Blood Picture of Tumor Lysis Syndrome
The characteristic laboratory findings of tumor lysis syndrome consist of hyperuricemia (>8 mg/dL in adults), hyperkalemia (≥6 mmol/L), hyperphosphatemia (>1.45 mmol/L in adults or >2.1 mmol/L in children), and hypocalcemia (≤1.75 mmol/L), with at least two of these abnormalities required for diagnosis of laboratory TLS. 1, 2
Core Laboratory Abnormalities
The metabolic derangements in TLS arise from massive tumor cell lysis releasing intracellular contents into the bloodstream 1, 3:
Hyperuricemia
- Uric acid >8 mg/dL in adults (or >476 μmol/L) defines hyperuricemia in TLS 1
- Results from catabolism of purine nucleic acids through hypoxanthine and xanthine to uric acid by xanthine oxidase 1
- Uric acid precipitates in renal tubules when concentration exceeds 15 mg/dL at the acidic pH (~5) of distal tubules, causing acute oliguric renal failure 1, 2
- Patients with baseline uric acid ≥8 mg/dL have an 11.66-fold increased relative risk of developing TLS compared to those with levels <4 mg/dL 1
Hyperkalemia
- Potassium ≥6.0 mmol/L (or ≥6 mEq/L) defines hyperkalemia in TLS 1
- Rapid release of intracellular potassium from lysed tumor cells, exacerbated by concurrent renal failure impairing excretion 1, 2
- Life-threatening manifestation causing cardiac arrhythmias, ventricular tachycardia, fibrillation, or cardiac arrest 1, 2
- In Burkitt's lymphoma cohorts, two of four TLS-related deaths were directly attributable to hyperkalemia-induced sudden death 2
- Also produces neuromuscular effects including muscle cramps and paresthesias 1, 2
Hyperphosphatemia
- Phosphorus >1.45 mmol/L (4.5 mg/dL) in adults or >2.1 mmol/L (6.5 mg/dL) in children defines hyperphosphatemia 1
- Released directly from lysed tumor cells into circulation 2, 4
- Precipitates with calcium forming calcium-phosphate crystals that deposit in renal tubules, worsening kidney injury 1, 2
Hypocalcemia
- Calcium ≤1.75 mmol/L (7 mg/dL) defines hypocalcemia in TLS 1
- Secondary to calcium-phosphate precipitation in tissues 2, 4
- Symptomatic hypocalcemia produces tetany and seizures 2
Diagnostic Criteria
Laboratory TLS requires two or more of the above metabolic abnormalities occurring within 3 days before or 7 days after initiation of anticancer therapy 1, 2. The definition also includes a >25% increase from baseline for each parameter if recent baseline values are available 1.
Clinical TLS is defined by laboratory TLS plus at least one clinical complication: renal failure (estimated GFR ≤60 mL/min), cardiac arrhythmia, or seizure 1, 5.
Additional Laboratory Findings
Renal Function Markers
- Elevated serum creatinine ≥1.5 times upper limit of normal indicates renal insufficiency 1, 2
- However, creatinine is a delayed and muscle-mass-dependent marker; estimated GFR using MDRD or Cockcroft-Gault equations provides more accurate assessment 1, 5
- Uremia (elevated BUN) commonly occurs from multiple mechanisms: uric acid crystal deposition, calcium-phosphate precipitation, xanthine crystallization, or drug-associated nephrotoxicity 1
Other Markers
- Elevated LDH >2 times upper normal limit is a high-risk feature and disease burden marker, not a diagnostic criterion but strongly associated with TLS development 5, 6
- Metabolic acidosis may develop as a complication 7
Timing of Laboratory Abnormalities
Laboratory derangements most frequently manifest within 12-72 hours after initiation of cytoreductive therapy, though spontaneous TLS can occur before chemotherapy in highly proliferative malignancies 1, 2.
Critical Pitfall to Avoid
Do not rely solely on serum creatinine for renal assessment in TLS—always calculate eGFR to detect early acute kidney injury, as creatinine levels depend on age, hydration status, and muscle mass 1, 5. This is particularly important because the mortality rate for clinical TLS reaches 83% versus 24% in those without clinical TLS 5, making early detection through accurate renal function assessment critical.