Lactate dehydrogenase (LDH) is a widely used blood test that measures an enzyme found inside the cells of nearly every tissue in the body. This enzyme is released into the bloodstream when cells are damaged or die, making it a non-specific indicator of injury or disease. LDH testing is highly sensitive to a pre-analytical error called hemolysis, which is the greatest challenge to obtaining an accurate result. Hemolysis, the rupture of red blood cells, causes a massive, artificial elevation in the measured LDH level, and this spurious result can mislead diagnostic efforts.
The Role of Lactate Dehydrogenase in the Body
Lactate dehydrogenase is a cytoplasmic enzyme fundamental to cellular energy production. Its primary function is to catalyze the reversible conversion of lactate to pyruvate, a necessary step in glycolysis and the anaerobic metabolic pathway. This reaction helps regenerate \(\text{NAD}^+\) so that energy production can continue, particularly when oxygen levels are low.
The enzyme is found across all tissues, with the highest concentrations located in the heart, liver, muscles, kidneys, and red blood cells. Because of its widespread distribution, elevated LDH in the blood indicates cell death or tissue turnover somewhere in the body. The enzyme exists in five different structural forms, known as isoenzymes, which are present in varying concentrations across different organs. Analyzing these isoenzymes can sometimes provide clues about the tissue source of the elevation, but this specialized testing is not routinely performed.
How Hemolysis Contaminates LDH Testing
Hemolysis is the breakdown or rupture of red blood cells, which releases their internal contents into the surrounding plasma or serum. Red blood cells contain extremely high concentrations of LDH, far exceeding the levels normally found circulating in the plasma. When these cells rupture, this massive internal store of LDH is instantly dumped into the liquid portion of the blood sample. This sudden release creates an artificially high, or spurious, LDH measurement that does not reflect the patient’s true physiological state. Even a small amount of red blood cell damage can dramatically inflate the result, making hemolysis the most common reason a laboratory must reject a sample or flag the LDH result as unreliable.
Causes of Sample Hemolysis
The vast majority of hemolysis affecting laboratory tests occurs outside the body, known as in vitro hemolysis. This damage results from pre-analytical errors during the collection, handling, or transport of the blood sample. Improper venipuncture technique is a frequent cause, such as using a needle with too small a bore, which forces red blood cells through a narrow opening and causes mechanical trauma.
Several factors related to sample handling can cause red blood cells to rupture:
- Aggressive suction during blood draw or forcibly expelling blood from a syringe into a collection tube.
- Vigorous shaking or mixing the blood tube instead of performing a gentle inversion.
- Temperature extremes, such as storing the sample in a freezer or exposing it to excessive heat.
- Delayed processing or prolonged storage before the plasma is separated from the cells.
Diagnostic Interpretation of LDH Levels
When in vitro sample hemolysis has been ruled out, an elevated LDH result becomes a valuable, non-specific indicator of tissue damage. The LDH test confirms that cell death has occurred somewhere in the body, aiding in the diagnosis and monitoring of various conditions. High LDH levels are commonly associated with acute events like a heart attack, where cardiac muscle cells have died, or with significant muscle trauma and bone fractures.
Elevations are also seen in conditions causing chronic cell turnover, such as liver diseases (hepatitis and cirrhosis) and kidney diseases. LDH is also a well-established marker in oncology, often elevated in cancers like lymphomas and leukemias, and is used to monitor disease progression or treatment effectiveness. It is important to distinguish this from in vivo hemolysis, which is true red blood cell destruction occurring inside the patient’s body, such as in hemolytic anemia. In this case, the elevated LDH is a genuine result of the disease process, serving as a biological marker of red blood cell breakdown.