Related Experiment Videos
Maturation of the hemostatic system during childhood
1Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
Insights
Pediatric hemostasis differs from adults, with lower coagulant levels and higher inhibitor levels in children. Age-matched reference ranges are crucial for diagnosing bleeding disorders in children.
Area of Science:
- Pediatric Hematology
- Hemostasis and Thrombosis Research
- Clinical Coagulation Studies
Background:
- Adult reference ranges are commonly used for pediatric hemostatic evaluation.
- The pediatric hemostatic system is not fully mature by 6 months of age.
- Limited comprehensive studies exist for healthy older children's hemostasis.
Purpose of the Study:
- To prospectively investigate the hemostatic system in healthy children.
- To establish age-specific reference ranges for hemostatic components.
- To identify physiological differences between pediatric and adult hemostasis.
Main Methods:
- Prospective cohort study of 246 healthy children (ages 1-16).
- Blood samples collected during elective day surgery for analysis of 33 hemostatic components.
- Measurement of functional and immunologic assays, and automated bleeding time.
Main Results:
- Eleven hemostatic components showed adult-like ranges.
- Seven coagulants (II, V, VII, IX, X, XI, XII) were significantly lower and age-dependent.
- Three inhibitors (alpha 2M, protein C, C1-Inh) differed from adults; alpha 2M and C1-Inh were elevated, protein C was low until age 11.
- Bleeding time was longer in children under 10, decreasing to adult levels in teenagers.
Conclusions:
- Significant physiological differences exist in the pediatric hemostatic system compared to adults.
- Lower coagulant and higher alpha 2M levels may contribute to reduced thrombotic risk in children.
- Age-matched controls are essential for evaluating hemostatic disorders in children.
Abstract:
The hemostatic system is assumed to be similar in children and adults and reference ranges established for adults are commonly used to evaluate children suspected of having congenital or acquired hemostatic problems. However, we know that the hemostatic system is not fully mature by 6 months of age and comprehensive studies of healthy older children have not been published. Therefore, we conducted a prospective cohort study of the hemostatic system in healthy children having minor, elective day surgery. After obtaining informed consent, a 3-mL blood sample was obtained at the time routine preoperative blood work was drawn. The plasma was fractioned and stored at -70 degrees C for batch assaying. We measured the concentration of 33 components of the hemostatic system (functional and immunologic assays) and the bleeding time (automated pediatric device) in 246 children aged 1 to 16 inclusive (a minimum of four subjects at each age). Eleven components of hemostasis (fibrinogen, prekallikrein, high-molecular weight kininogen, factors VIII and XIII, antithrombin III [ATIII], heparin cofactor II [HCII], alpha 1-antitrypsin [alpha 1AT], protein S, plasminogen, alpha 2-antiplasmin [alpha 2AP]) had mean values and ranges of normal that were similar to adults. Mean values of seven coagulants (II, V, VII, IX, X, XI, XII) were significantly lower than adult values and varied with age. Values for three inhibitors, alpha 2-macroglobulin (alpha 2M), protein C, and protein C1-inhibitor (C1-Inh) also differed from adults. Alpha 2M and C1-Inh inhibitor levels were elevated throughout childhood, whereas protein C levels were low, with a lower limit of normal of 0.40 U/mL until the age of 11. Finally, the upper limit of normal for the bleeding time was longer in children during the first 10 years of life, but decreased to adult values in the teenage years. In summary, there are important physiologic differences in the hemostatic system in children compared with adults. The decreased levels of several critical coagulants and increased levels of alpha 2M may contribute in part to the lower risk of thrombotic events in childhood. Age-matched controls should be used for evaluation of the hemostatic system in children with suspected congenital or acquired defects.