Abstract Number: PB0909
Meeting: ISTH 2021 Congress
Theme: Platelet Disorders, von Willebrand Disease and Thrombotic Microangiopathies » von Willebrand Factor Biology
Background: Age-specific differences in the concentration and function of several haemostatic proteins have been investigated previously and are encompassed under the concept of Developmental Haemostasis. However, few studies have investigated the effect of age and development on von Willebrand Factor (vWF) and its multimers. This is critical for accurate diagnosis and management of neonates and children with haematological complications, such as von Willebrand disorders.
Aims: To investigate age-specific changes in vWF and its multimers in a healthy population.
Methods: Blood samples were obtained via clean venepuncture from 20 healthy neonates and 60 healthy children undergoing elective surgery (e.g. circumcision) and citrated plasma was stored for batch testing. vWF concentration and activity were measured using the STA R Max® analyser and Stago reagents, STA® vWF antigen (vWF:Ag) and STA® Ristocetin cofactor activity (vWF:RCo) (Diagnostica Stago, France). vWF multimers were analysed using the Hydragel 11 vWF Multimer assay (Sebia, France). Results are expressed as mean with 95% confidence intervals and were analysed using an one-way ANOVA followed by Dunnett’s test to correct for multiple comparisons.
Results: Mean values and reference intervals according to age are presented in Table 1. The mean values for vWF low molecular weight multimer (lmwm) and vWF intermediate molecular weight multimer (imwm) differ significantly between neonates and adults.
| Neonates (h) | ≤ 2 years | >2 – 5 years | 6 – 10 years | 11 – 17 years | Adults | |
|---|---|---|---|---|---|---|
| subjects (n) median age age range sex |
20 47.8 24 to 96 10 M/10 F |
22 0.9 0 to 1 18 M/4 F |
11 3.5 2 to 4 5 M/6 F |
8 9.5 9 to 10 5 M/3 F |
19 13.9 11 to 17 10 M/9 F |
20 32.7 20 to 54 7 M/13 F |
| vWF:RCo mean 95% CI |
102.1 83.1 – 121.0 |
74.0 60.7 – 87.2 |
88.9 71.5 – 106.3 |
86.1 68.3 – 103.9 |
97.2 81.2 – 113.2 |
92.7 78.1 – 107.3 |
| vWF:Ag mean 95% CI |
112.6 96.3 – 128.9 |
83.8 71.0 – 96.5 |
98.8 82.2 – 115.4 |
91.3 70.2 – 112.3 |
89.8 68.9 – 110.5 |
101.9 88.6 – 115.2 |
| vWF lmwm mean 95% CI |
19.9* 17.1 – 22.7 |
17.7 15.7 – 19.7 |
18.3 14.5 – 22.1 |
15.5 13.9 – 17.1 |
15.4 12.7 – 18.1 |
15.5 14.0 – 17.0 |
| vWF imwm mean 95% CI |
27.5* 25.5 – 29.6 |
27.7* 26.5 – 28.8 |
26.9* 24.7 – 29.1 |
30.5 28.3 – 32.7 |
28.4 26.9 – 29.8 |
30.5 29.1 – 31.8 |
| vWF hmwm mean 95% CI |
52.6 48.3 – 56.8 |
54.6 52.6 – 56.7 |
54.8 49.7 – 59.8 |
54.0 51.4 – 56.6 |
56.2 53.1 – 59.3 |
54.0 51.8 – 56.3 |
| * P-value significantly different from adults (p=<0.05). h=hours | ||||||
Patient demographic data and mean values with age-specific reference ranges for vWF ristocetin cofactor activity (vWF:RCo), vWF antigen (vWF:Ag), vWF low molecular weight multimer (lmwm), vWF intermediate molecular weight multimer (imwm) and vWF high molecular weight multimer (hmwm). Test results are expressed as percentage (%).
Conclusions: This study confirms that vWF multimers vary significantly with age, emphasising the importance of developing age-specific reference ranges, to correctly diagnose neonates and children with haematological complications. Our findings highlight that age-specific differences that exist physiologically are not detected using less sensitive measures that, in this case, do not account for the specific forms of the VWF multimers. Our findings are different to previously published work, potentially related to differences in neonatal subjects (gestation and health status) or methodological differences. Further studies are required to establish a gold standard for vWF multimer testing.
To cite this abstract in AMA style:
Letunica N, Van Den Helm S, Barton R, Karlaftis V, Monagle P, VI. Age-specific Changes in von Willebrand Factor Multimers in Healthy Children and Adults [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 1). https://abstracts.isth.org/abstract/age-specific-changes-in-von-willebrand-factor-multimers-in-healthy-children-and-adults/. Accessed September 24, 2021.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/age-specific-changes-in-von-willebrand-factor-multimers-in-healthy-children-and-adults/