Background: Reference intervals (RIs) help physicians in differentiating healthy from sick individuals. The prothrombin time (PT) and International normalized ratio (INR) assess the integrity of the extrinsic and common coagulation pathways. These may be prolonged or shortened in various conditions and have significant interlaboratory variability due to the instrument/reagent used.

Aims: Establishment of RIs using a direct approach is difficult in children. Therefore, we chose an indirect data mining method for the determining PT/INR RIs.

Methods: Prothrombin Time/INR measurements performed for both inpatients and outpatients aged birth-18 years between January 2013 and December 2020, were retrieved from laboratory management system of the Aga Khan Hospital. Tests were analyzed on Sysmex instruments. Reference intervals were computed using an algorithm developed and validated by the German Society of Clinical Chemistry and Laboratory Medicine’s Working Group on Guide Limits. Assuming that, non-pathologic samples follow a Gaussian distribution (after Box-Cox transformation of the data), an elaborate statistical process was used to isolate distribution of physiological samples from mixed dataset and used to calculate RIs.

Results: A total of 56,712 and 52,245 values were retrieved for PT and INR respectively. After the exclusion of patients with multiple specimens obtained during the study period, RIs were calculated for 37,556 (PT) and 37,192 (INR) children with stratification into 9 age groups. A comparison of 2.5th and 97.5th percentile results with those of established RIs from SickKids Handbook of Pediatric Thrombosis and Hemostasis demonstrated good agreement in between different age groups (Figure 1 & 2).

Conclusion(s): This study supports data mining as an alternate indirect approach for establishing PT/INR RIs, specifically in resource-limited settings. The results obtained are specific to studied population and instrument/reagent used. The study also allows understanding of fluctuations in coagulation pathways with increasing age. These intervals therefore, will assist in better clinical decision-making based on PT and INR results.

Figure 1

Comparison of currently used and newly established Lower -LRI- and Upper Reference Intervals -URI- for Prothrombin Time -PT-

Figure 2

Newly established lower -LRI- and upper -URI- for INR.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/establishment-of-reference-intervals-for-prothrombin-time-and-international-normalized-ratio-in-pakistani-children-using-an-indirect-data-mining-approach/