Abstract

Developmental hemostasis, a concept first reported by M.Andrew et al. in the late 80s, is now universally accepted, as it is critical to ensure optimal prevention, diagnosis, and treatment of hemorrhagic and thrombotic diseases in children. As coagulation test results, particularly prothrombin time (PT), and activated partial thromboplastin time (aPTT), are known to vary with the reagents and analyzers used, it is recommended for each laboratory to define the age-dependent reference ranges by using its own technical condition (J Thromb Haemostas 2012; 10: 298). To address that issue, the present multicenter study was carried out in six centers using the same reagents and the same ACL TOP analyzer (all from Instrumentation Laboratory, Bedford, MA, USA). There were 598 samples obtained from pediatric patients (407 M and 191 F), aged between 2 Weeks and 17 Years. Samples were obtained from the routine workload in all participating centers. Indication for coagulation testing was pre-operative screening (non-acute) in most cases. They were divided in 6 age groups: <1 Month (median=3 Weeks, range 2-4 W, n=11), between 1 and 5 Months (median=3 Mo, n=135), between 6 and 12 Mo (median=8.5 Mo, n=73), between 1 and 5 Years (median=2 Y, n=238), between 6 and 10 Y (median=8 Y, n=49) and between 11 and 17 Y (median=13 Y, n=99). As the data obtained in the different centers were not significantly different, test results were pooled and further analyzed. In most cases, data were found to be normally distributed, allowing expression of the test results as the mean values with SDs. Alternatively, in the case of non-normal distribution, test results were expressed as the median values with their ranges.

PT (ratio) was found to be positively correlated with age (r=+0.61, p<0.0001), with shorter clotting times in younger children. The same applied to fibrinogen (Clauss) level (r=+0.47, p<0.0001). Conversely, aPTT (ratio) was negatively correlated with age (r=-0.15, p<0.01), with longer clotting times in younger children. Factor V (FV) and FVIII levels (Table) were found roughly unchanged during childhood, and the same applied to FX (not shown). In contrast, FII, FIX, FXI, and FXII levels were significantly decreased in youngest children particularly in those below 1 Mo, and then increased correlatively with age before reaching adult values in children above 10 Y. D-dimer levels (HemosIL D-dimer HS 500) were found higher in the first 6 months of life and remained slightly elevated during childhood before reaching adult values during puberty.

< 1 Mo1 - 5 Mo6 - 12 Mo1 - 5 Y6 - 10 Y11 - 16 Y
PT (ratio) 0.96+0.07 0.96+0.07 0.98+0.07 1.01+0.08 1.06+0.08 1.07+0.09 
aPTT (ratio) 1.19+0.12 1.11+0.11 1.08+0.13 1.07+0.14 1.07+0.10 1.03+0.09 
Fg (g/L) 2.53+0.20 2.36+0.52 2.46+0.51 2.84+0.59 2.81+0.60 2.84+0.58 
F V (%) 116+24 118+27 104+24 113+21 114+24 116+23 
F VIII (%) 98+41 88+25 87+18 86+17 99+17 93+22 
FIX (%) 47+13 60+18 73+17 85+14 85+17 95+19 
FXI (%) 59+10 69+26 85+20 94+21 84+13 89+19 
D-dimer (ng/mL) 495 (85-1200) 420 (90-1100) 292 (130-950) 280 (80-2100) 284+124 233+157 
< 1 Mo1 - 5 Mo6 - 12 Mo1 - 5 Y6 - 10 Y11 - 16 Y
PT (ratio) 0.96+0.07 0.96+0.07 0.98+0.07 1.01+0.08 1.06+0.08 1.07+0.09 
aPTT (ratio) 1.19+0.12 1.11+0.11 1.08+0.13 1.07+0.14 1.07+0.10 1.03+0.09 
Fg (g/L) 2.53+0.20 2.36+0.52 2.46+0.51 2.84+0.59 2.81+0.60 2.84+0.58 
F V (%) 116+24 118+27 104+24 113+21 114+24 116+23 
F VIII (%) 98+41 88+25 87+18 86+17 99+17 93+22 
FIX (%) 47+13 60+18 73+17 85+14 85+17 95+19 
FXI (%) 59+10 69+26 85+20 94+21 84+13 89+19 
D-dimer (ng/mL) 495 (85-1200) 420 (90-1100) 292 (130-950) 280 (80-2100) 284+124 233+157 

These data suggest that, at least in the described technical conditions, most coagulation test results are highly dependent on age, mainly during the first year of life, and that age-specific reference ranges must be used to ensure proper evaluation of coagulation in children.

Disclosures:

No relevant conflicts of interest to declare.

Author notes

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