Table 1.
Study details of the Andrew et al. series describing the developing hemostatic system during infancy, childhood, and adolescence (45–47).
| Year | Study details | Coagulation parameters | Notable findings |
|---|---|---|---|
| 1987 (45) | • Study population: Consecutively born term infants (37–42 weeks) at a single center over a 3-month period • Sample size: 118 total infants, 61–77 at each study timepoint • Timepoints: Day 1, 5, 30, 90, and/or 180 after birth • Relevant methods: ACL analyzer, chromogenic assays, ELISA |
All studies: • Global: aPTT, fibrinogen, PT • Coagulation: FII, FV, FVII, FVIII, FIX, FX, FXI, FXII, FXIIIa, FXIIIb, HMWK, PK, vWf • Fibrinolysis: α2-AP, plasminogen • Inhibitors: α1-AT, α2-M, AT, C1-INH, HCII, protein C, protein S |
General findings: • Normal values from birth to 6 months old in the healthy term infant and preterm infant, and from 1 to 16 years old in the child and adolescent were determined • Coagulation tests varied with age and different parameters showed different patterns of maturation Selected specific findings: • Global: • aPTT was prolonged at birth, remained prolonged throughout the postnatal period in preterm infants, and reached adult levels by 3 months in term infants • PT demonstrated variability at birth and shortened to adult levels by 1 month in both term and preterm infants • Despite an aPTT and PT similar to adults, BT was prolonged in children and adolescents at all ages compared to adults |
| 1988 (46) | • Study population: Preterm infants (born at 30–36 weeks) at a single center over a 3.25-year period • Sample size: 137 total infants, 40 to 96 at each study timepoint • Timepoints: Day 1, 5, 30, 90, and/or 180 after birth • Relevant methods: ACL analyzer, chromogenic assays, ELISA |
Term/preterm infant studies: • Global: TTChildren/adolescents study: • Global: BT, INR • Fibrinolysis: PAI, TPA |
• Coagulation: • Vitamin K-dependent factors (FII, FVII, FIX, FX, protein C, and protein S) were low throughout the postnatal period in term and preterm infants as well as in children and adolescents through age 16 compared to adults • FXI, FXII, HWMK, and PK were lower in term and preterm infants in the postnatal period compared to adults • FXI and FXII decreased at 11 to 16 years old compared to adults • FV decreased throughout childhood and was lowest in adolescence • FVIII and vWf were similar in term and preterm infants and reached near or above adult values by 6 months • Factor XIIIb was elevated in early childhood and decreased with age |
| 1992 (47) | • Study population: Healthy children and adolescents (1–16 years old) at a single center over a 2-year period • Sample size: 246 total patients, 4–7 at each age • Relevant methods: ACL analyzer, chromogenic assays, and ELISA |
• Fibrinolysis: • Plasminogen gradually rose to near adult levels by 6 months in term infants but remained persistently low in preterm infants • In children and adolescents, TPA levels were low and PAI levels were increased compared to adults • Inhibitors: • All inhibitors were low at birth in term and preterm infants but rose to or near to adult levels by 6 months of age • In preterm infants, α2-M which was above adult levels at birth and rose to twice adult levels by 6 months of age • Protein C and S remained below adult levels until adolescence |
aPTT, activated partial thromboplastin time; α1-AT, α1-antitrypsin; α2-M, α2-macroglobulin; α2-AP, α2-antiplasmin; AT, antithrombin or antithrombin III; BT, bleeding time; C1-INH, C1 inhibitor or C1 esterase inhibitor; ELISA, enzyme-linked immunosorbent assay; F, factor; INR, international normalized ratio; HCII, heparin cofactor II; HMWK, high-molecular-weight kininogen; PK, prekallikrein; PAI, plasminogen activator inhibitor; PT, prothrombin time; TPA, tissue plasminogen activator; TT, thrombin clotting time; vWf, von Willebrand factor.