Impact of Immunopathy and Coagulopathy on Multi-Organ Failure and Mortality in a Lethal Porcine Model of Controlled and Uncontrolled Hemorrhage.

Uncontrolled hemorrhage is a major preventable cause of death in patients with trauma. However, the majority of large animal models of hemorrhage have utilized controlled hemorrhage rather than uncontrolled hemorrhage to investigate the impact of immunopathy and coagulopathy on multi-organ failure (MOF) and mortality. This study evaluates these alterations in a severe porcine controlled and uncontrolled hemorrhagic shock (HS) model. Anesthetized female swine underwent controlled hemorrhage and uncontrolled hemorrhage by partial splenic resection followed with or without lactated Ringer solution (LR) or Voluven® resuscitation. Swine were surveyed 6 h after completion of splenic hemorrhage or until death. Blood chemistry, physiologic variables, systemic and tissue levels of complement proteins and cytokines, coagulation parameters, organ function, and damage were recorded and assessed. HS resulted in systemic and local complement activation, cytokine release, hypocoagulopathy, metabolic acidosis, MOF, and no animal survival. Resuscitation with LR and Voluven® after HS improved hemodynamic parameters (MAP and SI), metabolic acidosis, hyperkalemia, and survival but resulted in increased complement activation and worse coagulopathy. Compared with the LR group, the animals with hemorrhagic shock treated with Voluven® had worse dilutional anemia, coagulopathy, renal and hepatic dysfunction, increased myocardial complement activation and renal damage, and decreased survival rate. Hemorrhagic shock triggers early immunopathy and coagulopathy and appears associated with MOF and death. This study indicates that immunopathy and coagulopathy are therapeutic targets that may be addressed with a high-impact adjunctive treatment to conventional resuscitation.

Cell Therapies for Acute Radiation Syndrome.

The risks of severe ionizing radiation exposure are increasing due to the involvement of nuclear powers in combat operations, the increasing use of nuclear power, and the existence of terrorist threats. Exposure to a whole-body radiation dose above about 0.7 Gy results in H-ARS (hematopoietic acute radiation syndrome), which is characterized by damage to the hematopoietic system; higher doses result in further damage to the gastrointestinal and nervous systems. Only a few medical countermeasures for ARS are currently available and approved for use, although others are in development. Cell therapies (cells or products produced by cells) are complex therapeutics that show promise for the treatment of radiation injury and have been shown to reduce mortality and morbidity in animal models. Since clinical trials for ARS cannot be ethically conducted, animal testing is extremely important. Here, we describe cell therapies that have been tested in animal models. Both cells and cell products appear to promote survival and lessen tissue damage after whole-body irradiation, although the mechanisms are not clear. Because radiation exposure often occurs in conjunction with other traumatic injuries, animal models of combined injury involving radiation and future countermeasure testing for these complex medical problems are also discussed.

Cold storage of whole blood in an additive solution containing apoptotic and necrotic inhibitors.

BACKGROUND: Whole blood (WB) reigns superior to component therapy for the treatment of hemorrhagic shock on the battlefield. Though cold storage of WB offers a shelf life of 21 to 35 days, storage lesions and the potential for blood wastage remain. Storing WB in an additive solution (AS) containing apoptotic inhibitors may help preserve blood cell viability and improve blood quality over extended cold storage. STUDY DESIGN AND METHODS: Non-leukoreduced WB was obtained from healthy individuals and dosed with: AS, AS+Necrostatin-1 (AS+N1), AS+Boc-D-fmk (AS+B; apoptosis inhibitor), AS+Q-VD-OPh (AS+Q; apoptosis inhibitor), and Control (0.9% saline). Blood bags were kept refrigerated (1°-6°C) for 21 days. Bags were tested on days 0, 7, 14, and 21 for complete blood count, metabolism, clot formation, aggregation function, platelet activation, and red blood cell quality. RESULTS: Platelet count was better preserved in all AS-containing samples. All groups displayed increased glucose consumption and lactate production with storage. Furthermore, all groups displayed a similar decline in clot strength (max amplitude) over the 21-day storage period. Bags that received AS displayed greater preservation of GPIIb expression and lower phosphatidylserine exposure. P-selectin expression was increased in all AS groups. DISCUSSION: Treatment of hemorrhagic shock with WB transfusion is logistically simpler than component therapy. Results from our study suggest that refrigerated WB stored with an AS containing apoptotic and necrotic inhibitors helps better preserve platelet count but does not improve platelet function. The future development of WB ASs is warranted to optimize both platelet quality and hemostatic function.

Effects of radiation exposure and storage on the energy metabolome of platelets in whole blood.

BACKGROUND: Exposure to radiation through battlefield use of nuclear weapons, terrorist attacks or accidents at nuclear power plants is a current concern for the military. Beyond the risk of exposure to personnel is the intentional or accidental irradiation of our blood banking supply system. It is unknown how large doses of ionizing radiation affect storage of blood and blood products, including platelets. The major function of platelets is clot formation which includes aggregation, shape change, vesicle release, and fibrinogen attachment; these tasks require a significant amount of energy. Here, we determine whether the ionizing radiation effects the energy metabolome of platelets in storage. STUDY DESIGN AND METHODS: Fresh whole blood from healthy volunteers was subjected to 0, 25, or 75Gy of X-irradiation, and stored at 4°C. Platelets were isolated from stored WB at 0, 1, 7, 14, and 21 days of storage. Krebs cycle intermediates, nicotinamide adenine dinucleotides, and the tri-, di, and mono- phosphorylated versions of adenosine and guanosine were extracted and measured by tandem mass spectroscopy. RESULTS: Irradiation at either 25Gy or 75Gy had no significant effect on the amount of any metabolite measured compared to control (0Gy). However, there was a significant fall over time in storage for most of the metabolites measured. DISCUSSION: These data show that irradiation at high doses has no effect on the concentration of the energy metabolome of platelets derived from whole blood stored in 4°C for up to 21 days and suggests that platelets can maintain their metabolome even after radiation exposure.

Metabolic effects of radiation on red blood cells from cold stored whole blood.

BACKGROUND: The risk of military and civilian radiation exposure is increasing, and determining the effects of exposure is a high priority. Irradiation of the nearby blood supply after a nuclear event may impede mobilization of blood products for resuscitation at a time of great need. RBCs are administered to patients with trauma and hemorrhage to transport and deliver oxygen and avoid tissue hypoxia. Here we determine the effects of ionizing radiation on the energy metabolome of RBCs isolated from cold stored whole blood to determine if their stability is compromised by radiation exposure. STUDY DESIGN AND METHODS: Whole blood from healthy volunteers was subjected to 0, 25, or 75 Gy of X-irradiation, and stored at 4°C. RBCs were isolated from stored WB at 0, 1, 7, 14, and 21 days of storage. The levels of extracted Krebs cycle intermediates, nicotinamide adenine dinucleotides, and phosphorylated derivatives of adenosine and guanosine were determined by tandem mass spectroscopy. RESULTS: Irradiation at either 25Gy or 75Gy had no significant effect on any parameter measured compared to control (0Gy). However, there was a significant change over time in storage for ATP, GDP, and guanosine. DISCUSSION: Irradiation at doses up to 75Gy had no effect on the energy metabolome of RBCs prepared from blood stored at 4°C for up to 21 days, suggesting that the RBC energy metabolome is not affected by radiation exposure and the blood can still be used for resuscitation in trauma patients.

A narrative review of prehospital hemorrhagic shock treatment with non-blood product medications.

BACKGROUND: Hemorrhagic shock remains a leading cause of death in both military and civilian trauma casualties. While standard of care involves blood product administration, maintaining normothermia, and restoring hemostatic function, alternative strategies to treat severe hemorrhage at or near the point of injury are needed. We reviewed adjunct solutions for managing severe hemorrhage in the prehospital environment. METHODS: We performed a literature review by searching PubMed with a combination of several keywords. Additional pertinent studies were identified by crossreferencing primary articles. Clinical experience of each author was also considered. RESULTS: We identified several promising antishock therapies that can be utilized in the prehospital setting: ethinyl estradiol sulfate (EES), polyethylene glycol 20,000 (PEG20K), C1 esterase inhibitors (e.g. Berinert, Cinryze), cyclosporin A, niacin, bortezomib, rosiglitazone, icatibant, diazoxide, and valproic acid (VPA). CONCLUSION: Several studies show promising adjunct treatment options in the management of severe prehospital hemorrhage. While some are rarely used, many others are readily available and commonly utilized for other indications. This suggests the potential for future use in resourcelimited settings. Human studies and case reports supporting their use are currently lacking.

A prospective assessment of the time required to obtain one unit of fresh whole blood by civilian phlebotomists and Army laboratory technicians (68 K).

BACKGROUND: Resuscitation with blood products improves survival after major hemorrhage. Blood product administration at or near the point-of-injury (POI) amplifies this benefit. Size, weight, and cold-chain management challenges all limit the amount of blood medics can carry. Warm fresh whole blood (WFWB) transfusions from a pre-screened donor within the unit represent an alternative source of blood at the POI. We measured the time required for civilian and Army technicians performing phlebotomy frequently to obtain one unit of blood to serve as a goal metric for combat medics being trained in this skill. METHODS: We gathered demographic and experience data along with proportion of first intravenous cannulation attempt success, time to blood flow initiated, and time to unit draw complete. RESULTS: We prospectively enrolled 12 civilian phlebotomy technicians and 10 Army laboratory technicians performing whole blood collections on 50 and 68 donors respectively. The mean time from setup to needle insertion was 3.7 min for civilians versus 4.2 min for Army technicians. The mean time from blood flowing to the bag being full was 10.7 min versus 8.4 min for civilians versus Army technicians respectively. The mean bag weights were 514 g versus 522 g. First-pass intravenous cannulation success was 96% versus 98% respectively. CONCLUSIONS: We found a high first intravenous cannulation attempt success among both the civilian and Army technicians. Medians times were <5 min to obtain venipuncture and <11 min to obtain one unit. These findings provide time-based benchmarks for potential use during transfusion training among military medics.

Refrigerated human mesenchymal stromal cells as an alternative to cryostorage for use in clinical investigation.

BACKGROUND: Mesenchymal stromal cells (MSCs) and other therapeutic cells show efficacy for cardiac damage, neurological disease, chronic lung disease, pediatric graft versus host disease, and several inflammatory conditions. Based on their anti-inflammatory and immune-modulatory activities, responsiveness, and secretion of beneficial factors, cellular therapeutics may provide benefits in acute and chronic traumatic injury. However, the use of live cells presents logistical challenges, especially for military trauma. MSCs are generally shipped and stored frozen but require sterile handling before infusion. This requires skilled personnel and equipment not readily available in a forward medical treatment facility or even a small community hospital. METHODS: Commercial human bone marrow- and adipose-derived MSCs from multiple donors were cultured under standard conditions, harvested and stored at 4°C in solution for up to 21 days. Cell viability, ATP content, apoptosis, proliferation capability, immunomodulation activity, and responsiveness were assessed after different amounts of time. RESULTS: Human MSCs can be stored at 4°C in MSC culture medium for 14 days while maintaining a reasonable level of viability and function. Both viability and function are reduced when MSCs are stored in crystalloid solutions. CONCLUSIONS: This approach makes it feasible to prepare cellular therapeutic agents in a laboratory or commercial facility and ship them under refrigerated conditions. Once they reach their destination, they can be stored at 4°C under conditions similar to blood products. Cells prepared and stored this way could also be used directly with minimal handling, making them more practical for both civilian and military trauma.

Comparison of platelet quality and function across apheresis collection platforms.

BACKGROUND: Platelet concentrates (PLT) can be manufactured using a combination of apheresis collection devices and suspension media (plasma or platelet additive solution (PAS)). It is unclear how platelet quality and hemostatic function differ across the current in-use manufacturing methods in the United States. The objective of this study was therefore to compare baseline function of PLT collected using different apheresis collection platforms and storage media. STUDY DESIGN AND METHODS: PLT were collected at two sites with identical protocols (N = 5 per site, N = 10 total per group) on the MCS® + 9000 (Haemonetics; "MCS"), the Trima Accel® 7 (Terumo; "Trima"), and the Amicus Cell Separator (Fresenius Kabi, "Amicus"). MCS PLT were collected into plasma while Trima and Amicus PLT were collected into plasma or PAS (Trima into Isoplate and Amicus into InterSol; yielding groups "TP", "TI" and "AP", "AI", respectively). PLT units were sampled 1 h after collection and assayed to compare cellular counts, biochemistry, and hemostatic function. RESULTS: Differences in biochemistry were most evident between plasma and PAS groups, as anticipated. MCS and TP had the highest clot strength as assessed by viscoelastometry. AI had the lowest thrombin generation capacity. Both TP and TI had the highest responses on platelet aggregometry. AI had the greatest number of microparticles. DISCUSSION: Platelet quality and function differ among collection platforms at baseline. MCS and Trima platelets overall appear to trend toward higher hemostatic function. Future investigations will assess how these differences change throughout storage, and if these in vitro measures are clinically relevant.

A novel, quantitative clot retraction assay to evaluate platelet function.

Blood platelets are crucial to prevent excessive bleeding following injury to blood vessels. Platelets are crucial for the formation of clots and for clot strength. Platelet activation involves aggregation, attachment to fibrin and clot retraction. Most assays that address platelet function measure platelet aggregation, not clot retraction. Here, we describe a 96-well-based clot retraction assay that requires a relatively short runtime and small sample volume. The assay involves continuous optical density monitoring of platelet-rich plasma that is activated with thrombin. The data can be analyzed using time-series analytical tools to generate quantitative information about different phases of clot formation and clot retraction. The assay demonstrated good repeatability and reproducibility and was robust to different calcium concentrations. Impairment of platelet bioenergetics, actin polymerization, fibrin interaction, and signaling significantly affected clot retraction and was detected and showed good agreement with light transmission aggregometry, suggesting that clot retraction is predictive of platelet function. Using this microplate clot retraction assay, we showed a significant difference in platelets stored in autologous plasma compared with platelet additive solution after 7 days of room temperature storage.

Platelets are cell fragments in the blood that are necessary for clot formation. They are crucial to preventing excessive bleeding following trauma. To form clots, platelets clump (aggregate) and attach to fibrin protein and cells inside the blood vessels to form strong web-like structures. Platelets also contract to pull the edges of the wound close. Most measurements of platelet function involve aggregation. This paper focuses on platelet contraction. Here, we describe a new assay to measure platelets contraction that is repeatable and reproducible. The assay uses standard and common laboratory equipment and can be performed by most laboratory personnel and has the potential to detect clinical pathologies of clot formation. The assay could be developed for bedside patient care where platelet function could be assessed rapidly and assist in the diagnosis of coagulation and platelet disorders.

An analysis of early volume resuscitation and the association with prolonged mechanical ventilation.

BACKGROUND: Previous studies have found that intravenous fluid administration within the first 24 h may be associated with prolonged mechanical ventilation (PMV). We examined the association between initial 24 h fluids and PMV in combat casualties. METHODS: This is a secondary analysis of a previously described dataset from the Department of Defense Trauma Registry (DODTR). We included casualties with at least 24 h on the ventilator and no significant traumatic brain injury. The definition of PMV and associations were constructed using univariable and multivariable logistic regression models. RESULTS: We identified 1508 casualties available for analysis for this study - 1275 in the non-PMV cohort (<9 days on ventilator vs. 233 in the PMV cohort (≥9 days on ventilator). Explosives comprised the most common mechanism of injury for both groups (72% vs. 75%) followed by firearms (21% vs. 16%). The composite injury severity score (ISS) was lower in the non-PMV cohort (18 vs. 30, p < .001). There were lower volumes of all resuscitation fluid within the first 24 h in the non-PMV cohort. When adjusting for composite ISS and mechanism of injury in a multivariable logistic regression model with PMV as the outcome, crystalloid volume (unit odds ratio [UOR] 1.07) and colloid volume (UOR 1.03) were both associated with PMV. CONCLUSIONS: We found that volume of resuscitation fluids were substantially higher in the PMV cohort. Our findings suggest the need for caution with the routine use of crystalloid and colloid in the first 24 h of resuscitation.

The regional whole blood program in San Antonio, TX: A 3-year update on prehospital and in-hospital transfusion practices for traumatic and non-traumatic hemorrhage.

Low titer type O Rh-D + whole blood (LTO + WB) has become a first-line resuscitation medium for hemorrhagic shock in many centers around the World. Showing early effectiveness on the battlefield, LTO + WB is used in both the pre-hospital and in-hospital settings for traumatic and non-traumatic hemorrhage resuscitation. Starting in 2018, the San Antonio Whole Blood Collaborative has worked to provide LTO + WB across Southwest Texas, initially in the form of remote damage control resuscitation followed by in-hospital trauma resuscitation. This program has since expanded to include pediatric trauma resuscitation, obstetric hemorrhage, females of childbearing potential, and non-traumatic hemorrhage. The objective of this manuscript is to provide a three-year update on the successes and expansion of this system and outline resuscitation challenges in special populations.

An Analysis of 13 Years of Prehospital Combat Casualty Care: Implications for Maintaining a Ready Medical Force.

Background: Most potentially preventable deaths occur in the prehospital setting before reaching a military treatment facility with surgical capabilities. Thus, optimizing the care we deliver in the prehospital combat setting represents a ripe target for reducing mortality. We sought to analyze prehospital data within the Department of Defense Trauma Registry (DODTR). Materials and methods: We requested all encounters with any prehospital activity (e.g., interventions, transportation, vital signs) documented within the DODTR from January 2007 to March 2020 along with all hospital-based data that was available. We excluded from our search casualties that had no prehospital activity documented. Results: There were 28,950 encounters that met inclusion criteria. Of these, 25,897 (89.5%) were adults and 3053 were children (10.5%). There was a steady decline in the number of casualties encountered with the most notable decline occurring in 2014. U.S. military casualties comprised the largest proportion (n = 10,182) of subjects followed by host nation civilians (n = 9637). The median age was 24 years (interquartile range/IQR 21-29). Most were battle injuries (78.6%) and part of Operation ENDURING FREEDOM (61.8%) and Operation IRAQI FREEDOM (24.4%). Most sustained injuries from explosives (52.1%) followed by firearms (28.1%), with serious injury to the extremities (24.9%) occurring most frequently. The median injury severity score was 9 (IQR 4-16) with most surviving to discharge (95.0%). A minority had a documented medic or combat lifesaver (27.9%) in their chain of care, nor did they pass through an aid station (3.0%). Air evacuation predominated (77.9%). Conclusions: Within our dataset, the deployed U.S. military medical system provided prehospital medical care to at least 28,950 combat casualties consisting mostly of U.S. military personnel and host nation civilian care. There was a rapid decline in combat casualty volumes since 2014, however, on a per-encounter basis there was no apparent drop in procedural volume.

Effects of Intercept pathogen reduction treatment on extended cold storage of apheresis platelets.

BACKGROUND: Platelets pose the greatest transfusion-transmitted infectious risk among blood products. Refrigeration of platelets can mitigate bacterial contamination and extend platelet shelf life. Implementation of pathogen reduction technologies (PRTs) at blood banks has become increasingly popular to protect against emerging and reemerging infectious diseases. In this study, we sought to evaluate the effects of Intercept PRT on platelets collected on different platforms and cold-stored for up to 21 days in plasma and platelet additive solution (PAS). METHODS: Double-dose apheresis platelets were collected with use of a Trima or Amicus system into either 100% plasma or 65% InterSol PAS/35% plasma and split equally between two bags. One bag served as control, while the other received Intercept PRT treatment. Bags were stored unagitated in the cold and evaluated on Days 1, 7, 14, and 21 to assess platelet metabolism, activation, aggregation, and clot formation and retraction. RESULTS: By Day 14 of storage, lactate levels reached approximately 13 mmol/L for all samples irrespective of Intercept treatment. Mean clot firmness dropped from the 62.2- to 67.5-mm range (Day 1) to the 28.4- to 51.3-mm range (Day 21), with no differences observed between groups. Clot weights of Intercept-treated Trima/plasma samples were significantly higher than control by Day 14 of storage (P = .004), indicating a reduced clot retraction function. Intercept treatment caused a higher incidence of plasma membrane breakdown in plasma-stored platelets (P = .0013; Trima/plasma Day 14 Control vs Intercept). CONCLUSIONS: Intercept treatment of platelets and subsequent cold storage, in plasma or PAS, results in comparable platelet metabolism platelets for up to 14 days of storage but altered clotting dynamics. Pathogen-reduced platelets with an extended shelf life would be beneficial for the deployed setting and would greatly impact transfusion practice among civilian transfusion centers.

Coagulation function of never frozen liquid plasma stored for 40 days.

BACKGROUND: Never frozen liquid plasma (LP) has limited shelf life versus fresh frozen plasma (FFP) or plasma frozen within 24 h (PF24). Previous studies showed decreasing factor activities after Day (D)14 in thawed FFP but no differences between LP and FFP until D10. This study examined LP function through D40. STUDY DESIGN AND METHODS: FFP and PF24 were stored at -20°C until assaying. LP was assayed on D5 then stored (4°C) for testing through D40. A clinical coagulation analyzer measured Factor (F)V, FVIII, fibrinogen, prothrombin time (PT), and activated partial thromboplastin time (aPTT). Thromboelastography (TEG) and thrombogram measured functional coagulation. Ristocetin cofactor assay quantified von Willebrand factor (vWF) activity. Residual platelets were counted. RESULTS: FV/FVIII showed diminished activity over time in LP, while PT and aPTT both increased over time. LP vWF declined significantly by D7. Fibrinogen remained high through D40. Thrombin lagtime was delayed in LP but consistent to D40, while peak thrombin was significantly lower in LP but did not significantly decline over time. TEG R-time and angle remained constant. LP and PF24 (with residual platelets) had initially higher TEG maximum amplitudes (MA), but by D14 LP was similar to FFP. CONCLUSION: Despite significant declines in some factors in D40 LP, fibrinogen concentration and TEG MA were stable suggesting stored LP provides fibrinogen similarly to frozen plasmas even at D40. LP is easier to store and prepare for prehospital transfusion, important benefits when the alternative is crystalloid.

Cold-stored platelets have better preserved contractile function in comparison with room temperature-stored platelets over 21 days.

Although it is well established that transfusion of platelets in cases of severe bleeding reduces mortality, the availability of platelets is hampered by harsh restrictions on shelf life due to elevated risks of microbial contamination and functional losses with room temperature-stored platelets (RTP) kept at 22°C. In contrast, many recent studies have shown that 4°C cold-stored platelets (CSP) are able to overcome these shortcomings leading to the recent Food and Drug Administration licensure for 14-day stored CSP when conventional platelets are unavailable. This work expands the evidence supporting superiority of CSP function by assaying the less explored platelet-mediated clot retraction of RTP and CSP in either autologous plasma (AP) or platelet additive solution (PAS) for up to 21 days. The results demonstrate that CSP have better preservation of contractile function, exhibiting retraction for up to 21 days in both AP and PAS and forming highly ordered fibrin scaffolds similar to those of fresh platelets. In contrast, RTP stored in AP showed impaired contractile function by Day 5 with no retraction after 10 days, whereas PAS-stored RTP retained contractile function for up to 21 days. Collectively, these findings support extended storage of CSP and suggest that storage in PAS can mitigate functional losses in RTP.

Evaluation of KP-1199: a novel acetaminophen analog for hemostatic function and antinociceptive effects.

BACKGROUND: Acetaminophen (APAP) is a widely self-prescribed analgesic for mild to moderate pain, but overdose or repeat doses can lead to liver injury and death. Kalyra Pharmaceuticals has developed a novel APAP analog, KP-1199, currently in Phase 1 clinical studies, which lacks hepatotoxicity. In this study, the authors evaluated the antinociceptive effect of KP-1199 on thermal injury-induced nociceptive behaviors as well as hemostatic parameters using human blood samples. METHODS: Full-thickness thermal injury was induced in anesthetized adult male Sprague-Dawley rats. On day 7 post-injury, KP-1199 (30 and 60 mg/kg) or APAP (60 mg/kg) was administered orally. Antinociception of KP-1199 and APAP were assessed at multiple time points using Hargreaves' test. In separate experiments, human whole blood was collected and treated with either KP-1199, APAP, or Vehicle (citrate buffer) at 1× (214 µg/ml) and 10× (2140 µg/ml) concentrations. The treated blood samples were assessed for: clotting function, thrombin generation, and platelet activation. RESULTS: APAP did not produce antinociceptive activity. KP-1199 treatment significantly increased the nociceptive threshold, and the antinociceptive activity persisted up to 3 h post-treatment. In human samples, 10× APAP caused significantly prolonged clotting times and increased platelet activation, whereas KP-1199 had caused no negative effects on either parameter tested. CONCLUSION: These results suggest that KP-1199 possesses antinociceptive activity in a rat model of thermal injury. Since KP-1199 does not induce platelet activation or inhibit coagulation, it presents an attractive alternative to APAP for analgesia, especially for battlefield or surgical scenarios where blood loss and blood clotting are of concern.

More sophisticated than a drink cooler or an old sphygmomanometer but still not adequate for prehospital blood: A market review of commercially available equipment for prehospital blood transport and administration.

BACKGROUND: Hemorrhage is the leading cause of death in trauma patients with most fatalities occurring before reaching a higher level of care-this applies to both the civilian setting and the military combat setting. Hemostatic resuscitation with increased emphasis on blood transfusion while limiting use of crystalloids has become routine in trauma care. However, the prehospital setting-especially in combat-presents unique challenges with regard to storage, transport, and administration. We sought to evaluate available technology on the market for storage and administration technology that is relevant to the prehospital setting. STUDY DESIGN AND METHODS: We conducted a market review of available technology through subject-matter expert inquiry, reviews of published literature, reviews of Federal Drug Administration databases, internal military publications, and searches of Google. RESULTS: We reviewed and described a total of 103 blood transporters, 22 infusers, and 6 warmers. CONCLUSIONS: The risk of on-scene fatality in trauma patients and recent developments in trauma care demonstrate the need for prehospital transfusion. These transfusions have been logistically prohibited in many operations. We have reviewed the current commercially available equipment and recommended pursuit of equipment that improves accessibility to field transfusion. Current technology has limited applicability for the prehospital setting and is further limited for the military setting.

An analysis of outcomes for pediatric trauma warm fresh whole blood recipients in Iraq and Afghanistan.

BACKGROUND: Whole blood therapy-which contains the ideal balance of components, and particularly fresh whole blood-has been shown to be beneficial in adult trauma. It remains unclear whether there is potential benefit in the pediatric population. STUDY DESIGN AND METHODS: This is a secondary analysis of previously published data analyzing pediatric casualties undergoing massive transfusion in the Department of Defense Trauma Registry. Pediatric patients with traumatic injury who were transfused at least one blood product were included in the analysis. We compared children who received component therapy exclusively to those who received any amount of warm fresh whole blood. RESULTS: Of the 3439 pediatric casualties within our dataset, 1244 were transfused at least one blood product within the first 24 h. There were 848 patients without severe head injury. Within this cohort, 23 children received warm fresh whole blood overall, 20 of whom did not have severe head injury. In an adjusted analysis, the odds ratio (95% confidence interval [CI]) for survival for warm fresh whole blood recipients was 2.86 (0.40-20.45). After removing children with severe brain injury, there was an independent association with improved survival for warm fresh whole blood recipients with an odds ratio (95% CI) of 58.63 (2.70-1272.67). DISCUSSION: Our data suggest that warm fresh whole blood may be associated with improved survival in children without severe head injury. Larger prospective studies are needed to assess the efficacy and safety of whole blood in children with severe traumatic bleeding.

Cold storage of platelets in platelet additive solution maintains mitochondrial integrity by limiting initiation of apoptosis-mediated pathways.

BACKGROUND: Cold storage of platelets in plasma maintains hemostatic function and is an attractive alternative to room temperature platelets (RTPs). We have recently shown that functional differences between cold-stored platelets (CSPs) and RTPs after 5-day storage are associated with mitochondrial respiration and that CSPs in platelet (PLT) additive solution (PAS) can maintain hemostatic function for at least 15 days. STUDY DESIGN AND METHODS: This study tested the hypothesis that cold storage in PAS preserves mitochondrial integrity by reducing PLT apoptosis. CSPs and RTPs in plasma or PAS were stored and assayed for up to 15 days for mitochondrial function and integrity, mitochondrial-associated mRNA transcript expression, apoptotic proteins, and apoptotic flow cytometry metrics. RESULTS: CSP preserved mitochondria-associated mRNA comparable to baseline levels, improved mitochondrial respiration, and minimized depolarization to Day 15. Additionally, CSPs had minimal induction of caspases, preservation of plasma membrane integrity, and low expression of pro-apoptotic Bax. Storage in PAS appeared to be protective for RTPs in some parameters and enhanced the effects of CSPs. CONCLUSION: Mitochondrial function and molecular analyses defined CSP priming as distinctly different from the well-documented RTP storage lesion. While current blood bank storage at room temperature is limited to 5 to 7 days, refrigeration and storage in PAS for up to 15 days may represent an opportunity to enhance inventories and access to PLT hemostatic support for bleeding patients.