromide).
Aim: To highlight the main aspects of the laboratory processing of blood samples from hematological patients in both preanalytical and analytical phases, point out to some interpretation pitfalls. Material and Methods: A retrospective analysis of the routine laboratory results from the large consolidated laboratory with the regard to the diagnosis of hematopoietic disorders. Results: Preanalytical and analytical phases of testing and interpretation of laboratory findings may be influenced by the patient's hematological/hemato oncological diagnosis. Conclusion: In hematological patients individualized approach to the interpretation of laboratory test results in the closest possible clinical context should be followed.
A man, age 78 years, with a history of chronic lymphocytic leukemia presented to clinic for evaluation of a cough. On further evaluation, he was noted to have an elevated potassium level. This case report highlights the importance of distinguishing cases of true hyperkalemia from pseudohyperkalemia and reverse pseudohyperkalemia.
Abstract Severe hyperkalemia is a potentially life-threatening condition requiring immediate medical intervention. Pseudohyperkalemia can be misleading and result in incorrect interpretation and inappropriate patient management. Immediate recognition and appropriate interpretation of pseudohyperkalemia, on the other hand, prevents misdiagnosis and unnecessary intervention. Pseudohyperkalemia is induced by hemolysis and excessive leakage of potassium from cells during or after blood collection. It has been increasingly seen in many hematological disorders such as leukocytosis and thrombocytosis. Reverse pseudohyperkalemia has recently been reported in leukemic patients in whom the plasma potassium levels are greater than the serum potassium levels because of heparin-induced cell membrane damage. Although pseudohyperkalemia has long been recognized and understood, it continues to be misinterpreted. To improve patient care, an algorithm for investigation of pseudohyperkalemia and preventive measures should be established and implemented in the clinical laboratory.
Pseudohyperkalemia is diagnosed when the serum potassium level exceeds the plasma potassium level by 0.4 mmol/l. This is commonly encountered in settings of high leukocyte or platelet counts, since under these conditions, potassium, an intracellular cation, is released in supranormal amounts during the process of clotting. We report an unusual case wherein the reverse was true, i.e., the plasma potassium concentrations was higher than that found in the serum. Heparin, which is known to cause cell lysis, was used as the anti-coagulant in the plasma tubes. We propose that the underlying mechanism in this particular case is a heightened sensitivity to heparin-induced membrane damage in the face of a hematological malignancy.
The results of sending specimens through a computerized pneumatic airtransport system and manually delivering specimens were compared for 15 chemical tests and six hematologic procedures. All specimens were collected from inpatients and outpatients into evacuated glass containers. The specimens traversed a maximum of 829 feet (253 meters) involving 16 bends and eight transfer units at 25 feet/second (7.6 meters/second). Only the activity of lactate dehydrogenase exceeded the precision of the test in pneumatically transported specimens. Ruptured erythrocytes in incompletely filled vacuum tubes were the likely source of the increased lactate dehydrogenase activity. Neither the serum sodium, potassium, chloride, carbon dioxide, total protein, albumin, calcium, glucose, creatinine, total bilirubin, alkaline phosphatase, aspartate transaminase, acid phosphatase, uric acid, leukocyte count, erythrocyte count, hemoglobin, hematocrit, nor the prothrombin time and partial thromboplastin time were affected by pneumatic transport. It is concluded that the pneumatic system tested provides a safe, efficient method of transporting the blood specimens tested.
Two patients with chronic lymphocytic leukemia and pseudolhyperkalemia are described. Both patients had white blood cell counts exceeding 600,000 per cubic millimeter. Routine determinations of serum potassium were elevated while normal values were obtained when plasma and serum were separated within 30 minutes of venipuncture. Incubation of clotted and heparinized specimens for 6 hours was accompanied by a marked increase of potassium levels. This study indicates that extreme leukocytosis alone can give rise to apparent hyperkalemiamtrue values can be obtained if the determinations are performed quickly after venipuncture.
A computerized pneumatic tube specimen delivery system with system-wide air cushion soft handling features was evaluated. There were no significant differences in values (largely normal) for components of a standard chemical profile or complete blood count in specimens delivered from the outpatient center or neonatal intensive care unit by pneumatic tube compared to couriers. The pneumatic tube system also did not affect values for pO2, pCO2, and pH over a wide range (pO2, 25 to 438 mmHg) in specimens sent from the operating room during cardiac surgery. The pneumatic tube system decreased the median turnaround time for potassium and hemoglobin results on specimens from the emergency department by 25%. The system evaluated is a rapid, efficient mechanism for sending specimens to the clinical laboratory that produces no significant effects on analytical results and has the ability to decrease turnaround time.
CLINICIANS are occasionally confronted with the finding of an elevated serum or plasma potassium level in an otherwise healthy person. Such an abnormality may herald the presence of occult mineralocorticoid deficiency or a defect in renal tubular transport.1 Alternatively, it may represent so-called pseudohyperkalemia, caused by the release of potassium from formed elements in the blood in patients with leukocytosis or thrombocytosis.2 , 3 We report here on a patient in whom pseudohyperkalemia resulted from the common practice of repeatedly clenching and unclenching a fist during venipuncture. This maneuver, which has been passed on from generation to generation of house staff, medical . . .
Six automated instruments that measure sodium and potassium were tested for interference from two compounds used in catheters. Tridodecylmethylammonium heparin did not interfere with any of the methods. However, benzalkonium heparin falsely increased sodium measurement with the Kodak Ektachem, and falsely increased potassium measurements with three instruments (Beckman Astra, Baxter Paramax, and the Instrumentation Laboratory Monarch) in which ion-selective electrodes measure potassium in diluted serum. Three instruments in which ion-selective electrodes measure serum directly--Du Pont Dimension, Abbott Spectrum, and Kodak Ektachem--experienced no interference with potassium measurements. Interference of benzalkonium with potassium measurements may result from its interaction with the electrode membranes, which is accentuated in diluted serum.
A delay of only three hours between venepuncture and processing the blood can increase the level of potassium unpredictably and may be clinically significant.
This article has no abstract; the first 100 words appear below.
HYPERKALEMIA, such as occurs in renal failure or adrenal insufficiency, is associated with cardiac and neuromuscular abnormalities. Hartmann and his co-workers¹,² reported the phenomenon of pseudohyperkalemia, an elevation of serum potassium that does not reflect the level of plasma potassium in vivo. They concluded that the high potassium in serum developed in vitro by leakage from platelets during the clotting process. In the present study 2 patients with chronic myelogenous leukemia who demonstrated pseudohyperkalemia were investigated. A third patient in whom the phenomenon was demonstrated only by special study is included. In contrast to previous reports, the white cells and . . .
*From the Clinical Pathology Department, Clinical Center, National Institutes of Health, Medicine Branch and Laboratory of Chemical Pharmacology, National Cancer Institute, National Institutes of Health.
We are indebted to Miss Mary Edwina Cummings, Miss Vivian Franco and Mrs. Janet Rogers for technical assistance and to Dr. George Brecher for advice.
Source Information
BETHESDA, MARYLAND
†Assistant chief. Hematology Service, Clinical Pathology Department, Clinical Center, National Institutes of Health.
‡Clinical associate, Laboratory of Chemical Pharmacology, National Cancer Institute, National Institutes of Health.
§Head, Solid Tumor Service, Medicine Branch, National Cancer Institute, National Institutes of Health.
¶Chief, Clinical Chemistry Service, Clinical Pathology Department, Clinical Center, National Institutes of Health.
The occurrence of pseudohyperkalemia in acute myelocytic leukemia is, to the author's knowledge, previously undescribed. Pseudohyperkalemia may be caused by release of potassium from platelets or white blood cells during coagulation. The precise mechanisms responsible for these occurrences are not known.
Pseudohyperkalemia, or factitious hyperkalemia, constitutes an artificially high plasma potassium level (P(K)) from a variety of possible causes. Occasionally, the cause cannot be elucidated. Three patients who showed unusually large differences between free-flowing and tourniquet (stasis) potassium levels prompted us to investigate the influence of tourniquets in routine phlebotomy in eight healthy volunteers. P(K) showed a consistent but rather small average increase of 0.2 mEq/L (P < 0.001) during tourniquet use; however, the range was 10-fold, from 0.05 to 0.5 mEq/L in our subjects. We suggest there may be large variability leading to an excessive increase in P(K) in some individuals. In the three patients presented, average excessive increases in P(K) of 1.6, 1.3, and 1.7 mEq/L were seen. Although diagnosing and treating true hyperkalemia remains paramount, recognizing factitious hyperkalemia is important to preclude unnecessary investigations and potentially hazardous intervention.
Combined pseudohyperkalemia and pseudohypocalcemia have not been previously reported in the clinical setting. We report 2 cases in which specimen contamination during routine phlebotomy with ethylenediaminetetraacetic acid (EDTA) caused alteration in serum levels of potassium and calcium. This alteration could be misleading when making clinical decisions and could produce adverse patient outcomes.
Relationship of platelets to serum potassium concentration
- Hartmann