Phlebotomy Top Gun: Pseudohyperkalemia [Hot Topic]


Brad Karon, M.D., Ph.D.
Brad Karon, M.D., Ph.D.

Pseudohyperkalemia has many causes, from collection techniques, processing, and even transport. This presentation focuses on the various preanalytic and analytic causes of pseudohyperkalemia and what you as a phlebotomist can do to prevent it.

Presenters and Credentials:
Brad Karon, M.D., Ph.D., Consultant in the Division of Clinical Core Laboratory Services and Associate Professor of Laboratory Medicine and Pathology in the College of Medicine at Mayo Clinic in Rochester, Minnesota.



Dr. Karon, thank you for presenting today.Our speaker for this program is Dr. Brad Karon, a Consultant in the Division of Clinical Core Laboratory Services at Mayo Clinic in Rochester, Minnesota. Dr. Karon is also Associate Professor of Laboratory Medicine and Pathology in the College of Medicine.

Thank you, Cara. For those of you who have not attended our phlebotomy conference here in Rochester, the title of my hot topic today, “Phlebotomy Top Gun,” may seem a little odd, but I hope I’ll be able to explain to you what is, “Phlebotomy Top Gun” and why we try to do it at our annual phlebotomy conference.


I have no disclosures relevant to today’s presentation.


Every year at phlebotomy conference, I present a talk that’s always called “Phlebotomy Top Gun.” The format of “Phlebotomy Top Gun” is a case-based presentation. I solicit from you, the attendees, cases, issues, or questions  that you would like to hear about. I present these as case-based scenarios., Using an audience response voting mechanism, the attendees of the conference vote on what they believe to the correct action or answer.. I then present the collective experience from our practice; and the evidence and data that I can find related to the topic or question. At the end of the case the attendees vote again. For each case I can see whether I’ve been able to change anyone’s mind on the question at issue by presenting the data information relevant to the topic. This is an actual case from last year’s “Phlebotomy Top Gun” presentation. In this case the question was related to a phenomenon, likely familiar to everyone watching this video, called pseudohyperkalemia, or falsely elevated serum or plasma potassium. The attendee described both off-site collection facilities as well as a pneumatic tube system, and as you can see on the question I’ve copied verbatim on this slide, wanted direction on how to investigate, beyond the obvious variables, related to phlebotomy and processing and testing.

Based on the attendee question I showed you on the last slide, I made a case for the audience of the phlebotomy conference to consider. For this case I asked the question, “Data demonstrates that all of the following may reduce the rate of pseudohyperkalemia at an outpatient draw site except…..”

  • The first answer or choice for the audience would be—Preventing fist pumping.
  • The second choice would be—Preventing temperature extremes during transport.
  • The third choice would be—Repeating the centrifugation of serum separator tubes upon arrival in the laboratory.
  • And the fourth choice would be—Centrifuging whole blood onsite, before transport to the laboratory.

And at this point, during the live conference, attendees using an audience response system would vote for the answer they thought was most appropriate or correct, and we would get to see in real time the distribution of results that our audience felt was correct.

CLSI Guidelines

What I do next with each case in the “Phlebotomy Top Gun” presentation is go through any data, evidence, either internal or external to the Mayo Clinic practice,  that exists. At the end of each case I then  repoll the audience to see if anybody’s mind has been changed. Regarding causes of pseudohyperkalemia, Clinical Laboratory and Standards Institute (or CLSI) has a number of relevant recommendations in the guideline document CLSI GP41-A6, also called “Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture.” The guidelines suggest keeping tourniquet time under one minute, avoiding rigorous fist pumping, allowing disinfectant to dry, as well as a few other recommendations displayed on this slide.

Falsely Elevated K (Pseudohyperkalemia)

When I think about causes of pseudohyperkalemia, I often divide them into categories of hemolysis-related, biologic, analytic, and preanalytic. Pseudohyperkalemia from in vitro hemolysis is the most common cause of falsely elevated potassium, and is most often caused by pressure gradients created during draws, often with a syringe or from an indwelling catheter. Inverting tubes too rigorously is another potential cause of in vitro hemolysis, and underfilling of tubes is another cause that is not as well recognized as some of the others, but has been shown to greatly increase the odds of hemolysis. Biologic conditions, patient conditions (either congenital, acquired, or drug-induced), also exist that cause potassium to leak from patient red or white blood cells after blood collection, but these are relatively rare compared to other causes of pseudohyperkalemia.

Very common problem with many potential causes

Analytic interferences, where a substance in the blood sample interferes with the potassium measurement by direct or indirect electrode, have also been described in association with povidone-iodine and benzalkonium-heparin bonded catheters, but in our practice we do not see these interferences often, at least as far as we have been able to determine. Lastly there are a category of causes that I term nonhemolytic preanalytical causes of pseudohyperkalemia, because they can be observed either with or without the presence of free hemoglobin in the sample. Among these are some causes we will discuss in greater detail, including fist pumping, tourniquet time, transport temperature, and repeat centrifugation.

In order to understand how important these variables are to accurate potassium measurement, I will next review 2 studies examining the relationship of these preanalytical variables to potassium levels. The first study, published by a UK group in 2008, evaluated the impact of an educational intervention about minimizing fist pumping during blood collection. This group evaluated mean potassium levels and percent of samples with elevated potassium, both before and after the educational intervention. In this study, blood was collected at 2 satellite facilities, each a short distance from the testing laboratory. The study also looked at the impact of transport temperature on potassium levels.

Effects of fist pumping

Before the educational intervention to instruct blood collectors to avoid rigorous fist pumping during venipuncture, mean potassium levels were 4.7 mM in the winter months when temperatures were colder, and 4.4 mM in the summer months when temperatures were warmer. After the educational intervention, mean potassium levels were very similar in colder and warmer months. Before the intervention, 13% of samples collected during colder months had elevated potassium concentrations, compared to just 8% of samples collected during warmer months. After the intervention, fewer samples had elevated potassium levels (8% in cooler months and 5% in warmer months), and there was also less difference in the rates between the colder and warmer months.

Seasonal hyperkalemia Part 1

The authors concluded that tourniquet time, transport temperature, and fist pumping all contributed to the effects observed during the study. Fist pumping and increased tourniquet time cause pseduohyperkalemia through multiple mechanisms—hemolysis, release of potassium from muscle, pH changes in the sample, hemoconcentration, and water shift into cells. Cold weather may impact potassium levels in 2 ways—colder patients have veins that are harder to find, encouraging more fist pumping and leading to longer tourniquet times, and exposure of the sample to the cold during transport may cause potassium leak from cells. Thus fist pumping, cold temperature, and prolonged tourniquet time interact in a phenomenon that has been referred to as seasonal hyperkalemia. This study showed that an educational intervention to encourage good phlebotomy practice (avoid fist pumping and also minimize tourniquet time) can partially mitigate seasonal hyperkalemia.

Seasonal hyperkalemia Part 2

The next study I want to mention is also from the UK, and examined serum potassium concentrations from 87 general practice sites across a large geographic area. This study compared, again, mean potassium levels at general practices that centrifuged samples onsite, compared to practices that sent blood to the laboratory as whole blood. Unlike the previous study where blood collection was in close proximity to the laboratory, sample transport took 8 to 10 hours in this study. Like the previous study, potassium values were compared between the 2 groups, centrifuged onsite  or groups that sent blood as whole blood over several months to account for the effect of cold temperature. Between August and January, as the temperature became cooler, mean potassium concentration increased from 4.3 to 4.8 mM for samples that were being sent in as whole blood. In contrast, samples centrifuged onsite, before transport, showed little difference in mean potassium concentration between the months of August and January.

Other issues

Other issues to consider include use of a pneumatic tube and repeat centrifugation of samples. Pneumatic tubes can be associated with hemolysis and falsely increased potassium levels. These effects are related to the acceleration and deceleration rates in the tube system, the tube type and transport containers, and the path of the tube system ( ie, is it a straight path vs many turns or having right angles). Each tube system, unfortunately, must be evaluated empirically, then, to determine if its use contributes to sample hemolysis and, thus, falsely elevated potassium or psendoyhperkaliemia. For samples in separator tubes that have already been centrifuged, repeat centrifugation is a known cause of falsely elevated potassium. During centrifugation the gel layer in the tube compresses to allow serum or plasma to pass thru. Repeating centrifugation allows the cellular contents, highly enriched in potassium, to leak back into the serum or plasma resulting in pseudohyperkalemia. Thus, labs should not repeat centrifugation on serum or plasma separator tubes that are already centrifuged. The correct answer than to the polling question I asked initially would be repeating centrifugation, as this would be expected to make the problem of pseudohyperkalemia worse, not be a potential solution. Transporting centrifuged tubes upright in a holder is a best practice that can be used to avoid the need to repeat centrifugation.

Thank you for your time and attention today. If you liked today’s presentation, or even if you didn’t, please consider attending the upcoming Mayo Medical Laboratories phlebotomy conference: “Phlebotomy 2016: Restoring the Balance: People. Purpose. Passion.”  The conference with be held on April 14 and 15, 2016, in Rochester, Minnesota. As in previous years, the conference will feature presentations from expert speakers covering a variety of topics in phlebotomy skills, phlebotomy management, and other topics. Learning will take place via both large group didactic sessions, and small group break-out sessions that allow for more interaction with conference speakers. Tours of Mayo Clinic facilities will also be offered during the conference. I will also be presenting an all new “Phlebotomy Top Gun” presentation, addressing questions and issues submitted by attendees during the registration process. More information on the phlebotomy conference program can be found on the Mayo Medical Laboratories website. Thank you for listening today and have a wonderful day.

Welcome to Mayo Medical Laboratories Hot Topics. These presentations provide short discussion of current topics and may be helpful to you in your practice. Today our topic is Phlebotomy Top Gun: Pseudohyperkalemia.


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