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Age-specific Changes in von Willebrand Factor Multimers in Healthy Children and Adults

N. Letunica1, S. Van Den Helm1, R. Barton1,2,3, V. Karlaftis1,2, P. Monagle3,2,1, V. Ignjatovic2,1.

1Haematology Research Laboratory, Murdoch Children's Research Institute, Melbourne, Australia, 2Department of Paediatrics, The University of Melbourne, Melbourne, Australia, 3Department of Clinical Haematology, Royal Children's Hospital, Melbourne, Australia

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 2). https://abstracts.isth.org/abstract/age-specific-changes-in-von-willebrand-factor-multimers-in-healthy-children-and-adults/. Accessed September 22, 2023.

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