ECE2016 Eposter Presentations Adrenal cortex (to include Cushing's) (85 abstracts)
Pro-coagulant imbalance in patients with Cushing disease detected by thrombin generation assay is associated with increased levels of neutrophil extracellular trap-related factors
Elisa Verrua 1 , Elisa Sala 1 , Elena Malchiodi 1 , Emanuele Ferrante 1 , Giorgio Arnaldi 2 , Laura Trementino 2 , Armando Tripodi 3 , Fabrizio Semeraro 4 , Concetta T Ammollo 4 , Mario Colucci 3 , Lidia Padovan 3 , Veena Chantarangkul 3 , Flora Peyvandi 5 & Giovanna Mantovani 1
1Unit of Endocrinology and Diabetology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Department of Clinical Sciences and Community Health, University of Milan, Milano, Italy; 2Clinica di Endocrinologia e Malattie del Metabolismo, Ospedali Riuniti di Ancona, Ancona, Italy; 3Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Department of Clinical Sciences and Community Health, University of Milan, Milano, Italy; 4Department of Biomedical Sciences and Human Oncology, Aldo Moro University, Bari, Italy; 5Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Pathophysiology and Transplantation, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Milano, Italy.
Patients with Cushing disease (CD) are at increased risk of venous thromboembolism (VTE). It was surmised, but not conclusively shown that the risk is related to plasma hypercoagulability secondary to the effect of glucocorticoids. This study aimed at investigating the thrombin-forming potential of patients with CD in the presence of a functioning protein C system by adding its main physiological activator, thrombomodulin. Under these experimental conditions, which mimic closely the in vivo situation, we observed significantly enhanced thrombin-generation in patients with CD, as shown by the modification of thrombin generation parameters (i.e., shortened lag-time and time-to-peak, increased thrombin-peak and endogenous-thrombin-potential (ETP)). Moreover, the ETP ratio (with/without thrombomodulin), recognized as an index of hypercoagulability, was increased in patients as compared to controls, indicating that patients with CD are resistant to the anticoagulant action of thrombomodulin. We attempted to explain such hypercoagulability by measuring both pro- and anticoagulants factors and some other non-coagulation parameters (i.e., neutrophil extracellular traps (NET), recently associated with the risk of VTE and/or increased procoagulant imbalance. We show that the hypercoagulability detected by thrombin-generation in patients with CD is associated with increased levels of factor VIII and NET-related variables. Whether this plasma hypercoagulability can entirely explain the occurrence of VTE (first event or recurrence) in patients with CD should be investigated by ad hoc clinical trials. However, until these studies will be available the evidence for the hypercoagulability supports the concept that patients with CD are candidates for antithrombotic prophylaxis.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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