Biochemical and functional characteristics of stored (double-dose) buffy-coat platelet concentrates treated with amotosalen and a prototype UVA light-emitting diode illuminator.

BACKGROUND: Pathogen reduction of platelet concentrates (PCs) using amotosalen and broad-spectrum UVA illumination contributes to the safety of platelet transfusion by reducing the risk of transfusion-transmitted infections. We evaluated the in vitro quality of stored buffy-coat (BC) PCs treated with amotosalen and a prototype light-emitting diode (LED) illuminator. METHODS: Double-dose BC-PCs collected into PAS-III/plasma or SSP+ /plasma (55/45%) were treated with amotosalen in combination with either conventional UVA lamps (INT100 Illuminator 320-400 nm) or LED illuminators at 350 nm. Platelet quality and function were evaluated over 7 days. RESULTS: Platelet counts were conserved during storage in all groups, as was platelet swirling without appearance of macroscopic aggregates. Integrin αIIbß3 and glycoprotein (GP) VI expression remained stable, whereas GPIbα and GPV declined similarly in all groups. UV lamp- and LED-treated PCs displayed similar glucose consumption, lactate generation, and pH variation. Comparable spontaneous and residual P-selectin and phosphatidylserine exposure, activated αIIbß3 exposure, mitochondrial membrane potential, lactate dehydrogenase release, and adhesive properties under flow conditions were observed during storage. The use of SSP+ /plasma compared with PAS-III/plasma better preserved most of these parameters, especially during late storage, irrespective of the type of illuminator. CONCLUSION: Replacing the UVA lamp for photochemical treatment by LED illuminators had no impact on platelet metabolism, spontaneous activation, apoptosis or viability, or on the in vitro function of BC-PCs stored for 7 days in SSP+ or PAS-III/plasma. These findings support improved procedures for the pathogen reduction and storage of PCs, to ensure transfusion safety and retention of platelet functional properties.

Impact of COVID-19 and lockdown regarding blood transfusion.

BACKGROUND: The outbreak of a SARS-CoV-2 resulted in a massive afflux of patients in hospital and intensive care units with many challenges. Blood transfusion was one of them regarding both blood banks (safety, collection, and stocks) and consumption (usual care and unknown specific demand of COVID-19 patients). The risk of mismatch was sufficient to plan blood transfusion restrictions if stocks became limited. STUDY DESIGN AND METHODS: Analyses of blood transfusion in a tertiary hospital and blood collection in the referring blood bank between February 24 and May 31, 2020. RESULTS: Withdrawal of elective surgery and non-urgent care and admission of 2291 COVID-19 patients reduced global activity by 33% but transfusion by 17% only. Only 237 (10.3) % of COVID-19 patients required blood transfusion, including 45 (2.0%) with acute bleeding. Lockdown and cancellation of mobile collection resulted in an 11% reduction in blood donation compared to 2019. The ratio of reduction in blood transfusion to blood donation remained positive and stocks were slightly enhanced. DISCUSSION: Reduction of admissions due to SARS-CoV-2 pandemic results only in a moderate decrease of blood transfusion. Incompressible blood transfusions concern urgent surgery, acute bleeding (including some patients with COVID-19, especially under high anticoagulation), or are supportive for chemotherapy-induced aplasia or chronic anemia. Lockdown results in a decrease of blood donation by cancellation of mobile donation but with little impact on a short period by mobilization of usual donors. No mismatch between demand and donation was evidenced and no planned restriction to blood transfusion was necessary.

Hypersensitivity transfusion reactions to platelet concentrate: a retrospective analysis of the French hemovigilance network.

BACKGROUND: Among labile blood products, platelet concentrates (PCs) are the leading cause of hypersensitivity transfusion reactions (HTRs). These reactions often lead to interruption of PC transfusion and can result in a prolonged transfusion process leading to significant morbidity and use of premedication and close monitoring for patients with a history of allergic transfusion reactions. The French hemovigilance database is one of the largest standardized databases providing information on HTRs following administration of labile blood products. In this study, we analyzed this database to assess the relative risk of HTR for each type of PC. STUDY DESIGN AND METHODS: HTRs following PC transfusion were retrospectively extracted from the e-Fit Hemovigilance database of the French National Agency for Medicines and Health Products Safety (ANSM). Frequencies were calculated using the number of specific PCs transfused. RESULTS: Between 2008 and 2014, the overall estimated incidence of HTRs following PC administration was calculated at 232 HTRs per 100,000 PCs transfused. The rate of HTRs was significantly higher with apheresis PC (337/100,000) than with buffy-coat PC (94/100,000). Platelets in additive solutions (PAS) were associated with a significantly lower frequency of HTRs when compared with PCs in native plasma. Amotosalen/UVA- PCs (APCs and BCPCs) which are always in PAS in France, exhibited the lowest frequency of HTRs when compared with their corresponding PCs in native plasma or in PAS (p < 10-7 in all comparisons). CONCLUSION: Our results showed that the type of PC and its processing may have an impact on the risk of HTR.

Comparative effectiveness of plasma prepared with amotosalen-UVA pathogen inactivation and conventional plasma for support of liver transplantation.

BACKGROUND: Liver transplant may require large-volume plasma transfusion with increased risk of transfusion-transmitted infection (TTI). Pathogen inactivation of plasma with amotosalen-UVA offers the potential to mitigate TTI risk. STUDY DESIGN AND METHODS: A retrospective cohort design was used to compare the therapeutic efficacy and key safety outcomes for liver transplants supported with quarantine plasma (Q-FFP [reference]) or amotosalen-UVA plasma (IBS plasma [test]). The outcomes evaluated were volume of plasma, the numbers of red blood cell (RBC) components, and the total dose of platelets (PLTs) transfused during and 7 days after transplant. The safety outcomes were acute hepatic artery thrombosis (HAT) and mortality. RESULTS: Transplantation and transfusion records for 212 Q-FFP transplants and 215 IBS plasma transplants were reviewed. Not all transplants required plasma; 161 received Q-FFP and 174 received IBS plasma. Among the transplants that required plasma, there were significant differences in median values between cohorts for delay to transplantation (p=0.002), model end-stage liver disease score (p<0.001), pretransplant hematocrit (p=0.006), and graft cold perfusion time (p=0.033). The median volumes of plasma transfused were not different for test and reference (2.160 L vs. 1.969 L, p=0.292). Transplants in the test cohort required a mean of 3.7% more RBC components (p=0.767) and on average a 16.5% increase in total PLT dose (p=0.518). No significant differences were observed for the frequency of acute HAT or mortality. CONCLUSION: In this retrospective study, IBS plasma provided therapeutic support of liver transplant not different from Q-FFP.

Use of additive solutions and pathogen inactivation treatment of platelet components in a regional blood center: impact on patient outcomes and component utilization during a 3-year period.

BACKGROUND: The Etablissement Français du Sang Alsace (EFS Alsace) successively implemented universal use of platelet additive solutions (PASs) and pathogen inactivation (PI) for platelet components (PCs). To assess the impact of these changes, EFS Alsace evaluated PC use, red blood cell (RBC) component use, and transfusion-related adverse events after implementation of these new technologies. STUDY DESIGN AND METHODS: EFS Alsace prospectively collects data on production, distribution, and response to transfusion of all blood components with greater than 99.5% data acquisition. Adverse events attributed to platelet (PLT) transfusions were collected through a mandatory, active hemovigilance program. A retrospective review of prospectively collected data was conducted covering three periods: 1) apheresis and whole blood-derived PCs in plasma, 2) apheresis and whole blood-derived PCs with PAS, and 3) PCs prepared with PI and PAS. Data on component utilization were analyzed for all patients receiving PCs in each period and for the subset of hematology-oncology patients to evaluate PC use in an intensely transfused population. Values for all continuous variables were summarized as mean and standard deviation, median, and range. RESULTS: Approximately 2000 patients received PCs in each period. PLT and RBC use per patient was not increased after PI (analysis of variance, F = 1.9 and 2.9, respectively) and the incidence of acute transfusion reactions was significantly reduced (p < 0.001). CONCLUSIONS: Universal use of PI was implemented without impacting component use, as indicated by total dose of PLTs per patient, and outcomes to transfusion were improved.

An active hemovigilance program characterizing the safety profile of 7483 transfusions with plasma components prepared with amotosalen and UVA photochemical treatment.

BACKGROUND: Photochemical pathogen inactivation treatment (PCT) of plasma components with amotosalen and UVA has been implemented in Europe. To establish a postapproval safety database, an active hemovigilance (HV) program utilizing an electronic data capture system (EDCS) was initiated. STUDY DESIGN AND METHODS: The response to transfusion was documented after each PCT-plasma transfusion. The primary outcome was the incidence of acute transfusion reactions (ATRs) within 24 hours of transfusion. An ATR was defined as an adverse event (AE) possibly related, probably related, or related to the PCT-plasma transfusion. For AEs, the following were collected: time of event after transfusion, clinical description, vital signs, clinical and laboratory test results, severity (Grade 0-4), seriousness, and causal relationship to transfusion of PCT-plasma. RESULTS: To date, 3232 patients (59.1% male) with a primary indication for plasma transfusion due to a hematology disorder (23.1%), surgery (32.4%), or a general medical condition (44.4%) received 7483 PCT-plasma transfusions (composed of 19,069 apheresis plasma components). The mean age of the patient population was 57.3 years (2884 adults, 160 children, and 188 infants). ATRs were reported for 8/7483 transfusions (0.11%; 95% confidence interval [CI], 0.03-0.19) and 8/3232 patients (0.25%; 95% CI, 0.08-0.42%). Five ATRs were of Grade 1 severity. The remaining three ATRs were classified as serious. No deaths or episodes of transfusion-related acute lung injury attributed to a PCT-plasma transfusion were reported. CONCLUSION: PCT-plasma transfusions were well tolerated in routine clinical use. The EDCS HV program facilitated collection and reporting of safety information on a real-time basis from multiple sites.

Transfusion of platelet components prepared with photochemical pathogen inactivation treatment during a Chikungunya virus epidemic in Ile de La Réunion.

BACKGROUND: During the Chikungunya virus (CHIKV) epidemic on Ile de La Réunion, France, more than 30% of 750,000 inhabitants were infected. Local blood donation was suspended to prevent transfusion-transmitted infection (TT-CHIKV). To sustain the availability of platelet (PLT) components, the Etablissement Français du Sang implemented universal pathogen inactivation (INTERCEPT, Cerus Europe BV) of PLT components (CPAs). The study assessed the safety of PLT components treated with pathogen inactivation transfused in routine clinical practice. STUDY DESIGN AND METHODS: This was a retrospective observational study using patient medical records and the AFSSAPS hemovigilance database (eFIT) to identify TT-CHIKV and adverse events (AEs) classified as acute transfusion reactions (ATRs) to PLT components prepared with pathogen inactivation. RESULTS: During 1 year, 1950 INTERCEPT-CPAs were transfused to 335 adult, 51 pediatric, and 41 infant patients. Nineteen AEs were observed in 15 patients and 10 were classified as ATRs. Eight ATRs occurred in 6 pediatric hematology-oncology patients. No ATRs were observed in infants. The most frequently reported signs and symptoms were Grade 1 urticaria, itching, chills, fever, and anxiety. No cases of transfusion-related acute lung injury, TT-sepsis, or TT-CHIKV were detected. CONCLUSIONS: INTERCEPT-CPAs were well tolerated in a broad range of patients, including infants. ATR incidence was low and when present ATRs were of mild severity.

Photochemical treatment of plasma with amotosalen and UVA light: process validation in three European blood centers.

BACKGROUND: A photochemical treatment (PCT) process has been developed to inactivate pathogens and white blood cells (WBCs) in therapeutic plasma. Process validation studies were performed in three European blood centers under routine operating conditions. STUDY DESIGN AND METHODS: Each center prepared 30 apheresis and 30 to 36 whole blood-derived plasma units for PCT. Each whole blood-derived plasma unit contained a mixture of two to three matched donations. After removal of pretreatment control samples (control fresh-frozen plasma [C-FFP]), 546 to 635 mL of plasma was treated with 15 mL of 6 mmol per L amotosalen, 3 J per cm(2) UVA treatment, and removal of residual amotosalen with a compound adsorption device. After processing, plasma samples (PCT-FFP) were withdrawn, frozen at -60 degrees C within 8 hours of collection, and assayed for coagulation factors and residual amotosalen. RESULTS: A total of 186 units of plasma were processed. The mean prothrombin time (12.2 +/- 0.6 sec) and activated partial thromboplastin time (32.1 +/- 3.2 sec) of PCT-FFP were slightly prolonged compared to C-FFP. Fibrinogen and Factor (F)VIII were most sensitive to PCT (26% mean reduction). PCT-FFP, however, retained sufficient levels of fibrinogen (217 +/- 43 mg/dL) and FVIII (97 +/- 29 IU/dL) for therapeutic plasma. Mean levels of FII, FV, FVII, F IX, FX, FXI, and FXIII in PCT-FFP were comparable to C-FFP (81%-97% retention of activity). Antithrombotic proteins were not significantly affected by PCT with retention ranging between 83 and 97 percent. Mean residual amotosalen levels were 0.6 +/- 0.1 micromol per L. CONCLUSION: Process validation studies in three European centers demonstrated retention of coagulation factors in PCT-FFP within the required European and respective national standards for therapeutic plasma.

Plasma glycoprotein V levels in the general population: normal distribution, associated parameters and implications for clinical studies.

Soluble glycoprotein V (sGPV) is a new plasma marker of thrombosis released from the platelet surface by thrombin. sGPV levels are increased in patients with atherothrombotic diseases, but the determinants of sGPV levels are unknown in the general population. Identification of these potential confounding factors is needed for correct design and analysis of clinical studies on cardiovascular diseases. The aim of this study was to determine the normal range of plasma values and the factors controlling sGPV levels in a population of normal individuals. Three hundred blood donors were recruited at the Etablissement Français du Sang-Alsace for the measurement of plasma levels of sGPV, platelet factor 4 (PF4), thrombin-antithrombin complexes (TAT) and D-dimers. The plasma level of sGPV was (median [interquartile range]) 27.5 [23.5-34.4] microg/l and displayed a Gaussian distribution. sGPV had a lower interindividual coefficient of variation (33%) than PF4 (176%), TAT (87%) or D-dimers (82%). sGPV levels were independent of age and sex but sensitive to red cell (r = 0.412; p < 0.0001) and platelet counts (r = 0.267; p = 0.001), total cholesterol (r = -0.313; p < 0.0001), food intake (r = 0.184; p = 0.0014) and smoking (r = -0.154; p = 0.039). Contrary to PF4 and TAT, sGPV did not differ between venous and arterial blood samples of 12 healthy individuals. Red cell and platelet counts, total cholesterol, current smoking and recent food intake are important determinants of sGPV levels and must be taken into account in clinical studies using sGPV as a thrombosis marker. Normal distribution of sGPV levels in the general population supports its use in clinical applications.

Zonificación agroecológica de sistemas agroforestales: el caso café (coffea arabica L) palma camedor (chamaedoera elegans mart) / Agro-ecological zoning of agroforestry systems: the case coffee (coffea arabica L) parlor palm (chamaedorea elegans mart)

Ante el deterioro de los recursos naturales en zonas tropicales, los sistemas agroforestales han sido identificados como técnicas de manejo de la tierra que permiten una producción más sostenible. Por otra parte, las metodologías de zonificación agroecológica ayudan a ubicar aquellos tipos de uso del suelo que se ajustan mejor a las características físicas de una región. Sin embargo, aún no hay experiencias de zonificación agroecológica en sistemas agroforestales. En este trabajo se presenta una propuesta tomando como modelo al sistema café-palma camedor. La propuesta se basa en selección y categorización de variables ambientales, la construcción del modelo cartográfico y la síntesis cartográfica y validación. En el mapa de zonificación agroecológica se ubican los diferentes niveles de aptitud que se presentan en el área de estudio para este sistema, determinándose que 85,5 por ciento del área presenta restricciones ambientales. En la validación se utilizaron datos de distribución del sistema agroforestal y mediante la generación de modelos lineales generalizados se estimó el efecto que tienen las variables ambientales en su distribución. De las 11 variables solo la temperatura mínima (palma), la pedregosidad y la fertilidad del suelo no tuvieron significación estadística (P>0,05). Con los modelos lineales se elaboraron mapas de probabilidad de presencia del sistema agroforestal; en el aspecto climático se registró un coeficiente de determinación de 0,70 y en el ámbito edafológico de 0,45. Se realizaron análisis de correlación entre los mapas de aptitud y los mapas de presencia del sistema agroforestal, registrándose solo correspondencia en el aspecto climático (r= -0,88)

Therapeutic efficacy and safety of photochemically treated apheresis platelets processed with an optimized integrated set.

BACKGROUND: This multicenter, randomized, controlled, double-blind Phase III clinical study evaluated the therapeutic efficacy and safety of apheresis platelets (PLTs) photochemically treated (PCT) with amotosalen and ultraviolet A light (INTERCEPT Blood System, Baxter Healthcare Corp.) compared with conventional apheresis PLTs (reference). STUDY DESIGN AND METHODS: Forty-three patients with transfusion-dependent thrombocytopenia were randomly assigned to receive either PCT or reference PLT transfusions for up to 28 days. RESULTS: The mean 1- and 24-hour corrected count increments were lower in response to PCT PLTs (not significant). When analyzed by longitudinal regression analysis, the estimated effect of treatment on 1-hour PLT count was a decrease of 7.2 x 10(9) per L (p = 0.05) and on 24-hour PLT count a decrease of 7.4 x 10(9) per L (p = 0.04). Number, frequency, and dose of PLT transfusions; acute transfusion reactions; and adverse events were similar between the two groups. There was no transfusion-associated bacteremia. Four PCT patients experienced clinical refractoriness; however, only one exhibited lymphocytotoxicity assay seroconversion. Antibodies against potential amotosalen-related neoantigens were not detected. CONCLUSION: PCT PLTs provide effective and safe transfusion support for thrombocytopenic patients.

Assessment of complement activation during membrane-based plasmapheresis procedures.

Previous studies have suggested that plasmapheresis procedures using a separation membrane may activate the complement system and release anaphylatoxins. This study determines the content in C3a/C3a(des Arg) and C5a/C5a(des Arg) in plasma donations obtained by the new Haemonetics Filter Core (FC) procedure and compares it to Baxter Autopheresis C (Auto-C). FC performs sequential blood centrifugation and plasma filtration on a microporous polyethersulfone membrane, while Auto-C removes blood cells by simultaneous gravitation and filtration on a rotating nylon membrane. One group of 34 donors donated on FC and two groups of 30 and 10 donors on Auto-C. Plasma aliquots were taken from the plasma units within 30 min of the end of the collection procedures, frozen at < -30 degrees C and assessed for C3a and C5a at various time points of storage. Mean C3a/C3a(des Arg) in FC plasma (N = 34) was 1,151 (range: 526-2,991), 1,092 (range: 349-3498), and 507 (range: 307-815) ng/ml at time of collection and after 6 and 12 months of storage, respectively. Respective C5a/C5a(des Arg) was 26.6 (range 4.9-74), 18.9 (9.5-42.6), and 30.9 (range: 10.7-62.3) ng/ml. Mean C3a/C3a(des Arg) was higher in Auto-C (P < 0.001): 4,724 ng/ml (N = 10; range: 2,400-7 ,360) and > 4,149 ng/ml (N = 30; 2,408- > 6,430) after 3 and 18 months storage, respectively. Mean C5a/C5a(des Arg) was 32.1 ng/ml (N = 30; range: 10.6-57.2) after 18 months of storage. Complement activation in FC plasmas appears limited compared to Auto-C, suggesting better biocompatibility of this collection device and/or a favourable impact of the sequential cell centrifugation/filtration technology used. Further studies are needed to explain differences in complement activation between apheresis procedures and to assess clinical impacts, if any.

Heterogeneidad del paisaje y riqueza de flora: su relación en el Archipiélago Camagüey, Cuba / Landscape heterogeneity and plant richness: their relation in the Camagüey Archipielago, Cuba

El Archipiélago de Camagüey, en la costa norte de la zona centro-occidental de Cuba, se destaca por la presencia de elevados valores biológicos en paisajes bien conservados. Este trabajo explora la relación entre heterogeneidad de los paisajes físico-geográficos y la riqueza de flora vascular en este territorio. La riqueza y diversidad del paisaje resultaron variables explicativas de la riqueza de especies de flora. El modelo estadístico que se obtuvo explica más del 82 por ciento de la relación. Los resultados sugieren que la riqueza de flora puede ser predicha por los valores de heterogeneidad geoecológica. En este sentido, se sigiere explorar la probable exsitencia de zonas de elevada biodiversidad en áreas de difícil acceso o poco conocidas, mediante análisis de heterogeneidad de paisajes físico-geográfico