Determination of Age Dependent Reference Ranges for PT and aPTT

Background: The hemostatic system is a developing and changing process relative to age. Use of age-adjusted reference values is a valuable diagnostic tool for correct diagnosis and management of thrombotic and hemorrhagic disease in children.

There is a lack of reliable pediatric reference intervals for global hemostatic assays like PT and aPTT and they vary with utilized reagents and analyzers.

Aim of the present study was to determine pediatric reference intervals for the PT reagent Technoclot® PT Plus and the aPTT reagent Siron®LS on coagulation analyzer Ceveron®alpha in plasma samples from healthy children 0-18 years of age.

Methods: Blood samples were obtained from 70 healthy children, grouped as 0-3 years (n =20), 4-6 years (n = 18) and 7-18 years (n = 32). All samples were frozen after sampling and thawed at 37°C before starting the experiment. The validity of each assay was confirmed by recovering the assay controls within the confidence range.

Siron^®LS and Technclot^®PT Plus were measured according to manufacturer specifications and standard methods using the coagulation analyzer Ceveron®alpha. Reference intervals were established based on a nonparametric method ( CLSI Guideline C28-A3).

Results: The reference range for Siron^®LS on Ceveron^®alpha in pediatric samples is set to 23 -35 seconds, the reference range for Technoclot PT Plus is set to 43% -88% and 1.06INR -1.35INR respective. Calculation by age groups is ([Table 1]):

Table 1 Age specific ranges

Age group	0–3 yrs	4–6 yrs	7–18 yrs	0–18 yrs
Number of samples	20	18	32	70
Normal Range [sec ]	23.7–30.7	21.8–32.6	19.4–33.0	23–35
Normal Range [% ]	45.9–77.6	36.0–81.6	45.3–75.7	43–88
Normal Range [INR ]	1.06–1.31	1.04–1.47	1.07–1.32	1.06–1.35

For all 3 parameters there are differences to the normal ranges determined for adults, with a reference range of 25- 38 seconds for Siron® LS and Technoclot® PT Plus with >70%.

Conclusion: These data indicate physiologic differences in the hemostatic system between children of age groups and adults, conrming the phenomenon of developmental hemostasis. Our results underline the need for age-specic reference ranges to serve as a useful reference guide in interpreting test results for children with suspected bleeding disorders.