Abstract
Introduction: The hemostatic system is a developing and changing process relative to age. Although advances in the knowledge of hemostatic mechanisms have led to the development of new methods for measuring peptides or enzyme-inhibitor complexes, there are very limited data concerning normal reference values for these in children.
Objectives: The aim of this study is to distinguish the difference(s) in various endothelial cell activation and hemostatic parameters between children and adults, and to establish the normal range of these parameters in normal children in different age groups.
Materials and Methods: Blood was obtained from 96 normal Thai children and adults whose screening coagulation tests were normal. All children were categorized into 3 age groups: 1–5 yrs, 6–10 yrs, and 11–18 yrs. Endothelial cell activation parameters: von Willebrand Factor Antigen and Activity (VWF:Ag and VWF:Ac) and soluble thrombomodulin (sTM); coagulation parameters: activated Factor VII (FVIIa:C), tissue factor (TF), and Thrombin-Antithrombin Complex (TAT); and fibrinolytic parameters: tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1), D-dimer, thrombin activatable fibrinolysis inhibitor (TAFIa) and Protein C activity (PC:Ac) were measured.
| Tests . | Children’s Age Range . | Adults . | ||
|---|---|---|---|---|
| (Mean ± SD) . | 1–5 yr (n=19) . | 6–10 yr (n=26) . | 11–18 yr (n=25) . | (n=25) . |
| ANOVA *p ≤ 0.05 compared with adults; **p ≤ 0.001 compared with adults | ||||
| VWF:Ag (%) | 93.3 ± 25.7 | 110.3 ± 27.1 | 98.4 ± 31.0 | 100.5 ± 25.2 |
| VWF:Ac (%) | 72.1 ± 18.9 | 91.1 ± 20.6 | 82.0 ± 24.2 | 84.7 ± 21.8 |
| sTM (ng/mL) | 3.9 ± 1.6** | 3.1 ± 0.9 | 3.1 ± 1.3 | 2.4 ± 1.1 |
| Fibrinogen (mg/dL) | 360.7 ± 56.9 | 384.4 ± 78.9 | 410.1 ± 109.4 | 360.7 ± 51.0 |
| FVIIa:C (%) | 68.0 ± 23.8 | 69.9 ± 23.1 | 75.0 ± 22.9 | 75.6 ± 19.7 |
| TF (pg/mL) | 218.8 ± 57.8** | 152.7 ± 38.2 | 144.5 ± 46.7 | 126.6 ± 42.2 |
| TAT (ug/L) | 4.5 ± 3.3 | 2.2 ± 0.7 | 2.4 ± 1.2 | 3.7 ± 4.9 |
| t-PA (ng/mL) | 1.32 ± 0.56 | 1.19 ± 0.48 | 1.16 ± 0.28 | 1.27 ± 0.32 |
| PAI-1 (ng/mL) | 22.8 ± 13.2 | 29.4 ± 14.2* | 27.3 ± 18.3 | 18.8 ± 11.9 |
| D-dimer (mg/L) | 0.52 ± 0.42* | 0.44 ± 0.46 | 0.28 ± 0.33 | 0.21 ± 0.09 |
| TAFIa μg/mL) ( | 40.6 ± 9.7 | 44.4 ± 6.9 | 46.1 ± 6.1 | 42.2 ± 5.7 |
| Protein C:Ac (%) | 87.2 ± 18.3* | 101.7 ± 15.6 | 101.1 ± 22.5 | 102.4 ± 17.4 |
| Tests . | Children’s Age Range . | Adults . | ||
|---|---|---|---|---|
| (Mean ± SD) . | 1–5 yr (n=19) . | 6–10 yr (n=26) . | 11–18 yr (n=25) . | (n=25) . |
| ANOVA *p ≤ 0.05 compared with adults; **p ≤ 0.001 compared with adults | ||||
| VWF:Ag (%) | 93.3 ± 25.7 | 110.3 ± 27.1 | 98.4 ± 31.0 | 100.5 ± 25.2 |
| VWF:Ac (%) | 72.1 ± 18.9 | 91.1 ± 20.6 | 82.0 ± 24.2 | 84.7 ± 21.8 |
| sTM (ng/mL) | 3.9 ± 1.6** | 3.1 ± 0.9 | 3.1 ± 1.3 | 2.4 ± 1.1 |
| Fibrinogen (mg/dL) | 360.7 ± 56.9 | 384.4 ± 78.9 | 410.1 ± 109.4 | 360.7 ± 51.0 |
| FVIIa:C (%) | 68.0 ± 23.8 | 69.9 ± 23.1 | 75.0 ± 22.9 | 75.6 ± 19.7 |
| TF (pg/mL) | 218.8 ± 57.8** | 152.7 ± 38.2 | 144.5 ± 46.7 | 126.6 ± 42.2 |
| TAT (ug/L) | 4.5 ± 3.3 | 2.2 ± 0.7 | 2.4 ± 1.2 | 3.7 ± 4.9 |
| t-PA (ng/mL) | 1.32 ± 0.56 | 1.19 ± 0.48 | 1.16 ± 0.28 | 1.27 ± 0.32 |
| PAI-1 (ng/mL) | 22.8 ± 13.2 | 29.4 ± 14.2* | 27.3 ± 18.3 | 18.8 ± 11.9 |
| D-dimer (mg/L) | 0.52 ± 0.42* | 0.44 ± 0.46 | 0.28 ± 0.33 | 0.21 ± 0.09 |
| TAFIa μg/mL) ( | 40.6 ± 9.7 | 44.4 ± 6.9 | 46.1 ± 6.1 | 42.2 ± 5.7 |
| Protein C:Ac (%) | 87.2 ± 18.3* | 101.7 ± 15.6 | 101.1 ± 22.5 | 102.4 ± 17.4 |
As seen in the Table, children in all age groups showed no significant difference in mean levels of VWF:Ag and Ac, fibrinogen, FVIIa:C, TAT, t-PA and TAFIa compared to adults. However, compared to adults, children aged 1–5 had significantly higher mean values of sTM (p=0.001), TF (p=< 0.001), and D-dimer (p = 0.015) whereas they had significantly lower mean levels of PC:Ac (p=0.023). The mean levels of PAI-1 in children of all groups were high, especially in children in the 6–10 yr age group (p = 0.032). These data indicate a physiologic difference in endothelial cell activation and hemostatic system between children and adults. Our data will serve as a useful reference guide in interpreting test results from children with suspected bleeding disorders.
Author notes
Corresponding author
