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Recombinant Human Soluble Thrombomodulin in Patients With Sepsis-Associated Coagulopathy

Recombinant Human Soluble Thrombomodulin in Patients With Sepsis-Associated Coagulopathy Opinion EDITORIAL Recombinant Human Soluble Thrombomodulin in Patients With Sepsis-Associated Coagulopathy Another Negative Sepsis Trial? Tom van der Poll, MD, PhD Sepsis is a heterogeneous syndrome caused by an unbal- central coagulation protease thrombin. Thrombin com- anced host response to an infection resulting in organ plexed with thrombomodulin cannot cleave fibrinogen or dysfunction. Sepsis is associated with activation of the activate factor V or factor XIII but rather accelerates the con- coagulation system, and 30% to 60% of patients have dis- version from protein C to APC, a potent anticoagulant by vir- seminated intravascular tue of its capacity to inactivate clotting factors Va and VIIIa. coagulation (DIC). Fulmi- Thus, soluble human recombinant thrombomodulin has 2 Related article page 1993 nant DIC is characterized by` anticoagulant modes of action: direct, through inhibition of activation of the coagulation system combined with an the procoagulant activity of thrombin, and indirect by pro- impaired function of endogenous anticoagulant mechanisms moting protein C activation. resulting in widespread microvascular thrombosis and con- In addition, after binding by thrombomodulin, throm- current hemorrhage secondary to consumption of clotting bin is unable to cleave protease-activated receptor-1 or -3 on 3,4 factors and platelets. Strong and bimodal interactions exist http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA American Medical Association

Recombinant Human Soluble Thrombomodulin in Patients With Sepsis-Associated Coagulopathy

JAMA , Volume 321 (20) – May 28, 2019

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Publisher
American Medical Association
Copyright
Copyright 2019 American Medical Association. All Rights Reserved.
ISSN
0098-7484
eISSN
1538-3598
DOI
10.1001/jama.2019.5792
Publisher site
See Article on Publisher Site

Abstract

Opinion EDITORIAL Recombinant Human Soluble Thrombomodulin in Patients With Sepsis-Associated Coagulopathy Another Negative Sepsis Trial? Tom van der Poll, MD, PhD Sepsis is a heterogeneous syndrome caused by an unbal- central coagulation protease thrombin. Thrombin com- anced host response to an infection resulting in organ plexed with thrombomodulin cannot cleave fibrinogen or dysfunction. Sepsis is associated with activation of the activate factor V or factor XIII but rather accelerates the con- coagulation system, and 30% to 60% of patients have dis- version from protein C to APC, a potent anticoagulant by vir- seminated intravascular tue of its capacity to inactivate clotting factors Va and VIIIa. coagulation (DIC). Fulmi- Thus, soluble human recombinant thrombomodulin has 2 Related article page 1993 nant DIC is characterized by` anticoagulant modes of action: direct, through inhibition of activation of the coagulation system combined with an the procoagulant activity of thrombin, and indirect by pro- impaired function of endogenous anticoagulant mechanisms moting protein C activation. resulting in widespread microvascular thrombosis and con- In addition, after binding by thrombomodulin, throm- current hemorrhage secondary to consumption of clotting bin is unable to cleave protease-activated receptor-1 or -3 on 3,4 factors and platelets. Strong and bimodal interactions exist

Journal

JAMAAmerican Medical Association

Published: May 28, 2019

References