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Pseudohyperkalemia - Types, Causes, and Ways To Avoid It

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Pseudohyperkalemia is the false increase in potassium ions in the blood sample during laboratory analysis. Let us know more about it.

Medically reviewed by

Dr. Basuki Nath Bhagat

Published At October 10, 2022
Reviewed AtOctober 20, 2022

Introduction:

Before we go to pseudohyperkalemia, let us understand hyperkalemia. Hyperkalemia is a rare, life-threatening condition in which potassium ions are released by the cells into the plasma (the liquid portion of the blood). This affects the cardiovascular system and nervous system the most, causing irregular heartbeats, chest pain, blockage in the heart, weakness, numbness, and paralysis. The most common causes of hyperkalemia are chronic kidney disease, certain drug intake, and pseudohyperkalemia.

What Is Pseudohyperkalemia?

As the name suggests,’ pseudo’ means false, and ‘hyperkalemia’ means increased potassium concentration in the blood. It is a faulty interpretation by the laboratories performing blood tests. Pseudohyperkalemia is a condition in which the serum potassium levels are raised compared to the normal plasma potassium level. This means the calculated value of potassium is higher, but the actual value of potassium is within the normal range. Pseudohyperkalemia is also known as spurious hyperkalemia, factitious hyperkalemia, and artifactual hyperkalemia. It was first reported in the 1950s among individuals with thrombocytosis- a condition with increased platelets (cells that help in blood clotting). There are different types of pseudohyperkalemia, namely, reverse pseudo hyperkalemia, familial pseudohyperkalemia, and seasonal pseudo hyperkalemia.

What Are the Types of Pseudohyperkalemia?

  • Reverse Pseudohyperkalemia - This occurs when there is a high potassium concentration in the plasma and normal potassium in the serum. This is usually seen in leukemic individuals with a higher number of weak white blood cells. These cells rupture, releasing the potassium in the plasma.
  • Familial Pseudohyperkalemia - Also known as ‘leaky cell syndrome’ is a rare genetic type of pseudohyperkalemia.
  • Seasonal Pseudohyperkalemia - This form is temperature-dependent. Lower temperatures have been found to cause pseudohyperkalemia.

What Is the Mechanism Behind Pseudohyperkalemia?

The body needs potassium ions to properly function the heart and nerves and maintain optimum blood pressure. The normal range of potassium in the human body is 3.5-5.2 mmol/L. Potassium is usually found inside the cells (intracellular fluid), whereas sodium is present outside the cell (extracellular fluid). A slight disruption of the cell membrane by physical, chemical, or mechanical methods can lead potassium to leak out of the cells into the plasma. This causes a high potassium concentration.

  • Mechanical Causes: During blood collection, repeated clenching of fist to identify a vein, painful puncture of the vein, using a smaller gauge needle, non-usage of evacuated tube collection systems, using excessive pressure while drawing blood, and applying tourniquet for a longer period of time may disrupt the blood cell membranes leading to leakage of potassium from intracellular fluid to extracellular fluid. During sample processing, vigorous shaking of the sample vials, forceful centrifugation, and re-centrifugation can also cause hemolysis leading to pseudohyperkalemia. In centrifugation, the serum or plasma passes through a compressed layer of gel. Whereas during re-centrifugation, the blood cells with a high concentration of potassium leak back into the serum.

  • Temperature: Surrounding lower temperatures have also been associated with the release of potassium in the blood plasma. A delay in the processing of the blood sample when it is kept on ice or freezer for long causes disruption of the cells releasing potassium ions. Sodium and potassium exchanging ATPase is a compound responsible for properly maintaining sodium and potassium levels in the body. A lower than normal temperature decreases the activity of the compound, causing a shift of the potassium ions in the plasma.

  • Storage and Transportation of the Blood Sample: The use of vacuum tubes, delay in transportation, and a time lag in sample procession utilize the stored glucose (blood sugar) and make the sodium-potassium exchanging ATPase pump fails, and potassium moves out of the cells.

  • Contamination With Potassium: The most potent form of potassium contamination is the potassium salt K+EDTA added to the collection vials to prevent blood clotting. This happens when the blood is drawn to the EDTA vial rather than a sample bottle for potassium estimation.

  • Potassium contamination can also occur if the blood is drawn from the arm used for administering the potassium-infused intravenous injection in certain individuals.

  • Condition of the Individual: Broadly, there are three patient conditions that may cause pseudohyperkalemia. They are -

  1. An Increase in the Levels of Platelets (Thrombocytosis) - Platelets are the cells that help in a blood clot. In thrombocytosis, as the blood clots, potassium leaks into the plasma. So, the potassium concentration in the serum is higher than in the plasma.

  2. An Increase in the Levels of White Blood Cells - In individuals with chronic lymphocytic leukemia, the concentration of white blood cells increases. Some weak white blood cells rupture and release potassium into the plasma.

  3. An Inherited Defect in the Outer Layer of the Red Blood Cells - The genetic inheritance of certain defective protein that forms the outer layer of the red blood cells results in the rupture of the membrane causing potassium ions to move out of the cells. Splenectomy or removal of the spleen, a reservoir organ for platelets, has also been associated with increased serum potassium levels. Fear of getting punctured while drawing blood induced respiratory alkalosis (increased breathing), leading to hyperkalemia.

How Can Pseudohyperkalemia Be Avoided?

  • Thorough training and educating the phlebotomist to avoid prolonged fist clenching, minimize tourniquet application time, and avoid re-pricks.

  • Fist clenching should be avoided when the sample is collected for potassium estimation.

  • Reducing the sample transportation time.

  • Avoid prolonged storage of the samples on ice or in the freezer.

  • Avoid repeating centrifugation on samples already being centrifuged once.

  • Avoiding the use of vacuum tubes for sample collection.

  • For patients who have undergone splenectomy, utmost precaution should be taken as they are predisposed to thrombocytosis leading to pseudohyperkalemia.

  • Potassium estimation of blood done by a blood gas machine will give the correct diagnosis.

Conclusion-

Pseudohyperkalemia is a false interpretation of the serum potassium level. It is multifactorial. Early detection and diagnosis can prevent possible dangerous treatment, which might lower the actual potassium levels and cause hypokalemia. If pseudohyperkalemia is suspected, then the individual should be advised to get the samples tested again. Taking proper precautions and a mindful approach can keep a check on pseudohyperkalemia.

Frequently Asked Questions

1.

What Is the Cause of Pseudohyperkalemia?

Pseudohyperkalemia is induced by raised serum potassium levels in vitro (in the test tube) and is frequently accompanied by thrombocythemia. Although an increased potassium level is generally associated with impaired renal function, pseudohyperkalemia has infrequently been noted in individuals with chronic renal failure (which happens when a condition or disease damages kidney function, inducing kidney damage to deteriorate over months or years).

2.

What Is the Difference Between Pseudohyperkalemia and Hyperkalemia?

Hyperkalemia is a life-endangering electrolyte derangement that needs earlier diagnosis and immediate therapy to control considerable morbidity and mortality. Pseudohyperkalemia is an in vitro (in the test tube) elevation in serum potassium levels without in vivo (in living organism) elevation and therefore lacks clinical signs and symptoms of hyperkalemia.

3.

How Is Pseudohyperkalemia Diagnosed?

The detection of pseudohyperkalemia is created by comparing the serum and plasma potassium amounts with the expectation that the serum potassium will be more elevated than the plasma potassium. In this procedure, a plasma specimen is placed in a tube having heparin as the anticoagulant (employed to control and treat blood clots). The serum is gathered in a test tube that does not contain heparin or other anticoagulants. In the clotting technique, platelets experience accumulation and degranulation while also discharging potassium. Consequently, serum potassium is more elevated compared to plasma potassium levels.

4.

Is Pseudohyperkalemia Common?

Pseudohyperkalemia is moderately familiar in blood specimens collected in health care sectors, most frequently induced by inaccurate blood collection, improper storage conditions, and slowed transportation to the laboratory.

5.

Why Does Thrombocytosis Cause Pseudohyperkalemia?

The significant increase in platelet calculation (thrombocytosis) was the foremost recognized reason for pseudohyperkalemia. It is because of the raised in vitro (in the test tube) release of potassium from triggered platelets during the clotting process. It is thus only a concern if the serum is utilized to calculate potassium.

6.

How To Rule Out Pseudohyperkalemia?

Pseudohyperkalemia can be established by determining plasma potassium in void tubes with lithium heparin after centrifugation (splitting molecules containing distinct thicknesses by rotating them in solution about an axis at increased velocity) or by complete blood potassium determination in an electrolyte-counteracted lithium heparin needle.

7.

How Does Leukocytosis Cause Pseudohyperkalemia?

Extreme leukocytosis (elevated count of white cells in the blood) will have more increased consumption of metabolic powers that may direct to damaged or sodium or potassium ATPase (enzymes that catalyze the hydrolysis of a phosphate bond in adenosine triphosphate to create adenosine diphosphate) pump action, which may contribute to the liberation of potassium from the high number of white blood cells which in turn leads to pseudohyperkalemia.

8.

Which Drugs Can Cause High Potassium Levels?

Some drugs can induce hyperkalemia (high potassium levels) which are as follows:
- Angiotensin-converting enzyme inhibitors are used for high blood pressure and heart failure. This group of drugs possesses Lisinopril, Enalapril, and Quinapril.
- Angiotensin 2 receptor blockers are typical choices for angiotensin-converting enzyme inhibitors. They treat numerous identical medical conditions and possess drugs like Losartan and Valsartan. 
- Spironolactone, Amiloride, Triamterene, Ibuprofen, Naproxen, Cyclosporine, and Digoxintrimethoprim are some medications that increase the potassium levels in the body.

9.

Does High Potassium Make an Individual Tired?

Hyperkalemia symptoms include muscle fatigue and weakness that can create difficulty for an individual to perform basic daily activities. Having excessive potassium in the blood can be harmful. It can even induce a heart attack. If an individual feels symptoms, some of the most familiar are: Feeling tired or weak.

10.

Does leukemia cause high potassium?

Hyperleukocytosis (elevated white blood cell count) with white blood cell count greater than 120,000 per millimeter cube due to chronic lymphocytic leukemia (cancer of white blood cells in bone marrow)) can direct to falsely raised potassium levels because of cell brittleness and decomposition, resulting in potassium discharge as the cells are voluntarily suspended in plasma. Thus hyperleukocytosis in chronic lymphocytic leukemia patients can cause pseudohyperkalemia due to increased cell brittleness.

11.

Do Vitamin D Raise Potassium Levels?

Vitamin D3 (cholecalciferol) increases the body's retention of potassium and sodium. A significant exchange between dietary potassium and D3 levels, and vitamin D3 boosts the retention of potassium and sodium in the body.

12.

What Meat Is Lowest in Potassium?

The lowest potassium levels of meat are clams, oysters, and tuna. Chicken is not regarded as low-potassium meat but is lower in amount than other meats. Deli meats (Fresh or canned meat that includes pre-cooked, ready-to-eat meat loaves or sausages produced from pork, ham, or beef) are not only high in potassium but can also be high in sodium and contain phosphorus additives.

13.

Is High Potassium Reversible?

High potassium can be reversible by delivering calcium into veins (IV) to cure the muscle and heart outcomes of high potassium levels. Glucose and insulin (a hormone produced by the pancreas that controls the glucose level in the blood)are delivered into veins (IV) to decrease potassium levels long enough to fix the reason. Consuming water tablets or potassium binders, as suggested by the healthcare provider. Some individuals may also require medication to help eliminate excess potassium from the body and keep it from returning. It may include: Water pills (diuretics) to assist in ridding the body of excess potassium.

14.

How Do Platelets Affect Potassium?

Platelets in the blood specimens can impact the potassium levels when the calculations surpass 450 × 109 per liter. At a platelet count of 500 × 109 per liter or higher, the activation of extra platelets during blood clotting in the tubes has been documented to be primarily accountable for hyperkalemia.

15.

Does Salt Lower Potassium?

Potassium balances the outcomes of salt in the diet. If sodium raises high blood pressure, potassium lowers it; if sodium keeps water, potassium assists in removing it. Extra water intake may cause potassium loss when kidneys excrete sodium in the urine. So consuming too much sodium may reduce healthy potassium levels.
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Dr. Basuki Nath Bhagat
Dr. Basuki Nath Bhagat

Family Physician

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