Available evidence consistently shows that age- and context-specific reference intervals for international normalized ratio (INR) exist in neonates, but a laboratory critical INR threshold remains undefined. In healthy term neonates, an investigation utilizing point-of-care INR testing (CoaguChek XS) demonstrated a narrow reference interval at 4 days of life, with a median INR of 1.10 and a range of 0.90-1.30 after routine vitamin K administration, indicating that modest elevations above adult norms may still be physiologic in this population. Larger population-based data from the Copenhagen Baby Heart Study and COMPARE further confirm that normal neonatal INR values are higher than adult values and vary by gestational age, with reference intervals of approximately 1.1-1.7 in late-preterm/early-term neonates and 1.2-1.8 in full-term neonates, reinforcing that neonatal INR interpretation must be age-stratified rather than based on adult thresholds. [1], [2], [3], [4]

In contrast to healthy populations, studies in high-risk neonates illustrate how INR values may acquire clinical significance without constituting formal laboratory critical values. In one study assessing neonates with hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia, median admission INR was approximately 1.5, and an INR > 1.84 was identified as the optimal cutoff associated with increased bleeding risk. Importantly, this threshold was derived as a predictive risk marker, not as a standardized lab critical value, and its applicability is limited to this specific clinical context. The study also highlights that neonatal coagulation abnormalities often improve over time and with vitamin K administration, underscoring the dynamic nature of neonatal hemostasis. [1], [2], [3], [4]

Finally, a systematic review of neonatal laboratory data emphasize a fundamental limitation underlying all of these findings; there are no generally accepted, standardized age-appropriate reference ranges or actionable thresholds for neonatal laboratory values, including INR. Published data are heterogeneous, context-dependent, and inconsistently reported, which precludes the establishment of universal critical INR cutoffs for neonates or pediatric patients. Ultimately, these findings support the conclusion that INR interpretation in neonates relies on gestational age-specific reference intervals and clinical context, while critical INR values remain institution-defined rather than evidence-based or standardized across pediatric populations. [1], [2], [3], [4]

In broader pediatric population beyond neonates, several studies demonstrate that INR values in children are age-dependent and systematically higher than adult values, but no universal “critical INR” threshold exists for pediatric patients. In a Turkish pediatric cohort (0-18 years; n= 1065), age-stratified reference intervals (RIs) using the Cobas t511 analyzer showed a median INR of 1.02 with 95% limits of 0.93–1.17, and statistically significant variation across 18 age partitions. These RIs highlight the gradual decline in INR from birth toward a steady state after infancy and emphasize the importance of using pediatric-specific intervals for clinical interpretation. An indirect data-mining study in Pakistan analyzed ~37,000 INR values from children birth to 18 years, using the KOSMIC algorithm to separate physiological from pathological values. The study confirmed higher INRs at birth declining after the first month, followed by stable values through adolescence. Comparison with the SickKids Handbook of Pediatric Thrombosis and Hemostasis demonstrated strong concordance in age-related dynamics, but population- and analyzer-specific differences were noted, reinforcing that RIs should not be directly transferred between populations. Further data from 15,179 children aged 1-17 years confirmed that mean INR values were significantly higher in all pediatric age groups (1-5 y: 1.07 ± 0.16; 6-10 y: 1.08 ± 0.11; 11-17 y: 1.10 ± 0.09) than in adults aged 18-50 years (1.04 ± 0.11; p<0.01 for all comparisons). This demonstrates that adult reference limits underestimate normal INR in children and could lead to misinterpretation if applied indiscriminately. Overall, these studies show that pediatric INR interpretation should rely on age-specific reference intervals validated for the local population and analytical platform. [5], [6], [7]

Several institutional laboratory guidance documents define critical INR thresholds for pediatric testing, although most do not provide age-stratified cutoffs. At Seattle Children’s Hospital, critical values for warfarin-associated testing list a critical INR ≤ 1.5 or ≥ 4.0, with a corresponding critical prothrombin time (PT) > 39.2 seconds; however, these thresholds are reported without specification by pediatric age group. Children’s Mercy Hospital laboratory critical values define a critical INR > 5, again without neonatal versus older pediatric differentiation. Vanderbilt Medical Laboratories list a high critical INR > 6 for INR testing, applied across pediatric patients, but similarly do not provide age-specific stratification. Of note, these thresholds are derived from institutional laboratory policies intended for critical value notification, not population-based pediatric reference interval studies, and may vary by assay, reagent, and local clinical practice; therefore, they should be interpreted in conjunction with clinical context and institutional standards rather than as universally applicable pediatric norms. [8], [9], [10]