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1.
Lancet Glob Health ; 12(3): e522-e529, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38365422

ABSTRACT

In rural settings worldwide, many people live in effective blood deserts without access to any blood transfusion. The traditional system of blood banking is logistically complex and expensive for many resource-restricted settings and demands innovative and multidisciplinary solutions. 17 international experts in medicine, industry, and policy participated in an exploratory process with a 2-day hybrid seminar centred on three promising innovative strategies for blood transfusions in blood deserts: civilian walking blood banks, intraoperative autotransfusion, and drone-based blood delivery. Participant working groups conducted literature reviews and interviews to develop three white papers focused on the current state and knowledge gaps of each innovation. Seminar discussion focused on defining blood deserts and developing innovation-specific implementation agendas with key research and policy priorities for future work. Moving forward, advocates should prioritise the identification of blood deserts and address the context-specific challenges for these innovations to alleviate the ongoing crisis in blood deserts.


Subject(s)
Blood Banks , Blood Transfusion , Humans , Policy , Consensus , Rural Population
2.
J Spec Oper Med ; 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38408045

ABSTRACT

BACKGROUND: Tactical Combat Casualty Care (TCCC) guidelines recognize low-titer group O whole blood (LTOWB) as the resuscitative fluid of choice for combat wounded. Utilization of prescreened LTOWB in a walking blood bank (WBB) format has been well described by the Ranger O low-titer blood (ROLO) and the United States Marine Corps Valkyrie programs, but it has not been applied to the maritime setting. METHODS: We describe three WBB experiences of an expeditionary resuscitative surgical system (ERSS) team, attached to three nontraditional maritime medical receiving platforms, over 6 months. RESULTS: Significant variations were identified in the number of screened eligible donors, the number of LTOWB donors, and the timely arrival at WBB activation sites between the platforms. Overall, 95% and 84% of the screened eligible group O blood donors on the Arleigh Burke Class Destroyer (DDG) and Nimitz Class Aircraft Carrier (CVN), respectively, were determined to be LTOWB. However, only 37% of the eligible screened group O blood donors aboard the Harper's Ferry Class Dock Landing Ship (LSD) were found to be LTOWB. Of the eligible donors, 66% did not complete screening, with 52% citing a correctable reason for nonparticipation. CONCLUSION: LTOWB attained through WBBs may be the only practical resuscitative fluid on maritime platforms without inherent blood product storage capabilities to perform remote damage control resuscitation. Future efforts should focus on optimizing WBBs through capability development, education, and training efforts.

3.
Sci Rep ; 14(1): 3874, 2024 02 16.
Article in English | MEDLINE | ID: mdl-38365865

ABSTRACT

Pre-hospital potentially preventable trauma related deaths are mainly due to hypoperfusion-induced tissue hypoxia leading to irreversible organ dysfunction at or near the point of injury or during transportation prior to receiving definitive therapy. The prolyl hydroxylase domain (PHD) is an oxygen sensor that regulates tissue adaptation to hypoxia by stabilizing hypoxia inducible factor (HIF). The benefit of PHD inhibitors (PHDi) in the treatment of anemia and lactatemia arises from HIF stabilization, which stimulates endogenous production of erythropoietin and activates lactate recycling through gluconeogenesis. The results of this study provide insight into the therapeutic roles of MK-8617, a pan-inhibitor of PHD-1, 2, and 3, in the mitigation of lactatemia in anesthetized rats with polytrauma and hemorrhagic shock. Additionally, in an anesthetized rat model of lethal decompensated hemorrhagic shock, acute administration of MK-8617 significantly improves one-hour survival and maintains survival at least until 4 h following limited resuscitation with whole blood (20% EBV) at one hour after hemorrhage. This study suggests that pharmaceutical interventions to inhibit prolyl hydroxylase activity can be used as a potential pre-hospital countermeasure for trauma and hemorrhage at or near the point of injury.


Subject(s)
Prolyl-Hydroxylase Inhibitors , Shock, Hemorrhagic , Rats , Animals , Prolyl-Hydroxylase Inhibitors/pharmacology , Prolyl-Hydroxylase Inhibitors/therapeutic use , Pharmaceutical Preparations , Shock, Hemorrhagic/drug therapy , Hypoxia/drug therapy , Prolyl Hydroxylases , Hypoxia-Inducible Factor-Proline Dioxygenases
4.
Sci Adv ; 9(48): eadi0508, 2023 12.
Article in English | MEDLINE | ID: mdl-38039367

ABSTRACT

Platelet transfusions are essential for managing bleeding and hemostatic dysfunction and could be expanded as a cell therapy due to the multifunctional role of platelets in various diseases. Creating these cell therapies will require modifying transfusable donor platelets to express therapeutic proteins. However, there are currently no appropriate methods for genetically modifying platelets collected from blood donors. Here, we describe an approach using platelet-optimized lipid nanoparticles containing mRNA (mRNA-LNP) to enable exogenous protein expression in human and rat platelets. Within the library of mRNA-LNP tested, exogenous protein expression did not require nor correlate with platelet activation. Transfected platelets retained hemostatic function and accumulated in regions of vascular damage after transfusion into rats with hemorrhagic shock. We expect this technology will expand the therapeutic potential of platelets.


Subject(s)
Blood Platelets , Hemostatics , Humans , Rats , Animals , RNA, Messenger/genetics , RNA, Messenger/metabolism , Blood Platelets/metabolism , Blood Donors , Hemostatics/metabolism
5.
Front Immunol ; 14: 1225047, 2023.
Article in English | MEDLINE | ID: mdl-37822938

ABSTRACT

Introduction: Trauma patients are susceptible to coagulopathy and dysfunctional immune responses. Mesenchymal stromal cells (MSCs) are at the forefront of the cellular therapy revolution with profound immunomodulatory, regenerative, and therapeutic potential. Routine assays to assess immunomodulation activity examine MSC effects on proliferation of peripheral blood mononuclear cells (PBMCs) and take 3-7 days. Assays that could be done in a shorter period of time would be beneficial to allow more rapid comparison of different MSC donors. The studies presented here focused on assays for MSC suppression of mitogen-stimulated PBMC activation in time frames of 24 h or less. Methods: Three potential assays were examined-assays of apoptosis focusing on caspase activation, assays of phosphatidyl serine externalization (PS+) on PBMCs, and measurement of tumor necrosis factor alpha (TNFα) levels using rapid ELISA methods. All assays used the same initial experimental conditions: cryopreserved PBMCs from 8 to 10 pooled donors, co-culture with and without MSCs in 96-well plates, and PBMC stimulation with mitogen for 2-72 h. Results: Suppression of caspase activity in activated PBMCs by incubation with MSCs was not robust and was only significant at times after 24 h. Monitoring PS+ of live CD3+ or live CD4+/CD3+ mitogen-activated PBMCs was dose dependent, reproducible, robust, and evident at the earliest time point taken, 2 h, although no increase in the percentage of PS+ cells was seen with time. The ability of MSC in co-culture to suppress PBMC PS+ externalization compared favorably to two concomitant assays for MSC co-culture suppression of PBMC proliferation, at 72 h by ATP assay, or at 96 h by fluorescently labeled protein signal dilution. TNFα release by mitogen-activated PBMCs was dose dependent, reproducible, robust, and evident at the earliest time point taken, with accumulating signal over time. However, suppression levels with MSC co-culture was reliably seen only after 24 h. Discussion: Takeaways from these studies are as follows: (1) while early measures of PBMC activation is evident at 2-6 h, immunosuppression was only reliably detected at 24 h; (2) PS externalization at 24 h is a surrogate assay for MSC immunomodulation; and (3) rapid ELISA assay detection of TNFα release by PBMCs is a robust and sensitive assay for MSC immunomodulation at 24 h.


Subject(s)
Mesenchymal Stem Cells , T-Lymphocytes , Humans , Leukocytes, Mononuclear , Tumor Necrosis Factor-alpha/pharmacology , Mitogens/pharmacology , Immunosuppression Therapy/methods , Intercellular Signaling Peptides and Proteins/pharmacology , Caspases
6.
Am J Respir Crit Care Med ; 208(12): 1283-1292, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37797214

ABSTRACT

Rationale: Early post injury mitigation strategies in ARDS are in short supply. Treatments with allogeneic stromal cells are administered after ARDS develops, require specialized expertise and equipment, and to date have shown limited benefit. Objectives: Assess the efficacy of immediate post injury intravenous administration of autologous or allogeneic bone marrow-derived mesenchymal stromal cells (MSCs) for the treatment of acute respiratory distress syndrome (ARDS) due to smoke inhalation and burns. Methods: Yorkshire swine (n = 32, 44.3 ± 0.5 kg) underwent intravenous anesthesia, placement of lines, severe smoke inhalation, and 40% total body surface area flame burns, followed by 72 hours of around-the-clock ICU care. Mechanical ventilation, fluids, pressors, bronchoscopic cast removal, daily lung computed tomography scans, and arterial blood assays were performed. After injury and 24 and 48 hours later, animals were randomized to receive autologous concentrated bone marrow aspirate (n = 10; 3 × 106 white blood cells and a mean of 56.6 × 106 platelets per dose), allogeneic MSCs (n = 10; 6.1 × 106 MSCs per dose) harvested from healthy donor swine, or no treatment in injured control animals (n = 12). Measurements and Main Results: The intravenous administration of MSCs after injury and at 24 and 48 hours delayed the onset of ARDS in swine treated with autologous MSCs (48 ± 10 h) versus control animals (14 ± 2 h) (P = 0.004), reduced ARDS severity at 24 (P < 0.001) and 48 (P = 0.003) hours, and demonstrated visibly diminished consolidation on computed tomography (not significant). Mortality at 72 hours was 1 in 10 (10%) in the autologous group, 5 in 10 (50%) in the allogeneic group, and 6 in 12 (50%) in injured control animals (not significant). Both autologous and allogeneic MSCs suppressed systemic concentrations of TNF-α (tumor necrosis factor-α). Conclusions: The intravenous administration of three doses of freshly processed autologous bone marrow-derived MSCs delays ARDS development and reduces its severity in swine. Bedside retrieval and administration of autologous MSCs in swine is feasible and may be a viable injury mitigation strategy for ARDS.


Subject(s)
Burns , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Respiratory Distress Syndrome , Swine , Animals , Bone Marrow , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/pathology , Tumor Necrosis Factor-alpha , Administration, Intravenous , Burns/pathology , Mesenchymal Stem Cell Transplantation/methods
7.
ASAIO J ; 69(12): 1074-1082, 2023 12 01.
Article in English | MEDLINE | ID: mdl-37801726

ABSTRACT

Extracorporeal membrane oxygenation (ECMO) supplies circulatory support and gas exchange to critically ill patients. Despite the use of systemic anticoagulation, blood exposure to ECMO surfaces causes thromboembolism complications. Inhibition of biomaterial surface-mediated activation of coagulation factor XI (FXI) may prevent device-associated thrombosis. Blood was collected from healthy volunteers (n = 13) following the U.S. Army Institute of Surgical Research standard operating procedure for testing in an ex vivo ECMO circuit. A roller-pump circuit circulated either 0.5 U/ml of unfractionated heparin alone or in combination with the anti-FXI immunoglobulin G (IgG) (AB023) for 6 hours or until clot formation caused device failure. Coagulation factor activity, platelet counts, time to thrombin generation, peak thrombin, and endogenous thrombin potential were quantified. AB023 in addition to heparin sustained circuit patency in all tested circuits (5/5) after 6 hours, while 60% of circuits treated with heparin alone occluded (3/8), log-rank p < 0.03. AB023 significantly prolonged the time to clot formation as compared to heparin alone (15.5 vs . 3.3 minutes; p < 0.01) at the 3-hour time point. AB023 plus heparin significantly reduced peak thrombin compared to heparin alone (123 vs . 217 nM; p < 0.01). Inhibition of contact pathway activation of FXI may be an effective adjunct to anticoagulation in extracorporeal life support.


Subject(s)
Extracorporeal Membrane Oxygenation , Thrombosis , Humans , Child , Heparin/adverse effects , Factor XI , Extracorporeal Membrane Oxygenation/methods , Thrombin , Thrombosis/etiology , Thrombosis/prevention & control , Anticoagulants/adverse effects
8.
Platelets ; 34(1): 2254403, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37700390

ABSTRACT

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.


Subject(s)
Platelet Activation , Platelet-Rich Plasma , Humans , Reproducibility of Results , Platelet Function Tests , Fibrin
9.
J Trauma Acute Care Surg ; 95(5): 746-754, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37431975

ABSTRACT

BACKGROUND: The beneficial effects of estrogens on survival from hemorrhage have been suggested in some preclinical models. This study investigated the effects of ethynylestradiol-3-sulfate (EE-3-S) on coagulation, metabolism and survival in pigs following traumatic hemorrhage. METHODS: Twenty-six pigs were randomized into: normal saline group (NS, n = 10), EE-3-S group (EE-3, n = 11) groups, and no resuscitation group (NR, n = 5). Femur fracture was performed in each pig's left leg, followed by hemorrhage of 55% of estimated blood volume and a 10-minute shock period. Afterward, pigs were resuscitated with a small volume of either NS alone (4 mL/kg) or EE-3-S with NS (1 mL/kg at concentration of 1 mg/mL, plus NS solution of 3 mL/kg). Pigs in NR group were not resuscitated with any fluid. All pigs were then monitored for 6 hours or until death, with hemodynamics and survival times recorded. Blood samples were taken during the study for measurements of oxygen metabolism (oxygen delivery, extraction, and consumption) and coagulation function (using Rotem with Extem reagents). RESULTS: All baseline measurements were similar among the three groups. In the NS group, femur fracture and hemorrhage immediately reduced mean arterial pressure (MAP, 74 ± 3 mm Hg to 44 ± 4 mm Hg) and increased heart rate (97 ± 5 bpm to 218 ± 14 bpm, both p < 0.05). Similar changes in MAP and heart rate were observed in the EE-3 and NR groups. There were no differences observed in changes of Rotem ® measurements or oxygen metabolism among the groups during the study. At 6 hours, four pigs in NS, four pigs in EE-3-S, and two pigs in the NR group survived to the end of the study. The mean survival times were similar among the NS (212 ± 43 minutes), EE-3 (212 ± 39 minutes), and NR (223 ± 63 minutes) groups ( p = 0.9845). CONCLUSION: Following severe traumatic hemorrhage, hypotensive resuscitation with EE-3-S did not impact coagulation, metabolism, or survival in pigs.


Subject(s)
Hemorrhage , Shock, Hemorrhagic , Animals , Blood Coagulation , Ethinyl Estradiol/pharmacology , Oxygen , Resuscitation , Swine
10.
Transfusion ; 63(7): 1366-1375, 2023 07.
Article in English | MEDLINE | ID: mdl-37293980

ABSTRACT

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.


Subject(s)
Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Humans , Child , Cells, Cultured , Immunomodulation , Freezing , Culture Media , Cell Proliferation
12.
Shock ; 60(2): 199-205, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37335312

ABSTRACT

ABSTRACT: Background: Hemorrhage remains the leading cause of death on the battlefield. This study aims to assess the ability of an artificial intelligence triage algorithm to automatically analyze vital-sign data and stratify hemorrhage risk in trauma patients. Methods: Here, we developed the APPRAISE-Hemorrhage Risk Index (HRI) algorithm, which uses three routinely measured vital signs (heart rate and diastolic and systolic blood pressures) to identify trauma patients at greatest risk of hemorrhage. The algorithm preprocesses the vital signs to discard unreliable data, analyzes reliable data using an artificial intelligence-based linear regression model, and stratifies hemorrhage risk into low (HRI:I), average (HRI:II), and high (HRI:III). Results: To train and test the algorithm, we used 540 h of continuous vital-sign data collected from 1,659 trauma patients in prehospital and hospital (i.e., emergency department) settings. We defined hemorrhage cases (n = 198) as those patients who received ≥1 unit of packed red blood cells within 24 h of hospital admission and had documented hemorrhagic injuries. The APPRAISE-HRI stratification yielded a hemorrhage likelihood ratio (95% confidence interval) of 0.28 (0.13-0.43) for HRI:I, 1.00 (0.85-1.15) for HRI:II, and 5.75 (3.57-7.93) for HRI:III, suggesting that patients categorized in the low-risk (high-risk) category were at least 3-fold less (more) likely to have hemorrhage than those in the average trauma population. We obtained similar results in a cross-validation analysis. Conclusions: The APPRAISE-HRI algorithm provides a new capability to evaluate routine vital signs and alert medics to specific casualties who have the highest risk of hemorrhage, to optimize decision-making for triage, treatment, and evacuation.


Subject(s)
Artificial Intelligence , Triage , Humans , Triage/methods , Hemorrhage/diagnosis , Hemorrhage/therapy , Algorithms , Emergency Service, Hospital
14.
Transfusion ; 63 Suppl 3: S77-S82, 2023 05.
Article in English | MEDLINE | ID: mdl-37066994

ABSTRACT

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.


Subject(s)
Military Personnel , Humans , Prospective Studies , Blood Transfusion , Hemorrhage , Resuscitation
15.
Transfusion ; 63 Suppl 3: S146-S158, 2023 05.
Article in English | MEDLINE | ID: mdl-37070399

ABSTRACT

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.


Subject(s)
Blood Platelets , Hemostatics , Humans , Plateletpheresis/methods , Cell Separation , Cell Count
16.
Transfusion ; 63 Suppl 3: S249-S255, 2023 05.
Article in English | MEDLINE | ID: mdl-37097201

ABSTRACT

BACKGROUND: The U.S. Department of Defense (DoD) collects blood from volunteer DoD donors in U.S. Food and Drug Administration (FDA)-regulated centers, and from emergency donor panels in overseas operations. Emerging infectious diseases could reduce DoD access to blood products. In August 2016, FDA determined that Zika virus was transfusion-transmitted and advised that donated blood should be screened for Zika utilizing one of two investigational new drug (IND) applications. The Armed Services Blood Program (ASBP) tested blood using its own protocol concurrently with the IND study sponsored by Roche Molecular Systems, Inc., titled "A Prospective Study to Evaluate the Specificity of the cobas Zika test for use on the cobas 6800/8800 System for Screening of Blood Donations for the Presence of Zika virus RNA." STUDY DESIGN AND METHODS: This prospective clinical trial (September 2016-August 2017) evaluated the specificity of the cobas Zika 6800/8800 System. Consenting volunteers were screened for Zika by participating reference labs. Participants with positive screens were offered a follow-up study using alternative PCR and serology assays. RESULTS: 92,618 DoD donors enrolled; four tested positive on screening (0.0043%; CI 0.001176896%, 0.01105894%). Three enrolled in follow-up testing and none were positive. These results were comparable to all U.S. donors: 3,858,114 enrolled (excluding Puerto Rico) with 459 positive screens (0.0119%; CI 0.01083582%, 0.01303962%). CONCLUSION: The study demonstrated the effectiveness of the cobas Zika test. DoD donors, who are included in emergency donor panels during military operations, were at no higher risk for Zika than the overall U.S. donor population.


Subject(s)
Communicable Diseases, Emerging , Military Personnel , Zika Virus Infection , Zika Virus , Humans , Zika Virus/genetics , Communicable Diseases, Emerging/diagnosis , Communicable Diseases, Emerging/epidemiology , Communicable Diseases, Emerging/prevention & control , Follow-Up Studies , Prospective Studies , Zika Virus Infection/diagnosis , Zika Virus Infection/epidemiology , Zika Virus Infection/prevention & control , Blood Donors
18.
Anesthesiology ; 139(1): 77-90, 2023 07 01.
Article in English | MEDLINE | ID: mdl-37027803

ABSTRACT

BACKGROUND: The use of low-titer group O whole blood is increasing. To reduce wastage, unused units can be converted to packed red blood cells. Supernatant is currently discarded post-conversion; however, it could be a valuable transfusable product. The aim of this study was to evaluate supernatant prepared from late-storage low-titer group O whole blood being converted to red blood cells, hypothesizing it will have higher hemostatic activity compared to fresh never-frozen liquid plasma. METHODS: Low-titer group O whole blood supernatant (n = 12) prepared on storage day 15 was tested on days 15, 21, and 26 and liquid plasma (n = 12) on 3, 15, 21, and 26. Same-day assays included cell counts, rotational thromboelastometry, and thrombin generation. Centrifuged plasma from units was banked for microparticle characterization, conventional coagulation, clot structure, hemoglobin, and additional thrombin generation assays. RESULTS: Low-titer group O whole blood supernatant contained more residual platelets and microparticles compared to liquid plasma. At day 15, low-titer group O whole blood supernatant elicited a faster intrinsic clotting time compared to liquid plasma (257 ± 41 vs. 299 ± 36 s, P = 0.044), and increased clot firmness (49 ± 9 vs. 28 ± 5 mm, P < 0.0001). Low-titer group O whole blood supernatant showed more significant thrombin generation compared to liquid plasma (day 15 endogenous thrombin potential 1,071 ± 315 vs. 285 ± 221 nM·min, P < 0.0001). Flow cytometry demonstrated low-titer group O whole blood supernatant contained significantly more phosphatidylserine and CD41+ microparticles. However, thrombin generation in isolated plasma suggested residual platelets in low-titer group O whole blood supernatant were a greater contributor than microparticles. Additionally, low-titer group O whole blood supernatant and liquid plasma showed no difference in clot structure, despite higher CD61+ microparticle presence. CONCLUSIONS: Plasma supernatant produced from late-storage low-titer group O whole blood shows comparable, if not enhanced, in vitro hemostatic efficacy to liquid plasma.


Subject(s)
Hemostatics , Thrombin , Thrombin/analysis , Hemostasis , Blood Coagulation , Blood Platelets , Thrombelastography
19.
Transfusion ; 63 Suppl 3: S120-S125, 2023 05.
Article in English | MEDLINE | ID: mdl-37072924

ABSTRACT

BACKGROUND: Platelets stored at room temperature (22-24°C) for transfusion purposes have a shelf life of 5-7 days, or 72 h when stored refrigerated (1-6°C). The limited shelf life of platelet products severely compromises platelet inventory. We hypothesized that cold storage of platelets in 100% plasma using xenon gas under high pressure would extend shelf life to 14 days. STUDY DESIGN AND METHODS: Double apheresis platelet units were collected and split equally between two bags. One unit was placed in a hyperbaric chamber, pressurized to 4 bars with a xenon/oxygen gas mixture, and placed in a refrigerator for 14 days (Xe). The remaining unit was aliquoted into mini-bags (10 ml) for storage at room temperature (RTP) or in cold (CSP). Samples were assayed on days 5 (RTP) or 14 (Xe and CSP) for count, metabolism, clot strength, platelet aggregation, and activation markers. RESULTS: The platelet count in Xe samples was lower than that of RTP but significantly higher than CSP. Despite similar levels of glucose and lactate, the pH of Xe samples was significantly lower than CSP. Glycoprotein expression was better preserved by Xe storage compared to CSP, but no differences in activation were observed. Thromboelastography and aggregometry results were comparable between all groups. DISCUSSION: Cold storage of platelets in plasma with hyperbaric xenon provides no significant improvement in platelet function over cold storage alone. The use of a hyperbaric chamber and the slow off-gassing of Xe-stored units complicate platelet storage and delivery logistics.


Subject(s)
Blood Platelets , Blood Preservation , Humans , Blood Preservation/methods , Blood Platelets/metabolism , Cryopreservation/methods , Cold Temperature , Platelet Aggregation
20.
Transfusion ; 63 Suppl 3: S67-S76, 2023 05.
Article in English | MEDLINE | ID: mdl-36971031

ABSTRACT

BACKGROUND: Data demonstrate the benefit of blood product administration near point-of-injury (POI). Fresh whole blood transfusion from a pre-screened donor provides a source of blood at the POI when resources are constrained. We captured transfusion skills data for medics performing autologous blood transfusion training. METHODS: We conducted a prospective, observational study of medics with varying levels of experience. Inexperienced medics were those with minimal or no reported experience learning the autologous transfusion procedures, versus reported experience among special operations medics. When available, medics were debriefed after the procedure for qualitative feedback. We followed them for up to 7 days for adverse events. RESULTS: The median number of attempts for inexperienced and experienced medics was 1 versus 1 (interquartile range 1-1 for both, p = .260). The inexperienced medics had a slower median time to needle venipuncture access for the donation of 7.3 versus 1.5 min, needle removal after clamping time of 0.3 versus 0.2 min, time to bag preparation of 1.9 versus 1.0 min, time to IV access for reinfusion of 6.0 versus 3.0 min, time to transfusion completion of 17.3 versus 11.0 min, and time to IV removal of 0.9 versus 0.3 min (all p < .05). We noted one administrative safety event in which an allogeneic transfusion occurred. No major adverse events occurred. Qualitative data saturated around the need for quarterly training. CONCLUSIONS: Inexperienced medics have longer procedure times when training autologous whole blood transfusion skills. This data will help establish training measures of performance for skills optimization when learning this procedure.


Subject(s)
Blood Transfusion, Autologous , Military Personnel , Humans , Prospective Studies , Blood Transfusion , Tissue Donors
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