TY - JOUR
T1 - ADAMTS13 activity, high VWF and FVIII levels in the pathogenesis of deep vein thrombosis
AU - Pagliari, Maria Teresa
AU - Boscarino, Marco
AU - Cairo, Andrea
AU - Mancini, Ilaria
AU - Martinelli, Ida
AU - Bucciarelli, Paolo
AU - Rossi, Federica
AU - Rosendaal, Frits Richard
AU - Peyvandi, Flora
N1 - Funding Information:
This project was supported by the Italian Ministry of Health – Grant No. GR-2011-02351977 awarded to M.T. Pagliari. This work was partially supported by the Italian Ministry of Health - Bando Ricerca Corrente 2020 .
Publisher Copyright:
© 2020 Elsevier Ltd
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2021/1
Y1 - 2021/1
N2 - Background: Deep vein thrombosis (DVT) is a common multi-factorial disease with a partially understood aetiology. Although the roles of high factor (F)VIII and von Willebrand factor (VWF) levels are recognized, that of ADAMTS13 is still unclear. Aim: To assess the association between ADAMTS13 activity levels, VWF antigen (VWF:Ag) and FVIII coagulant activity (FVIII:C) levels and DVT. Materials and methods: 365 Italian DVT patients and 292 age- and sex-matched controls were considered. Plasma ADAMTS13 activity was measured using FRETS-VWF73 assay. VWF:Ag and FVIII:C were measured using immunoassay and one-stage clotting assay (ACL TOP analyzer), respectively. Quartile analyses were performed to evaluate the individual association between ADAMTS13 activity, VWF:Ag, FVIII:C and DVT. The combined effect of high VWF levels (> 4th quartile) and low ADAMTS13 levels (< 1st quartile) was evaluated using binary variables. All models were age- and sex-adjusted. Estimated risks were reported as Odds ratio (OR) with 95% confidence intervals (CI). Results: ADAMTS13 activity was lower in DVT patients (94% vs. 98% of controls). Patients with an ADAMTS13 activity <1st quartile (86%) showed a 1.6-fold increased risk of DVT (95%CI, 1.05–2.55). The combination of low ADAMTS13 activity and high VWF:Ag levels was associated with a 15–fold increased risk (95%CI, 7.80–33.80). VWF:Ag and FVIII:C were associated to DVT with a dose-response relationship. Conclusions: ADAMTS13 activity < 86% was associated with a moderate risk of DVT. The co-presence of low ADAMTS13 activity and high VWF levels resulted in a strong synergistic effect on DVT risk. The association of VWF:Ag and FVIII:C with DVT was confirmed.
AB - Background: Deep vein thrombosis (DVT) is a common multi-factorial disease with a partially understood aetiology. Although the roles of high factor (F)VIII and von Willebrand factor (VWF) levels are recognized, that of ADAMTS13 is still unclear. Aim: To assess the association between ADAMTS13 activity levels, VWF antigen (VWF:Ag) and FVIII coagulant activity (FVIII:C) levels and DVT. Materials and methods: 365 Italian DVT patients and 292 age- and sex-matched controls were considered. Plasma ADAMTS13 activity was measured using FRETS-VWF73 assay. VWF:Ag and FVIII:C were measured using immunoassay and one-stage clotting assay (ACL TOP analyzer), respectively. Quartile analyses were performed to evaluate the individual association between ADAMTS13 activity, VWF:Ag, FVIII:C and DVT. The combined effect of high VWF levels (> 4th quartile) and low ADAMTS13 levels (< 1st quartile) was evaluated using binary variables. All models were age- and sex-adjusted. Estimated risks were reported as Odds ratio (OR) with 95% confidence intervals (CI). Results: ADAMTS13 activity was lower in DVT patients (94% vs. 98% of controls). Patients with an ADAMTS13 activity <1st quartile (86%) showed a 1.6-fold increased risk of DVT (95%CI, 1.05–2.55). The combination of low ADAMTS13 activity and high VWF:Ag levels was associated with a 15–fold increased risk (95%CI, 7.80–33.80). VWF:Ag and FVIII:C were associated to DVT with a dose-response relationship. Conclusions: ADAMTS13 activity < 86% was associated with a moderate risk of DVT. The co-presence of low ADAMTS13 activity and high VWF levels resulted in a strong synergistic effect on DVT risk. The association of VWF:Ag and FVIII:C with DVT was confirmed.
KW - ADAMTS13 human protein
KW - Deep vein thrombosis
KW - Factor VIII
KW - Risk factor
KW - von Willebrand factor
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U2 - 10.1016/j.thromres.2020.10.037
DO - 10.1016/j.thromres.2020.10.037
M3 - Article
AN - SCOPUS:85096197872
VL - 197
SP - 132
EP - 137
JO - Thrombosis Research
JF - Thrombosis Research
SN - 0049-3848
ER -