Microvesicles generated following traumatic brain injury induce platelet dysfunction via adenosine diphosphate receptor

Martin, Grace E.; Pugh, Amanda M.; Moran, Ryan; Veile, Rosalie; Friend, Lou Ann; Pritts, Timothy A.; Makley, Amy T.; Caldwell, Charles C.; Goodman, Michael D.

doi:10.1097/ta.0000000000002171

Cited by 17 publications

(9 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Certainly, some of these patients may demonstrate platelet counts deemed acceptable during an acute trauma resuscitation, but the lower MA seen by TEG highlights the important of adequate platelet resuscitation for dysfunction (and not simply for platelet count). Others have proposed a concept of platelet exhaustion in trauma as an etiology of platelet dysfunction (despite adequate number) [23,24]. Our work agrees with this concept of platelet exhaustion.…”

Section: Discussionsupporting

confidence: 90%

It is time for TEG in pediatric trauma: unveiling meaningful alterations in children who undergo massive transfusion

et al. 2021

View full text Add to dashboard Cite

Background Hemorrhage is the leading cause of preventable death in pediatric trauma patients. In adults, goal-directed thrombelastography (TEG) has been shown to reduce mortality when used to guide massive transfusion (MT) resuscitation. There remains a paucity of data on the utility of TEG in directing resuscitation of pediatric trauma patients. We hypothesize that abnormalities on admission TEG will differ in pediatric trauma patients who undergo MT, compared to those who do not. Methods Pediatric patients (≤ 18 years) who were highest level trauma activations at two trauma centers from 2015 to 2018 were analyzed. We included patients who had admission TEGs and excluded those who did not. Patients were stratified into two groups: those who received MT (> 40 cc/kg total blood product within 6 h of admission) and those who did not. We defined TEG abnormalities based on each institution's normative values and compared TEG abnormalities between the groups. Results Of 117 children included, 39 had MT. MT patients had higher injury severity scores (30 vs. 23, p = 0.0004), lactates levels (7.0 vs. 3.5, p < 0.001), base deficit levels ( − 12.2 vs. − 5.8, p < 0.001), and INR values (1.8 vs. 1.3, p < 0.001). MT patients had significantly shortened alpha-angles (35.9% vs. 15.4%, p = 0.023), maximum amplitude (MA) values (43.6% vs. 10.3%, p < 0.001), and significantly lower platelet counts (165 vs. 281, p < 0.001) compared to those who did not receive MT. There was no difference in the trends in R-time, LY30 (lysis or shutdown), or fibrinogen concentration between the groups. Logistic regression identified a decreased MA as a significant predictor for MT )] Conclusions Pediatric trauma patients who undergo MT are more likely to have lower alpha-angles and MA values, as well as lower platelet counts. These findings support the use of TEG to identify hemorrhaging pediatric trauma patients, who may benefit from cryoprecipitate and/or platelet transfusions. TEG provides real-time information on coagulation status, which may expedite the delivery of specific blood products during trauma resuscitation. Level of evidence: Level III Type of study: Retrospective comparative study.

show abstract

Section: Discussionsupporting

confidence: 90%

It is time for TEG in pediatric trauma: unveiling meaningful alterations in children who undergo massive transfusion

et al. 2021

View full text Add to dashboard Cite

show abstract

“… 14 , 29 Prior research has established the time course of coagulopathy in experimental closed‐skull TBI. There is an immediate hypocoagulation phase 30 followed by a period of hypercoagulation. 31 This period of hypercoagulability is the focus of this study, highlighting our selection of 6‐hour and 24‐hour time points.…”

Section: Resultsmentioning

confidence: 99%

Tissue factor release following traumatic brain injury drives thrombin generation

Hubbard

Sim

Saatman

et al. 2022

Research and Practice in Thrombosis and Haemostasis

View full text Add to dashboard Cite

Background Traumatic brain injury (TBI) results in neurovascular damage that initiates intrinsic mechanisms of hypercoagulation, which can contribute to the development of life‐threatening complications, such as coagulopathy and delayed thrombosis. Clinical studies have hypothesized that tissue factor (TF) induces hypercoagulability after TBI; however, none have directly shown this relationship. Objectives In the current study, we took a stepwise approach to understand what factors are driving thrombin generation following experimental TBI. Methods We employed the contusion‐producing controlled cortical impact (CCI) model and the diffuse closed head injury (CHI) model to investigate these mechanisms as a function of injury severity and modality. Whole blood was collected at 6 hours and 24 hours after injury, and platelet‐poor plasma was used to measure thrombin generation and extracellular vesicle (EV) TF. Results We found that plasma thrombin generation, dependent on TF present in the plasma, was greater in CCI‐injured animals compared to sham at both 6 hours (120.4 ± 36.9 vs 0.0 ± 0.0 nM*min endogenous thrombin potential) and 24 hours (131.0 ± 34.0 vs 32.1 ± 20.6 nM*min) after injury. This was accompanied by a significant increase in EV TF at 24 hours (328.6 ± 62.1 vs 167.7 ± 20.8 fM) after CCI. Further, EV TF is also increased at 6 hours (126.6 ± 17.1 vs 63.3 ± 14.4 fM) but not 24 hours following CHI. Conclusion TF‐mediated thrombin generation is time‐dependent after injury and TF increases resolve earlier following CHI as compared to CCI. Taken together, these data support a TF‐mediated pathway of thrombin generation after TBI and pinpoint TF as a major player in TBI‐induced coagulopathy.

show abstract

“…Extracellular vesicles, many of which are platelet-derived, have independent thrombotic activity and their release after TBI can influence platelet function. In a mouse model of TBI, it was found that EVs released after TBI cause platelet hypoaggregation ( 32 ). These researchers also found that the EVs released after TBI contained the Adenosine diphosphate (ADP) P2Y 12 receptor, a key receptor for increasing the sensitivity of platelet aggregation ( 32 ).…”

Section: Extracellular Vesicles As Mediators In Traumamentioning

confidence: 99%

Extracellular Vesicles as Regulators of Immune Function in Traumatic Injuries and Sepsis

Seim

Willis

Wallet

et al. 2022

Shock

View full text Add to dashboard Cite

Despite advancements in critical care and resuscitation, traumatic injuries are one of the leading causes of death around the world and can bring about long-term disabilities in survivors. One of the primary causes of death for trauma patients are secondary phase complications that can develop weeks or months after the initial insult. These secondary complications typically occur because of systemic immune dysfunction that develops in response to injury, which can lead to immunosuppression, coagulopathy, multiple organ failure, unregulated inflammation, and potentially sepsis in patients. Recently, extracellular vesicles (EVs) have been identified as mediators of these processes because their levels are increased in circulation after traumatic injury and they encapsulate cargo that can aggravate these secondary complications. In this review, we will discuss the role of EVs in the posttrauma pathologies that arise after burn injuries, trauma to the central nervous system, and infection. In addition, we will examine the use of EVs as biomarkers for predicting late-stage trauma outcomes and as therapeutics for reversing the pathological processes that develop after trauma. Overall, EVs have emerged as critical mediators of trauma-associated pathology and their use as a therapeutic agent represents an exciting new field of biomedicine.

show abstract

Microvesicles generated following traumatic brain injury induce platelet dysfunction via adenosine diphosphate receptor

Cited by 17 publications

References 33 publications

It is time for TEG in pediatric trauma: unveiling meaningful alterations in children who undergo massive transfusion

It is time for TEG in pediatric trauma: unveiling meaningful alterations in children who undergo massive transfusion

Tissue factor release following traumatic brain injury drives thrombin generation

Extracellular Vesicles as Regulators of Immune Function in Traumatic Injuries and Sepsis

Contact Info

Product

Resources

About