Low PaO 2 with normal saturation: beyond leukocyte-mediated hypoxemia

Objectives Spurious hypoxemia – a low PaO 2 with preserved, directly measured oxyhemoglobin saturation (sO 2 ) – is traditionally attributed to extreme leukocytosis or thrombocytosis (“leukocyte larceny”). We assessed how often it instead reflects PaO 2 temperature reporting or neonatal fetal-hemoglobin physiology. Methods We retrospectively analyzed 7,473 arterial blood-gas specimens from 2,647 patients (September 2020–January 2026) with co-oximetry-derived sO 2 , complete blood count, and metabolic panel data; regression analyses used the 7,431 specimens reported within 80 min of collection. Spurious hypoxemia was defined as PaO 2 <60 torr (8.0 kPa) referenced to 37 °C at measured pH, with sO 2 ≥92 %. Firth logistic regression, Kaplan–Meier analysis, and receiver-operating-characteristic curves evaluated temperature correction, neonatal status, and extreme leukocytosis (≥50 × 10 9 /L) or thrombocytosis (≥500 × 10 9 /L). Results Spurious hypoxemia affected 74 specimens (1.0 %). Among hypothermic specimens, the apparent rate fell from 3.5 % with PaO 2 reported at patient temperature to 0.9 % when referenced to 37 °C. Rates were higher in normothermic infants than adults (5.4 vs. 0.3 %), consistent with fetal hemoglobin. Extreme leukocytosis was associated with the outcome (adjusted odds ratio 20.2; 95 % confidence interval 5.6–60.9), but all four events occurred in neonates. Longer collection-to-reporting time was modestly associated (odds ratio 1.45 per 10 min), mainly in neonates. No non-neonatal specimen with a white-cell count ≥30 × 10 9 /L met the outcome (0/139), and extreme thrombocytosis showed no association (0/126). Conclusions Apparent spurious hypoxemia was more often explained by temperature reporting and fetal hemoglobin than oxygen metabolism by leukocytes; the leukocytosis signal could not be separated from neonatal physiology. Laboratories should identify the PaO 2 reporting temperature, and clinicians should consider fetal-hemoglobin physiology before invoking leukocyte-mediated hypoxemia in neonates.