R4208

Altered Coagulation Parameters and D-Dimer Measurements in Sepsis are useful in Scoring the Risk Stratification

 

Divya Joshi1, Emily Bontekoe1, Matthew Rondina2, Elizabeth Middleton2, Antoinette Blair2, Fakiha Siddiqui1, Debra Hoppensteadt1, Jawed Fareed1
1Loyola University Medical Center, 2University of Utah School of Medicine

Background: Sepsis is characterized by a simultaneous activation of inflammation and hemostasis in response to microbial infection. This systemic inflammatory response is due to the release of pro-inflammatory cytokines, pro-coagulants and adhesion molecules from immune cells and/or damaged endothelial tissue. Simultaneous activation of coagulation and fibrinolysis eventually leads to consumption coagulopathy and severe vascular dysfunction. This study was designed to profile coagulation parameters in a defined clinically confirmed sepsis population in conjunction with an IRB approved clinical trial.

Materials & Methods: Plasma samples from septic shock patients (n=78) were collected in citrated tubes within 72 hours of ICU admission under an IRB approved protocol in conjunction with ongoing trial at the University of Utah and Veteran’s Affair FFC Health Care System VAMC. Normal controls were comprised of commercially available 25 male and 25 female samples of citrated plasma (George King Biomedical, Overland Park, Kansas City). D-Dimer was measured using a commercially available sandwich ELISA methods. PT/INR, aPTT and fibrinogen measurements were based on clot-based assays. All results were compiled as mean ± SD and SEM.

Results: D-Dimer levels were markedly increase in sepsis patients (23-fold) in comparison to control. Significant elevation of clotting parameters such as PT/INR (2.0-fold), aPTT (2.5-fold) and fibrinogen (2.0-fold) was noted in the sepsis patients in comparison to controls. These differences were significant (p value ≤0.0009) for all of the parameters except fibrinogen (p value 0.4694). There was no correlation between D-dimer and fibrinogen in the sepsis patients.

Summary & Conclusion: In comparison to the control group, the sepsis patients showed wide variations in all of the parameters investigated in this study. The marked prolongation of PT and aPTT are suggestive of both the extrinsic and intrinsic pathway defects and consumption of clotting factors. The aPTT data showed wider scatter in comparison to PT data. The fibrinogen levels were also elevated and nearly 1/3 of the patients showed >1000 mg/dL levels. Marked elevation of D-Dimer is indicative of endogenous fibrin formation and its consumption consistent with activation of secondary fibrinolysis. These results further underscore the importance of including the clotting parameters and D-dimer in scoring the coagulopathies associated with sepsis such as disseminated intravascular coagulation.