Clinical Trial: Thrombin Generation and Thromboelastography in Non-overt DIC
Study Status: Terminated
Recruit Status: Terminated
Study Type: Observational
Official Title: Use of Whole Blood and Cell-rich Coagulation Assays for the Detection of Non-Overt DIC in Sepsis
Brief Summary: Sepsis is the 13th most common cause of death in the United States, causing approximately 210,000 deaths per year. Once DIC has developed, irreversible organ injury has already occurred and the mortality rate is 70%. Inhibition of systemic coagulation with activated protein C concentrate has been the only therapy for sepsis introduced in the past several decades which has improved outcomes. Elucidation of the coagulopathic mechanisms early in the development of DIC may give rise to targeted therapies and strategies for early intervention. We hypothesize that an increase in endogenous thrombin potential precedes the development of overt DIC by a clinically significant time period. Our primary objective is to determine if endogenous thrombin potential (ETP) measured at first diagnosis of sepsis prior to the onset of DIC and organ failure is predictive of overt DIC and/or poor outcome. We will compare ETP to standard coagulation assays and the clinical assessment of DIC using the ISTH criteria for overt DIC. A secondary objective of this study is to determine if host coagulation variables predispose to the development of DIC and poor clinical outcome during sepsis.
Detailed Summary:
Activation of the coagulation system occurs early in patients with sepsis, although clinically overt disseminated intravascular coagulation (DIC) is identified in only a minority of patients with severe sepsis. Uncontrolled activation of the coagulation system may contribute to the pathophysiology of multiple organ failure and the subsequent morbidity and mortality of sepsis. Identification of risk factors predicting progression to severe sepsis and DIC has been elusive. We propose that whole blood and cell-rich coagulation assays will offer improved sensitivity to both the procoagulant and anti-coagulant changes which occur early in sepsis and will improve recognition of non-overt DIC. Future studies will address whether these assays have sufficiently high predictive value to identify subgroups of patients who could benefit from early intervention.
Specific Aims:
- We hypothesize that increased thrombin generation will precede development of overt DIC by a clinically significant time period. Our primary objective is to determine if endogenous thrombin potential measured at first diagnosis of sepsis prior to the onset of DIC and organ failure is predictive of overt DIC.
- There is significant individual variation among the healthy population in endogenous thrombin generation due to known and unknown polymorphisms within coagulation proteins. We predict that host variables in thrombin generation will contribute to susceptibility to DIC and poor outcome during sepsis. A secondary objective of this study is to determine if host coagulation variables predispose to the morbidity and mortality associated with sepsis.
Experimental Design and Methods
The study des
Sponsor: The University of Texas Health Science Center, Houston
Current Primary Outcome: Mortality [ Time Frame: 28 days ]
Original Primary Outcome:
Current Secondary Outcome:
Original Secondary Outcome:
Information By: The University of Texas Health Science Center, Houston
Dates:
Date Received: March 3, 2006
Date Started: October 2006
Date Completion:
Last Updated: February 6, 2013
Last Verified: February 2013
