Abstract
There is a lack of reliable pediatric reference intervals for many clinical laboratory tests. In 2002, the Children’s Health Improvement through Laboratory Diagnostics (CHILDx) organization initiated a project to collect blood and urine samples from healthy children 7 – 17 years of age with the goal of establishing reference intervals for many laboratory tests. The purpose of the present study was to determine pediatric reference intervals for ten coagulation proteins associated with common bleeding and thrombotic disorders. All assays were functional except for vonWillebrand factor antigen. All were measured according to manufacturer specifications and standard methods using the STA-R coagulation analyzer (Diagnostica Stago), with the exception of the ristocetin cofactor assay, which was performed on the BCS (Dade Behring). Samples used to establish adult reference intervals were purchased from George King Bio-Medical, Precision Biologic, and also drawn in-house. At each age of life, 62 individuals (31 girls/31 boys) were drawn for a minimum of 124 individuals for each age group. Reference intervals were established based on a nonparametric method (NCCLS C28-A).
RESULTS: 1. Although pediatric PTT values do not differ from adult values, the mean pediatric PT values are about 1 sec longer, 2. Pediatric FIX levels trend upward until ages 16-17 when adult levels are reached, 3. FVIII, FXI, RCF and vWFAg demonstrate higher reference values in younger ages, 4. The lower limit of pediatric AT levels is significantly higher than adults, 5. The lower limit of pediatric protein C levels is significantly lower than adults, however, this difference is not seen for protein S levels. In conclusion, a number of significant differences between pediatric and adult reference intervals have been found supporting the use of these newer reference intervals.
Age N PT PTT F VIII F IX F XI 7–9 186 13.1–15.4* 27–38 78–199* 71–138* 70–138 10–11 124 12.9–15.5* 27–38 83–226* 72–159* 63–137 12–13 124 13.1–15.2* 27–38 74–205* 73–152* 65–130* 14–15 124 12.9–15.4* 26–35 69–241* 80–162 57–125* 16–17 121 12.6–15.9* 26–35 63–225* 85–175 64–160 Adult 125 12.3–14.4 26–38 56–190 78–184 56–153 Age AT RCF VWF Ag PC PS-Male PS-Female * The t-test of the means, F-test of the SD, or both is statistically different (p< 0.05) from adult reference values. 7–9 96–135* 51–172* 62–176 71–143* 64–141 58–154 10–11 92–134* 61–195* 61–201* 76–146* 68–150 68–140* 12–13 92–128* 47–183* 61–186* 68–162* 65–143 60–150 14–15 95–135* 50–215* 57–204* 69–170* 66–149 53–147* 16–17 94–131* 47–206* 51–211 70–170* 75–157* 51–150* Adult 76–128 44–195 51–185 83–168 66–143 57–131
Collaborative derivation of reference intervals for major clinical laboratory tests in Japan