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Data mining for prothrombin time and international normalized ratio reference intervals in children
Muhammad Shariq Shaikh1, Sibtain Ahmed1
1Department of Pathology and Laboratory Medicine, Aga Khan University, Karachi, Pakistan.
Insights
Establishing pediatric reference intervals (RIs) for prothrombin time (PT) and International Normalized Ratio (INR) is crucial. An indirect data mining method using the KOSMIC algorithm was effective for determining these PT/INR RIs in children.
Area of Science:
- Clinical Biochemistry
- Pediatric Hematology
- Data Mining in Healthcare
Background:
- Reference intervals (RIs) are essential for clinical diagnosis, but establishing them for coagulation tests like prothrombin time (PT) and International Normalized Ratio (INR) in children presents challenges.
- Interlaboratory variability in PT/INR measurements arises from differences in instruments and reagents.
- Direct methods for determining pediatric RIs are often logistically difficult, costly, and ethically restricted.
Purpose of the Study:
- To determine pediatric reference intervals (RIs) for prothrombin time (PT) and International Normalized Ratio (INR) using an indirect data mining approach.
- To evaluate the feasibility of the KOSMIC algorithm for establishing PT/INR RIs in a pediatric population.
- To provide age-stratified PT/INR RIs for improved clinical decision-making in children.
Main Methods:
- Retrospective analysis of PT/INR measurements from 37,356 (PT) and 37,192 (INR) children aged 0-18 years.
- Application of the indirect KOSMIC algorithm, assuming Gaussian distribution of non-pathologic samples after Box-Cox transformation.
- Stratification of RIs into nine distinct age groups.
Main Results:
- The KOSMIC algorithm successfully computed PT/INR reference intervals for the pediatric cohort.
- Calculated RIs showed good agreement with established pediatric thrombosis and hemostasis guidelines across different age groups.
- The study demonstrated the utility of data mining for establishing PT/INR RIs in resource-limited settings.
Conclusions:
- Indirect data mining using the KOSMIC algorithm is a viable and efficient alternative for establishing pediatric PT/INR reference intervals.
- The derived RIs can aid clinicians in better interpreting coagulation test results in children.
- This approach facilitates understanding of age-related coagulation pathway dynamics and supports evidence-based clinical practice.
Abstract:
Reference intervals (RIs) help physicians in differentiating healthy from sick individuals. The prothrombin time (PT) and International normalized ratio (INR) fluctuate in coagulation pathway defects and have interlaboratory variability due to the instrument/reagent used. As direct method is difficult in children, we chose an indirect data mining method for the determining PT/INR RIs. The indirect method overcomes the substantial financial and logistic challenges, and ethical restrictions in children, moreover, allows partitioning in more fine-grained age groups. Prothrombin Time/INR measurements performed in patients aged birth-18 years between January 2013 and December 2020, were retrieved from laboratory management system of the Aga Khan Hospital. Reference intervals were computed using an indirect KOSMIC algorithm. The KOSMIC package function on the assumption that the non-pathologic samples follow a Gaussian distribution (after Box-Cox transformation of the data), following an elaborate statistical process to isolate distribution of physiological samples from mixed dataset. 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 37,356 (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. This study supports data mining as an alternate 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 and hence better clinical decision-making based on PT and INR results.
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