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Fibrin Strands Will Grow from Soluble Fibrin and Hang Up In an ex vivo Microcirculatory Viscoelastic Model: Is This a Major Cause of Covid-19 Associated Coagulopathy?
Bull, B.S.; Hay, K.L.; Herrmann, P.C. Fibrin Strands Will Grow from Soluble Fibrin and Hang Up in an In Vitro Microcirculatory Viscoelastic Model: Is This a Major Cause of COVID-19 Associated Coagulopathy? J. Clin. Med.2022, 11, 2084.
Bull, B.S.; Hay, K.L.; Herrmann, P.C. Fibrin Strands Will Grow from Soluble Fibrin and Hang Up in an In Vitro Microcirculatory Viscoelastic Model: Is This a Major Cause of COVID-19 Associated Coagulopathy? J. Clin. Med. 2022, 11, 2084.
Bull, B.S.; Hay, K.L.; Herrmann, P.C. Fibrin Strands Will Grow from Soluble Fibrin and Hang Up in an In Vitro Microcirculatory Viscoelastic Model: Is This a Major Cause of COVID-19 Associated Coagulopathy? J. Clin. Med.2022, 11, 2084.
Bull, B.S.; Hay, K.L.; Herrmann, P.C. Fibrin Strands Will Grow from Soluble Fibrin and Hang Up in an In Vitro Microcirculatory Viscoelastic Model: Is This a Major Cause of COVID-19 Associated Coagulopathy? J. Clin. Med. 2022, 11, 2084.
Abstract
Viscoelastic testing (VET) by both TEG and ROTEM has demonstrated hypercoagulability early in Covid Associated Coagulopathy (CAC). Additional VET studies demonstrated fibrinolytic shutdown late in a majority of severely ill Covid-19 patients with associated elevation of D-dimer. Elevated d-dimer confirms that coagulation, followed by fibrinolysis, has occurred. These findings imply that, during CAC, three enzymes—thrombin, Factor XIIIa and plasmin—must have acted in sequence. However, limitations in standard VET analyses preclude exploration of the earliest phases of clot induction, as well as clot formation and clot dissolution in flowing blood. Herein we describe a novel method illuminating aspects of this unexplored area. In addition, we created an ex vivo blood flow model in which the interactions of thrombin, Factor XIII and plasmin with fibrinogen can be studied, allowing determination of Soluble Fibrin (SF), the highly unstable form of fibrin that precedes the appearance of a visible clot. This model allows determination of the SF level at which fibrin microclots begin to form and the length of time the resulting microclots persist under normal fibrinolytic attack. In addition, the flow model allows exploration of the late fibrinolytic shutdown that VET has previously demonstrated in CAC through standard methodology.
Medicine and Pharmacology, Pathology and Pathobiology
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