VPB0527 - Experimental model of rodent disseminated intravascular coagulation

Background: Sepsis is a syndrome characterized by a deregulated systemic inflammatory response of the organism during infectious processes. The systemic inflammation promotes a transition from an antithrombotic and anticoagulant endothelial phenotype that limits platelet adhesion and maintains hemostasis, to a highly adhesive phenotype characterized by increased expression of pro adhesive and procoagulant proteins. During its progression to severe sepsis, coagulation, and fibrinolysis, giving rise to a syndrome characterized by intravascular activation of coagulation without specific localization called disseminated intravascular coagulation (DIC). The processes described above are associated with microcirculation dysfunction, generating hypoperfusion, reducing the supply of oxygen and nutrients to the different tissues, causing organ failure, and finally death. Currently, DIC has become a very difficult to treat syndrome faced by patients and the medical team. This is directly related to the fact that DIC mortality has remained at very high levels over the last few years.

Aims: To generate a highly representative and rapid model of disseminated intravascular coagulation.

Methods: Male Sprague-Dawley rats aged 8 weeks were anesthetized with isoflurane and by intravenous infusion of LPS (30 mg/kg/hr serotype O55:B5) (n=8) or the same volume of saline (n = 3). At 3 hours post-infusion blood were collected, it was determined (I) prothrombin time (PT), (II) partial thromboplastin time (APTT), (III) fibrinogen levels (Fib), (IV) platelet count, (V) D-dimer and (VI) percentage of perfused microvasculature by Sidestream Dark Field (SDF). The results are presented as ±SD. Significant differences were assessed by the t-student test (Mann-Whitney).

Results: LPS treated rats exhibited a decrease in platelet count, plasma fibrinogen and percentage of perfused vessels. On the other hand, we observed an increase in prothrombin time (PT), partial thromboplastin (APTT) and D-Dimer in plasma.

Conclusion(s): This methodology will allow studying in an easy and fast way the alterations of hemostasis produced by systemic inflammation.