ABSTRACT
B Introduction: b Severe COVID-19 has been associated with aberrant coagulation factor activities, particularly in patients with a thrombotic event (TE). This study evaluates a point-of-care (POC), functional, clot-time-based coagulation test to detect the anticoagulant effect of therapeutic unfractionated heparin (UFH) in hospitalized SARS-CoV-2-positive patients who developed a TE. [Extracted from the article] Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)
ABSTRACT
Coagulopathy is associated with both inflammation and infection, including infections with novel severe acute respiratory syndrome coronavirus-2, the causative agent Coagulopathy is associated with both inflammation and infection, including infection with novel severe acute respiratory syndrome coronavirus-2, the causative agent of COVID-19. Clot formation is promoted via cAMP-mediated secretion of von Willebrand factor (vWF), which fine-tunes the process of hemostasis. The exchange protein directly activated by cAMP (EPAC) is a ubiquitously expressed intracellular cAMP receptor that plays a regulatory role in suppressing inflammation. To assess whether EPAC could regulate vWF release during inflammation, we utilized our EPAC1-null mouse model and revealed increased secretion of vWF in endotoxemic mice in the absence of the EPAC1 gene. Pharmacological inhibition of EPAC1 in vitro mimicked the EPAC1-/- phenotype. In addition, EPAC1 regulated tumor necrosis factor-α-triggered vWF secretion from human umbilical vein endothelial cells in a manner dependent upon inflammatory effector molecules PI3K and endothelial nitric oxide synthase. Furthermore, EPAC1 activation reduced inflammation-triggered vWF release, both in vivo and in vitro. Our data delineate a novel regulatory role for EPAC1 in vWF secretion and shed light on the potential development of new strategies to control thrombosis during inflammation.