Fresh frozen plasma and spray-dried plasma mitigate pulmonary vascular permeability and inflammation in hemorrhagic shock

Potter, Daniel R.; Baimukanova, Gail; Keating, Sheila M.; Deng, Xutao; Chu, Jeffrey A.; Gibb, Stuart L.; Peng, Zhanglong; Muench, Marcus O.; Fomin, Marina E.; Spinella, Philip C.; Kozar, Rosemary A.; Pati, Shibani

doi:10.1097/ta.0000000000000630

Cited by 63 publications

(79 citation statements)

References 36 publications

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“…Nanoparticles tend to distribute to organs with high vascular permeability, and even though the lung vasculature is not usually permeable, vascular permeability increases during hemorrhage. 20 In summary, we have developed a TF-targeted nanofiber that specifically binds to the site of hemorrhage and reduces blood loss.…”

Section: Discussionmentioning

confidence: 99%

Tissue-Factor Targeted Peptide Amphiphile Nanofibers as an Injectable Therapy To Control Hemorrhage

et al. 2015

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Noncompressible torso hemorrhage is a leading cause of mortality in civilian and battlefield trauma. We sought to develop an i.v.-injectable, tissue factor (TF)-targeted nanotherapy to stop hemorrhage. Tissue factor was chosen as a target because it is only exposed to the intravascular space upon vessel disruption. Peptide amphiphile (PA) monomers that self-assemble into nanofibers were chosen as the delivery vehicle. Three TF-binding sequences were identified (EGR, RLM, and RTL), covalently incorporated into the PA backbone, and shown to self-assemble into nanofibers by cryo-transmission electron microscopy. Both the RLM and RTL peptides bound recombinant TF in vitro. All three TF-targeted nanofibers bound to the site of punch biopsy-induced liver hemorrhage in vivo, but only RTL nanofibers reduced blood loss versus sham (53% reduction, p < 0.05). Increasing the targeting ligand density of RTL nanofibers yielded qualitatively better binding to the site of injury and greater reductions in blood loss in vivo (p < 0.05). In fact, 100% RTL nanofiber reduced overall blood loss by 60% versus sham (p < 0.05). Evaluation of the biocompatibility of the RTL nanofiber revealed that it did not induce RBC hemolysis, did not induce neutrophil or macrophage inflammation at the site of liver injury, and 70% remained intact in plasma after 30 min. In summary, these studies demonstrate successful binding of peptides to TF in vitro and successful homing of a TF-targeted PA nanofiber to the site of hemorrhage with an associated decrease in blood loss in vivo. Thus, this therapeutic may potentially treat noncompressible hemorrhage.

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Section: Discussionmentioning

confidence: 99%

Tissue-Factor Targeted Peptide Amphiphile Nanofibers as an Injectable Therapy To Control Hemorrhage

et al. 2015

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“…This is consistent with other studies in animal hemorrhage models where plasma repaired the pulmonary endothelial injury induced by hemorrhagic shock. 8,9,10 A retrospective study by Peiniger et al analyzed 1,250 massively transfused trauma patients with and without TBI and found that a high plasma:RBC transfusion ratio of >1:2 was an independent predictor of decreased mortality (OR 0.48, 95% CI 0.29 – 0.81) in patients with TBI. 21 However, another retrospective study by Spinella et al examined 850 massively transfused patients and found that a high plasma:RBC transfusion ratio was associated with increased survival in non-TBI patients, while a high platelet:RBC ratio was associated with survival in TBI patients.…”

Section: Discussionmentioning

confidence: 99%

“…5,6,7 This effect may be due to plasma’s ability to repair endothelial injury and reduce vascular permeability, which has been demonstrated in vitro and in animal models of hemorrhagic shock. 8,9,10 In a large animal model of combined TBI and hemorrhagic shock, plasma-based resuscitation reduced secondary brain injury 11 and improved neurologic recovery. 12 This benefit was attributed to improved cerebral perfusion, mitigation of glutamine-mediated excitotoxicity, and reduced mitochondrial dysfunction with plasma resuscitation.…”

Section: Introductionmentioning

confidence: 99%

Early plasma transfusion is associated with improved survival after isolated traumatic brain injury in patients with multifocal intracranial hemorrhage

Chang

Folkerson

Sloan

et al. 2017

Surgery

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Background Plasma-based resuscitation improves outcomes in trauma patients with hemorrhagic shock, while large animal and limited clinical data suggest that it also improves outcomes and is neuroprotective in the setting of combined hemorrhage and traumatic brain injury (TBI). However, the choice of initial resuscitation fluid including the role of plasma is unclear for patients after isolated TBI. Methods We reviewed adult trauma patients admitted from January 2011 to July 2015 with isolated TBI. “Early plasma” was defined as transfusion of plasma within 4 hours. Purposeful multiple logistic regression modeling was performed to analyze the relationship of early plasma and in-hospital survival. After testing for interaction, sub-group analysis was performed based on pattern of brain injury on initial head CT: epidural hematoma, intraparenchymal contusion, subarachnoid hemorrhage, subdural hematoma, or multifocal intracranial hemorrhage (MIH). Results Of the 633 isolated TBI patients included, 178 (28%) who received early plasma were more severely injured, coagulopathic, hypoperfused, and hypotensive on admission. Survival was similar in the early plasma versus no early plasma groups (78% versus 84%, p=0.08). After adjustment for covariates, early plasma was not associated with improved survival (odds ratio [OR] 1.18, 95% confidence interval [CI] 0.71 – 1.96). On subgroup analysis, multifocal intracranial hemorrhage (MIH) was the largest subgroup with 242 patients. Of these, 61 (25%) received plasma within 4 hours. Within-group logistic regression analysis with adjustment for covariates found that early plasma was associated with improved survival (OR 3.34, 95% CI 1.20 – 9.35). Conclusion Although early plasma transfusion was not associated with improved in-hospital survival for all isolated TBI patients, early plasma was associated with increased in-hospital survival in those with MIH.

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“…Liberal resuscitation with crystalloids and artificial colloids increases hydrostatic pressure without repairing the endothelial injury, resulting in edema and the edema-related complications which were common in the pre-DCR era (Figure 1). In contrast, in vitro 72,73,74 and animal models 75,76 of hemorrhagic shock demonstrate that plasma restores microvascular integrity, in part by repair of the endothelial glycocalyx layer (EGL). In a large animal model of concomitant hemorrhagic shock and TBI, resuscitation with FFP resulted in less secondary brain injury compared to resuscitation with crystalloid or artificial colloid, likely secondary to restoration of cerebral endothelium.…”

Section: Pharmacologic Treatment Optionsmentioning

confidence: 98%

Optimal Fluid Therapy for Traumatic Hemorrhagic Shock

Chang¹,

Holcomb²

2017

Critical Care Clinics

111

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The resuscitation of traumatic hemorrhagic shock has undergone a paradigm shift in the last 20 years with the advent of damage control resuscitation (DCR). Major principles of DCR include minimization of crystalloid, permissive hypotension, transfusion of a balanced ratio of blood products, and goal-directed correction of coagulopathy. In particular, plasma has replaced crystalloid as the primary means for volume expansion for traumatic hemorrhagic shock. Predicting which patient will require DCR by prompt and accurate activation of a massive transfusion protocol, however, remains a challenge.

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Fresh frozen plasma and spray-dried plasma mitigate pulmonary vascular permeability and inflammation in hemorrhagic shock

Abstract: Both FFP and SDP similarly modulate pulmonary vascular integrity, permeability, and inflammation in vitro and in vivo in a murine model of HS and trauma.

Cited by 63 publications

References 36 publications

Tissue-Factor Targeted Peptide Amphiphile Nanofibers as an Injectable Therapy To Control Hemorrhage

Tissue-Factor Targeted Peptide Amphiphile Nanofibers as an Injectable Therapy To Control Hemorrhage

Early plasma transfusion is associated with improved survival after isolated traumatic brain injury in patients with multifocal intracranial hemorrhage

Optimal Fluid Therapy for Traumatic Hemorrhagic Shock

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