What Every Pharmacist Should Know about Pseudohyperkalemia
Steph’s Note: This week, we welcome a new author to the tl;dr scene: Cara Clayton. Cara graduated from the University of Texas at Austin College of Pharmacy in 2018 and completed her PGY-1 Pharmacy Residency at Baylor Scott & White Medical Center - Temple prior to working as an Oncology Pharmacist with HCA Healthcare. Fun fact: Cara moved from the US to Sydney, Australia, in January 2023 and took a few months to explore Australia, New Zealand, and Southeast Asia. She is now navigating the process of obtaining pharmacist licensure and finding employment down unda’. Stay tuned for more on her adventures as an overseas pharmacist, but in the meantime, let’s hear from her about a not-so-commonly covered topic!
I appreciate the confidence, but…maybe hold that thought for a hot minute. (Image)
If you’re like most pharmacists, you’ve probably never heard of pseudohyperkalemia. You may see this term and think, “What? NBD, I know how to treat hyperkalemia because I’ve memorized tl;dr’s post, so management of pseudohyperkalemia will be a breeze.”
If this is you, think again!
What is Pseudohyperkalemia?
Pseudohyperkalemia is described as a falsely (this is where “pseudo” comes in) elevated serum potassium level despite a normal physiologic potassium level. Remember the normal potassium range is 3.5 - 5 mEq/L (for a thorough electrolyte review, check out this post). Pseudohyperkalemia most often occurs due to disruption of cells during collecting or processing a blood sample, and it may be caused by factors such as tourniquet use, vacuum tubes, prolonged incubation time, and pneumatic tube transportation (similar to hemolysis).
HOWEVER, this false elevation may occasionally occur in patients with extreme leukocytosis, which is what we will be focusing on in this article.
Pseudohyperkalemia resulting from extreme leukocytosis is rare, and incidence is hard to define, as most available literature is in the form of case reports. Regardless, it is important to be aware of this therapeutic unicorn, as mismanagement can result in hypokalemia and subsequent complications.
Pseudohyperkalemia is most likely to occur in patients with extreme leukocytosis, defined as a white blood cell (WBC) count > 100 x 10^9 cells/L. WBC counts this high typically occur in patients with acute, chronic, or undiagnosed leukemia. At this point, you may stop reading and think to yourself, “Leukemia?! No way am I touching anything oncology-related with a 10-foot pole! This post is no longer for me.” (If this is you, you should also read this. It’s made for you!)
Shooting y’all straight here. Even if you have absolutely no interest in becoming a heme/onc pharmacist, this post is still useful for you!
How so, you may ask…
When providers see a potassium level > 5.5 mEq/L on the lab results. (Image)
A patient with undiagnosed leukemia, WBC > 100 x 10^9 cells/L, and serum K+ > 6 mEq/L will often first present to the emergency department, where an ER physician or resident with likely minimal knowledge of heme/onc or pseudohyperkalemia will immediately order calcium gluconate IV, regular insulin IV + dextrose, furosemide IV, and/or sodium bicarbonate IV before confirming if the elevated K+ level is real or not.
Since true hyperkalemia is often an emergency requiring immediate medical intervention, throwing the gamut of potassium-lowering medications at these patients is a valid first instinct. Except for in cases of suspected pseudohyperkalemia!! As a result, ER pharmacists and other non-oncology pharmacists are in a perfect position to intervene.
Now that I’ve digressed enough to keep everyone reading, let’s get back to the fun stuff, shall we?
Pathophysiology and Diagnosis of Pseudohyperkalemia
Extreme leukocytosis leads to increased WBC fragility, which can then result in white blood cell lysis. This is also known as leukolysis, which leads to the release of intracellular potassium. Leukolysis may drastically impact the potassium concentration that is reported by the lab. To make things even more complicated, leukolysis may not be recognized like hemolysis typically is, as the red blood cells may remain intact.
So those nice ** statements on a hemolyzed potassium sample may not necessarily show up on a sample with leukolysis. Rats.
Now that we know the pathophysiology of pseudohyperkalemia and why considering this possibility in select patients is important, let’s move on to diagnosis. Luckily, diagnosis of pseudohyperkalemia is relatively simple and involves only 3 main steps. These steps can be done concurrently or in any order.
Of note, it is appropriate to administer calcium gluconate 1 - 2 grams IV push to stabilize the myocardial cell membranes prior to doing anything else. This will minimize the risk of arrhythmias that can occur with true hyperkalemia without lowering the potassium level in instances of pseudohyperkalemia. So it’s kind of a win win until you know for sure what you’re dealing with!
Now, moving on to the aforementioned diagnostic steps:
Common EKG changes associated with hyperkalemia. (Image)
Obtain a repeat potassium level using a plasma, whole blood, or arterial blood gas specimen. These specimens are thought to be more reflective of a true physiologic potassium level due to the way the blood is drawn and rapid analysis of the sample, which limit the possibility of leukolysis.
Obtain an ECG to assess for typical changes associated with hyperkalemia, such as peaked T waves, ST segment elevation, a prolonged PR interval, and/or a prolonged QRS complex.
Assess for symptoms of hyperkalemia, such as heart palpitations, muscle weakness, abdominal or chest pain, nausea or vomiting, and/or shortness of breath.
If the repeat potassium level is within normal limits, the ECG is absent of typical changes, and/or typical symptoms of hyperkalemia are absent, then pseudohyperkalemia is the likely culprit.
What Should You Do if Pseudohyperkalemia is Diagnosed?
I mean, the long and the short of it is this…nothing. The potassium level is falsely elevated on the lab, so in reality there’s nothing to treat as far as the potassium level goes.
If you recognize pseudohyperkalemia and treatment for it has already been started, just don’t be Kevin. (Image)
That being said, if the diagnosis of pseudohyperkalemia is confirmed and potassium-lowering therapies have already been started, don’t panic! Simply discontinue these medications, repeat further K+ levels using plasma, whole blood, or arterial blood gas specimens, and replace potassium if needed. That’s right, now you need to make sure the potassium levels don’t go too low because you tried to correct what was actually a normal (rather than elevated) level. Oopsy.
If pseudohyperkalemia is thought to be caused by leukocytosis, it’s also appropriate to consult heme/onc for cytoreduction strategies. Cytoreduction is a technique to decrease the number of WBCs in the blood, which should stabilize the cells. This can minimize the chance of leukolysis and subsequent intracellular potassium release.
The tl;dr of Pseudohyperkalemia
In summary, pseudohyperkalemia occurs when a patient’s serum potassium level is falsely high compared to their physiologic potassium level. This may occur due to mechanical factors or extreme leukocytosis.
If pseudohyperkalemia is suspected, it is important to confirm the diagnosis before initiating potassium-lowering therapies that can cause hypokalemia, although you may administer calcium gluconate to stabilize the myocardial cell membranes as a precaution.
The diagnosis can be confirmed by repeating potassium levels using plasma, whole blood or arterial blood gas specimens; obtaining an ECG; and assessing for symptoms of hyperkalemia. If the diagnosis is confirmed, discontinue any potassium-lowering therapies that were already initiated, replace potassium if hypokalemia has developed, and, in the cases of leukocytosis-induced pseudohyperkalemia, consult heme/onc for cytoreduction strategies.
There you have it! Keep your critical eyes open for possible pseudohyperkalemia cases no matter where you practice.