Tissue-inhibitors of metalloproteinase-1 and vascular-endothelial growth-factor in severe haemophilia A children on low dose prophylactic recombinant factor VIII: Relation to subclinical arthropathy.
Biomarkers
/ blood
Case-Control Studies
Child
Child, Preschool
Cross-Sectional Studies
Early Diagnosis
Factor VIII
/ therapeutic use
Hemophilia A
/ blood
Humans
Joint Diseases
/ diagnostic imaging
Magnetic Resonance Imaging
/ methods
Male
Sensitivity and Specificity
Severity of Illness Index
Synovitis
/ diagnosis
Tissue Inhibitor of Metalloproteinase-1
/ blood
Vascular Endothelial Growth Factor A
/ blood
MRI joint score
arthropathy
inflammatory markers
severe haemophilia A
Journal
Haemophilia : the official journal of the World Federation of Hemophilia
ISSN: 1365-2516
Titre abrégé: Haemophilia
Pays: England
ID NLM: 9442916
Informations de publication
Date de publication:
Jul 2020
Jul 2020
Historique:
received:
03
03
2020
revised:
22
04
2020
accepted:
29
04
2020
pubmed:
24
5
2020
medline:
20
5
2021
entrez:
24
5
2020
Statut:
ppublish
Résumé
Subclinical synovitis occur long before clinical haemophilic arthropathy (HA). New biomarkers are needed for early detection of HA. To compare the levels of tissue inhibitors of metalloproteinase-1 (TIMP-1) and vascular endothelial growth factor (VEGF)in severe haemophilia A boys on prophylaxis and on-demand therapy to healthy boys and correlate them with the haemophilia joint health score (HJHS) & the Denver magnetic resonance imaging (MRI) scale; hence, determine their values in early detection of HA. Haemophilia joint health score, serum TIMP-1, VEGF and Denver MRI score were assessed in 50 boys with severe haemophilia A (31 on prophylactic factor VIII therapy (62%) with a dose of 15 IU/kg/twice weekly) and 50 age-matched healthy boys. Boys with severe haemophilia A had significantly higher TIMP-1 240 ng/mL, SD200-350 (P < .001) and VEGF 600 pg/mL, SD400-1100 (P < .001). Their mean HJHS was 4.5 ± 3.0 (0-11) and their mean Denver MRI score was 5.55 ± 1.6 (2.00-8.00). A significant positive correlation was found between TIMP-1 and VEGF (P < .001), BMI Z-score (P = .029), HJHS (P = .041)and total MRI score (<.001). Significant correlations were found between VEGF and age (P < .001), HJHS (P = .003) and total MRI score (P < .001). Boys with severe haemophilia A on prophylaxis therapy had significantly lower HJHS (P = .021), VEGF (P < .001), TIMP-1 (P = .002) and total MRI score (P = .021) than those on on-demand therapy. Receiver operating characteristic curve, defined a cut-off value of 160 ng/mL for TIMP-1 with a sensitivity of 90% and specificity of 60% and that of 350 pg/mL for VEGF with a sensitivity of 78% and specificity of 88% for discrimination between severe haemophilia A and healthy boys. Vascular endothelial growth factor and TIMP-1 can be used for early detection of HA. Further prospective studies should include larger study populations. In addition, studies should address the role of various anti-VEGFs as potential therapy for HA and their impact on prevention and treatment of HA.
Sections du résumé
BACKGROUND
BACKGROUND
Subclinical synovitis occur long before clinical haemophilic arthropathy (HA). New biomarkers are needed for early detection of HA.
AIM
OBJECTIVE
To compare the levels of tissue inhibitors of metalloproteinase-1 (TIMP-1) and vascular endothelial growth factor (VEGF)in severe haemophilia A boys on prophylaxis and on-demand therapy to healthy boys and correlate them with the haemophilia joint health score (HJHS) & the Denver magnetic resonance imaging (MRI) scale; hence, determine their values in early detection of HA.
METHODS
METHODS
Haemophilia joint health score, serum TIMP-1, VEGF and Denver MRI score were assessed in 50 boys with severe haemophilia A (31 on prophylactic factor VIII therapy (62%) with a dose of 15 IU/kg/twice weekly) and 50 age-matched healthy boys.
RESULTS
RESULTS
Boys with severe haemophilia A had significantly higher TIMP-1 240 ng/mL, SD200-350 (P < .001) and VEGF 600 pg/mL, SD400-1100 (P < .001). Their mean HJHS was 4.5 ± 3.0 (0-11) and their mean Denver MRI score was 5.55 ± 1.6 (2.00-8.00). A significant positive correlation was found between TIMP-1 and VEGF (P < .001), BMI Z-score (P = .029), HJHS (P = .041)and total MRI score (<.001). Significant correlations were found between VEGF and age (P < .001), HJHS (P = .003) and total MRI score (P < .001). Boys with severe haemophilia A on prophylaxis therapy had significantly lower HJHS (P = .021), VEGF (P < .001), TIMP-1 (P = .002) and total MRI score (P = .021) than those on on-demand therapy. Receiver operating characteristic curve, defined a cut-off value of 160 ng/mL for TIMP-1 with a sensitivity of 90% and specificity of 60% and that of 350 pg/mL for VEGF with a sensitivity of 78% and specificity of 88% for discrimination between severe haemophilia A and healthy boys.
CONCLUSION
CONCLUSIONS
Vascular endothelial growth factor and TIMP-1 can be used for early detection of HA. Further prospective studies should include larger study populations. In addition, studies should address the role of various anti-VEGFs as potential therapy for HA and their impact on prevention and treatment of HA.
Substances chimiques
Biomarkers
0
Tissue Inhibitor of Metalloproteinase-1
0
Vascular Endothelial Growth Factor A
0
Factor VIII
9001-27-8
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
607-614Informations de copyright
© 2020 John Wiley & Sons Ltd.
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