Rasburicase Causes Falsely Low Uric Acid Laboratory Values Due to Ex Vivo Enzymatic Degradation
Rasburicase will artificially lower uric acid measurements in blood samples unless they are immediately placed on ice and analyzed within 4 hours, because the enzyme continues to degrade uric acid after the blood is drawn. 1, 2
Mechanism of Laboratory Interference
- Rasburicase is a recombinant urate oxidase enzyme that catalyzes the oxidation of uric acid to allantoin, and this enzymatic activity continues at room temperature in collected blood samples 2, 3
- At room temperature, rasburicase causes enzymatic degradation of uric acid in blood/plasma/serum samples, potentially resulting in spuriously low plasma uric acid assay readings 2
- This ex vivo degradation can lead to falsely low measurements that do not reflect the patient's true in vivo uric acid levels 3
Mandatory Sample Handling Protocol
To obtain accurate uric acid measurements in patients receiving rasburicase, you must follow this exact protocol: 1, 2
- Collect blood into pre-chilled tubes containing heparin anticoagulant (uric acid must be analyzed in plasma, not serum) 1, 2
- Immediately immerse the collection tube in an ice water bath upon drawing the blood 1, 2
- Centrifuge the sample in a pre-cooled centrifuge (4°C) to separate plasma 1, 2
- Maintain plasma samples in an ice water bath until analysis 1, 2
- Analyze the sample within 4 hours of collection to prevent degradation 1, 2
Clinical Implications
- Failure to follow this protocol will result in artificially low uric acid readings that underestimate the patient's true hyperuricemia and may lead to inadequate treatment decisions 3
- The FDA drug label explicitly warns that laboratory test interference occurs with rasburicase, and the special sample handling procedure must be followed to avoid ex vivo uric acid degradation 2
- This is not a theoretical concern—case reports document clinically significant falsely low uric acid measurements when proper sample handling was not performed 3
Pharmacodynamic Effects on True Uric Acid Levels
- When administered correctly, rasburicase rapidly decreases plasma uric acid levels within 4 hours through enzymatic conversion to allantoin 2
- Following administration of 0.15-0.20 mg/kg rasburicase daily, plasma uric acid levels were maintained below 7.5 mg/dL in 98% of adult and 90% of pediatric patients for at least 7 days 2
- The mean terminal half-life of rasburicase ranges from 15.7 to 22.5 hours, with minimal drug accumulation (<1.3-fold) between days 1 and 5 of dosing 2