Background
There is a global increase in whole blood usage and at the same time, emerging pathogens give cause for pathogen reduction technology (PRT). The Mirasol PRT has shown promising results for ...plasma and platelet concentrate products. Treatment of whole blood with subsequent platelet survival and recovery analysis would be of global value.
Study Design and Methods
A two‐arm, open‐label laboratory study was performed with 40 whole blood collections in four groups: non‐leukoreduced non‐PRT‐treated, non‐leukoreduced PRT‐treated, leukoreduced non‐PRT‐treated, and leukoreduced PRT‐treated.
Leukoreduction and/or PRT‐treatment was performed on the day of collection, then all WB units were stored at room temperature for 24 h. Sampling was performed after hold‐time and after 24‐h storage in RT. If PRT‐treatment or leukoreduction, samples were also taken subsequently after treatment.
Thirteen healthy volunteer blood donors completed the in vivo study per protocol. All WB units were non‐leukoreduced and PRT‐treated. Radioactive labeling of platelets from RT‐stored, PRT‐treated whole blood, sampling of subjects, recovery, and survival calculations were performed according to the Biomedical Excellence for Safer Transfusion Collaborative protocol.
Results
In vitro characteristics show that PRT‐treatment leads to increased levels of hemolysis, potassium, and lactate, while there are decreased levels of glucose, FVIII, and fibrinogen after 24 h of storage. All values are within requirements for WB.
In vivo recovery and survival of platelets were 85.4% and 81.3% of untreated fresh control, respectively.
Conclusions
PRT‐treatment moderately reduces whole blood quality but is well within the limits of international guidelines. Recovery and survival of platelets are satisfactory after Mirasol treatment.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
BACKGROUND
Some jurisdictions require leukoreduction of cellular blood components. The only whole blood collection set with a platelet‐saving filter uses citrate‐phosphate‐dextrose (CPD) as storage ...solution. Substituting CPD with citrate‐phosphate‐dextrose‐adenine (CPDA‐1) increases shelf life from 21 to 35 days. This would simplify prehospital and rural resupply and reduce wastage. We investigated in vitro quality and hemostatic properties of CPDA‐1 whole blood leukoreduced with a platelet‐saving filter.
STUDY DESIGN AND METHODS
CPDA‐1 whole blood was leukoreduced using a platelet‐saving filter and stored 35 days. EDQM requirements, hematology, metabolic parameters, thromboelastography, light transmission aggregometry, fibrinogen, factor VIII, and interleukin‐6 were measured on Days 0, 1, 14, 21, and 35 and compared to non‐leukoreduced blood.
RESULTS
All units met EDQM requirements. Leukoreduction yielded residual white blood cell count <1 × 106 and 87% platelet recovery on Day 1. It caused reduction in thromboelastography parameters, but not aggregometry response. No hemolysis >0.8% was observed. Factor VIII was higher on Day 35 in the leukoreduced group, 37.9 (95% CI: 26.0, 49.8) versus 13.8 (9.4, 18.2) IU/dL. In both groups, aggregation was significantly reduced by Day 14. Thromboelastography showed remaining platelet activity on Day 35, MA 46.9 (42.1, 51.7) in the leukoreduced and 44.3 (39.6, 49.0) mm in the non‐leukoreduced group. Fibrinogen was within reference ranges at Day 35 (>2 g/dL). Interleukin‐6 was not detectable.
CONCLUSION
Leukoreducing CPDA‐1 whole blood with a platelet‐saving filter did not compromise hemostatic properties. We encourage development of a single bag CPDA‐1 whole blood collection set with in‐line platelet‐saving filter.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
BACKGROUND:This pilot trial focused on feasibility and safety to provide preliminary data to evaluate the hemostatic potential of cold-stored platelets (2° to 6°C) compared with standard room ...temperature–stored platelets (20° to 24°C) in adult patients undergoing complex cardiothoracic surgery. This study aimed to assess feasibility and to provide information for future pivotal trials.
METHODS:A single center two-stage exploratory pilot study was performed on adult patients undergoing elective or semiurgent complex cardiothoracic surgery. In stage I, a two-armed randomized trial, platelets stored up to 7 days in the cold were compared with those stored at room temperature. In the subsequent single-arm stage II, cold storage time was extended to 8 to 14 days. The primary outcome was clinical effect measured by chest drain output. Secondary outcomes were platelet function measured by multiple electrode impedance aggregometry, total blood usage, immediate and long-term (28 days) adverse events, length of stay in intensive care, and mortality.
RESULTS:In stage I, the median chest drain output was 720 ml (quartiles 485 to 1,170, n = 25) in patients transfused with room temperature–stored platelets and 645 ml (quartiles 460 to 800, n = 25) in patients transfused with cold-stored platelets. No significant difference was observed. The difference in medians between the room temperature– and cold-stored up to 7 days arm was 75 ml (95% CI, −220, 425). In stage II, the median chest drain output was 690 ml (500 to 1,880, n = 15). The difference in medians between the room temperature arm and the nonconcurrent cold-stored 8 to 14 days arm was 30 ml (95% CI, −1,040, 355). Platelet aggregation in vitro increased after transfusion in both the room temperature– and cold-stored platelet study arms. Total blood usage, number of adverse events, length of stay in intensive care, and mortality were comparable among patients receiving cold-stored and room temperature–stored platelets.
CONCLUSIONS:This pilot trial supports the feasibility of platelets stored cold for up to 14 days and provides critical guidance for future pivotal trials in high-risk cardiothoracic bleeding patients.
Background and Objectives
Based on previous success using apheresis platelets, we wanted to investigate the in vitro quality and platelet function in continuously cold‐stored and delayed cold‐stored ...platelet concentrates (PCs) from interim platelet units (IPUs) produced by the Reveos system.
Materials and Methods
We used a pool‐and‐split design to prepare 18 identical pairs of PCs. One unit was stored unagitated and refrigerated after production on day 1 (cold‐stored). The other unit was stored agitated at room temperature until day 5 and then refrigerated (delayed cold‐stored). Samples were taken after pool‐and‐split on day 1 and on days 5, 7, 14 and 21. Swirling was observed and haematology parameters, metabolism, blood gas, platelet activation and platelet aggregation were analysed for each sample point.
Results
All PCs complied with European recommendations (EDQM 20th edition). Both groups had mean platelet content >200 × 109/unit on day 21. The pH remained above 6.4 for all sample points. Glucose concentration was detectable in every cold‐stored unit on day 21 and in every delayed cold‐stored unit on day 14. The cold‐stored group showed a higher activation level before stimulation as measured by flow cytometry. The activation levels were similar in the two groups after stimulation. Both groups had the ability to form aggregates after cold storage and until day 21.
Conclusion
Our findings suggest that PCs from IPUs are suitable for cold storage from day 1 until day 21 and delayed cold storage from day 5 until day 14.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
BACKGROUND
Increasing numbers of emergency medical service agencies and hospitals are developing the capability to administer blood products to patients with hemorrhagic shock. Cold‐stored whole ...blood (WB) is the only single product available to prehospital providers who aim to deliver a balanced resuscitation strategy. However, there are no data on the safety and in vitro characteristics of prehospital stored WB. This study aimed to describe the effects on in vitro quality of storing WB at remote helicopter bases in thermal insulating containers.
STUDY DESIGN AND METHODS
We conducted a two‐armed single‐center study. Twenty units (test) were stored in airtight thermal insulating containers, and 20 units (controls) were stored according to routine procedures in the Haukeland University Hospital Blood Bank. Storage conditions were continuously monitored during emergency medical services missions and throughout remote and blood bank storage. Hematologic and metabolic variables, viscoelastic properties, and platelet (PLT) aggregation were measured on Days 1, 8, 14, and 21.
RESULTS
Storage conditions complied with the EU guidelines throughout remote and in‐hospital storage for 21 days. There were no significant differences in PLT aggregation, viscoelastic properties, and hematology variables between the two groups. Minor significantly lower pH, glucose, and base excess and higher lactate were observed after storage in airtight containers.
CONCLUSION
Forward cold storage of WB is safe and complies with EU standards. No difference is observed in hemostatic properties. Minor differences in metabolic variables may be related to the anaerobic conditions within the thermal box.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
Collection of non‐leukoreduced citrate‐phosphate‐dextrose‐adenine (CPDA‐1) whole blood is performed in walking blood banks. Blood collected under field conditions may have increased risk ...of bacterial contamination. This study was conducted to examine the effects of WBC reduction and storage temperature on growth of Escherichia coli (ATCC® 25922™) in CPDA‐1 whole blood.
Methods
CPDA‐1 whole blood of 450 ml from 10 group O donors was inoculated with E. coli. Two hours after inoculation, the test bags were leukoreduced with a platelet‐sparing filter. The control bags remained unfiltered. Each whole blood bag was then split into three smaller bags for further storage at 2–6°C, 20–24°C, or 33–37°C. Bacterial growth was quantified immediately, 2 and 3 h after inoculation, on days 1, 3, 7, and 14 for all storage temperatures, and on days 21 and 35 for storage at 2–6°C.
Results
Whole blood was inoculated with a median of 19.5 (range 12.0–32.0) colony‐forming units per ml (CFU/ml) E. coli. After leukoreduction, a median of 3.3 CFU/ml (range 0.0–33.3) E. coli remained. In the control arm, the WBCs phagocytized E. coli within 24 h at 20–24°C and 33–37°C in 9 of 10 bags. During storage at 2–6°C, a slow self‐sterilization occurred over time with and without leukoreduction.
Conclusions
Storage at 20–24°C and 33–37°C for up to 24 h before leukoreduction reduces the risk of E. coli‐contamination in CPDA‐1 whole blood. Subsequent storage at 2–6°C will further reduce the growth of E. coli.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background and Objectives
In a previous pilot study, we demonstrated significantly lower haemoglobin (Hb) increment after red‐blood‐cell (RBC) transfusions in febrile patients compared to patients ...without fever. The aim of this study was to examine associations between inflammatory mediators and post‐transfusion haemoglobin increment in patients with haematological diseases.
Materials and Methods
Twenty‐seven patients (eight women, 19 men), median age 56 years receiving RBC transfusion, were included in the study. Hb increment per unit transfused was corrected for estimated patient blood volume and the amount of Hb transfused. A wide spectrum of inflammatory mediators was determined by multiplex technology. Association between post‐transfusion haemoglobin increment, plasma inflammatory mediators and patient characteristics was analysed using a mixed linear regression model.
Results
Febrile patients had significantly lower corrected Hb increment, significantly increased values of IL‐6, IL‐8, IL‐10 and G‐CSF, significantly reduced levels of CCL5 and CXCL10, and significantly higher pretransfusion levels of CRP. There was a significant association between pretransfusion CRP levels and corrected Hb increment for the whole patient cohort, but not within each of the two groups. Results demonstrated an association between haemoglobin increment, fever and inflammatory mediators. Febrile patients had a significantly lower corrected Hb increment compared to nonfebrile patients, when adjusting for mediators. When fever was kept constant, a significant negative association between haemoglobin increment and the proinflammatory mediators IL‐6 and IL‐8 was observed.
Conclusion
Both fever and the inflammatory mediators IL‐6 and IL‐8 were negatively associated with post‐transfusion haemoglobin increment.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Background Human platelet lysate (HPL) is emerging as the preferred xeno-free supplement for the expansion of mesenchymal stromal cells (MSCs) for bone tissue engineering (BTE) applications. Due to a ...growing demand, the need for standardization and scaling-up of HPL has been highlighted. However, the optimal storage time of the source material, i.e., outdated platelet concentrates (PCs), remains to be determined. The present study aimed to determine the optimal storage time of PCs in terms of the cytokine content and biological efficacy of HPL. Methods Donor-matched bone marrow (BMSCs) and adipose-derived MSCs (ASCs) expanded in HPL or fetal bovine serum (FBS) were characterized based on in vitro proliferation, immunophenotype, and multi-lineage differentiation. Osteogenic differentiation was assessed at early (gene expression), intermediate alkaline phosphatase (ALP) activity, and terminal stages (mineralization). Using a multiplex immunoassay, the cytokine contents of HPLs produced from PCs stored for 1-9 months were screened and a preliminary threshold of 4 months was identified. Next, HPLs were produced from PCs stored for controlled durations of 0, 1, 2, 3, and 4 months, and their efficacy was compared in terms of cytokine content and BMSCs' proliferation and osteogenic differentiation. Results BMSCs and ASCs in both HPL and FBS demonstrated a characteristic immunophenotype and multi-lineage differentiation; osteogenic differentiation of BMSCs and ASCs was significantly enhanced in HPL vs. FBS. Multiplex network analysis of HPL revealed several interacting growth factors, chemokines, and inflammatory cytokines. Notably, stem cell growth factor (SCGF) was detected in high concentrations. A majority of cytokines were elevated in HPLs produced from PCs stored for less than or equai to 4 months vs. > 4 months. However, no further differences in PC storage times between 0 and 4 months were identified in terms of HPLs' cytokine content or their effects on the proliferation, ALP activity, and mineralization of BMSCs from multiple donors. Conclusions MSCs expanded in HPL demonstrate enhanced osteogenic differentiation, albeit with considerable donor variation. HPLs produced from outdated PCs stored for up to 4 months efficiently supported the proliferation and osteogenic differentiation of MSCs. These findings may facilitate the standardization and scaling-up of HPL from outdated PCs for BTE applications. Keywords: Platelet lysate, Mesenchymal stromal cells, Bone tissue engineering, Regenerative medicine
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
Civilian and military guidelines recommend early balanced transfusion to patients with life‐threatening bleeding. Low titer group O whole blood was introduced as the primary blood product ...for resuscitation of massive hemorrhage at Haukeland University Hospital, Bergen, Norway, in December 2017. In this report, we describe the whole blood program and present results from the first years of routine use.
Study design and methods
Patients who received whole blood from December 2017 to April 2020 were included in our quality registry for massive transfusions. Post‐transfusion blood samples were collected to analyze isohemagglutinin (anti‐A/‐B) and hemolysis markers. Administration of other blood products, transfusion reactions, and patient survival (days 1 and 30) were recorded. User experiences were surveyed for both clinical and laboratory staff.
Results
Two hundred and five patients (64% male and 36% female) received 836 units in 226 transfusion episodes. Patients received a mean of 3.7 units (range 1–35) in each transfusion episode. The main indications for transfusion were trauma (26%), gastrointestinal (22%), cardiothoracic/vascular (18%), surgical (18%), obstetric (11%), and medical (5%) bleeding. There was no difference in survival between patients with blood type O when compared with non‐group O. Haptoglobin level was lower in the transfusion episodes for non‐O group patients, however no clinical hemolysis was reported. No patients had conclusive transfusion‐associated adverse events. Both clinical and laboratory staff preferred whole blood to component therapy for massive transfusion.
Discussion
The experience from Haukeland University Hospital indicates that whole blood is feasible, safe, and effective for in‐hospital treatment of bleeding.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Damage control resuscitation principles advocate the use of blood to treat traumatic hemorrhage. Hemorrhage is a leading cause of preventable death on the battlefield, but making blood components ...available far forward presents logistical challenges due to shelf life and storage requirements. Whole blood simplifies logistics and enables collection in the field but can cause leukocyte-related transfusion reactions. A field-adapted leukoreduction system must be fast and safe, and storage of whole blood should preserve hemostatic function.
Blood was collected using Imuflex WB-SP and leukoreduced at 0, 150, or 300 mm Hg. Additional bags were stored at 4°C for 21 days unagitated, mixed daily, agitated or head-over-heel rotated, at 22°C for 3 days, or 32°C for 2 hours. Hematology, coagulation, CD62P/CD42b, thromboelastography (TEG)/thromboelastometry (ROTEM), and Multiplate was performed.
Filtration time was 35 ± 1, 14 ± 0, and 9 ± 0 minutes at 0, 150, and 300 mm Hg, respectively. One of 10 units at 150 mm Hg and 4 of 11 at 300 mm Hg had residual whole blood cells greater than 5.0 × 10 per unit. One of 11 at 300 mm Hg had platelet recovery of less than 80%. Hemolysis was less than 0.2%. Filtration decreased thromboelastography/thromboelastometry and Multiplate aggregation response. Stored at 4°C, α and MA/MCF moderately decreased regardless of mixing. Significant loss of aggregation response and increased CD62P expression was seen by Day 10. By Day 3, storage at 22°C caused loss of most aggregation. Two-hour storage at 32°C did not significantly affect hemostatic capacity.
Forced filtration reduced leukoreduction time, but increased residual whole blood cells reduced hemostatic function. Aggregation response deteriorated early in storage, while viscoelastic assays decreased more gradually. Mixing showed no benefits.
Diagnostic study, level IV.
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