tetano
Editor, Senior Moderator
J Thromb Haemost
. 2021 Jul 5.
doi: 10.1111/jth.15445. Online ahead of print.
Imbalanced of von Willebrand factor and ADAMTS13 axis is rather a biomarker of strong inflammation and endothelial damage than a cause of thrombotic process in critically-ill COVID-19 patients
Bérangère S Joly[SUP] 1 2 [/SUP], Michael Darmon[SUP] 3 [/SUP], Charlotte Dekimpe[SUP] 4 [/SUP], Thibault Dupont[SUP] 3 [/SUP], Guillaume Dumas[SUP] 3 [/SUP], Elise Yvin[SUP] 3 [/SUP], Nicolas Beranger[SUP] 1 2 [/SUP], Karen Vanhoorelbeke[SUP] 4 [/SUP], Elie Azoulay[SUP] 3 [/SUP], Agnès Veyradier[SUP] 1 2 [/SUP]
Affiliations
Abstract
Background: Critically ill patients with coronavirus disease 2019 (COVID-19) are prone to develop macrothrombosis and microthrombosis. COVID-19 has been reported to be rarely associated with thrombotic microangiopathies. ADAMTS13 severe deficiency, the hallmark of thrombotic thrombocytopenic purpura (TTP), induces the formation of platelet-unusually large von Willebrand factor (VWF) multimers microthrombi. In immune-mediated TTP, ADAMTS13 adopts specifically an open conformation. The VWF/ADAMTS13 couple may contribute to the microthrombi formation in pulmonary alveolar capillaries in COVID-19.
Objective: To investigate clinical features, hemostatic laboratory parameters, VWF/ADAMTS13 axis and ADAMTS13 conformation in critically ill COVID-19 patients at admission.
Methods and results: Among 53 critically ill COVID-19 patients enrolled between March 18 and May 9 2020 in a monocentric hospital, the median age was 59 years, the male-to-female ratio was 2.8/1. We reported 7 pulmonary embolisms and 15 deaths. Biological investigations showed increased fibrinogen and factor V levels, and strongly increased D-dimers correlated with mortality. No patient presented severe thrombocytopenia nor microangiopathic hemolytic anemia. An imbalance between high VWF antigen levels and normal or slightly decreased ADAMTS13 activity levels (strongly elevated VWF/ADAMTS13 ratio) was correlated with mortality. Three patients had a partial quantitative deficiency in ADAMTS13. We also reported a closed conformation of ADAMTS13 in all patients, reinforcing the specificity of an open conformation of ADAMTS13 as a hallmark of TTP.
Conclusion: We suggest that slightly decreased or normal ADAMTS13 activity and highly elevated VWF are rather biomarkers reflecting both the strong inflammation and the endothelial damage rather than drivers of the thrombotic process of COVID-19.
Keywords: ADAMTS13; ADAMTS13 conformation; COVID-19; thrombotic microangiopathy; von Willebrand factor.
. 2021 Jul 5.
doi: 10.1111/jth.15445. Online ahead of print.
Imbalanced of von Willebrand factor and ADAMTS13 axis is rather a biomarker of strong inflammation and endothelial damage than a cause of thrombotic process in critically-ill COVID-19 patients
Bérangère S Joly[SUP] 1 2 [/SUP], Michael Darmon[SUP] 3 [/SUP], Charlotte Dekimpe[SUP] 4 [/SUP], Thibault Dupont[SUP] 3 [/SUP], Guillaume Dumas[SUP] 3 [/SUP], Elise Yvin[SUP] 3 [/SUP], Nicolas Beranger[SUP] 1 2 [/SUP], Karen Vanhoorelbeke[SUP] 4 [/SUP], Elie Azoulay[SUP] 3 [/SUP], Agnès Veyradier[SUP] 1 2 [/SUP]
Affiliations
- PMID: 34219357
- DOI: 10.1111/jth.15445
Abstract
Background: Critically ill patients with coronavirus disease 2019 (COVID-19) are prone to develop macrothrombosis and microthrombosis. COVID-19 has been reported to be rarely associated with thrombotic microangiopathies. ADAMTS13 severe deficiency, the hallmark of thrombotic thrombocytopenic purpura (TTP), induces the formation of platelet-unusually large von Willebrand factor (VWF) multimers microthrombi. In immune-mediated TTP, ADAMTS13 adopts specifically an open conformation. The VWF/ADAMTS13 couple may contribute to the microthrombi formation in pulmonary alveolar capillaries in COVID-19.
Objective: To investigate clinical features, hemostatic laboratory parameters, VWF/ADAMTS13 axis and ADAMTS13 conformation in critically ill COVID-19 patients at admission.
Methods and results: Among 53 critically ill COVID-19 patients enrolled between March 18 and May 9 2020 in a monocentric hospital, the median age was 59 years, the male-to-female ratio was 2.8/1. We reported 7 pulmonary embolisms and 15 deaths. Biological investigations showed increased fibrinogen and factor V levels, and strongly increased D-dimers correlated with mortality. No patient presented severe thrombocytopenia nor microangiopathic hemolytic anemia. An imbalance between high VWF antigen levels and normal or slightly decreased ADAMTS13 activity levels (strongly elevated VWF/ADAMTS13 ratio) was correlated with mortality. Three patients had a partial quantitative deficiency in ADAMTS13. We also reported a closed conformation of ADAMTS13 in all patients, reinforcing the specificity of an open conformation of ADAMTS13 as a hallmark of TTP.
Conclusion: We suggest that slightly decreased or normal ADAMTS13 activity and highly elevated VWF are rather biomarkers reflecting both the strong inflammation and the endothelial damage rather than drivers of the thrombotic process of COVID-19.
Keywords: ADAMTS13; ADAMTS13 conformation; COVID-19; thrombotic microangiopathy; von Willebrand factor.