Platelet Concentrates Transfusion Research Articles

Introduction of 7-day amotosalen/ultraviolet A light pathogen-reduced platelets in Honduras: Impact on platelet availability in a lower middle-income country.

Honduras became the first lower middle-income country (LMIC) to adopt amotosalen/UVA pathogen-reduced (PR) platelet concentrates (PCs) as a national platelet safety measure in 2018. The Honduran Red Cross (HRC) produces ~70% of the national platelet supply using the platelet-rich plasma (PRP) method. Between 2015 and 2018, PCs were screened with bacterial culture and issued as individual, non-pooled PRP units with weight-based dosing and 5-day shelf-life. PR PCs were produced in six-PRP pools with a standardized dose (≥3.0 × 1011), no bacterial screening and 7-day shelf-life. Gamma irradiation and leukoreduction were not used. PC production and distribution data were retrospectively analysed in two periods. Period 1 (P1) included 3 years of PRP PCs and a transition year (2015-18). Period 2 (P2) included 5 years of PR PCs (2019-23). PC doses were standardized to an equivalent adult dose for both periods. Descriptive statistics were calculated. HRC produced 10% more PC doses per year on average in P2 compared to P1. Mean annual waste at HRC declined from 23.9% in P1 to 1.1% in P2. Two urban regions consumed 96% of PC doses in P1 and 88.3% in P2. PC distributions increased in 14/18 regions. Standardized dosage, PR and 7-day shelf-life increased PC availability, reduced waste, eliminated bacterial screening and avoided additional costs for arboviral testing, leukoreduction and irradiation. Access to PC transfusion remains limited in Honduras; however, the conversion to pooled PR PCs illustrates the potential to sustainably expand PC distribution in an LMIC.

Modulation of Staphylococcus aureus gene expression during proliferation in platelet concentrates with focus on virulence and platelet functionality.

Staphylococcus aureus is a well-documented bacterial contaminant in platelet concentrates (PCs), a blood component used to treat patients with platelet deficiencies. This bacterium can evade routine PC culture screening and cause septic transfusion reactions. Here, we investigated the gene expression modulation within the PC niche versus trypticase soy media (TSB) of S. aureus CBS2016-05, a strain isolated from a septic reaction, in comparison to PS/BAC/317/16/W, a strain identified during PC screening. RNA-seq analysis revealed upregulation of the capsule biosynthesis operon (capA-H), surface adhesion factors (sasADF), clumping factor A (clfA), protein A (spa), and anaerobic metabolism genes (pflAB, nrdDG) in CBS2016-05 when grown in PCs versus TSB, implying its enhanced pathogenicity in this milieu, in contrast to the PS/BAC/317/16/W strain. Furthermore, we investigated the impact of S. aureus CBS2016-05 on platelet functionality in spiked PCs versus non-spiked PC units. Flow cytometry analyses revealed a significant decrease in glycoprotein (GP) IIb (CD41) and GPIbα (CD42b) expression, alongside increased P-selectin (CD62P) and phosphatidylserine (annexin V) expression in spiked PCs compared to non-spiked PCs (p = 0.01). Moreover, spiked PCs exhibited a drastic reduction in MitoTrack Red FM and Calcein AM positive platelets (87.3% vs. 29.4%, p = 0.0001 and 95.4% vs. 24.7%, p = 0.0001) in a bacterial cell density manner. These results indicated that S. aureus CBS2016-05 triggers platelet activation and apoptosis, and compromises mitochondrial functionality and platelet viability, in contaminated PCs. Furthermore, this study enhanced our understanding of the effects of platelet-bacteria interactions in the unique PC niche, highlighting S. aureus increased pathogenicity and deleterious effect on platelet functionality in a strain specific manner. Our novel insights serve as a platform to improve PC transfusion safety.

Clinical impacts of severe thrombocytopenia in the first cycle of azacitidine monotherapy and cytogenetics in patients with myelodysplastic syndrome: The Kyoto Conditional Survival Scoring System.

Azacitidine (AZA) has been one of the standard treatments for transplantation-ineligible patients with myelodysplastic syndrome (MDS); however, hematological toxicities frequently cause treatment interruption in the early phase of the therapy. The present study conducted a multicenter retrospective study to investigate the prognostic impacts of various factors, including factors included in the Revised International Prognostic Scoring System (IPSS-R) and severe cytopenia in the early phase of AZA monotherapy in 212 patients with MDS. Severe cytopenia was evaluated after the initiation of therapy by absolute neutrophil counts on the 29th day after AZA (ANC29) initiation, and red cell concentrates (RCC) and platelet concentrate (PC) transfusion units required within 28 days from the start of AZA, designated in the present study as RCC28 and PC28, respectively. The survival period was determined from the 29th day of AZA treatment to death from any cause as the conditional survival period after the first cycle of AZA (CS-AZA1). Multivariate analysis demonstrated that severe thrombocytopenia defined by >30 units of PC28 and very poor risk cytogenetics according to IPSS-R were independent prognostic factors for CS-AZA1. The Kyoto Conditional Survival Scoring System was subsequently developed by incorporating severe thrombocytopenia defined by PC28 and very poor risk cytogenetics, which successfully stratified the risks of the patients in CS-AZA1. In conclusion, extreme PC transfusion dependency during the first cycle of AZA and very poor risk cytogenetics are important prognostic factors in AZA monotherapy for MDS.

Apoptotic Pathway Inhibition in Cold-Stored Platelet Concentrates Facilitates Retained Ability to Form Thrombi

Introduction: Platelet concentrates (PCs) are used to treat or prevent bleeding in patients with impaired platelet function or after injury. However, the standard storage of PCs at room-temperature (RT) increases the risk of bacterial contamination and is associated with reduced platelet functionality due to storage lesions. Our group reported that cold-stored PCs have better functionality compared to RT-stored PCs but reduced in vivo circulation time due to cold-induced apoptosis. In order to investigate cold-stored PCs hemostatic functionality with and without apoptosis inhibition, we established an ex vivo model simulating physiological conditions of blood flow to evaluate the contribution of cold-stored PCs in thrombus formation. Methods: Apheresis-derived PCs were stored for 1, 4, 7 and 10 days under agitation at 4°C or RT either with or without the apoptosis inhibitor G04 (RhoA GTPase inhibitor). Next, PCs were stained with CD41 antibody, recalcified and incubated with TRAP6 (thrombin receptor-activating peptide 6) to initiate thrombus formation. Platelet-depleted whole blood samples from healthy donors were spiked-in with PCs and administered to the microfluidic channels of the ex vivo system (Bioflux), under physiological shear pressure. After five minutes of perfusion the resulting thrombi were imaged and analyzed. Ability to form thrombi was further assessed by thromboelastography and impedance aggregometry. Results: Platelets from 24h storage PCs showed stable thrombus formation upon activation with TRAP6. Unstimulated platelets did not form any thrombi during the entire period of perfusion. To evaluate the effect of cold storage on platelet functions we analyzed the extent of thrombus formation of PCs stored at RT and 4°C upon CD41 staining. Our results indicate that cold-stored platelets form larger clots under flow conditions and maintain higher functionality compared to PCs stored at RT. Moreover, incubation of cold-stored PCs with the apoptosis inhibitor G04 improved ex vivo thrombus formation compared to PCs stored without the inhibitor, without inducing any adverse effects (Figure 1). Conclusion: The results indicate that our ex vivo assay, which simulates PC transfusion in thrombocytopenic patients, is suitable to test the hemostatic functions of PCs under physiological flow conditions. We demonstrated that PCs stored at 4°C show better thrombus formation ability upon stimulation by agonists compared to RT-stored PCs and that the ability to form clots under shear stress is still preserved after incubation with the apoptosis inhibitor. To conclude, cold-storage of PCs in combination with apoptosis inhibition is a promising stragedy to reduce the risk of bacterial contamination and prolong in vivo survival time while preserving platelet's hemostatic functionality.

Let Us Know Transfusion Triggers for Prophylactic Use of Platelet Concentrate-Analysis of Compliance with Recent Transfusion Guidelines in a Large Academic Medical Center.

Platelet concentrate (PC) is a blood component that is used to prevent or manage bleeding associated with thrombocytopenia or impaired platelet function. The aim of our study was to assess the compliance of ordering physicians with the most recent PC transfusion guidelines in our academic medical center. All PC transfusions performed between January 2019 and December 2022 were analyzed. The appropriateness of PC transfusions was assessed based on the most recent PC transfusion guidelines. During 2019-2022, there were 362 (0.2%) PC recipients out of 161,762 hospitalized patients. There were 971 PCs transfused during the analyzed period. Inappropriate transfusions accounted for 53.3% of cases, and most of them were given prophylactically (80.2%). Compliance with platelet transfusion guidelines varied among departments. The overall percentage of inappropriately transfused PC ranged from 50.7% to 60.8% in successive years. Educational activities should target clinicians performing procedures associated with high rates of inappropriate PC transfusions. Implementing clinical decision support systems can help reduce unnecessary PC transfusions and associated costs. The majority of inappropriate PC transfusions in our medical center were given as prophylaxis against bleeding. Prescribers should be educated about evidence-based transfusion triggers for the prophylactic use of PC in various clinical scenarios.

Effect of linezolid on platelet count in critically ill patients with thrombocytopenia.

Linezolid (LZD) is one of the antibiotics used to treat methicillin-resistant Staphylococcus aureus. In Japan, the dose of LZD is not generally adjusted by renal function or therapeutic drug monitoring and is readily available for critically ill patients. The adverse effects of LZD include pancytopenia, especially thrombocytopenia. We investigated the effect of LZD on platelet counts in critically ill patients with thrombocytopenia during admission to the intensive care unit (ICU). Fifty-five critically ill patients with existing thrombocytopenia (platelet count < 100 ×103 /μL) who received LZD for five days or more during the period from January 2011 to October 2018 were included. Changes in platelet count and frequency of platelet concentrate (PC) transfusion were evaluated retrospectively. Mean (± standard error) platelet count prior to initiation of LZD was 47 ± 4 ×103 /uL, which increased significantly to 86 ± 13 ×103 /uL on day 15 (p<0.01). Median [interquartile range] duration of LZD therapy was 9 [8-12] days. Thirty-two patients (58.2%) required PC transfusion in the 15-day study period. The daily rate of PC transfusion decreased from 30.2% on days 1-5 to 18.2% on days 11-15. Similar tendencies were observed in patients with non-hematological and hematological disease. Thrombocytopenia in critically ill patients in the ICU did not worsen after initiation of LZD therapy, and may be considered for the treatment of MRSA in this setting.

The efficacy and safety of intravenous administration of tranexamic acid in patients undergoing cardiac surgery: Evidence from a single cardiovascular center.

The current study was performed to systemically review the efficacy and safety of tranexamic acid (TXA) in patients undergoing cardiac surgery at a single large-volume cardiovascular center. A computerized search of electronic databases was performed to identify all relevant studies using search terms till December 31st, 2021. The primary outcomes were postoperative blood loss and the composite incidence of mortality and morbidities during hospitalization. Secondary outcomes included postoperative massive bleeding and transfusion, postoperative recovery profiles, coagulation functions, inflammatory variables, and biomarkers of vital organ injury. Database search yielded 23 qualified studies including 27,729 patients in total. Among them, 14,136 were allocated into TXA group and 13,593 into Control group. The current study indicated that intravenous TXA significantly reduced total volume of postoperative bleeding in both adult and pediatric patients, and that medium- and high-dose TXA were more effective than low-dose TXA in adult patients (P < .05). The current study also demonstrated that intravenous TXA, as compared to Control, remarkably reduced postoperative transfusion incidences and volume of red blood cell and fresh frozen plasma, and reduced postoperative transfusion incidence of platelet concentrates (PC) (P < .05) without obvious dose-effects (P > .05), but TXA did not reduce PC transfusion volume postoperatively in adult patients (P > .05). For pediatrics, TXA did not significantly reduce postoperative transfusion incidence and volume of allogenic red blood cell, fresh frozen plasma and PC (P > .05). Additionally, the current study demonstrated that intravenous TXA did not influence the composite incidence of postoperative mortality and morbidities in either adults or pediatrics during hospitalization (P > .05), and that there was no obvious dose-effect of TXA in adult patients (P > .05). This current study suggested that intravenous TXA significantly reduced total volume of postoperative bleeding in both adult and pediatric patients undergoing cardiac surgery at the single cardiovascular center without increasing the composite incidence of mortality and morbidities.

Two cases of Streptococcus dysgalactiae subspecies equisimilis infection transmitted through transfusion of platelet concentrate derived from separate blood donations by the same donor.

Transfusion-transmitted bacterial infections (TTBIs) in Japan have been largely prevented due to a short shelf life of 3.5 days after blood collection for platelet concentrate (PC) and washed PCs (WPCs; PC in which 95% plasma is replaced by platelet additive solution). Case 1: In January 2018, a woman in her 50s with aplastic anaemia who received WPC transfusion and developed a fever the next day and Streptococcus dysgalactiae subspecies equisimilis (SDSE) was detected in the residual WPC. Case 2: In May 2018, a man in his 60s with a haematologic malignancy who received PC transfusion and developed chills during the transfusion. SDSE was detected in the patient's blood and residual PC. The contaminated platelet products were both manufactured from blood donated by the same donor. The multi-locus sequencing typing revealed that SDSE detected in case 1 was identical to that from case 2; however, whole blood subsequently obtained from the donor was culture negative. WPC and PC produced from two blood donated 106 days apart by the same donor were contaminated with SDSE of the same strain and both caused TTBIs. Safety measures should be considered regarding blood collection from a donor with a history of bacterial contamination.

Retrospective evaluation of fresh platelet concentrate administration in dogs: Patient characteristics, outcomes, and transfusion practices in 189 transfusion episodes (2008-2019).

To describe patient characteristics, underlying disease processes, clinical outcomes, transfusion dose and type (therapeutic or prophylactic), platelet count changes, and adverse events associated with platelet concentrate (PC) administration in dogs. Retrospective study. University teaching hospital. A total of 149 dogs, representing 189 PC transfusion episodes. None. In this population, 39 of 149 dogs (26.2%) were diagnosed with primary immune-mediated thrombocytopenia, 22 of 149 (14.8%) had decreased bone marrow production, 12 of 149 (8.0%) received PC during a massive transfusion, 3 of 149 (2.0%) had congenital thrombocytopathia, 59 of 149 (39.6%) had severe thrombocytopenia of other causes, and 14 of 149 (9.4%) underwent transfusion for miscellaneous causes without a documented severe thrombocytopenia. In 117 of 149 dogs (78.5%), >1 site of hemorrhage was noted. The most common sites of hemorrhage were the gastrointestinal (GI) tract in 89 of 149 (59.7%) and the skin in 78 of 149 (52.3%). Overall survival to discharge was 59.1% (88/149). The median PC dose was 0.8 units per 10kg of body weight per transfusion episode (range: 0.2-6.7). Of 189 episodes, 29 of 189 (15.7%) were prophylactic, and 158 of 189 (83.6%) were therapeutic. For 99 of 189 transfusion episodes, paired pre- and postplatelet counts were available within 24hours. The median platelet count change was 5.0×109 /L (5000/μL; range: -115×109 /L to 158×109 /L [-115,000 to 158,000/μL]); the posttransfusion platelet count was significantly higher than pretransfusion (P<0.0001). The increase in platelet count after transfusion was greater in the prophylactic group than the therapeutic group (P=0.0167). Transfusion reactions were suspected during 2 of 168 episodes (1.2%). Immune-mediated thrombocytopenia was the most common disease process that resulted in PC transfusion. PC was more frequently administered to animals with active hemorrhage rather than prophylactically, and most dogs had evidence of hemorrhage in multiple organ systems, particularly the GI tract and skin. PC transfusions typically appeared safe, and the median platelet count increased after transfusion.

Factors Affecting Day-to-Day Variations in Tacrolimus Concentration among Children and Young Adults Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Tacrolimus is widely used as prophylaxis for graft-versus-host disease (GVHD) in allogeneic stem cell transplantation (allo-HSCT). It has a narrow therapeutic index range. High tacrolimus concentrations are associated with toxicity, while low concentrations are associated with an increased risk of GVHD. Although dose adjustments based on therapeutic drug monitoring are performed, unexpected large variations in tacrolimus concentration are sometimes encountered. Thus far, the available evidence suggests that the factors affecting tacrolimus concentration are not fully understood. This study was primarily aimed at investigating the factors affecting day-to-day variations in tacrolimus concentration among children and young adults who received continuous tacrolimus infusion after allo-HSCT. The secondary objective was identifying the factors causing large variations (> 20%) in tacrolimus concentrations. This was a retrospective cohort study of 123 consecutive pediatric and young adult patients, aged < 25 years, who received continuous intravenous tacrolimus infusion after allo-HSCT at Shinshu University Hospital, Matsumoto, Japan, between January 2009 and December 2021. To compare day-to-day variations in tacrolimus concentrations without consideration of the tacrolimus dose, two consecutive days when the tacrolimus dose was not changed were selected from the first day when the tacrolimus concentration was higher than 7 ng/mL after allo-HSCT to day 28 after allo-HSCT. Subsequently, information for the following 24-h was collected in addition to the tacrolimus concentrations and hematocrit values. Tacrolimus concentration was determined using whole blood samples. Tacrolimus concentrations significantly increased in patients who received red blood cell concentrate (RCC) transfusion (p < 0.0001) and methotrexate (p = 0.0162), patients with persistent fever (p = 0.0056), and patients with a decline in fever (p = 0.0003). In contrast, tacrolimus concentrations decreased significantly in patients who received platelet concentrate (PC) transfusion (p < 0.0001), redeveloped fever (p = 0.0261), and received replaced tacrolimus administration route set (p = 0.0008). Variations in tacrolimus concentration significantly correlated with variations in hematocrit (r = 0.556, p < 0.0001). Body weight (p < 0.0001), RCC transfusion (p < 0.0001), methotrexate use (p = 0.0333), persistent fever (p = 0.0150), and decline in fever (p = 0.0073) were associated with a sharp increase in tacrolimus concentration. In contrast, body weight (p < 0.0001), PC transfusion (p = 0.0025), and replacement of the tacrolimus administration route set (p = 0.0025) were associated with a sharp decrease in tacrolimus concentration. RCC and PC transfusions, fever, methotrexate administration, and replacement of the tacrolimus administration route set were independent factors affecting day-to-day variations in tacrolimus concentration. In addition to these factors, low body weight was a risk factor for both a sharp increase and decrease in tacrolimus concentration. These findings suggest the need for better control of tacrolimus concentrations using whole blood samples.

Health Economic Aspects of Platelet Concentrates: Comparing Cost and Reimbursement of Pathogen Inactivated and Conventional Platelet Concentrates in a German Comprehensive Cancer Center.

Pathogen inactivation (PI) utilizing amotosalen and UVA light (INTERCEPT® Blood System) is a well-established method for the production of safer platelet concentrates (PCs). While many studies describe clinical and logistical benefits of PI, the implications and potential challenges from a hospital management perspective have not yet been analyzed - health economic analyses considering reimbursement of PI are lacking. The objective of this analysis was to examine the real-life inpatient treatment costs from a hospital perspective and to assess the economic impact of PI-PC versus conventional PC (CONV-PC) administration in Germany. Real-life cost data for inpatient cancer cases from 2020 of the University Hospital Cologne were identified by operating and procedure codes. The German diagnosis-related groups, extra fees, case mix index (CMI), length of stay (LOS), and average resource consumption of PC were evaluated from a micro-management perspective. The potential economic impact of implementing PI-treated PCs was modeled retrospectively. In total, 951 inpatient cases were analyzed (CMI [median 4.7-9.9], LOS [median 26 days], number of cases in intensive care units [38%]). The median DRG fee was between EUR 13,800 and EUR 26,400. According to our model, the use of PI-PC compared to CONV-PC would result in savings between EUR 184 and EUR 306 per case. From a hospital management perspective, oncological cases requiring PC transfusion are associated with a high CMI (reimbursement per DRG flat fee) and moderate costs with sufficient add-on payment for PI on a case level. Investment and process costs for PI implementation can be analyzed for site-specific scenarios.

Analysis of Transfusion-Transmitted Bacterial Infections according to German Hemovigilance Data (2011–2020)

Introduction: Following the first assessment of the effects of safety measures taken against transfusion-transmitted bacterial infections (TTBI), the Paul-Ehrlich-Institut (PEI) decided to newly analyze risk minimization measures (RMM) using German hemovigilance data from 2011 to 2020, focusing on blood components, recipients, and bacterial strains. Materials and Methods: The PEI assessed the imputability of all reported serious adverse reactions (SAR) relying mainly on microbiological test results. Reporting rates (RR) of suspected, confirmed, and fatal confirmed TTBI were calculated and compared to the previous reporting 10-year period (2001–2010) using Poisson regression to estimate RR ratios (RRR). Furthermore, details on blood component age, patients’ medical history, and bacterial pathogenicity were collected. Results: With respect to the previous 10-year period, the number of suspected TTBI increased (n = 403), while fewer cases were confirmed (n = 40); the number of deaths remained more or less unchanged (n = 8). The RR for suspected TTBI were 7.9, 18.7, and 1.6 cases per million units transfused for red blood cells (RBC), platelet concentrates (PC), and fresh frozen plasma (FFP), respectively. RRR showed a statistically significant 2.5-fold increase in the RR for suspected TTBI after RBC administration from 2001–2010 to the period under review (p < 0.0001). The RR for confirmed TTBI were 0.4, 5.0, and 0.0 cases per million units transfused for RBC, PC, and FFP, respectively. Compared to the period 2001–2010, there was a statistically significant decrease in the RR of confirmed TTBI by half for PC (p = 0.0052). The RR for confirmed PC-caused TTBI with fatal outcome was 1.4 cases per million units transfused. Regardless of type of blood product transfused and outcome of SAR, the majority of TTBI occurred after administration of a product at the end of shelf life (40.0%) and to recipients of advanced age (median age: 68.5 years) and/or with severe immunosuppression (72.5%) due to decreased myelopoiesis (62.5%). 72.5% of the involved bacteria had a middle/high human pathogenicity. Conclusion: Despite a significant decrease in confirmed TTBI following PC transfusion in Germany after implementation of RMM, the current manufacture of blood products can still not prevent TTBI with fatal outcomes. As demonstrated in various countries, RMM like bacterial screening or pathogen reduction may measurably improve the safety of blood transfusion.

Cryopreserved platelets: a narrative review of its current role in transfusion therapy

Background: The short shelf life of platelet concentrates (PCs) provokes logistic problems in providing timely PC transfusions during long holiday periods when long or major transportation barriers exists (severe weather, military operations…) or for patients highly alloimmunized by human leukocyte antigens (HLA)/human platelet antigens (HPA) antibodies. In the European Union the only approved strategy authorized to circumvent the limited storage time of PCs is the cryopreservation using 6% dimethyl sulfoxide (DMSO), at temperature of –80 ℃ or below.

Abstract 158: Bioactive Lipids As Biomarkers Of Severe Adverse Reaction Associated With Apheresis Platelet Concentrate Transfusion

Blood transfusion is a life-saving procedure in which whole blood, or blood components are provided to a patient. Platelet concentrates (PC) may sometimes induce adverse reactions, that are occasionally severe. PC comprise active biomolecules such as cytokines and lipid mediators. Platelet storage lesions are structural and biochemical changes in PC and vary in collection and processing conditions. We investigated lipid mediators as bioactive molecules along storage conditions and in adverse reactions after transfusion. The PC left over were analysed after transfusion, classified with/out severe reaction. Our data presented a decrease of lysophosphatidylcholine species to produce lysophosphatidic acid species. This balance could lead and be correlated with complication symptoms, as other lipids. Lysophosphatidic acid increased with primarily platelet-inhibitor-lipids when single donor apheresis platelet upon storage. Anti-inflammatory and platelet-induced-inhibition lipids were weakly expressed in case of severe adverse reaction. Thus, a decrease in lysophosphatidylcholine and an increase in lysophosphatidic acid could be reliable predictors of serious adverse transfusion reactions transfusion. These data highlighted the importance of PC manufacturing and storage processing, not only to maximize clinical efficacy but also to minimize adverse reactions.

Blood Transfusion Predicts Prolonged Mechanical Ventilation in Acute Stanford Type A Aortic Dissection Undergoing Total Aortic Arch Replacement.

BackgroundThis research aimed to evaluate the impacts of transfusing packed red blood cells (pRBCs), fresh frozen plasma (FFP), or platelet concentrate (PC) on postoperative mechanical ventilation time (MVT) in patients with acute Stanford type A aortic dissection (ATAAD) undergoing after total arch replacement (TAR).MethodsThe clinical data of 384 patients with ATAAD after TAR were retrospectively collected from December 2015 to October 2017 to verify whether pRBCs, FFP, or PC transfusion volumes were associated with postoperative MVT. The logistic regression was used to assess whether blood products were risk factors for prolonged mechanical ventilation (PMV) in all three endpoints (PMV ≥24 h, ≥48 h, and ≥72 h).ResultsThe mean age of 384 patients was 47.6 ± 10.689 years, and 301 (78.39%) patients were men. Median MVT was 29.5 (4–574) h (h), and 213 (55.47%), 136 (35.42%), and 96 (25.00%) patients had PMV ≥24 h, ≥48 h, and ≥72 h, respectively. A total of 36 (9.38%) patients did not have any blood product transfusion, the number of patients with transfusion of pRBCs, FFP, and PC were 334 (86.98%), 286 (74.48%), and 189 (49.22%), respectively. According to the multivariate logistic regression of three PMV time-endpoints, age was a risk factor [PMV ≥ 24 h odds ratio (ORPMV≥24) = 1.045, p = 0.005; ORPMV≥48 = 1.060, p = 0.002; ORPMV≥72 = 1.051, p = 0.011]. pRBC transfusion (ORPMV≥24 = 1.156, p = 0.001; ORPMV≥48 = 1.156, p < 0.001; ORPMV≥72 = 1.135, p ≤ 0.001) and PC transfusion (ORPMV≥24 = 1.366, p = 0.029; ORPMV≥48 = 1.226, p = 0.030; ORPMV≥72 = 1.229, p = 0.011) were independent risk factors for PMV. FFP had no noticeable effect on PMV [ORPMV≥48 = 0.999, 95% confidence interval (CI) 0.998–1.000, p = 0.039; ORPMV≥72 = 0.999, 95% CI: 0.998–1.000, p = 0.025].ConclusionsIn patients with ATAAD after TAR, the incidence of PMV was very high. Blood products transfusion was closely related to postoperative mechanical ventilation time. pRBC and PC transfusions and age increased the incidence of PMV at all three endpoints.

Transparency on Platelet Transfusion in Routine Cancer Care: The Key for Optimal Blood Usage?

Introduction: In Germany, up to 75% of platelet concentrates (PCs) are administered to haematological and oncological patients. Only limited transparency exists on the characteristics of haematological/oncological patients receiving PC transfusions, treatment patterns, and guideline adherence in daily clinical routine care. This information would be key for managing platelet supply and optimal platelet usage strategies. This study aimed to analyse data from clinical routine transfusions to fill the aforementioned information gaps and to create an inventory as a blueprint for electronic data capturing systems that allow simplified, recurring analyses. Methods: Prospective open-label, single-centre, observational study in a German tertiary teaching haematological/oncological setting. All inpatients who received any transfusion of PCs (pathogen-inactivated or conventional) in routine use over a period of 3 months (March 2015–May 2015) were consecutively included. Except for age (≥18 years), no exclusion criteria were applied. For guideline adherence, the Cross-Sectional Guidelines for Therapy with Blood Components and Plasma Derivatives – amended edition 2020 were used. An inventory blueprint was created through a narrative literature review and the data collected in this study. Results: Ninety-four patients received 942 PCs. The mean (±SD) age was 54.6 (±13.9) years, 68% were male and 86% were diagnosed with a haematological disease. Thirteen patients received 42% of all transfused PCs. The mean ± SD number of transfused PC per patient was 10.81 ± 9.24. Five (0.5% per transfusion) minor adverse events were documented. Approximately 19% of PCs were not administered according to existing guidelines. The mean transfusion interval was 1.71 ± 1.1 days, and the mean increment was 12.62 ± 14.7 G/L. The inventory showed which platelet transfusion-specific data should be documented for answering questions in terms of quality, effectiveness, and management of PC transfusions. Conclusions: Platelet transfusions in a haematological/oncological setting are highly individual in terms of the total number of transfusions and transfusion intervals. The majority of all PC transfusions were given to only a small group of patients. Continuous, structured real-world data collection/evaluation and benchmarking with data from more centres seems essential in determining specific needs in this vulnerable patient group, assessing the quality of transfusion practices, determining effectiveness, and anticipating future demand for platelets and a sustainable blood supply. So far, not all relevant data are collected routinely. The advancing digitalization of health systems offers opportunities to collect and link data and thus make them more accessible and evaluable.

Platelet procoagulant potential is reduced in platelet concentrates ex vivo but appears restored following transfusion.

The procoagulant profile of platelet concentrates (PCs) following transfusion has been difficult to evaluate due to lack of specific markers. This study aimed to characterize procoagulant platelets in PCs and the effect of transfusion. Buffy coat-derived PCs from 12 donors were pooled, split, then stored conventionally, cold (2-6°C) or cryopreserved (-80°C). Procoagulant platelet profiles were assessed by flow cytometry (GSAO+ /P-selectin+ ), lactadherin-binding, and calibrated automated thrombogram, during storage, unstimulated, or after thrombin and collagen stimulation and compared with blood from healthy volunteers. Platelet activation (P-selectin) and procoagulant platelet formation potential were measured (flow cytometry) in patients receiving clinically indicated conventional PC transfusion. Independent of significant increases with storage, procoagulant platelet proportions with and without agonist stimulation were significantly blunted in conventionally stored PCs (stimulated day 5 conventional PC 4.2 ± 1.3%, healthy volunteer blood 11.1 ± 2.9%; p< .0001). Cryopreserved PCs contained the highest proportion of procoagulant platelets (unstimulated: cryopreserved 25.6 ± 1.8% vs. day 5 conventional 0.5 ± 0.1% vs. day 14 cold-stored 5.8 ± 1.0%, p< .0001), but demonstrated minimal increase with agonist. Transfusion of PCs was associated with an increase in procoagulant platelets (2.2 ± 1.4% vs. 0.6 ± 0.2%; p= .004) and reversal of the blunted agonist response (15.8 ± 5.9% vs. 4.0 ± 1.6%; p< .0001). Procoagulant responses post-transfusion were significantly higher than healthy controls, suggesting a priming effect. The P-selectin agonist response was not restored upon transfusion (79.4 ± 13.9% vs. 82.0 ± 2.5%). Storage blunts the procoagulant platelet response to agonist stimulation in PCs. Despite this, conventionally stored PCs have high procoagulant potential following transfusion, with a discordant, persistent reduction in P-selectin response.

The Differences Levels of RANTES and PF4 Based on the Storage of Platelet Concentrate

Blood component transfusion is often used as the primary therapy as it is still considered safe. Platelet Concentrate (PC) transfusion plays a critical role in preventing bleeding in patients with severe thrombocytopenia. Allergic reactions are the most frequent transfusion reactions after PC administration. Regulated on Activation Normal T-Cell Expressed and Secreted (RANTES) and Platelet Factor 4 (PF4) cytokines released by platelets during PC storage are responsible for allergic reactions after transfusion. The purpose of this study was to analyze changes in RANTES and PF4 levels during PC storage. This study was an observational analytical research with a time series design carried out at the Clinical Pathology Laboratory and Blood Bank of the Dr. Soetomo Hospital, Surabaya, from June to July 2019. RANTES and PF4 levels in 27 bags derived from Platelet Rich Plasma (PRP) on storage for day 1, day 3, and day five were measured using the ELISA sandwich method. Subject same variant test or Friedman test was used for statistical analysis. The results showed no significant differences in RANTES and PF4 levels based on the storage duration of PCs on days 1, 3, and 5, with p=0.717, and p=0.614, respectively. There was no difference in the storage of PCs from day 1 to day five, and there was no effect on allergic reactions after PC transfusion.

Platelet Refractoriness Evaluation after Platelet Concentrate Transfusion in Pediatric Leukemia

Platelet transfusion is being used in 67%-75% of hematology malignancies including leukemia. Platelet refractoriness is the failure to achieve satisfactory responses to platelet transfusions. Many transfusion centres use 1 hour and 24 hours after transfusion Corrected Count Increment (CCI) value to define platelet refractoriness. To analyze platelet refractory based on CCI-1h and CCI-24h value after Platelet Concentrate (PC) tranfusion in pediatric leukemia and the effect of non immune factors on platelet refractoriness. Subjects were evaluated for platelet count after 10-120 minutes and 18-24 hours of PC tranfusion to calculate CCI-1h and CCI-24h. Platelet Refractoriness was defined when CCI-1h &lt;5×109/L and CCI-24h &lt;4.5×109/L. Each subject was observed for non-immune platelet refractory factors. Interestingly, from 25 PC transfusion there was 20% platelet refractoriness of CCI-1h and 40% of CCI-24h. There was a significant difference CCI-1h and CCI-24h (p=0.027). Non immune factor had no effect for platelet refractoriness. Platelet count should be analyzed after 24 hours PC transfusion to diagnose platelet refractoriness. Further research including immune factor examination is needed.

Underlying Inflammation Impacts Immune Modulation Following Exposure to Platelet Concentrates and Packed Red Blood Cells

IntroductionTransfusion of platelet concentrates (PC) and packed red blood cells (PRBC) are lifesaving treatments for patients suffering from thrombocytopenia, haematological disorders, severe trauma and cancer. Platelets play a central role in mediating coagulation and wound healing, inflammation and innate immune responses. Red blood cells are crucial for delivery of oxygen to surrounding tissues and translocation of carbon dioxide in the lungs. In Australia, PC and PRBC are routinely stored for up to 5- or 42- days respectively prior to transfusion. Storage related changes of PC and PRBC may contribute to adverse patient outcomes and include increased release of biological mediators (sCD40L, IL-8), partial platelet activation, loss of 2,3-diphosphoglycerate and ATP, change in oxygen dissociation and altered morphology. Despite the therapeutic benefits of PC and PRBC transfusion, clinical studies suggest transfusion-associated modulation of the recipient immune response contributes to adverse outcomes including infection and mortality. Underlying inflammation is an important factor contributing to the development of transfusion-related acute lung injury (TRALI), a pro-inflammatory response, whereas in vitro transfusion models largely report leucocyte suppression following exposure to PC and PRBC. The relationship between the level of underlying inflammation and the impact on cell function post-transfusion remains unclear. We investigated the relationship between inflammation and modulation of dendritic cell (DC) and monocyte phenotype following exposure to PC and PRBC.MethodsAn in-vitro transfusion model was used to investigate changes in DC and monocyte phenotype following exposure to PC-supernatants (PC-SN) or PRBC-supernatants (PRBC-SN) in co-culture with a range of lipopolysaccharide concentrations (LPS; 0 µg/mL (no LPS), 0.25 µg/mL, 0.5 µg/mL, 0.75 µg/mL, 1 µg/mL LPS) to model different levels of underlying inflammation. Based on results of recent randomised controlled trials, we used fresh PC- and PRBC- SN. Freshly collected whole blood was cultured with RPMI media and day 2 (D2) PC-SN or D2 PRBC-SN at doses representing a 1 (10%), or 2-3 (25%) unit transfusion. Golgi-plug (containing Brefeldin-a) was used to inhibit protein release to facilitate intracellular staining of cytokines (IL-6, IL-8, IL-10, IL-12, IL-1α, TNF-α, MIP-1α, MIP-1β, MCP-1, IP-10) from DC and monocytes using via flow cytometry. Changes in monocyte and DC cytokine and chemokine production at different concentrations of LPS were assessed by a repeated measures one-way ANOVA with Tukey's post-test (P<0.05).ResultsCulture with LPS alone resulted in a concentration dependent decrease in the production of most monocyte and DC cytokines. Modelling a low dose (1 unit) transfusion with D2 PC-or PRBC- SN resulted in a reduction in monocyte and DC cytokine production in the presence of 0.25 µg/mL and 0.5 µg/mL LPS. This effect was less evident when higher concentrations of LPS (0.75 µg/mL, 1 µg/mL) were used. When modelling a high dose (2-3 unit) transfusion, exposure to D2 PC-or PRBC- SN resulted in a predominant suppression of monocyte and DC responses at all LPS concentrations tested.ConclusionOur data provides evidence that the level of underlying inflammation differentially affects DC and monocyte responses following exposure to PC-SN or PRBC-SN. Dose in combination with level of underlying inflammation significantly impacts monocyte and DC responses which may contribute and increase the risk of transfusion-associated poor patient outcomes including infection. DisclosuresNo relevant conflicts of interest to declare.