FFP maintains normal coagulation while Kcentra induces a hypercoagulable state in a porcine model of pulmonary contusion and hemorrhagic shock

Dixon, Alexandra; Beiling, Marissa; Smith, Sawyer; Behrens, Brandon; Appleman, Luisa; Rick, Elizabeth A.; Murphy, James M.; Madtson, Brianne M.; McCully, Belinda H.; Goodman, Andrew L.; Kanlerd, Amonpon; Schaller, Traci; Subramanian, Sarayu; Trivedi, Alpa; Pati, Shibani; Schreiber, Martin A.

doi:10.1097/ta.0000000000003584

Cited by 2 publications

(7 citation statements)

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“…17 PCC induced more rapid clot propagation than FFP in treating coagulopathy in pigs but resulted in lower clot strength and a higher degree of clot lysis at later time points, indicating a delayed consumptive coagulopathy. 92 Furthermore, studies have demonstrated that the ovine model of traumatic coagulopathy is essential for exploring the complex interactions between hemodynamic, metabolic, and coagulation functions in sheep. 23 Hemorrhage Combined with Femur Fractures, Liver Injury, and Hypothermia Animal models that simulate multiple traumatic injuries are useful for studying the complex interactions between injuries that can exacerbate tissue ischemia, organ dysfunction, and failure.…”

Section: Blunt Chest Injury Combined With Hemorrhage and Liver Injurymentioning

confidence: 99%

The Use of Large Animal Models in Trauma and Bleeding Studies

Rayatdoost,

Grottke

2023

Hamostaseologie

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Background Major trauma often results in significant bleeding and coagulopathy, posing a substantial clinical burden. To understand the underlying pathophysiology and to refine clinical strategies to overcome coagulopathy, preclinical large animal models are often used. This review scrutinizes the clinical relevance of large animal models in hemostasis research, emphasizing challenges in translating findings into clinical therapies. Methods We conducted a thorough search of PubMed and EMBASE databases from January 1, 2010, to December 31, 2022. We used specific keywords and inclusion/exclusion criteria centered on large animal models. Results Our review analyzed 84 pertinent articles, including four animal species: pigs, sheep, dogs, and nonhuman primates (NHPs). Eighty-five percent of the studies predominantly utilized porcine models. Meanwhile, sheep and dogs were less represented, making up only 2.5% of the total studies. Models with NHP were 10%. The most frequently used trauma models involved a combination of liver injury and femur fractures (eight studies), arterial hemorrhage (seven studies), and a combination of hemodilution and liver injury (seven studies). A wide array of coagulation parameters were employed to assess the efficacy of interventions in hemostasis and bleeding control. Conclusions Recognizing the diverse strengths and weaknesses of large animal models is critical for trauma and hemorrhage research. Each model is unique and should be chosen based on how well it aligns with the specific scientific objectives of the study. By strategically considering each model's advantages and limitations, we can enhance our understanding of trauma and hemorrhage pathophysiology and further advance the development of effective treatments.

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Section: Blunt Chest Injury Combined With Hemorrhage and Liver Injurymentioning

confidence: 99%

The Use of Large Animal Models in Trauma and Bleeding Studies

Rayatdoost,

Grottke

2023

Hamostaseologie

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“…Patients with TEG results meeting criteria for TIC have been shown to require more transfusions and to have higher rates of mortality 4,6 . Trauma-induced coagulopathy is also associated with higher rates of intensive care needs 8 . While both TIC has been linked to adverse clinical outcomes, there is evidence that resuscitation strategies can target these issues.…”

Section: Trauma-induced Coagulopathymentioning

confidence: 99%

“…Multiple studies, including two in our laboratory, 9,10 have found that fresh frozen plasma (FFP) reverses coagulopathy in trauma. In addition, work from our laboratory has shown that in the setting of pulmonary contusion and hemorrhagic shock in swine with coagulation abnormalities, administration of prothrombin complex concentrate (PCC) produces more rapid clot formation 8 …”

Section: Trauma-induced Coagulopathymentioning

confidence: 99%

“…4,6 Trauma-induced coagulopathy is also associated with higher rates of intensive care needs. 8 While both TIC has been linked to adverse clinical outcomes, there is evidence that resuscitation strategies can target these issues. Multiple studies, including two in our laboratory, 9,10 have found that fresh frozen plasma (FFP) reverses coagulopathy in trauma.…”

mentioning

confidence: 99%

“…In addition, work from our laboratory has shown that in the setting of pulmonary contusion and hemorrhagic shock in swine with coagulation abnormalities, administration of prothrombin complex concentrate (PCC) produces more rapid clot formation. 8 Although TIC data may be helpful in guiding trauma resuscitation, they are not sufficient. There are mixed data on the utility of VET in guiding resuscitation protocols.…”

mentioning

confidence: 99%

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Principal component analysis of a swine injury model identifies multiple phenotypes in trauma

Buzzard,

Smith,

Dixon

et al. 2023

J Trauma Acute Care Surg

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Background Trauma is the third leading cause of death in the United States and the primary cause of death for people between the ages of 1 and 44. In addition to tissue damage, trauma may also activate an inflammatory state known as Trauma-Induced Coagulopathy (TIC) that is associated with clotting malfunctions, acidemia, and end-organ dysfunction. Prior work has also demonstrated benefit to acknowledging the type and severity of endothelial injury, coagulation derangements, and systemic inflammation in the management of trauma patients. This study builds upon prior work by combining laboratory, metabolic, and clinical metrics into an analysis of trauma phenotypes, evolution of phenotypes over time after trauma, and significance of trauma phenotype on mortality. Methods 70 female 3-month-old female Yorkshire crossbred swine were randomized to injury and resuscitation groups. Principal Component Analysis (PCA) of longitudinal swine TEG data (Reaction time, Alpha-Angle, Maximum Amplitude, and Clot Lysis at 30 minutes), pH, lactate, and MAP was completed in R at baseline, 1 hour post-injury, 3 hours post-injury, 6 hours post-injury, and 12 hours post-injury. Subjects were compared by principal component factor scores to assess differences in survival, injury severity, and treatment group. Results Among injured animals, three phenotypes were observed at each time point. Five phenotypes were associated with differences in survival, and of these, four were associated with differences in injury severity. Phenotype alignment was not significantly different by treatment group. Conclusion This application of PCA to a set of coagulation, hemodynamic, and organ perfusion variables has identified multiple evolving phenotypes after trauma. Some of these phenotypes may correlate with injury severity and may have implications for survival. Next steps include validating these findings over greater numbers of subjects and exploring other machine-learning techniques for phenotype identification. LEVEL OF EVIDENCE Level IV, Therapeutic/Care Management

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FFP maintains normal coagulation while Kcentra induces a hypercoagulable state in a porcine model of pulmonary contusion and hemorrhagic shock

Abstract: Severe injury with hemorrhagic shock induced a coagulopathy in swine. While FFP maintained normal coagulation following injury, Kcentra induced more rapid initial clot propagation in injured animals, reflective of an early hypercoagulable state.

Cited by 2 publications

References 24 publications

The Use of Large Animal Models in Trauma and Bleeding Studies

The Use of Large Animal Models in Trauma and Bleeding Studies

Principal component analysis of a swine injury model identifies multiple phenotypes in trauma

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