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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. [ABSTRACT FROM AUTHOR]

Introduction: We conducted a prospective observational study on 205 trauma patients at a level I trauma facility to test the hypothesis that a compensatory reserve measurement (CRM) would identify higher risk for progression to shock and/or need a life-saving interventions (LSIs) earlier than systolic blood pressure (SBP) and blood lactate (LAC).Methods: A composite outcome metric included blood transfusion, procedural LSI, and mortality. Discrete measures assessed as abnormal (ab) were SBP <90 mmHg, CRM <60%, and LAC >2.0. A graded categorization of shock was defined as: no shock (normal [n] SBP [n-SBP], n-CRM, n-LAC); sub-clinical shock (ab-CRM, n-SBP, n-LAC); occult shock (n-SBP, ab-CRM, ab-LAC); or overt shock (ab-SBP, ab-CRM, ab-LAC).Results: Three patients displayed overt shock, 53 displayed sub-clinical shock, and 149 displayed no shock. After incorporating lactate into the analysis, 86 patients demonstrated no shock, 25 were classified as sub-clinical shock, 91 were classified as occult shock, and 3 were characterized as overt shock. Each shock subcategory revealed a graded increase requiring LSI and transfusion. Initial CRM was associated with progression to shock (odds ratio = 0.97; p < .001) at an earlier time than SBP or LAC.Conclusions: Initial CRM uncovers a clinically relevant subset of patients who are not detected by SBP and LAC. Our results suggest CRM could be used to more expeditiously identify injured patients likely to deteriorate to shock, with requirements for blood transfusion or procedural LSI. [ABSTRACT FROM AUTHOR]

The article discusses the clinical use of multipotent mesenchymal stromal cell therapeutics. It outlines the clinical evaluation of mesenchymal stem cell in cancer and osteogenesis imperfecta patients. It notes that mesenchymal stromal cell therapies have been applied in numerous clinical trials targeting various diseases such as ischemic, pulmonary and neurologic pathologies.

Background: There are data suggesting that free hemoglobin (Hb), heme, and iron contribute to infection, thrombosis, multiorgan failure, and death in critically ill patients. These outcomes may be mitigated by haptoglobin.Study Design and Methods: 164 consecutively treated children undergoing surgery for congenital heart disease were evaluated for associations between free Hb and haptoglobin and clinical outcomes, physiologic metrics, and biomarkers of inflammation RESULTS: Higher perioperative free Hb levels (and lower haptoglobin levels) were associated with mortality, nosocomial infection, thrombosis, hours of intubation and inotropes, increased interleukin-6, peak serum lactate levels, and lower nadir mean arterial pressures. The median free Hb in patients without infection (30 mg/dL; 29 interquartile range [IQR], 24-52 mg/dL) was lower than in those who became infected (39 mg/dL; IQR, 33-88 mg/ 31 dL; p = 0.0046). The median mechanical ventilation requirements were 19 (IQR, 7-72) hours in patients with higher levels of haptoglobin versus 48 (IQR, 18-144) hours in patients with lower levels (p = 0.0047). Transfusion dose, bypass duration, and complexity of surgery were all significantly correlated with Hb levels and haptoglobin levels. Multivariate analyses demonstrated that these variables were independently and significantly associated with outcomes.Conclusions: Elevated pre- and postoperative levels of free Hb and decreased levels of haptoglobin were associated with adverse clinical outcomes, inflammation, and unfavorable physiologic metrics. Transfusion, RACHS score, and duration of bypass were associated with increased free Hb and decreased haptoglobin. Further investigation of the role of hemolysis and haptoglobin as potential mediators or markers of outcomes is warranted. [ABSTRACT FROM AUTHOR]

Background Volume-reduced washed platelets ( VR- wPLTs), which are prepared by concentrating platelets ( PLTs) into a smaller volume of additive solution ( AS), may prevent not only circulatory overload, but also adverse reactions caused by plasma components. Although VR- wPLTs may be quickly degraded due to high PLT concentrations, few studies have examined the effects of storage on VR- wPLTs. We examined here the in vitro properties of VR- wPLTs prepared with M-sol AS during their storage for 7 days. Study Design and Methods Platelet concentrates ( PCs) were divided into two equal aliquots (control group and test group). After the centrifugation of both aliquots and removal of as much supernatant as possible, the pellet of the control group was resuspended in 160 mL of M-sol while that of the test group was resuspended in 80 or 40 mL of M-sol. The w PLTs of both groups were stored in polyolefin bags with agitation at 20 to 24° C for 7 days. Results The pH values of both groups were maintained at higher than 7.0 during the 7-day storage. Differences in %disk, CD62 P, annexin V, percent hypotonic shock response, and aggregation values between the test group and control group were small for at least 2 days after washing. Conclusions The in vitro properties of VR- wPLTs were not markedly degraded for at least 2 days. Therefore, the storage properties of PLTs may be maintained in VR- wPLTs prepared at blood centers until they are administered to patients in hospitals. [ABSTRACT FROM AUTHOR]

Background Over the past decade there has been a growth in the development of pathogen reduction technologies to protect the blood supply from emerging pathogens. This development has proven to be difficult for red blood cells ( RBCs). However the S-303 system has been shown to effectively inactivate a broad spectrum of pathogens, while maintaining RBC quality. Study Design and Methods A paired three-arm study was performed to compare the in vitro quality of S-303-treated RBCs with RBCs stored at room temperature ( RT) for the duration of the treatment (18-20 hr) and control RBCs stored at 2 to 6° C. Products were sampled weekly over 42 days of storage (n = 10) and tested using an array of in vitro assays to measure quality, metabolism, and functional variables. Results During S-303 treatment there was a slight loss of RBCs and hemoglobin ( Hb < 5 g). Hemolysis, glucose consumption, and potassium release were similar in all groups during the 42 days of storage. S-303-treated RBCs had a significantly lower lactate concentration and pH compared to the paired controls. The S-303-treated RBCs had significantly higher adenosine triphosphate than the RT and control RBCs. There was a significant loss of 2,3-diphosphoglycerate in the S-303-treated products, which was also observed in the RT RBCs. Flow cytometry analysis demonstrated similar RBC size, morphology, expression of CD47, and glycophorin A in all groups. Conclusion RBCs treated with S-303 for pathogen reduction had similar in vitro properties to the paired controls and were within transfusion guidelines. [ABSTRACT FROM AUTHOR]

BACKGROUND: There is little knowledge how different hold times of hyperconcentrated platelet (PLT) suspensions (HPSs) before the addition of platelet additive solution (PAS) might affect PLT quality. We compared the in vitro quality of single-donor PLT concentrates (SDPs) with immediate or delayed PAS addition and studied the quality of collected concurrent plasma (CP). STUDY DESIGN AND METHODS: We collected 6 × 1011 PLTs in 175 of mL plasma and CP from 31 donors. The HPSs were split into two parts, with 162 mL of modified PAS III (PAS-IIIM) added immediately (0hr-SDP) or 2 hours later (2hr-SDP). Final SDPs had a targeted concentration of 1.2 × 1012 PLTs/L and a PAS proportion of 65%. On Days 1, 5, and 7 we determined glucose and lactate concentration, pH, P-selectin expression, hypotonic shock response (HSR), and extent of shape change (ESC). Clotting Factor V (FV) and VIII (FVIII) activities and D-dimer concentration were determined in CP and donor. RESULTS: Glucose utilization, lactate production, and pH were similar for both kinds of products. Low P-selectin expression indicated no relevant PLT activation during storage. HSR and ESC were similarly well preserved. Recoveries of FV and FVIII were 100.0 ± 14.0 and 98.6 ± 14.9%, respectively. Concentrations of D-dimers in the donor and CP were 173.7 ± 90.1 and 177.6 ± 91.2 ng/dL, respectively. CONCLUSIONS: Adding PAS immediately or 2 hours after collection does not result in different in vitro quality of PLTs stored up to 7 days. The good recovery of clotting factors with no signs of activation indicates a good quality of CP. [ABSTRACT FROM AUTHOR]

BACKGROUND: Collecting apheresis platelets (PLTs) into additive solution has many potential benefits. The new Trima software (Version 6.0, CaridianBCT) allows automated addition of PLT additive solution (PAS) after collection, compared to Trima Version 5.1, which only collects PLTs into plasma. The aim of this study was to compare PLT quality during extended storage, after collection with the different Trima systems. STUDY DESIGN AND METHODS: Apheresis PLTs were collected using both Trima Accel apheresis systems. The test PLT units (n = 12) were collected using the new Trima Version 6.0 into PLT AS (PAS-IIIM), while the control units (n = 8) were collected into autologous plasma using Trima Version 5.1. All units were stored for 9 days, and in vitro cell quality variables were evaluated during this time. RESULTS: PLTs collected in PAS-IIIM maintained a stable pH between 7.2 and 7.4, whereas plasma-stored apheresis units exhibited significantly increased acidity during storage, due to lactate accumulation and bicarbonate exhaustion. Plasma-stored PLTs also demonstrated a more rapid consumption of glucose. However, there was little difference in PLT activation or cytokine secretion between PAS-IIIM and control PLTs. CONCLUSION: These data indicate that apheresis PLT concentrates collected in PAS-IIIM, using Trima Version 6.0 software, maintained acceptable PLT metabolic and cellular characteristics until Day 9 of storage. [ABSTRACT FROM AUTHOR]

BACKGROUND: Platelet (PLT) storage adversely affects PLT structure and function in vitro and is associated with decreased PLT recovery and function in vivo. In pediatric transfusion medicine, it is not uncommon for small residual volumes to remain in parent units after aliquot preparation of leukoreduced apheresis-derived PLTs (LR-ADP). However, limited data exist regarding the impact of storage on residual small-volume LR-ADP. STUDY DESIGN AND METHODS: Standard metabolic testing was performed on residual volumes of LR-ADP after aliquot removal and PLT aggregometry using a dual agonist of ADP and collagen was performed on stored, small-volume aliquots (10-80 mL) created from an in vitro model of PLT storage. RESULTS: Seventy-seven LR-ADP underwent metabolic (n = 67) or metabolic and aggregation (n = 10) studies. All products maintained a pH value of more than 6.89 throughout storage. Lactate and pCO2 increased proportionally with longer storage time. Regardless of acceptable metabolism during storage, aggregation in 10- to 20-mL aliquots was impaired by Day 4 and aliquots less than 40 mL demonstrated the most dramatic decrease in aggregation from baseline. CONCLUSIONS: Despite maintenance of acceptable metabolic conditions, residual volumes of LR-ADP develop impaired aggregation in vitro that may adversely affect PLT survival and function in vivo. At volumes below 40 mL, LR-ADP revealed reduced aggregation. As a result, it is recommended to monitor and record volumes of LR-ADP used for pediatric transfusion. Moreover, once LR-ADP attain a volume of 50 mL or less on Day 4 or Day 5 of storage, consider discarding these products until their in vivo efficacy can be studied. [ABSTRACT FROM AUTHOR]

BACKGROUND: In high-volume processing environments, manual breakage of in-line closures can result in repetitive strain injury (RSI). Furthermore, these closures may be incorrectly opened causing shear-induced hemolysis. To overcome the variability of in-line closure use and minimize RSI, Fresenius Kabi developed a new in-line closure, the CompoFlow, with mechanical openers. STUDY DESIGN AND METHODS: The consistency of the performance of the CompoFlow closure device was assessed, as was its effect on component quality. A total of 188 RBC units using CompoFlow blood bag systems and 43 using the standard bag systems were produced using the buffy coat manufacturing method. Twenty-six CompoFlow platelet (PLT) concentrates and 10 control concentrates were prepared from pools of four buffy coats. RBCs were assessed on Days 1, 21, and 42 for cellular variables and hemolysis. PLTs were assessed on Days 1, 3, and 7 for morphology, CD62P expression, glucose, lactate, and pH. A total of 308 closures were excised after processing and the apertures were measured using digital image analysis. RESULTS: The use of the CompoFlow device significantly improved the mean extraction time with 0.46 ± 0.11 sec/mL for the CompoFlow units and 0.52 ± 0.13 sec/mL for the control units. The CompoFlow closures showed a highly reproducible aperture after opening (coefficient of variation, 15%) and the device always remained opened. PLT and RBC products showed acceptable storage variables with no differences between CompoFlow and control. CONCLUSIONS: The CompoFlow closure devices improved the level of process control and processing time of blood component production with no negative effects on product quality. [ABSTRACT FROM AUTHOR]

BACKGROUND: The platelet (PLT) storage lesion is characterized metabolically by a pH value associated with lactic acid generation. PLT storage conditions support the growth of Staphylococcus epidermidis, the most common organism implicated in bacterial contamination of PLT concentrates (PCs). Here, different factors that influence bacterial growth in PCs are discussed and the relation between pH values of PCs and citrate plasma (CP) is studied, with emphasis on bacterial proliferation. STUDY DESIGN AND METHODS: The PLT lesion with regard to pH decrease and lactic acid production was monitored during storage and correlated to bacterial proliferation properties. A total of 115 coagulase-negative staphylococci, especially S. epidermidis isolates, were characterized for their proliferation in different blood components (CP, buffy coat–derived, and apheresis PCs). Furthermore, the influence of donor-specific, product-specific, species-specific, and strain-specific factors on bacterial proliferation was investigated. RESULTS: PCs showed a lower pH value in comparison to plasma during storage. Bacterial proliferation in PCs and the failure to grow in CP were determined with all organisms tested. No correlation to donor-specific, species-specific, or strain-specific factors was observed. Lowering the pH of CP resulted in bacterial proliferation, whereas a pH increase in the PC unit inhibited the proliferation of S. epidermidis. CONCLUSION: With emphasis on bacterial proliferation, the significant difference between PC and CP is the presence of metabolizing PLTs. The pH values of stored PLTs, but not those of stored plasma, support the growth of S. epidermidis. [ABSTRACT FROM AUTHOR]

BACKGROUND: The Atreus 2C+ system (Gambro BCT) automatically separates whole blood (WB) into buffy coat (BC), red blood cells (RBC), and plasma and transfers the components into separate containers. After processing with the Atreus, 4 to 6 BC units can be pooled and processed into leukoreduced platelets (PLTs) by use of the automated OrbiSac BC system (Gambro BCT). The aim of our in vitro study was to investigate the effects of holding either WB or BC overnight before preparation of PLTs by use of the Atreus 2C+ system for BC preparation. A standard routine procedure involving conventional blood containers for the preparation of BC combined with the OrbiSac process (top-and-top system; Terumo) was used as a reference. STUDY DESIGN AND METHODS: WB was either processed within 8 hours after collection (“fresh blood”) or stored overnight before processing. WB units were separated into BC, RBC, and plasma units and transferred into individual containers. Either the BC or the WB units rested overnight at 22 ± 2°C. Six ABO-identical BCs, obtained from either fresh or overnight-stored WB, were pooled and processed with the OrbiSac BC system to obtain leukoreduced PLTs. In total, 20 Atreus and 10 reference (leukoreduced PLTs) samples were analyzed for various in vitro variables during the 7-day storage period. RESULTS: No significant difference in glucose consumption, lactate production, mean PLT volume, LDH activity, bicarbonate, ATP, RANTES, and the expression of CD62p and CD42b between groups was detected. pH was maintained at greater than 7.0 (Day 7). Swirling remained at the highest levels (score, 2) for all units throughout storage. CONCLUSION: PLTs derived from BCs, obtained from either fresh or overnight-stored WB processed on the novel automated Atreus 2C+ system, were equivalent to control PLTs with regard to PLT in vitro characteristics during 7 days of storage. Stable recovery of PLTs and satisfactory PLT content according to current standards were also found. [ABSTRACT FROM AUTHOR]

BACKGROUND: For logistic reasons, possibilities to produce both platelet (PLT) concentrates prepared from fresh or overnight-stored whole blood (fresh and o/n PCs, respectively) are convenient. The consequences of both possibilities are not well described. The PLT pooling system used might also influence the condition of PCs. Our aim was to compare fresh and o/n PCs with different PLT pooling systems. STUDY DESIGN AND METHODS: Fresh and o/n PCs were prepared from buffy coats and plasma in PLT pooling systems of Baxter, Fresenius, Terumo, or Pall (n = 5). PCs were stored for 9 days. The in vitro quality was determined by the PLT count, pH, glucose, lactate, pO2, pCO2, CD62P expression, and annexin V binding. RESULTS: The o/n PCs showed higher PLT count (approx. 460 × 109/PC vs. approx. 310 × 109/PC), pCO2, and lactate concentration and lower pH, pO2, glucose concentration, CD62P expression (until Day 5), and annexin V binding (until Day 7) compared with fresh PCs (p < 0.05). Only for o/n PCs in the Baxter and Fresenius systems did the pH and glucose concentration remain higher, and the lactate concentration and CD62P expression remained lower than that of o/n PCs in the Pall and Terumo systems. The pH for fresh PCs in the Baxter and Fresenius systems was more often greater than 7.4 than for fresh PCs in the Terumo or Pall systems. CONCLUSION: The quality of PCs depended on whether PCs were prepared from fresh or overnight-stored whole blood and on the used PLT pooling system. The main difference between fresh and o/n PCs was the PLT count. [ABSTRACT FROM AUTHOR]

BACKGROUND: The quality of platelets (PLTs) stored in PLT additive solution (PAS) is dependent on the type and proportion of the used PAS. No data are available as to whether a different hold time before the addition of PAS to hyperconcentrated PLT suspensions has an impact on PLT quality. The in vitro quality between single-donor PLT concentrates was compared with two different hold times with two PASs. STUDY DESIGN AND METHODS: On two occasions, 6 × 1011 PLTs in 150 mL of plasma were collected from 20 blood donors. The units were split into two equal parts, and 140 mL of PAS-II or PAS-IIIM (randomized sequence) was added after 2 or 8 hours resulting in a PAS proportion of 65 percent. On Days 1, 5, and 7, glucose and lactate concentration, pH value, PLTs’ P-selectin expression, response to hypotonic shock, and release of transforming growth factor-β1 were determined. RESULTS: On all days, the lactate concentrations were higher and pH values were lower in units with an 8-hour hold time, whereas the results of in vitro tests relating to the in vivo viability and activation of PLTs were similar for both groups. PAS-IIIM–stored PLTs showed a lower glycolytic activity and better results in all performed in vitro tests than PAS-II–stored PLTs. CONCLUSIONS: Although the metabolism of glucose was enhanced during hold time, the differences between both hold time groups are not meaningful from a biological viewpoint. Therefore, an 8-hour hold time is feasible. PLT storage in PAS-IIIM results in a PLT in vitro quality superior to that of PLTs stored in PAS-II. [ABSTRACT FROM AUTHOR]

BACKGROUND: Stress-enhanced platelet (PLT) storage lesions include increased glycolysis, discoid-to-sphere morphology change, and spontaneous PLT activation. It is not clear if reduction in glycolysis can alleviate storage lesion development. STUDY DESIGN AND METHODS: Apheresis PLT concentrates were exposed to 17.2 J/mL UV light and 50 µM riboflavin, followed by storage with various concentrations of 2-deoxyglucose (2-DOG) for 5 days. The control had no UV or 2-DOG exposure. RESULTS: Lactate production and glucose consumption were increased significantly to 0.1371 ± 0.0281 and 0.0724 ± 0.0151 mmol per 1012 cells per hour for UV-treated PLTs, respectively, when compared to control samples. UV treatment induced a decline in pH to 6.55 ± 0.26 for treated PLTs on Day 5, hypotonic shock response (HSR) 33 ± 25 percent, extent of shape change (ESC) to 3.8 ± 3.6 percent, swirl 1.0 ± 1.0 and increased P-selectin expression 85.2 ± 9.4 percent. Addition of 2-DOG up to 20 mmol per L significantly reduced lactate production to 0.0515 ± 0.0045 mmol per 1012 cells per hour (p < 0.05) and glucose consumption to 0.0293 ± 0.0060 mmol per 1012 cells per hour and increased pH to 7.35 ± 0.09 in a dose-dependent manner. 2-DOG, however, had no effects on HSR, ESC, swirl, and P-selectin expression. Furthermore, an exaggeration of UV-stressed PLT aggregation by addition of 2-DOG was also observed. CONCLUSIONS: Increased glycolytic flux is not a direct cause for PLT morphology change and spontaneous activation during storage lesion development. Reduction of glucose utilization may increase PLT loss during storage. [ABSTRACT FROM AUTHOR]

Advantages to storing whole blood–derived platelets (PLTs) as a pool for 7 days would include operational efficiencies and facilitation of bacterial testing and pathogen inactivation. The in vitro quality of pre-storage pooled PLTs stored for up to 7 days was assessed.Leukoreduced PLTs were pooled before storage (5 units/pool) and stored for either 5 or 7 days. Samples were collected at the time of pooling and either on Day 5 (n = 16-29) or on Day 7 (n = 4-30) and tested for biochemical and activation markers and morphology and/or shape change. Control PLTs were stored individually for 5 or 7 days and then tested as indicated above.The mean PLT counts (×109/L) were similar: control PLTs, 1344 (464 SD); and prestorage pooled PLTs, 1327 (220 SD; p = 0.93). On Day 5, the pH value was significantly lower (p ≤ 0.0001) for the prestorage pooled PLTs. Lactate and partial pressure of O2 (pO2) were significantly higher (p ≤ 0.003). On Day 7 of storage, significant differences were noted with pH, pCO2, and hypotonic shock all being lower with the prestorage pooled product, whereas pO2, lactate, and morphology scores were higher (p values all< 0.03). Although significant differences were found, the magnitude of the difference would not be expected to impact on transfusion outcomes.These results suggest that prestorage pooled PLTs can be stored for up to 7 days; however, studies are needed to ensure that the clinical benefit of PLTs stored as a pool is not inferior to those stored individually. [ABSTRACT FROM AUTHOR]

Previous studies showed that Mirasol (Navigant Biotechnologies, Inc.) pathogen reduction technology (PRT) treatment resulted in an increase in platelet (PLT) glucose consumption and lactate production rates and decrease in pH in media during PLT storage. Increased glycolytic flux could result from damage to mitochondria and/or increased ATP consumption.PLT concentrates were collected by standard automated blood component collection system (Trima, Gambro BCT) procedure on Day 0 and treated with Mirasol PRT treatment on Day 1. PLT mitochondrial transmembrane potential was evaluated by staining PLTs with JC-1 followed by flow cytometry analysis. Mitochondrial enzymatic activity was measured by the MTT assay. ATP content and pH were also quantified. The values for these measurements were compared among control, untreated, and pathogen reduction technology (PRT)-treated PLTs during PLT storage for up to 7 days.No significant changes were found in pH, JC-1 signal, MTT activity, and ATP content of the PLTs immediately after PRT treatment. The treated PLTs exhibited a moderate but significantly accelerated decrease in pH and lower ATP content after 7-day storage when compared to control PLTs. Neither the JC-1 assay nor the MTT assay, however, showed a significant difference between control and treated PLTs during PLT storage.There is no evidence from these studies that Mirasol PRT treatment alters PLT mitochondrial structural and functional integrity immediately after treatment and during PLT storage. An increased demand for ATP may be the driving force for observed increases in both the glycolytic flux and the oxidative metabolism observed in treated PLTs. [ABSTRACT FROM AUTHOR]