E. F. Midura1, C. C. Caldwell1, M. D. Goodman1 1University Of Cincinnati,Cincinnati, OH, USA
Introduction: Traumatic brain injury (TBI) is known to result in a sub-acute, post-traumatic, hypercoagulable state, however the pathophysiology behind this alteration is poorly understood. Platelet-based contribution to clot is known to decrease over time following trauma and microparticles have also been shown to be changed after TBI. Whether platelets and microparticles interact to influence coagulation has not been determined. Using a murine model, we hypothesized that microparticle and platelet contributions to clot formation would be altered after TBI.
Methods: An established weight-drop model was used to induce TBI in anesthetized mice. Sham mice underwent anesthesia without TBI. Blood samples were collected 24 hours after injury, and circulating microparticle and platelet counts determined. Thromboelastometry (ROTEM) was used to evaluate changes in hemostasis. ROTEM was then repeated on sham and post-injury blood treated with normalized concentrations of microparticles isolated from sham mice (sham microparticles), TBI mice (TBI microparticles), or microparticle-free saline. A microparticle pro-coagulant assay was used to compare activity in sham and TBI mice.
Results: One day after TBI, we observed a decrease in overall microparticle concentrations (3.6 vs. 1.9 x 108 microparticles/ml, p < 0.001). Overall platelet counts did not change after injury. ROTEM demonstrated a reduced platelet contribution to hemostasis 24 hours after TBI compared to sham (62.9% vs. 48.0%, p < 0.01). When TBI microparticles were added to sham blood, a significant decrease in platelet contribution to clot was seen compared to saline (Figure 1). Conversely, when sham microparticles were added to blood from injured mice, there was a normalization of platelet contribution to clot formation when compared to saline (Figure 1). Furthermore, when microparticle pro-coagulant activity was assayed, TBI microparticles had increased activity compared to sham microparticles (3.28 vs. 1.72, p = 0.04).
Conclusion: Our data demonstrate that after TBI, 1) circulating microparticles are decreased, 2) platelet contribution to clot formation is decreased despite unchanged platelet count, and 3) TBI microparticles independently augment post-traumatic clot formation. Post-TBI microparticles may therefore be responsible for the altered platelet role in coagulation and the development of a post-traumatic hypercoagulable state.
