Metabolic Confusion: High Lactate Dehydrogenase and the Case of the Misleading Bicarbonate

Introduction: Serum bicarbonate measurements are essential to assessing acid-base status. When there is a discrepancy between bicarbonate values on basic metabolic profiles(BMP) and arterial blood gas(ABG), the cause is often attributed to physiological variation or sampling errors. However, extreme elevations in lactate dehydrogenase(LDH) can introduce unexpected analytical interference. Case Description: A 34-year-old woman with AML was admitted for induction chemotherapy. She developed mixed shock requiring ICU transfer, intubation, vasopressors, and CRRT. Labs noted a significant discrepancy in bicarbonate values: 42 mmol/L on BMP versus 23 mmol/L on ABG, coinciding with an LDH >15,000 IU/L. As her LDH levels declined, the discrepancy resolved. Given this correlation, nephrology consulted the pathology lab after identifying a 2013 study describing falsely elevated bicarbonate results due to interference from high LDH when using nicotinamide-adenine dinucleotide hydroxide (NAD)H-based enzymatic assays. Our lab utilizes an analyzer which shares similar reagents with the platform discussed in the 2013 study. To test this, the pathology department spiked a serum pool with purified LDH at concentrations ranging from 2,000 to 27,000 U/L. When LDH activity exceeded 5,000 U/L in this protocol, bicarbonate levels were falsely elevated in a dose-dependent manner. Discussion: This case highlights a significant lab variation due to an interference caused by extreme LDH levels. NADH-based assays used for bicarbonate measurement can yield falsely high results when LDH exceeds 5,000 U/L due to overlapping enzymatic activity. Importantly, ABG-derived bicarbonate values, based on direct pCO2 measurement, remain unaffected. As a result, the lab amended its standard operating procedures for bicarbonate to flag LDH >5,000 U/L as an interfering factor and recommend confirmation with ABG when relevant. This emphasizes the importance of interdisciplinary collaboration in identifying unexpected sources of error, preventing diagnostic confusion, and guiding accurate patient care.