Changes in Complement Levels and Activity of Red Blood Cells, Fresh Frozen Plasma, and Platelet Concentrates During Storage.
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SUBMITTER: Liu X
PROVIDER: S-EPMC7900354 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundPlatelet transfusions can be associated with adverse reactions, such as febrile non-haemolytic transfusion reaction (FNHTR). It has been suggested that damage-associated molecular patterns (DAMP) and complement play a role in FNHTR. This study investigated the nature of DAMPs and complement activation products contained in platelet concentrates during storage, with a specific focus on different platelet storage solutions.Materials and methodsBuffy coats (BC) from healthy donors were pooled (15 BC per pool) and divided into three groups of the same volume. After addition of different storage solutions (plasma, platelet additive solutions [PAS]-C or PAS-E; n=6 for each group), BC pools were processed to platelet concentrates (PC). Leukoreduced PCs were stored on a shaking bed at 20-24°C and sampled on days 1, 2, 6 and 8 after collection for selected quality parameters: platelet activation, DAMPs (High Mobility Group Box 1 [HMGB1], nucleosomes), and complement activation products.ResultsDuring storage, equal levels of free nucleosomes and increasing concentrations of HMGB1 were present in all groups. Complement activation was observed in all PC. However, by day 8, the use of PAS had reduced C3b/c levels by approximately 90% and C4b/c levels by approximately 65%.DiscussionNucleosomes and HMGB1 were present in PCs prepared in plasma and PAS. Complement was activated during storage of platelets in plasma and in PAS. The use of PAS is associated with a lower amount of complement activation products due to the dilution of plasma by PAS . Therefore, PC in PAS have less complement activation products than platelets stored in plasma. These proinflammatory mediators in PC might induce FNHTR.
| S-EPMC10072994 | biostudies-literature
Project description:BackgroundBlood product transfusions are associated with increased morbidity and mortality. The purpose of this study was to determine if implementation of a restrictive protocol for packed red blood cell (PRBC) and fresh frozen plasma (FFP) transfusion safely reduces blood product utilization and costs in a surgical intensive care unit (SICU).Study designWe performed a retrospective, historical control analysis comparing before (PRE) and after (POST) implementation of a restrictive PRBC/FFP transfusion protocol for SICU patients. Univariate analysis was utilized to compare patient demographics and blood product transfusion totals between the PRE and POST cohorts. Multivariate logistic regression models were developed to determine if implementation of the restrictive transfusion protocol is an independent predictor of adverse outcomes after controlling for age, illness severity, and total blood products received.Results829 total patients were included in the analysis (PRE, n=372; POST, n=457). Despite higher mean age (56 vs. 52 years, p=0.01) and APACHE II scores (12.5 vs. 11.2, p=0.006), mean units transfused per patient were lower for both packed red blood cells (0.7 vs. 1.2, p=0.03) and fresh frozen plasma (0.3 vs. 1.2, p=0.007) in the POST compared to the PRE cohort, respectively. There was no difference in inpatient mortality between the PRE and POST cohorts (7.5% vs. 9.2%, p=0.39). There was a decreased risk of urinary tract infections (OR 0.47, 95%CI 0.28-0.80) in the POST cohort after controlling for age, illness severity and amount of blood products transfused.ConclusionsImplementation of a restrictive transfusion protocol can effectively reduce blood product utilization in critically ill surgical patients with no increase in morbidity or mortality.
| S-EPMC4444010 | biostudies-literature
Project description:BackgroundPlatelets are anucleated blood cells and contain various RNA species. We investigated the changes in the whole transcriptome expression profile of platelet concentrates (PC) during storage to explore biological functions and biomarkers in platelet storage damage.Materials and methodsPlatelets were collected by apheresis from eight healthy blood donors and stored from day 0 to day 4. Platelet phenotyping and function analysis were used to detect platelet activity during storage. RNA-sequencing was used to detect changes in expression of mRNA, lncRNA and circRNA in the PC during storage. Gene ontology and KEGG analyses were applied to predict the functional distribution of differential expression of mRNA. Gene set enrichment analysis was used to analyze the differential levels of gene pathways. Finally, polymerase chain reaction (PCR) analysis was performed to verify the expression of three mRNA (POLE2, DCUN1D4, DAD1).ResultsIn total, 10,767 mRNA, 2,923 lncRNA and 68,550 circRNA were detected in the PC by RNA-sequencing. The expression levels of 222 mRNA changed significantly from day 0 to day 4 of storage: 58 increased continuously and 145 decreased continuously. Differentially expressed mRNA may be involved in physiological processes such as platelet activation, platelet aggregation, endocytosis, and apoptosis. Expression levels of 1,413 lncRNA were obvious. The levels of 42 species increased and the levels of 28 species decreased. The expression levels of 198 species of circRNA changed significantly, with those of 13 species changing continuously. The differential levels of expression of DAD1, DCUN1D4 and POLE1 mRNA, shown by RNA sequencing, were validated by PCR assay.DiscussionChanges in mRNA, lncRNA and circRNA during platelet storage may be closely related to platelet apoptosis and physiological functions in the platelet storage lesion. The expression levels of DAD1, DCUN1D4 and POLE1 could be biomarkers to monitor platelet status in PC bags.
| S-EPMC10072990 | biostudies-literature
Project description:ImportanceHemostatic resuscitation has been shown to be beneficial for patients with trauma, but there is little evidence that it is equally beneficial for bleeding patients without trauma. The practice of a high transfusion ratio of fresh frozen plasma (FFP) to red blood cells (RBCs) has spread to other surgical and medical fields.ObjectiveTo identify whether ratio-based resuscitation in patients without trauma is associated with improved survival.Design, setting, and participantsThis study is a retrospective review of all massive transfusions provided in an urban academic hospital from January 1, 2009, through December 31, 2012. Massive transfusion was defined as the transfusion of at least 10 U of RBCs in the first 24 hours after a patient's admission to the operating room, emergency department, or intensive care unit. All patients who received massive transfusions within the study period and survived more than 30 minutes after hospital arrival were counted (n=865). Patients were grouped into those with trauma and those without trauma. Sources of data included the Research Patient Data Registry, patients' medical records, and blood bank records. All data collection occurred between April 26, 2013, and April 26, 2015. Data analysis took place from April 27, 2015, and June 22, 2016.Main outcomes and measuresExamination of FFP:RBC transfusion ratios for patients without trauma.ResultsThere were 865 massive transfusion events that occurred within 4 years, transfusing 16 569 U of RBCs, 13 933 U of FFP, 5228 U of cryoprecipitate, and 22 635 U of platelets. Most of these transfusions were received by patients without trauma (767 [88.7%]), by men (582 [67.3%]), and for intraoperative bleeding (544 [62.9%]). The FFP:RBC ratios of survivors and nonsurvivors were nearly identical: the ratio for survivors was 1:1.5 (interquartile range [IQR], 1:1.1-1:2.2) and for nonsurvivors was 1:1.4 (IQR, 1:1.1-1:1.9; P = .43). Among the 767 patients without trauma, there was no difference in the adjusted odds ratio (aOR) for 30-day mortality when comparing the high FFP:RBC ratio vs the low FFP:RBC ratio subgroups (aOR, 1.10; 95% CI, 0.72-1.70; P = .65). In vascular surgery, the aOR for death favored the high FFP:RBC ratio subgroup (aOR, 0.16; 95% CI, 0.03-0.79; P = .02). However, in general surgery and medicine, the aOR for death favored the low FFP:RBC ratio subgroup; general surgery: aOR, 4.27 (95% CI, 1.28-14.22; P = .02); medicine: aOR, 8.48 (95% CI, 1.50-47.75; P = .02).Conclusions and relevanceHigh FFP:RBC transfusion ratios are applied mostly to patients without trauma, who account for nearly 90% of all massive transfusion events. Thirty-day survival was not significantly different in patients who received a high FFP:RBC ratio compared with those who received a low ratio.
| S-EPMC5831422 | biostudies-literature
Project description:Platelet transfusion has become essential therapy in modern medicine. Although the clinical advantage of platelet transfusion has been well established, adverse reactions upon transfusion, especially transmission of bacterial infection, still represent a major challenge. While bacterial contamination is favored by the storage of platelets at room temperature, cold storage may represent a solution for this important clinical issue. In this study, we aimed to clarify whether plasma has protective or detrimental effects on cold-stored platelets. We investigated the impact of different residual plasma contents in apheresis-derived platelet concentrates, stored at 4°C or room temperature, on platelet function and survival. We found that platelets stored at 4°C have higher expression of apoptosis marker compared to platelets stored at room temperature, leading to accelerated clearance from the circulation in a humanized animal model. While cold-induced apoptosis was independent of the residual plasma concentration, cold storage was associated with better adhesive properties and higher response to activators. Interestingly, delta (?) granule-related functions, such as ADP-mediated aggregation and CD63 release, were better preserved at 4°C, especially in 100% plasma. An extended study to assess cold-stored platelet concentrates produced under standard care Good Manufacturing Practice conditions showed that platelet function, metabolism and integrity were better compared to those stored at room temperature. Taken together, our results show that residual plasma concentration does not have a cardinal impact on the cold storage lesions of apheresis-derived platelet concentrates and indicate that the current generation of additive solutions represent suitable substitutes for plasma to store platelets at 4°C.
| S-EPMC6312032 | biostudies-literature
Project description:Red blood cells and platelets are anucleate blood components indispensable for oxygen delivery and hemostasis, respectively. Derivation of these blood elements from induced pluripotent stem (iPS) cells has the potential to develop blood donor-independent and genetic manipulation-prone products to complement or replace current transfusion banking, also minimizing the risk of alloimmunization. While the production of erythrocytes from iPS cells has challenges to overcome, such as differentiation into adult-type phenotype that functions properly after transfusion, platelet products are qualitatively and quantitatively approaching a clinically-applicable level owing to advances in expandable megakaryocyte (MK) lines, platelet-producing bioreactors, and novel reagents. Guidelines that assure the quality of iPS cells-derived blood products for clinical application represent a novel challenge for regulatory agencies. Considering the minimal risk of tumorigenicity and the expected significant demand of such products, ex vivo production of iPS-derived blood components can pave the way for iPS translation into the clinic.
| S-EPMC5789275 | biostudies-literature
Project description:ObjectiveAccording to the international guidelines, fresh frozen plasma (FFP) is unanimously used to treat coagulation disorders. The quality of FFP is critical for the clinical transfusion. Till now, few studies have integratedly evaluated the differences of FFP from blood donors at between high altitude (HA) and low altitude (LA). Besides, there were no special quality standards for HA FFP in China.Materials and methodsUp to 41 HA (Lhasa, 3700 m) and 46 LA (Chengdu, 500 m) blood donors were included in our study to estimate the differences of FFP from HA and LA blood donors. The concentration of total plasma proteins, prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), fibrinogen (Fbg), factor (F) II, FV, FVII, FVIII, FIX, FX, FXI, FXII, D-dimer, protein C (PC), protein S (PS), antithrombin III (ATIII) and von Willebrand factor antigen (vWF:Ag) were determined, respectively.ResultsAs compared with FFP of LA blood donors, the total protein content of HA blood donors showed a significant decrease (65.2±8.9 vs.57.2±6.3 g/L; p<0.001); PT, aPTT, TT were significantly increased (p<0.001); the levels of FII, FV, FVII, FVIII, FIX, FX, FXI, FXII and vWF:Ag were notably decreased (all p<0.05), whereas Fbg and D-dimer were dramaticly increased (p = 0.038). Additionly, in HA blood donors, vWF: Ag and FVIII:C of O-group was significantly lower (p<0.05) than that of non-O-group. It should be noted that FVIII:C of HA blood donors (0.64±0.10 IU/mL) was lower than the current Chinese quality requirements for FFP (? 0.7 IU/ml). No significant differences were observed in PC, PS and ATIII.ConclusionIn general, our findings showed that the quality of FFP was significantly different between HA and LA blood donors, and the current Chinese quality requirements of FFP are not suitable for HA FFP. Therefore, setting up a special quality requirement for HA is quite necessary and meaningful.
| S-EPMC5400266 | biostudies-literature
Project description:Nearly 10% of premature and critically ill infants receive fresh-frozen plasma (FFP) transfusions to reduce their high risk of bleeding. The authors have only limited data to identify relevant clinical predictors of bleeding and to evaluate the efficacy of FFP administration. There is still no consensus on the optimal use of FFP in infants who have abnormal coagulation parameters but are not having active bleeding. The aims of this review are to present current evidence derived from clinical studies focused on the use of FFP in neonatology and then use these data to propose best practice recommendations for the safety of neonates receiving FFP.
| S-EPMC9631350 | biostudies-literature
Project description:Backgroundγ-irradiation is used to treat red blood cell (RBC) concentrates (RCCs) transfused to immunosuppressed patients. This treatment damages RBCs and increases storage lesions. Several studies have shown the beneficial effect of reducing O2 content during RBC storage. The present research work investigated the effect of γ-irradiation on RCCs stored under normal and hypoxia/hypocapnia conditions.Materials and methodsO2 concentration (measured as oxyhaemoglobin fraction, sO2) and ABO-matched RCCs from whole blood donations, leukoreduced and prepared in phosphate, adenine, glucose, guanosine, saline and mannitol (PAGGSM) were pooled and split in two identical RCCs within 24 h post donation. One bag (Hx) was submitted to O2 and CO2 adsorption for 3 h on an orbital shaker at 22±2 °C and then transferred to a storage bag impermeable to gas. The other bag (Ctrl) was left as it was. The two bags were then stored at 4 °C. γ-irradiation (25 Gy) was applied at day 2 or 14, and the RCCs were stored until day 43. Different parameters (metabolites, haemolysis, morphology) were measured.ResultsStarting sO2 values were 63.7±18.4% (n=12) in Ctrl and 20.8±9.8% (n=12) in Hx bags, and reached 90.8±9.1% and 6.6±5.9% at day 43, respectively. As expected, an increase in glycolysis rate was observed after deoxygenation. Extracellular potassium concentrations were identical and reached around 70 mM at expiry with an irradiation-dependent kinetic release. No difference in haemolysis was observed after irradiation on day 2 in either group (<0.40%, p>0.9999). When irradiated at day 14, haemolysis was lower (p=0.033) in RCCs under hypoxia at the end of storage (day 28, 0.67±0.16%) compared to control (1.06±0.33%). Percentages of spherocytes were lower under hypoxia.DiscussionThe storage under hypoxia provided equivalent storage when RCCs were irradiated at day 2 and was advantageous when irradiated at day 14. In summary, O2-depletion of RCCs enable a better storage of RBCs, particularly when late irradiation is applied.
| S-EPMC8297680 | biostudies-literature
Project description:Human α2-macroglobulin (hα2M) is a large homotetrameric protein involved in the broad inhibition of endopeptidases. Following cleavage within a bait region, hα2M undergoes stepwise transitions from its native, expanded, highly flexible, active conformation to an induced, compact, triggered conformation. As a consequence, the peptidase is entrapped by an irreversible Venus flytrap mechanism. Given the importance of hα2M, biochemical studies galore over more than seven decades have attempted to ascertain its role, typically using authentic hα2M purified from frozen and non-frozen fresh blood plasma, and even outdated plasma. However, hα2M is sensitive once isolated and purified, and becomes heterogeneous during storage and/or freezing, raising concerns about the functional competence of frozen plasma-derived hα2M. We therefore used a combination of native and sodium dodecylsulfate polyacrylamide gel electrophoresis, affinity and ion-exchange chromatography, multi-angle laser light scattering after size-exclusion chromatography, free cysteine quantification, and peptidase inhibition assays with endopeptidases of two catalytic classes and three protein substrates, to characterize the biochemical and biophysical properties of hα2M purified ad hoc either from fresh plasma or frozen fresh plasma after thawing. We found no differences in the molecular or functional properties of the preparations, indicating that protective components in plasma maintain native hα2M in a functionally competent state despite freezing.
| S-EPMC10027685 | biostudies-literature