Systemic Platelet Dysfunction Is the Result of Local Dysregulated Coagulation and Platelet Activation in the Brain in a Rat Model of Isolated Traumatic Brain Injury

Abstract

Coagulopathy after severe traumatic brain injury (TBI) has been extensively reported. Clinical studies have identified a strong relationship between diminished platelet-rich thrombus formation, responsiveness to adenosine diphosphate agonism, and severity of TBI. The mechanisms that lead to platelet dysfunction in the acute response to TBI are poorly understood. The development of a rodent model of TBI that mimics the coagulopathy observed clinically has recently been reported. Using immunohistochemical techniques and thromboelastography platelet mapping, the current study demonstrated that the expression of coagulation (tissue factor and fibrin) and platelet activation (P-selectin) markers in the injured brain paralleled the alteration in systemic platelet responsiveness to the agonists, adenosine diphosphate and arachodonic acid. Results of this study demonstrate that local procoagulant changes in the injured brain have profound effects on systemic platelet function.

Microparticles impact coagulation after traumatic brain injury

“…In addition, similar to our murine study, other human studies have shown that platelet contribution to clot strength steadily decreases over the 72 h after trauma, with a resulting increase in fibrinogen contribution [31]. Animal models have investigated altered platelet function after head injury [36]; however, our study is the first to demonstrate similar temporal changes in coagulation, specifically the platelet contribution to clot strength, after TBI using thromboelastometry in a murine model. With these new data, we are closer to both understanding the mechanisms behind coagulation changes after TBI and also to identifying appropriate therapeutic targets to prevent thromboembolic complications.…”

Deciphering glycomics and neuroproteomic alterations in experimental traumatic brain injury: Comparative analysis of aspirin and clopidogrel treatment

“…This has been shown by Davis et al. and Ploplis et al.’s work where they reported that a significant decrease in the platelet thrombotic activity is noticed in responses to ADP and arachidonic acid in TBI rat research models when compared to controls .…”

Coagulopathy induced by traumatic brain injury: systemic manifestation of a localized injury

“…Platelets from TBI patients and those from rats and pigs subjected to experimental TBI have moderately low counts, are often activated, produce MVs, and express procoagulant activity. [55][56][57] Pulmonary and cerebral microthrombosis is also reported in animal models of TBI. 58 The cerebral microthrombi are mostly detected in the pericontusion cortex 59,60 and contain not only fibrin 61 but also platelets 58,60 and von Willebrand factor.…”