Design and Development of a Clot Burst Pressure Device to Investigate Resuscitation Strategies.

INTRODUCTION: A reduction in clot strength is a hallmark feature of trauma-induced coagulopathy. A better understanding of clot integrity can optimize resuscitation strategies. We designed a device to gauge clot strength by pressurizing fluids over a formed clot and measuring the pressure needed to dislodge the clot. We hypothesized that this device could distinguish between clots formed in hypocoagulable and hypercoagulable states by observing differences in the clot burst pressure. METHODS: Whole blood from healthy volunteers was collected into sodium citrate tubes and was treated with heparin or fibrinogen to generate clots in a hypocoagulable or hypercoagulable state, respectively. Small bore holes were drilled into polystyrene plates, and recalcified blood was pipetted into the holes. Plates were incubated at 37°C for 30 min to form clots. A pressure cap with an inlet for fluid from a syringe pump and an outlet leading to a measurement column was secured in the wells with a watertight seal. RESULTS: Clot burst pressure was normalized to individual baseline values to account for inherent differences in clot strength. The 1.0 g/L and 2.0 g/L fibrinogen groups were 1.65 ± 0.07 (P = 0.0078) and 2.26 ± 0.16 (P = 0.0078) times as strong as baseline, respectively. The 0.10, 0.15, or 0.20 USP units/mL groups were 0.388 ± 0.07 (P = 0.125), 0.31 ± 0.07 (P = 0.125), 0.21 ± 0.07 (P = 0.125) times as strong as baseline, respectively. Data were analyzed using Wilcoxon matched pairs signed rank testing. CONCLUSIONS: This device tests clot strength using burst pressure, an easily interpreted clinical parameter not measured in existing devices. Future work can test blood from trauma patients to better understand trauma pathophysiology.

Predictors of 30-Day Stroke and Death After Transcarotid Revascularization.

INTRODUCTION: Much of the previous robust analyses of the results associated with transcarotid revascularization (TCAR) derives from industry-sponsored trials or the Vascular Quality Initiative (VQI). This investigation was performed to identify preoperative predictors of 30-day stroke and death using institutional databases. METHODS: A retrospective analysis was performed of carotid revascularization databases created at two high-volume TCAR centers and maintained independently of the VQI carotid module between December 2015 and December 2021. The primary outcome of interest was a composite of perioperative (30-day) stroke and death. Univariate regression analyses, followed by multivariate regression analyses, were performed to identify potential predictors of adverse events. RESULTS: During the study period, 750 TCAR procedures were performed at our combined health systems, resulting in 24 (3.2%) individuals who experienced either stroke and/or death in the perioperative period. Of these, we observed nine (1.2%) mortality events and 18 (2.4%) strokes. On univariate analysis, candidate protectors of stroke/death were found to be coronary artery disease (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.18-1.01; P = 0.05) and protamine reversal (0.51; 0.21-1.21; P = 0.15). Candidate predictors of the primary outcome were anticoagulant usage (3.03; 1.26-7.24; P = 0.01), postprocedural debris in the filter (2.30; 0.97-5.43; P = 0.06), symptomatic carotid lesion (2.03; 0.90-4.50), and cardiac arrhythmia (1.98; 0.80-4.03; P = 0.14). On multivariate analysis, two predictors remained, cardiac arrhythmia (4.21; 1.10-16.16; P = 0.04) and symptomatic carotid lesion (14.49; 1.80-116.94; P = 0.01). CONCLUSIONS: A symptomatic carotid lesion, and to a lesser extent cardiac arrhythmia, are strong predictors of 30-day stroke/death after TCAR. Surgeons should be cognizant of the increased risk of adverse events in the perioperative period in these patients.

Perfecting the venerable SSC.

Stainless steel crowns (SSCs) are the preferred restoration of pediatric dentists for children requiring a pediatric dental rehabilitation due to their low cost and durability. Despite low technique sensitivity SSC placement can be challenging in some clinical situations including when placed on primary canines. Primary canines restored with SSCs often result in premature contacts and posterior open bite making acquiring an "as the patient presented" (ATPP) occlusion difficult when providing a pediatric dental rehabilitation. Opening of the posterior occlusion due to premature canine contact in a dental rehabilitation is often viewed as unavoidable. This technique article describes a simple method to address this clinical situation and reviews basic principles and techniques for placing SSCs.

Adverse events are not increased with trainee participation in transcarotid revascularization.

OBJECTIVE: To determine whether a vascular surgery trainee's participation in transcarotid revascularization (TCAR), a new technology, affects patient safety and outcomes. DESIGN: Retrospective, institutional review of our carotid database was performed. Patients who underwent TCAR were stratified based on whether a vascular trainee was present during the procedure. Relevant demographics, comorbidities, anatomical indication, perioperative courses, and adverse events in the postoperative period were captured for statistical analysis. SETTING: Data were obtained from affiliated Memorial Hermann Hospitals in Houston, Texas. PARTICIPANTS: All patients who underwent TCAR from September 2017 to January 2022 were included. RESULTS: Of 486 patients who underwent TCAR, 173 (35.6%) were performed in the presence of a trainee, and 313 (64.4%) were performed without a trainee. Subjects in the trainee cohort had more challenging anatomy, defined as a higher rate of carotid bifurcation above C2, restenotic disease, previous ipsilateral neck dissection, and neck radiation. The trainee cohort had higher rates of estimated blood loss (61.1 ± 66 vs. 35.5 ± 39 mL, p < 0.01), longer operative time (64.8 ± 30.3 vs. 57.9 ± 20.4 min, p < .01), longer cerebral blood flow reversal time (8.9 ± 6.1 vs. 7.9 ± 6.6 min, p = .01), and higher contrast administration (25.7 ± 12.0 vs. 21.1 ± 9.4 mL, p < .01). The ability to achieve technical success was similar between the two cohorts. There was no difference in the rates of cranial nerve palsy, ipsilateral stroke, hematoma, and stent thrombosis. Hospital length of stay, death (0% vs. 1.6%, p = .10), and stroke (1.1% vs. 2.8%, p = .22) were also similar between the two cohorts. CONCLUSION: Vascular surgery trainee's involvement during TCAR did not increase adverse outcomes, such as stroke and death, in the perioperative period. The results presented herein should encourage other teaching institutions to provide surgical trainees with supervised, hands-on experience during TCAR.

The Impact of Rapid Infuser Use on the Platelet Count, Platelet Function, and Hemostatic Potential of Whole Blood.

BACKGROUND: Rapid infusion pumps employing filters, roller pumps, and heat exchangers for the administration of blood products are not approved for platelets or cryoprecipitate. This technology may decrease platelet count and degrade coagulation proteins. The effect of rapid infusers on the hemostatic potential of whole blood is unknown. METHODS: Five units of low titer O+ whole blood were obtained from anonymous donors. Each unit was subjected to infusion by five different techniques: (1) gravity infusion without a filter, (2) gravity infusion with a filter, (3) Belmont rapid infuser at 70 mL/min, (4) Belmont at 100 mL/min, and (5) pressurized infusion with a pneumatic pressure bag and filter. After infusion, platelet count, platelet function, thrombin generation, and hemostatic potential were measured for each aliquot. Infusion techniques were compared, using gravity infusion without a filter as the control. RESULTS: There was a significant decrease in platelet count from baseline (168,000) in the BELMONT70 (97,000) and BELMONT100 (94,000) groups (P < 0.05). However, there were no differences in platelet function (all P > 0.20). While there were no differences in thromboelastography parameters between control and infusion models (all P > 0.20), there were significant increases in thrombin generation parameters by CAT in both the BELMONT70 and BELMONT100 groups (all P < 0.05). CONCLUSIONS: The use of a rapid infuser decreases the platelet count of WB but does not decrease platelet function or overall hemostatic potential. In fact, thrombin generation and thrombin potential are actually increased. Rapid infusers are safe for the transfusion of WB.

Microelectromechanical System Measurement of Platelet Contraction: Direct Interrogation of Myosin Light Chain Phosphorylation.

Myosin Light Chain (MLC) regulates platelet contraction through its phosphorylation by Myosin Light Chain Kinase (MLCK) or dephosphorylation by Myosin Light Chain Phosphatase (MLCP). The correlation between platelet contraction force and levels of MLC phosphorylation is unknown. We investigate the relationship between platelet contraction force and MLC phosphorylation using a novel microelectromechanical (MEMS) based clot contraction sensor (CCS). The MLCK and MLCP pair were interrogated by inhibitors and activators of platelet function. The CCS was fabricated from silicon using photolithography techniques and force was validated over a range of deflection for different chip spring constants. The force of platelet contraction measured by the clot contraction sensor (CCS) was compared to the degree of MLC phosphorylation by Western Blotting (WB) and ELISA. Stimulators of MLC phosphorylation produced higher contraction force, higher phosphorylated MLC signal in ELISA and higher intensity bands in WB. Inhibitors of MLC phosphorylation produced the opposite. Contraction force is linearly related to levels of phosphorylated MLC. Direct measurements of clot contractile force are possible using a MEMS sensor platform and correlate linearly with the degree of MLC phosphorylation during coagulation. Measured force represents the mechanical output of the actin/myosin motor in platelets regulated by myosin light chain phosphorylation.

A Novel Platelet Function Assay for Trauma.

BACKGROUND: Platelet function tests such as thrombelastography platelet mapping and impedance aggregometry have demonstrated universal platelet dysfunction in trauma patients. In this study, we introduce the measurement of platelet contraction force as a test of platelet function. We hypothesize that force will correlate with established coagulation tests such as thrombelastography, demonstrate significant differences between healthy subjects and trauma patients, and identify critically ill trauma patients. METHODS: Blood samples were prospectively collected from level 1 trauma patients at initial presentation, assayed for force of and time to contraction and compared with thrombelastography. Blood from healthy subjects was assayed to establish a reference range. Results from trauma patients were compared with healthy controls and trauma patients that died. RESULTS: The study includes one hundred trauma patients with mean age 45 y, 74% were male, and median injury severity score of 14 ± 12. Patients that survived (n = 90) demonstrated significantly elevated platelet contraction force compared with healthy controls (n = 12) (6390 ± 2340 versus 4790 ± 470 µN, P = 0.043) and trauma patients that died (n = 10) (6390 ± 2340 versus 2860 ± 1830 µN, P = 0.0001). Elapsed time to start of platelet contraction was faster in trauma patients that survived compared with healthy controls (660 ± 467 versus 1130 ± 140 s, P = 0.0022) and those that died (660 ± 470 versus 1460 ± 1340 s, P < 0.0001). CONCLUSIONS: In contrast with all existing platelet function tests reported in the literature, which report platelet dysfunction in trauma patients, contractile force demonstrates hyperfunction in surviving trauma patients and dysfunction in nonsurvivors. Platelet contraction reflects platelet metabolic reserve and thus may be a potential biomarker for survival after trauma. Contractile force warrants further investigation to predict mortality in severely injured trauma patients.

A Morphometric Model for Endovascular Occlusion of The Retrohepatic Vena Cava in Pediatric Trauma.

BACKGROUND: The resuscitative endovascular balloon occlusion of the aorta (REBOA) device has been adapted for inferior vena cava (IVC) use in both animal models and adult case reports. The aim of this study is to examine the feasibility for use of the REBOA device for pediatric IVC injuries and create a potential framework for implementation. MATERIALS AND METHODS: A simulated venous system was designed with modeled IVC components based on 290 abdominal computed tomography scans of pediatric trauma patients. These patients were randomly selected to represent the ten Broselow categories. These IVC segments were selected to represent the posthepatic and prehepatic diameters for the five largest Broselow categories. A closed circulatory model was created with steady-state flow designed to model the venous system. The REBOA device was inserted into the system with the balloon in the IVC segment. Pressure monitors were placed distally and in the closed system, replicating the capacitance of the venous system. A flow meter was placed distally to the segment and balloon. Flow and pressure readings were recorded as the REBOA device was inflated and total occlusion was achieved. RESULTS: Suprahepatic IVC diameters ranged from 1.14 to 2.71 cm, while infrahepatic IVC diameters ranged from 0.76 to 2.39 cm. There was significant overlap in the measurements of the IVC, allowing five modeled segments to represent ten different IVCs. The venous model demonstrated a significant delay between balloon inflation and vessel occlusion. Approximately 80%-90% of the REBOA inflation volume results in approximately an initial 10% reduction in flow. Flow was completely obstructed which corresponded with a small increase in pressure difference between the proximal and distal pressure monitors, reflecting the capacitance in the venous system with inflation. CONCLUSIONS: Pediatric IVC injuries with significant hemorrhage should be amenable to endovascular occlusion as an adjunct to resuscitation and operative management.

Platelet biomechanics, platelet bioenergetics, and applications to clinical practice and translational research.

The purpose of this review is to explore the relationship between platelet bioenergetics and biomechanics and how this relationship affects the clinical interpretation of platelet function devices. Recent experimental and technological advances highlight platelet bioenergetics and biomechanics as alternative avenues for collecting clinically relevant data. Platelet bioenergetics drive energy production for key biomechanical processes like adhesion, spreading, aggregation, and contraction. Platelet function devices like thromboelastography, thromboelastometry, and aggregometry measure these biomechanical processes. Platelet storage, stroke, sepsis, trauma, or the activity of antiplatelet drugs alters measures of platelet function. However, the specific mechanisms governing these alterations in platelet function and how they relate to platelet bioenergetics are still under investigation.

Differences in vascular function between trained and untrained limbs assessed by near-infrared spectroscopy.

PURPOSE: The aim of this study was to examine whether differences in vascular responsiveness associated with training status would be more prominent in the trained limb (leg) than in the untrained limb (arm) microvasculature. METHODS: Thirteen untrained (26 ± 5 year) and twelve trained (29 ± 4 year) healthy men were submitted to a vascular occlusion test (VOT) (2 min baseline, 5 min occlusion, and 8 min re-oxygenation). The oxygen saturation signal (StO2) was assessed using near-infrared spectroscopy (NIRS) throughout the VOT. Vascular responsiveness within the microvasculature was evaluated by the re-oxygenation Slope 2 (Slope 2 StO2) and the area under the curve (StO2AUC) of (StO2) signal during re-oxygenation in the leg and arm. RESULTS: There was a significant interaction between training status and limb for the slope 2 StO2 (P < 0.01). The leg of the trained group showed a steeper slope 2 StO2 (1.35 ± 0.12% s-1) when compared to the slope 2 StO2 of the leg in their untrained counterparts (0.86 ± 0.09% s-1) (P < 0.05). There was a medium effect size of 0.58 for slope 2 StO2 on the arm and a large effect size of 1.21 for slope 2 StO2 on the leg. In addition, there was a small effect size of 0.24 for StO2AUC on the arm and a medium effect size of 0.64 for StO2AUC on the leg. CONCLUSION: The present study suggests that the vascular adaptations induced by lower limb endurance exercise training are more prominent in the trained limb than in the untrained limb microvasculature.

3D Printed Surgical Instruments: The Design and Fabrication Process.

BACKGROUND: 3D printing is an additive manufacturing process allowing the creation of solid objects directly from a digital file. We believe recent advances in additive manufacturing may be applicable to surgical instrument design. This study investigates the feasibility, design and fabrication process of usable 3D printed surgical instruments. METHODS: The computer-aided design package SolidWorks (Dassault Systemes SolidWorks Corp., Waltham MA) was used to design a surgical set including hemostats, needle driver, scalpel handle, retractors and forceps. These designs were then printed on a selective laser sintering (SLS) Sinterstation HiQ (3D Systems, Rock Hill SC) using DuraForm EX plastic. The final printed products were evaluated by practicing general surgeons for ergonomic functionality and performance, this included simulated surgery and inguinal hernia repairs on human cadavers. Improvements were identified and addressed by adjusting design and build metrics. RESULTS: Repeated manufacturing processes and redesigns led to the creation of multiple functional and fully reproducible surgical sets utilizing the user feedback of surgeons. Iterative cycles including design, production and testing took an average of 3 days. Each surgical set was built using the SLS Sinterstation HiQ with an average build time of 6 h per set. CONCLUSIONS: Functional 3D printed surgical instruments are feasible. Advantages compared to traditional manufacturing methods include no increase in cost for increased complexity, accelerated design to production times and surgeon specific modifications.

Transcarotid stenting of extracranial carotid artery aneurysm with covered stents and flow reversal.

Introduction: An extracranial carotid artery aneurysm (ECAA) is a rare pathology comprising <1% of all arterial aneurysms. The etiology includes trauma, previous surgery, radiation, and infection. Treatment of ECAAs has evolved from open repair to endovascular repair with stenting. Reports of endovascular repair describe the transfemoral approach; however, little more than case reports are available describing the transcarotid approach for ECAAs. In this study, we describe a cohort of patients who safely underwent transcarotid repair of ECAAs. Methods: We performed a retrospective medical record review of all cases of transcarotid stenting using covered stents for a carotid aneurysm within 11 different hospitals within the Memorial Hermann Health System from December 2019 through December 2022. Technical success is defined as coverage of the aneurysm with no endoleak. We report the patient demographics, clinical presentation, intraoperative metrics, and outcomes. Results: Seven patients underwent transcarotid covered stent placement using flow reversal for neurologic protection. Their average age was 65 years, and four of the seven patients were men. Three patients presented with pain, two with transient ischemic attack, one with stroke, and one with a pulsatile mass. Technical success was 100%. All the patients were treated with transcarotid stenting, and the average aneurysm size was 13 mm. The average operative time was 69 minutes, and the flow reversal time was 9 minutes. No postoperative stroke, myocardial infarction, or death occurred. The average length of hospital stay was 2.7 days. Conclusions: A transcarotid approach for endovascular treatment of ECAAs was safe for this cohort of patients, with no postoperative death, stroke, or myocardial infarction. Also, the technical success was 100%.

Dual Institutional Experience with Transcarotid Artery Revascularization.

INTRODUCTION: Transcarotid artery revascularization (TCAR) is a hybrid open and endovascular technique to treat carotid stenosis. The purpose of this study is to present a large cohort of patients who underwent TCAR at 2 high-volume TCAR health systems. METHODS: This study was a retrospective chart review of all instances of TCAR within the Memorial Hermann Health System and Indiana University Health, from December 2015-January 2022, using the ENROUTE Neuroprotection Device (Silk Road Medical, Sunnyvale, CA). We report patient demographics, intraoperative metrics, 30-day results and long-term results. RESULTS: In all, 750 patients underwent TCAR in the designated time period. Average patient age was 73 years, with 68% being male. Overall, 53.9% of patients had coronary artery disease, 45.4% had diabetes, and 36.9% were symptomatic. Technical success was achieved in 98.8% of patients with conversion to open endarterectomy in 1.1%. Average reverse flow time was 9.1 minutes with length of stay greater than 1 day 38%. Ipsilateral stroke rate within 30 days was 2.3% and long-term cumulative stroke rate was 3.0%. Death within 30 days occurred in 1.2% of patients and in 5.9% over long-term follow up. In all, 1% of patients required reintervention. CONCLUSIONS: TCAR is a safe and effective treatment modality for carotid artery stenotic disease. Its outcomes are similar to historical results associated with carotid endarterectomy, long considered the gold standard.

An Analysis of Sex-Based Outcomes Following Transcarotid Artery Revascularization.

OBJECTIVE: Several studies suggest that females have higher perioperative adverse events and decreased benefit from carotid artery revascularization with transfemoral carotid artery stenting and carotid endarterectomy (CEA) compared to males. However, there are limited data of sex-based outcomes for transcarotid artery revascularization (TCAR). METHODS: A retrospective review of prospectively maintained system-wide TCAR databases was performed between December 2015-January 2022. Patients who underwent TCAR were stratified based on sex. Relevant demographics, medical conditions, anatomical characteristics, intra- and postoperative courses, and adverse events were captured. RESULTS: 729 patients underwent TCAR, 486 (66.6%) male and 243 (33.3%) female. Males were more likely to be diagnosed with coronary artery disease (56.9% vs 47.7%, P<.01) and were active smokers (30.4% vs 21.4%, P < .01). Age, symptomatic status, BMI, hypertension, hyperlipidemia, diabetes mellitus, arrhythmia, chronic obstructive pulmonary disease, history of myocardial infarction, heart failure with reduced ejection fraction <30%, end-stage renal disease and Charlson Comorbidity Index were similar. In the perioperative period, there was no significant difference in reintervention rates (1.6% vs 1.2%, P = .75), cranial nerve palsy (.6% vs .4%, P > .99), ipsilateral stroke (1.9% vs 3.3%, P = .29), stent thrombosis (.4% vs .8%, P > .99), myocardial infarction (0% vs 0%, P > .99) and death (1.2% vs 1.2%, P > .99). In follow-up, no significant difference was found in reintervention, ipsilateral stroke, contralateral stroke, myocardial infarction, in-stent restenosis >50%, stent thrombosis, and death. CONCLUSIONS: Males and females did not have a statistically significant difference in outcomes when comparing ipsilateral stroke, in-stent thrombosis, conversion to CEA, and death after TCAR. However, our cohort comprised predominantly male patients and may conceal statistical significance as the females in our cohort did have a higher tendency toward developing complications. Future studies with a larger female cohort should be conducted to determine whether there is a true disparity of outcomes between the males and females undergoing TCAR.

3D printing in aortic endovascular therapies.

Endovascular treatment of aortic disease, including aneurysm or dissection, is expanding at a rapid pace. Often, the specific patient anatomy in these cases is complex. Additive manufacturing, also known as three-dimensional (3D) printing, is especially useful in the treatment of aortic disease, due to its ability to manufacture physical models of complex patient anatomy. Compared to other surgical procedures, endovascular aortic repair can readily exploit the advantages of 3D printing with regard to operative planning and preoperative training. To date, there have been numerous uses of 3D printing in the treatment of aortic pathology as an adjunct in presurgical planning and as a basis for training modules for fellows and residents. In this review, we summarize the current uses of 3D printing in the endovascular management of aortic disease. We also review the process of producing these models, the limitations of their applications, and future directions of 3D printing in this field.

PLATELET FUNCTION IN TRAUMA: IS CURRENT TECHNOLOGY IN FUNCTION TESTING MISSING THE MARK IN INJURED PATIENTS?

ABSTRACT: Platelets are subcellular anucleate components of blood primarily responsible for initiating and maintaining hemostasis. After injury to a blood vessel, platelets can be activated via several pathways, resulting in changed shape, adherence to the injury site, aggregation to form a plug, degranulation to initiate activation in other nearby platelets, and acceleration of thrombin formation to convert fibrinogen to fibrin before contracting to strengthen the clot. Platelet function assays use agonists to induce and measure one or more of these processes to identify alterations in platelet function that increase the likelihood of bleeding or thrombotic events. In severe trauma, these assays have revealed that platelet dysfunction is strongly associated with poor clinical outcomes. However, to date, the mechanism(s) causing clinically significant platelet dysfunction remain poorly understood. We review the pros, cons, and evidence for use of many of the popular assays in trauma, discuss limitations of their use in this patient population, and present approaches that can be taken to develop improved functional assays capable of elucidating mechanisms of trauma-induced platelet dysfunction. Platelet dysfunction in trauma has been associated with need for transfusions and mortality; however, most of the current platelet function assays were not designed for evaluating trauma patients, and there are limited data regarding their use in this population. New or improved functional assays will help define the mechanisms by which platelet dysfunction occurs, as well as help optimize future treatment.

Hemostatic potential of cold-stored non-leukoreduced whole blood over time: An assessment of platelet function and thrombin generation for optimal shelf life.

OBJECTIVES: Cold-stored low-titer whole blood (WB) is becoming increasingly used as the preferred product for initial hemorrhagic shock resuscitation. The purpose of this study was to identify whether the current 21-day shelf life is the optimal duration for storage of WB, maintaining hemostatic efficacy. METHODS: Five units of fresh low-titer group O WB (non-leukoreduced) were acquired from our regional blood center. These units were stored at 4°C for up to 21 days as per current clinical storage guidelines in our emergency department. Hemostatic parameters were measured in vitro at 0 days, 7 days, 14 days, and 21 days. Assessments of hemostatic potential included cell count, rapid thrombelastography (r-TEG) and kaolin thrombelastography (TEG), multiplate impedance aggregometry, and calibrated automated thrombogram (CAT). Univariate analysis, including one-way analysis of variance with repeated measures, was performed (STATA 12.1). RESULTS: Compared with baseline product (0 days), both platelet count and platelet function of WB showed sharp decreases at 7 days and again at 14 days. Platelet function deterioration was noted by r-TEG c (MA), TEG-MA, and multiplate arachidonic acid and adenosine diphosphate (all p < 0.001). With respect to clot initiation, r-TEG ACT and TEG R-time were similar over the 21-day shelf life (p = 0.058 and p = 0.620, respectively). Thrombin generation assessed by CAT demonstrated stable endogenous thrombin potential over the course of storage (p = 0.162), but increased peak thrombin generation and quicker time to peak generation after 7 days. CONCLUSION: While the platelet function of WB degrades significantly at 7 days (and again at 14 days), clot initiation remains stable over time, and thrombin generation appears to be improved at 7 days. This study supports a current storage limit for cold-stored, low-titer WB of 14 days.

Morphometric and Physiologic Modeling Study for Endovascular Occlusion in Pediatric Trauma Patients.

The use of the resuscitative endovascular balloon occlusion of the aorta (REBOA) device is expanding in adult trauma. Reports of its use in pediatric patients have been published, but no guidelines currently exist nor has it been Food and Drug Administration approved in pediatrics. This project develops a model to determine appropriate balloon inflation volumes in pediatric patients to guide potential use. Artificial aortas were three-dimensional (3D) printed using synthetic polymers. Segments were created based on aortic diameters from 289 pediatric trauma patients' computer tomography (CT) scans. These aortic segments were inserted into a circulatory system model featuring two branches to simulate abdominal and upper body perfusion (cerebral, cardiac, and upper extremities). Sonographic flow meters and pressure transducers were placed along the circuit, and measurements were recorded as a REBOA device was inflated in the aortic segment. A negative sigmoidal relationship was observed between device inflation and aortic flow occlusion, with the initial 50% of inflation causing a 10% reduction in flow, followed by a steep decline. With increasing inflation, distal aortic flow and pressure were found to have an inverse relationship with the upper body branch metrics. In conclusion, pediatric patients present with a range of vessel diameters that occlude at various REBOA balloon inflation volumes. This study provides a basis to establish initial inflation volumes for safe REBOA deployment in appropriate pediatric trauma patients.

Procoagulant in vitro effects of clinical cellular therapeutics in a severely injured trauma population.

Clinical trials in trauma populations are exploring the use of clinical cellular therapeutics (CCTs) like human mesenchymal stromal cells (MSC) and mononuclear cells (MNC). Recent studies demonstrate a procoagulant effect of these CCTs related to their expression of tissue factor (TF). We sought to examine this relationship in blood from severely injured trauma patients and identify methods to reverse this procoagulant effect. Human MSCs from bone marrow, adipose, and amniotic tissues and freshly isolated bone marrow MNC samples were tested. TF expression and phenotype were quantified using flow cytometry. CCTs were mixed individually with trauma patients' whole blood, assayed with thromboelastography (TEG), and compared with healthy subjects mixed with the same cell sources. Heparin was added to samples at increasing concentrations until TEG parameters normalized. Clotting time or R time in TEG decreased relative to the TF expression of the CCT treatment in a logarithmic fashion for trauma patients and healthy subjects. Nonlinear regression curves were significantly different with healthy subjects demonstrating greater relative decreases in TEG clotting time. In vitro coadministration of heparin normalized the procoagulant effect and required dose escalation based on TF expression. TF expression in human MSC and MNC has a procoagulant effect in blood from trauma patients and healthy subjects. The procoagulant effect is lower in trauma patients possibly because their clotting time is already accelerated. The procoagulant effect due to MSC/MNC TF expression could be useful in the bleeding trauma patient; however, it may emerge as a safety release criterion due to thrombotic risk. The TF procoagulant effect is reversible with heparin.

TEG Lysis Shutdown Represents Coagulopathy in Bleeding Trauma Patients: Analysis of the PROPPR Cohort.

BACKGROUND: Thrombelastography (TEG) fibrinolysis shutdown after trauma is associated with increased mortality due to hypercoagulability-associated organ failure. However, a lack of mechanistic data has precluded the development of novel interventions to treat shutdown. OBJECTIVES: To define the pathophysiology of TEG shutdown in severely injured, bleeding patients through secondary analysis of the PROPPR trial. METHODS: Fibrinolysis was characterized in PROPPR subjects using admission TEG lysis at 30 min (LY30) or plasmin-antiplasmin (PAP) levels. LY30 categories were low (<0.9%), moderate (0.9-2.9%), or high (≥ 3%). PAP was classified as low (<1,500 µg/L), moderate (1,500-20,000 µg/L), or high (>20,000 µg/L). Demographics, outcomes, admission TEG values, platelet count and function, standard coagulation tests, and coagulation proteins were compared. RESULTS: Five hundred forty-seven patients had TEG data and 549 patients had PAP data available. Low LY30 was associated with reduced platelet count and aggregation, poorer TEG clot formation, prolonged clotting times, and reduced fibrinogen and alpha2 antiplasmin. Compared to moderate PAP, low PAP subjects had similar platelet parameters, TEG values, fibrinogen, and alpha2 antiplasmin, but reduced tPA, and elevated PAI-1. D-Dimer values increased as PAP increased, however patients with low LY30 had elevated D-Dimer compared with moderate LY30 patients. Most low LY30 deaths were due to TBI (45%) and hemorrhage (42%) versus one of each cause (TBI, hemorrhage, MOF) in low PAP patients. CONCLUSIONS: Low TEG LY30 does not reflect shutdown of enzymatic fibrinolysis with hypercoagulability, but rather a coagulopathic state of moderate fibrinolysis with fibrinogen consumption and platelet dysfunction that is associated with poor outcomes.