Investigation of factors that may affect the foveal avascular zone: An optical coherence tomography angiography study.

SIGNIFICANCE: An understanding of factors that affect the foveal avascular zone (FAZ) in healthy eyes may aid in the early identification of patients at risk of retinal pathology, thereby allowing better management and preventive measures to be implemented. PURPOSE: The size and shape of the FAZ can change due to retinal diseases associated with oxidative stress, including diabetic retinopathy, glaucoma, and macular degeneration. This study aimed to assess the relationship, if any, between factors that may affect the superficial FAZ (i.e., vessel density, vessel perfusion, overweight/obesity) and possible links with macular pigment optical density in young, healthy participants. METHODS: One hundred thirty-nine participants aged 18 to 35 years were recruited to this cross-sectional study. The superficial FAZ area, foveal vascularity, and central macular thickness (CMT) were assessed using the Cirrus 5000. Health parameters, body mass index, trunk fat %, and macular pigment were analyzed to determine possible associations with the superficial FAZ. RESULTS: Mean FAZ area was 0.23 ± 0.08 mm2. Females had a significantly larger mean FAZ area than males (p=0.002). The FAZ area was positively correlated with body mass index (Pearson's r = 0.189, p=0.026). Significant correlates of the FAZ area in the multivariate model included vessel perfusion (central), CMT, and trunk fat %, collectively explaining 65.1% of the overall variability. CONCLUSIONS: Study findings suggest that reduced vessel perfusion, thinner CMT, and higher trunk fat % are plausible predictors of a larger FAZ area in healthy Caucasian adults. Low macular pigment optical density was, however, not associated with increased FAZ size in young healthy eyes. Noninvasive optical coherence tomography angiography testing, in association with these predictors, may aid in the early detection and monitoring of retinal diseases associated with oxidative stress.

Low doses of ionising radiation: definitions and contexts.

The term 'low dose' is applied to different levels of dose depending on the circumstances of exposure, with the potential for confusion unless the reasoning is clear. The United Nations Scientific Committee on the Effects of Ionising Radiation has defined low absorbed doses of ionising radiation as below about 100 mGy, and low dose rates as below 0.1 mGy min-1 (6 mGy h-1). These values relate to the interpretation of scientific evidence from epidemiological and biological studies. The International Commission on Radiological Protection has used similar values of 100 mSv and 5 mSv h-1 and applied this categorisation directly to the specific situation of patients undergoing diagnostic procedures: doses below 100 mSv were referred to as 'low' and doses below 10 mSv as 'very low'. Consideration of other exposure situations suggest that the same terms can be used for exposures received by emergency workers. However, for workers and members of the public in planned exposure situations, it is suggested that the term 'low dose' applies to doses below 10 mSv and 1 mSv, respectively - that is, below the dose limits. In each case, dose is being used as a surrogate for risk - risks at low doses are uncertain and estimates may change, but order of magnitude considerations are sufficient in most cases. Doses of < 100 mSv, < 10 mSv and < 1 mSv correspond to life-time cancer risk estimates of the order of < 10-2, < 10-3 and < 10-4, respectively. .

A rapid ABO and RhD test demonstrates high fidelity to blood bank testing for RhD typing.

BACKGROUND: The rapid provision of blood products is life-saving for patients with massive hemorrhage. Ideally, RhD-negative blood products would be supplied to a woman of childbearing potential whose Rh type is unknown due to the risk of D-alloimmunization and the potential for hemolytic disease of the fetus and newborn to occur if RhD-positive blood products are transfused. Therefore, there is a need for a test that rapidly determines her RhD type. This study compared the RhD type determined using a rapid ABO and RhD test to the RhD type determined by an immunohematology reference laboratory. METHODS: After receiving ethics review board approval, 200 random, unique, deidentified patient samples that had undergone routine pretransfusion testing in an immunohematology reference laboratory using column agglutination technology were collected and tested using a rapid ABO and RhD test (Eldoncard Home kit 2511). The RhD typing results from these two methods were compared to determine the accuracy of the rapid ABO and RhD test. RESULTS: The rapid ABO and RhD test produced results that were concordant with the transfusion service's results in 199/200 (99.5%) of cases, with a negative predictive value of 98.2% and 99.3% sensitivity. The single outlier was likely an RhD variant due to its serological characteristics. DISCUSSION: These data indicate that this rapid ABO and RhD test could be used for the rapid determination of a patient's RhD type, perhaps even in the emergency department, which could guide the selection of blood products provided during their resuscitation.

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.

Hemostatic In Vitro Properties of Novel Plasma Supernatants Produced from Late-storage Low-titer Type O Whole Blood.

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.

Cold-stored platelet function is not significantly altered by agitation or manual mixing.

BACKGROUND: Cold storage of platelets (CS-PLT), results in better maintained hemostatic function compared to room-temperature stored platelets (RT-PLT), leading to increased interest and use of CS-PLT for actively bleeding patients. However, questions remain on best storage practices for CS-PLT, as agitation of CS-PLT is optional per the United States Food and Drug Administration. CS-PLT storage and handling protocols needed to be determined prior to upcoming clinical trials, and blood banking standard operating procedures need to be updated accordingly for the release of units due to potentially modified aggregate morphology without agitation. STUDY DESIGN AND METHODS: We visually assessed aggregate formation, then measured surface receptor expression (GPVI, CD42b (GPIbα), CD49 (GPIa/ITGA2), CD41/61 (ITGA2B/ITGB3; GPIIB/GPIIIA; PACI), CD62P, CD63, HLAI), thrombin generation, aggregation (collagen, adenosine diphosphate [ADP], and epinephrine activation), and viscoelastic function (ExTEM, FibTEM) in CS-PLT (Trima collection, 100% plasma) stored for 21 days either with or without agitation (Phase 1, n = 10 donor-paired units) and then without agitation with or without daily manual mixing to minimize aggregate formation and reduce potential effects of sedimentation (Phase 2, n = 10 donor-paired units). RESULTS: Agitation resulted in macroaggregate formation, whereas no agitation caused film-like sediment. We found no substantial differences in CS-PLT function between storage conditions, as surface receptor expression, thrombin generation, aggregation, and clot formation were relatively similar between intra-Phase storage conditions. DISCUSSION: Storage duration and not condition impacted phenotype and function. CS-PLT can be stored with or without agitation, and with or without daily mixing and standard metrics of hemostatic function will not be significantly altered.

The risk of thromboembolic events with early intravenous 2- and 4-g bolus dosing of tranexamic acid compared to placebo in patients with severe traumatic bleeding: A secondary analysis of a randomized, double-blind, placebo-controlled, single-center trial.

BACKGROUND: Screening for the risk of thromboembolism (TE) due to tranexamic acid (TXA) in patients with severe traumatic injury has not been performed in randomized clinical trials. Our objective was to determine if TXA dose was independently-associated with thromboembolism. STUDY DESIGN AND METHODS: This is a secondary analysis of a single-center, double-blinded, randomized controlled trial comparing placebo to a 2-g or 4-g intravenous TXA bolus dose in trauma patients with severe injury. We used multivariable discrete-time Cox regression models to identify associations with risk for thromboembolic events within 30 days post-enrollment. Event curves were created using discrete-time Cox regression. RESULTS: There were 50 patients in the placebo group, 49 in the 2-g, and 50 in the 4-g TXA group. In adjusted analyses for thromboembolism, a 2-g dose of TXA had an hazard ratio (HR, 95% confidence interval [CI]) of 3.20 (1.12-9.11) (p = .029), and a 4-g dose of TXA had an HR (95% CI) of 5.33 (1.94-14.63) (p = .001). Event curves demonstrated a higher probability of thromboembolism for both doses of TXA compared to placebo. Other parameters independently associated with thromboembolism include time from injury to TXA administration, body mass index, and total blood products transfused. DISCUSSION: In patients with severe traumatic injury, there was a dose-dependent increase in the risk of at least one thromboembolic event with TXA. TXA should not be withheld, but thromboembolism screening should be considered for patients receiving a dose of at least 2-g TXA intravenously for traumatic hemorrhage.

Thrombogenicity of biomaterials depends on hemodynamic shear rate.

BACKGROUND: While it is well recognized that different biomaterials induce thrombosis at low shear rates, the effect of high shear rates may be quite different. We hypothesize that the amount of thrombus formation on a given material can be greatly influenced by the local shear rate. METHODS: We tested this hypothesis with two different whole blood perfusion loop assays to quantify biomaterial thrombogenicity as a function of shear stress. One assay uses obstructive posts (pins) of material positioned centrally in a tube perfused at high shear rate of >5000/s for 24 h. A second assay uses a parallel plate chamber to perfuse low (<150/s), medium (~500/s), and high shear rates over 96 h. We evaluated the thrombogenicity of seven different biomaterials including stainless steel, acrylic, ceramic, Dacron, polytetrafluoroethylene (PTFE), silicone, and polyvinyl chloride (PVC). RESULTS: For the pin assay, thrombus mass was significantly greater for stainless steel than either zirconia ceramic or acrylic (p < 0.001). Similarly, the parallel plate chamber at high shear showed that steel and PTFE (p < 0.02) occluded the chamber faster than acrylic. In contrast, a low shear parallel plate chamber revealed that stainless steel and PTFE were least thrombogenic, while silicone, Dacron, and other plastics such as acrylic were most thrombogenic. Histology revealed that high shear thrombi had a large proportion of platelets not seen in the low shear fibrin-rich thrombi. CONCLUSION: This differential thrombogenicity based on shear rate conditions may be important in the selection of biomaterials for blood-contacting devices.

Effects of pathogen reduction technology and storage duration on the ability of cryoprecipitate to rescue induced coagulopathies in vitro.

BACKGROUND: Fibrinogen concentrates and cryoprecipitate are currently used for fibrinogen supplementation in bleeding patients with dysfibrinogenemia. Both products provide an abundant source of fibrinogen but take greater than 10 min to prepare for administration. Fibrinogen concentrates lack coagulation factors (i.e., factor VIII [FVIII], factor XIII [FXIII], von Willebrand factor [VWF]) important for robust hemostatic function. Cryoprecipitate products contain these factors but have short shelf lives (<6 h). Pathogen reduction (PR) of cryoprecipitate would provide a shelf-stable immediately available adjunct containing factors important for rescuing hemostatic dysfunction. STUDY DESIGN AND METHODS: Hemostatic adjunct study products were psoralen-treated PR-cryoprecipitated fibrinogen complex (PR-Cryo FC), cryoprecipitate (Cryo), and fibrinogen concentrates (FibCon). PR-Cryo FC and Cryo were stored for 10 days at 20-24°C. Adjuncts were added to coagulopathies (dilutional, 3:7 whole blood [WB]:normal saline; or lytic, WB + 75 ng/ml tissue plasminogen activator), and hemostatic function was assessed by rotational thromboelastometry and thrombin generation. RESULTS: PR of cryoprecipitate did not reduce levels of FVIII, FXIII, or VWF. PR-Cryo FC rescued dilutional coagulopathy similarly to Cryo, while generating significantly more thrombin than FibCon, which also rescued dilutional coagulopathy. Storage out to 10 days at 20-24°C did not diminish the hemostatic function of PR-Cryo FC. DISCUSSION: PR-Cryo FC provides similar and/or improved hemostatic rescue compared to FibCon in dilutional coagulopathies, and this rescue ability is stable over 10 days of storage. In hemorrhaging patients, where every minute delay is associated with a 5% increase in mortality, the immediate availability of PR-Cryo FC has the potential to improve outcomes.

Metabolic phenotypes of standard and cold-stored platelets.

BACKGROUND: Conventional platelet (PLT) storage at room temperature under continuous agitation results in a limited shelf life (5 days) and an increased risk of bacterial contamination. However, both of these aspects can be ameliorated by cold storage. Preliminary work has suggested that PLTs can be cold stored for up to 3 weeks, while preserving their metabolic activity longer than in PLTs stored at room temperature. As such, in the present study, we hypothesized that the metabolic phenotypes of PLTs stored at 4°C for 3 weeks could be comparable to that of room temperature-stored PLTs at 22°C for 5 days. STUDY DESIGN AND METHODS: Metabolomics analyses were performed on nine apheresis PLT concentrates stored either at room temperature (22°C) for 5 days or refrigerated conditions (4°C) for up to 3 weeks. RESULTS: Refrigeration did not impact the rate of decline in glutamine or the intracellular levels of Krebs cycle metabolites upstream to fumarate and malate. It did, however, decrease oxidant stress (to glutathione and purines) and slowed down the activation of the pentose phosphate pathway, glycolysis, and fatty acid metabolism (acyl-carnitines). CONCLUSION: The overall metabolic phenotypes of 4°C PLTs at Storage Day 10 are comparable to PLTs stored at 22°C at the end of their 5-day shelf life, while additional changes in glycolysis, purine, and fatty acid metabolism are noted by Day 21.

The use of low-titer group O whole blood is independently associated with improved survival compared to component therapy in adults with severe traumatic hemorrhage.

BACKGROUND: There is a resurgence in the use of low-titer group O whole blood (LTOWB) for hemorrhagic shock. We hypothesized the use of LTOWB compared to component therapy (CT) would be independently associated with improved 24-hour mortality. STUDY DESIGN AND METHODS: In this prospective observational study, trauma patients 18 years of age or older with massive transfusion protocol activations were included from August 17, 2018, to May 14, 2019. The primary outcome was 24-hour mortality. Secondary outcomes included 72-hour blood product totals, multiple organ dysfunction scores (MODS), and 28-day mortality. Multivariable logistic regression (MVLR) and Cox regression were performed to determine independent associations. RESULTS: There were no clinically meaningful differences in measures of injury severity between study groups (CT, n = 42; LTOWB, n = 44). There was no difference in MODS between study groups. The unadjusted mortality was not statistically different between the study groups (9/42 [21%] for CT vs. 7/44 [16%] for LTOWB; p = 0.518). In the MVLR model, LTOWB increased the odds of 24-hour survival by 23% (odds ratio 0.81, 95% confidence interval 0.69-0.96; p = 0.017). Adjusted survival curve analysis indicated improved survival at both 24 hours and 28 days for LTOWB patients (p < 0.001). Further stratification showed an association between LTOWB use and survival when maximum clot firmness (MCF) was 60 mm or less (p = 0.009). CONCLUSIONS: The use of LTOWB is independently associated with improved 24-hour and 28-day survival, and does not increase organ dysfunction at 72 hours. Use of LTOWB most impacted survival of patients with reduced clot firmness (MCF ≤60 mm). Collectively, these data support the clinical use and continued study of LTOWB for hemostatic resuscitation.

Effect of leukoreduction and pathogen reduction on the hemostatic function of whole blood.

BACKGROUND: There is renewed interest in the use of whole blood (WB) for resuscitation of patients in hemorrhagic shock. Leukoreduction with platelet-sparing filters and pathogen reduction may be used to improve the safety profile of WB, yet the effects of leukoreduction and pathogen reduction on WB hemostatic function are not well characterized. STUDY DESIGN AND METHODS: Blood from 32 healthy group O donors was divided into treatment groups (n = 8 for each group): untreated, pathogen reduced (PR+ ), leukoreduced using an in-line filter (LR+ ), or PR+ LR+ . Units were stored without agitation for 21 days between 1° and 6°C, with sampling on days 0 (pre- and post-treatments), 1, 3, 5, 10, 15, and 21 for hemostatic function as assessed by thromboelastometry, thrombin generation, platelet activation factors, and platelet impedance aggregometry. RESULTS: From day 3 (D3) to D15 of storage, platelet count was reduced in PR+ /LR+ units compared to PR- /LR- units. From D10 to D21 of storage, maximum clot firmness (MCF) was reduced in PR+ /LR+ units compared to PR- /LR- units. From D3 to D21 of storage, platelet aggregation was reduced in PR+ /LR+ units compared to PR- /LR- units. Total thrombin generation was similar in all groups from D0 to D21. CONCLUSIONS: The combination of LR with a platelet-sparing filter and PR significantly reduces hemostatic function compared to either treatment alone or untreated WB. The clinical consequences of LR and PR of WB in patients with severe bleeding should be examined in trials before both are used in combination in patients.

Both rejection and tolerance of allografts can occur in the absence of secondary lymphoid tissues.

In this study, we showed that aly/aly mice, which are devoid of lymph nodes and Peyer's patches, acutely rejected fully allogeneic skin and heart grafts. They mounted potent inflammatory direct alloresponses but failed to develop indirect alloreactivity after transplantation. Remarkably, skin allografts also were rejected acutely by splenectomized aly/aly (aly/aly-spl(-)) mice devoid of all secondary lymphoid organs. In these recipients, the rejection was mediated by alloreactive CD8(+) T cells presumably primed in the bone marrow. In contrast, cardiac transplants were not rejected by aly/aly-spl(-) mice. Actually, aly/aly-spl(-) mice that spontaneously accepted a heart allotransplant and displayed donor-specific tolerance also accepted skin grafts from the same, but not a third-party, donor via a mechanism involving CD4(+) regulatory T cells producing IL-10 cytokine. Therefore, direct priming of alloreactive T cells, as well as rejection and regulatory tolerance of allogeneic transplants, can occur in recipient mice lacking secondary lymphoid organs.

Primary vascularization of allografts governs their immunogenicity and susceptibility to tolerogenesis.

We investigated the influence of allograft primary vascularization on alloimmunity, rejection, and tolerance in mice. First, we showed that fully allogeneic primarily vascularized and conventional skin transplants were rejected at the same pace. Remarkably, however, short-term treatment of mice with anti-CD40L Abs achieved long-term survival of vascularized skin and cardiac transplants but not conventional skin grafts. Nonvascularized skin transplants triggered vigorous direct and indirect proinflammatory type 1 T cell responses (IL-2 and IFN-γ), whereas primarily vascularized skin allografts failed to trigger a significant indirect alloresponse. A similar lack of indirect alloreactivity was also observed after placement of different vascularized organ transplants, including hearts and kidneys, whereas hearts placed under the skin (nonvascularized) triggered potent indirect alloresponses. Altogether, these results suggest that primary vascularization of allografts is associated with a lack of indirect T cell alloreactivity. Finally, we show that long-term survival of vascularized skin allografts induced by anti-CD40L Abs was associated with a combined lack of indirect alloresponse and a shift of the direct alloresponse toward a type 2 cytokine (IL-4, IL-10)-secretion pattern but no activation/expansion of Foxp3(+) regulatory T cells. Therefore, primary vascularization of allografts governs their immunogenicity and tolerogenicity.

Differing coagulation profiles of patients with monoclonal gammopathy of undetermined significance and multiple myeloma.

The link between myeloma and thrombosis is well established. Monoclonal gammopathy of undetermined significance (MGUS) has also been associated with an increased risk of thrombosis. It was recently demonstrated that patients with myeloma display changes in thromboelastometry that may indicate a prothrombotic state. There is little data with regard to changes in thromboelastography in patients with myeloma or MGUS. The aim of this study was to investigate the differing coagulation profiles of patients of patients with myeloma and MGUS by means of conventional coagulation tests and thromboelastography. Blood was taken by direct venepuncture from patients with myeloma, MGUS and normal controls. Routine coagulation tests were performed in an accredited hospital laboratory. Thromboelastography (TEG(®)) was performed as per the manufacturer's protocol. Eight patients were recruited in each group. Patients with myeloma had a significantly lower mean haemoglobin level than patients with MGUS or normal controls (p < 0.001). Patients with myeloma had a significantly more prolonged mean prothrombin time than normal controls (p = 0.018) but not patients with MGUS. Patients with myeloma had significantly higher median D-dimer levels than normal controls (p = 0.025), as did patients with MGUS (p = 0.017). Patients with myeloma had a significantly higher mean factor VIII level than normal controls (p = 0.009) and there was a non-significant trend towards patients with MGUS having higher factor VIII levels than normal controls (p = 0.059). There was no significant difference in thromboelastographic parameters between the three groups. Patients with MGUS appear to have a distinct coagulation profile which is intermediate between patients with myeloma and normal controls.

Associations between health literacy and beliefs about medicines in an Irish obstetric population.

The authors wanted to determine the prevalence of limited health literacy, and the relation between health literacy and beliefs about medicines, in an obstetric population. A survey was administered in Cork University Maternity Hospital, Cork, Ireland. The Rapid Estimate of Adult Literacy in Medicine and the general section of the Beliefs About Medicines Questionnaire were used. Of 404 women, 15.3% (n=62) displayed limited health literacy. Age and health literacy were significantly associated with one another, as were health literacy and level at which participants completed formal education. In the general harm domain, level of education and health literacy were associated with stronger beliefs: M=11.85, SD=2.81 vs. M=9.75, SD=2.11; F(3)=13.69, p<.001. In the general overuse domain, those with limited literacy scored higher compared with those with adequate health literacy: M=12.48, SD=2.73 versus M=11.51, SD=2.63 (p=.01). These associations remained despite controlling for age (and education) in multivariable analyses. More than 1 in 7 had limited health literacy; these women may benefit from educational initiatives. Limited health literacy is associated with a more negative perception of medicines in this cohort.

Doing more with less: low-titer group O whole blood resulted in less total transfusions and an independent association with survival in adults with severe traumatic hemorrhage.

BACKGROUND: Low-titer group O whole blood (LTOWB) or component therapy (CT) may be used to resuscitate hemorrhaging trauma patients. LTOWB may have clinical and logistical benefits and may improve survival. OBJECTIVES: We hypothesized LTOWB would improve 24-hour survival in hemorrhaging patients and would be safe and equally efficacious in non-group O compared with group O patients. METHODS: Adult trauma patients with massive transfusion protocol activations were enrolled in this observational study. The primary outcome was 24-hour mortality. Secondary outcomes included 72-hour total blood product use. A Cox regression determined the independent associations with 24-hour mortality. RESULTS: In total, 348 patients were included (CT, n = 180; LTOWB, n = 168). Demographics were similar between cohorts. Unadjusted 24-hour mortality was reduced in LTOWB vs CT: 8% vs 19% (P = .003), but 6-hour and 28-day mortality were similar. In an adjusted analysis with multivariable Cox regression, LTOWB was independently associated with reduced 24-hour mortality (hazard ratio, 0.21; 95% CI, 0.07-0.67; P = .004). LTOWB patients received significantly less 72-hour total blood products (80.9 [41.6-139.3] mL/kg vs 48.9 [25.9-106.9] mL/kg; P < .001). In stratified 24-hour survival analyses, LTOWB was associated with improved survival for patients in shock or with coagulopathy. LTOWB use in non-group O patients was not associated with increased mortality, organ injury, or adverse events. CONCLUSION: In this hypothesis-generating study, LTOWB use was independently associated with improved 24-hour survival, predominantly in patients with shock or coagulopathy. LTOWB also resulted in a 40% reduction in blood product use which equates to a median 2.4 L reduction in transfused products.

Novel tubing connectors reduce ECMO circuit thrombosis.

BACKGROUND: Thrombosis within extracorporeal membrane oxygenation (ECMO) circuits is a common complication that dominates clinical management of patients receiving mechanical circulatory support. Prior studies have identified that over 80% of circuit thrombosis can be attributed to tubing-connector junctions. METHODS: A novel connector was designed that reduces local regions of flow stagnation at the tubing-connector junction to eliminate a primary source of ECMO circuit thrombi. To compare clotting between the novel connectors and the traditional connectors, both in vitro loops and an in vivo caprine model of long-term (48 h) ECMO were used to generate tubing-connector junction clots. RESULTS: In vitro, the traditional connectors uniformly (9/9) formed large thrombi, while novel connectors formed a small thrombus in only one of nine (p < 0.0001). In the long-term goat ECMO circuits, the traditional connectors exhibited more thrombi (p < 0.04), and these thrombi were more likely to protrude into the lumen of the tubing (p < 0.001). CONCLUSION: Both in vitro and in vivo validation experiments successfully recreated circuit thrombosis and demonstrate that the adoption of novel connectors can reduce the burden of circuit thrombosis.

Cold-stored platelet hemostatic capacity is maintained for three weeks of storage and associated with taurine metabolism.

BACKGROUND: Platelet (PLT) product transfusion is a life-saving therapy for actively bleeding patients. There is an urgent need to maintain PLT function and extend shelf life to improve outcomes in these patients. Cold-stored PLT (CS-PLT) maintain hemostatic potential better than room temperature-stored PLT (RT-PLT). However, whether function in long-term CS-PLT is maintained under physiological flow regimes and/or determined by cold-induced metabolic changes is unknown. OBJECTIVES: This study aimed to (i) compare the function of RT-PLT and CS-PLT under physiological flow conditions, (ii) determine whether CS-PLT maintain function after 3 weeks of storage, and (iii) identify metabolic pathways associated with the CS-PLT lesion. METHODS: We performed phenotypic and functional assessments of RT- and CS-PLT (22 °C and 4 °C storage, respectively; N = 10 unique donors) at storage days 0, 5, and/or 21 via metabolomics, flow cytometry, aggregation, thrombin generation, viscoelastic testing, and a microfluidic assay to measure primary hemostatic function. RESULTS: Day 21 4 °C PLT formed an occlusive thrombus under arterial shear at a similar rate to day 5 22 °C PLT. Day 21 4 °C PLTs had enhanced thrombin generation capacity compared with day 0 PLT and maintained functionality comparable to day RT-PLT across all assays performed. Key metrics from microfluidic assessment, flow cytometry, thrombin generation, and aggregation were associated with 4 °C storage, and metabolites involved in taurine and purine metabolism significantly correlated with these metrics. Taurine supplementation of PLT during storage improved hemostatic function under flow. CONCLUSION: CS-PLT stored for 3 weeks maintain hemostatic activity, and storage-induced phenotype and function are associated with taurine and purine metabolism.