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1.
Transfusion ; 63(10): 1937-1950, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37615493

RESUMEN

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.


Asunto(s)
Furocumarinas , Rayos Ultravioleta , Humanos , Furocumarinas/farmacología , Plaquetas/metabolismo , Transfusión de Plaquetas , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/metabolismo , Conservación de la Sangre/métodos
2.
Transfusion ; 62(5): 1073-1083, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35385146

RESUMEN

BACKGROUND: Plasmodium falciparum is the parasite responsible for most malaria cases globally. The risk of transfusion-transmitted malaria (TTM) is mitigated by donor deferrals and blood screening strategies, which adversely impact blood availability. Previous studies showed robust inactivation of P. falciparum using nucleic acid-targeting pathogen reduction technologies (PRT) for the treatment of plasma and platelet components or whole blood (WB). The efficacy of the amustaline-glutathione (GSH) PRT to inactivate P. falciparum is here evaluated in red blood cells (RBC), as well the impact of PRT on parasite loads, stages, and strains. STUDY DESIGN AND METHODS: RBC units resuspended in AS-1 or AS-5 additive solutions were spiked with ring stage-infected RBC and treated with the amustaline-GSH PRT. Parasite loads and viability were measured in samples at the time of contamination, and after treatment, using serial 10-fold dilutions of the samples in RBC cultures maintained for up to 4 weeks. RESULTS: P. falciparum viability assays allow for the detection of very low levels of parasite. Initial parasite titer was >5.2 log10 /ml in AS-1/5 RBC. No infectious parasites were detected in amustaline-GSH-treated samples after 4 weeks of culture. Amustaline-GSH inactivated high parasite loads regardless of parasite stages and strains. Amustaline readily penetrates the parasite, irreversibly blocks development, and leads to parasite death and expulsion from RBC. DISCUSSION: Amustaline-GSH PRT demonstrated robust efficacy to inactivate malaria parasites in RBC concentrates. This study completes the portfolio of studies demonstrating the efficacy of nucleic acid-targeting PRTs to mitigate TTM risks as previously reported for platelet concentrates, plasma, and WB.


Asunto(s)
Malaria Falciparum , Ácidos Nucleicos , Acridinas , Eritrocitos/metabolismo , Glutatión/metabolismo , Humanos , Malaria Falciparum/prevención & control , Compuestos de Mostaza Nitrogenada , Ácidos Nucleicos/metabolismo , Plasmodium falciparum , Inactivación de Virus
3.
Transfusion ; 61(3): 919-930, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33527430

RESUMEN

BACKGROUND: Deterioration in quality of platelet concentrates (PCs) during storage results from the appearance of storage lesions affecting the hemostatic functions and posttransfusion survival of platelets. These lesions depend on the preparation and pathogen inactivation methods used, duration of storage, and platelet additive solutions (PASs) present in storage bags. METHODS: We investigated the effects of citrate contained in third-generation PAS (PAS-III) on storage lesions in buffy-coat PCs with or without photochemical (amotosalen-ultraviolet A) treatment over 7 days. RESULTS: Platelet counts were conserved in all groups during storage, as was platelet swirling without appearance of macroscopic aggregates. Glycoprotein (GP) IIbIIIa and GPVI expression remained stable, whereas GPIbα declined similarly in all groups during storage. Removal of citrate from PAS-III, resulting in global reduction of citrate from 11 to 5 mM, led to a significant decrease in glucose consumption, which largely countered a modest deleterious effect of photochemical treatment. Citrate reduction also resulted in decreased lactate generation and better maintenance of pH during storage, while photochemical treatment had no impact on these parameters. Moreover, citrate-free storage significantly reduced exposure of P-selectin and the apoptosis signal phosphatidylserine, thereby abolishing the activating effect of photochemical treatment on both parameters. Citrate reduction benefited platelet aggregation to various agonists up to Day 7, whereas PCT had no impact on these responses. CONCLUSION: Removal of citrate from PAS-III has a beneficial impact on platelet metabolism, spontaneous activation, and apoptosis, and improves platelet aggregation, irrespective of photochemical treatment, which should allow transfusion of platelets with better and longer-lasting functional properties.


Asunto(s)
Plaquetas/metabolismo , Conservación de la Sangre/métodos , Ácido Cítrico/farmacología , Agregación Plaquetaria/efectos de los fármacos , Apoptosis/efectos de los fármacos , Furocumarinas/farmacología , Hemostasis/efectos de los fármacos , Humanos , Concentración de Iones de Hidrógeno , Ácido Láctico/metabolismo , Selectina-P/metabolismo , Fosfatidilserinas , Recuento de Plaquetas , Pruebas de Función Plaquetaria , Complejo GPIb-IX de Glicoproteína Plaquetaria/metabolismo , Glicoproteínas de Membrana Plaquetaria/metabolismo
4.
Transfusion ; 61(5): 1642-1653, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33580977

RESUMEN

BACKGROUND: The production of platelet concentrates (PCs) is evolving, and their survival capacity needs in vivo evaluation. This requires that the transfused platelets (PLTs) be distinguished from those of the recipient. Labeling at various biotin (Bio) densities allows one to concurrently trace multiple PLT populations, as reported for red blood cells. STUDY DESIGN AND METHODS: A method is described to label human PLTs at two densities of Bio for future clinical trials. Injectable-grade PLTs were prepared in a sterile environment, using injectable-grade buffers and good manufacturing practices (GMP)-grade Sulfo-NHS-Biotin. Sulfo-NHS-Biotin concentrations were chosen to maintain PLT integrity and avoid potential alloimmunization while enabling the detection of circulating BioPLTs. The impact of biotinylation on human PLT recirculation was evaluated in vivo in a severe immunodeficient mouse model using ex vivo flow cytometry. RESULTS: BioPLTs labeled with 1.2 or 10 µg/ml Sulfo-NHS-Biotin displayed normal ultrastructure and retained aggregation and secretion capacity and normal expression of the main surface glycoproteins. The procedure avoided detrimental PLT activation or apoptosis signals. Transfused human BioPLT populations could be distinguished from one another and from unlabeled circulating mouse PLTs, and their survival was comparable to that of unlabeled human PLTs in the mouse model. CONCLUSIONS: Provided low Sulfo-NHS-Biotin concentrations (<10 µg/ml) are used, injectable-grade BioPLTs comply with safety regulations, conserve PLT integrity, and permit accurate in vivo detection. This alternative to radioisotopes, which allows one to follow different PLT populations in the same recipient, should be valuable when assessing new PC preparations and monitoring PLT survival in clinical research.


Asunto(s)
Biotina/análogos & derivados , Plaquetas/citología , Rastreo Celular , Succinimidas/análisis , Animales , Biotina/análisis , Biotinilación , Plaquetas/química , Plaquetas/ultraestructura , Supervivencia Celular , Femenino , Humanos , Ratones , Recuento de Plaquetas , Transfusión de Plaquetas , Coloración y Etiquetado
5.
Vox Sang ; 113(7): 622-631, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30079963

RESUMEN

BACKGROUND AND OBJECTIVES: Small batch-pooled (mini-pool) whole blood (WB)-derived plasma could be an alternative cost-effective source of therapeutic plasma (TP), but carries an increased risk of transfusion-transmitted infection due to exposure of the recipient to several donors. This risk can be mitigated by inactivation of pathogens susceptible to the amotosalen-UVA (AUVA)-treatment. We evaluated the conservation of coagulation factors in AUVA-plasma prepared from WB stored overnight under routine operating conditions, to determine its therapeutic efficacy. Thrombin generation (TG) by the AUVA-plasma was used to provide an integrated measure of the hemostatic capacity. MATERIALS AND METHODS: WB-donations (~450 ml) stored overnight were processed to prepare five leucocyte-depleted plasma mini-pools (1300 ml), which were divided into two parts and treated with AUVA. Each mini-pool yielded six AUVA-plasma units (200 ml) which were frozen (-25°C) within 19 h of WB-collection. Their hemostatic quality was evaluated before and after treatment for up to 12 months of storage. RESULTS: Immediately after AUVA-treatment, the regulatory criteria for FVIII activity and fibrinogen content were met. As compared to untreated plasma there was a reduction in fibrinogen (14%), FV (9%), FVII (25%) and FVIII (32%). However, TG was similar in treated and untreated plasma at all-time-points. CONCLUSIONS: Frozen WB-derived AUVA-plasma prepared from mini-pools within 19 h of WB-collection met the quality standards required for TP and retained hemostatic capacity for up to 12 months. This product could provide a cost-effective convenient substitute for apheresis plasma.


Asunto(s)
Conservación de la Sangre/métodos , Furocumarinas/farmacología , Plasma/efectos de los fármacos , Factores de Coagulación Sanguínea/metabolismo , Conservación de la Sangre/normas , Hemostasis , Humanos , Plasma/efectos de la radiación , Rayos Ultravioleta
6.
Transfusion ; 56(9): 2239-47, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27250038

RESUMEN

BACKGROUND: The INTERCEPT Blood System (IBS) using amotosalen-HCl and ultraviolet (UV)A inactivates a large spectrum of microbial pathogens and white blood cells in therapeutic plasma. Our aim was to evaluate to what extent IBS modifies the capacity of plasma to generate thrombin and induces qualitative or quantitative modifications of plasma proteins. STUDY DESIGN AND METHODS: Plasma units from four donors were collected by apheresis. Samples were taken before (control [CTRL]) and after IBS treatment and stored at -80°C until use. The activities of plasma coagulation factors and inhibitors and the thrombin generation potential were determined using assays measuring clotting times and the calibrated automated thrombogram (CAT), respectively. The proteomic profile of plasma proteins was examined using a two-dimensional differential in-gel electrophoresis (2D-DIGE) method. RESULTS: Nearly all of the procoagulant and antithrombotic factors tested retained at least 78% of their initial pre-IBS activity. Only FVII and FVIII displayed a lower level of conservation (67%), which nevertheless remained within the reference range for conventional plasma coagulation factors. The thrombin generation profile of plasma was conserved after IBS treatment. Among the 1331 protein spots revealed by 2D-DIGE analysis, only four were differentially expressed in IBS plasma compared to CTRL plasma and two were identified by mass spectrometric analysis as transthyretin and apolipoprotein A1. CONCLUSION: The IBS technique for plasma moderately decreases the activities of plasma coagulation factors and antithrombotic proteins, with no impact on the thrombin generation potential of plasma and very limited modifications of the proteomic profile.


Asunto(s)
Conservación de la Sangre/métodos , Furocumarinas/farmacología , Plasma/química , Factores de Coagulación Sanguínea/análisis , Proteínas Sanguíneas/química , Proteínas Sanguíneas/efectos de los fármacos , Humanos , Proteómica/métodos , Rayos Ultravioleta
7.
Transfusion ; 53(6): 1187-200, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23067365

RESUMEN

BACKGROUND: Platelet concentrate (PC) functionality decreases during storage. This is referred to as the storage lesion. Pathogen inactivation may accelerate or induce lesions, potentially accounting for reduced viability. Our aim was to characterize functional and biochemical properties of platelets (PLTs) from photochemically treated buffy-coat PCs (PCT-PCs) compared to those from conventional PCs. STUDY DESIGN AND METHODS: Four PCT-PCs and four conventional PCs were stored for 6.5 days and PLT function and proteomic profiles were examined at various time points during storage. To evaluate their intrinsic properties, samples of stored PLTs were taken, washed, and suspended in Tyrode's buffer before testing. RESULTS: PLT counts and morphology were conserved although a slight increase in the PLT volume was observed after PCT. Glycoprotein (GP) IIbIIIa, IaIIa, and VI expression remained stable while GPIbα declined similarly in both types of PCs. A steep decrease (50%) in GPV occurred on Day 1.5 in PCT-PCs and Day 2.5 in control PCs. For both PCT- and control PCs, P-selectin expression and activated GPIIbIIIa remained low during storage. PCT- and control PCs were fully responsive to aggregation agonists up to Day 4.5 and exhibited similar perfusion functionality. Mitochondrial membrane potential and annexin A5 binding of PCT-PCs and control PCs were comparable. Two-dimensional differential in-gel electrophoresis and mass spectrometry profiles for 1882 protein spots revealed only three proteins selectively changed in PCT-PCs compared to control-PCs. CONCLUSION: Washed treated and untreated PCs have similar functional, morphologic, and proteomic characteristics provided that PLTs are suspended in an appropriate medium during testing.


Asunto(s)
Plaquetas/citología , Conservación de la Sangre/métodos , Seguridad de la Sangre/métodos , Patógenos Transmitidos por la Sangre/efectos de la radiación , Furocumarinas/farmacología , Rayos Ultravioleta , Anexina A5/metabolismo , Almacenamiento de Sangre/métodos , Capa Leucocitaria de la Sangre/citología , Capa Leucocitaria de la Sangre/microbiología , Plaquetas/metabolismo , Plaquetas/microbiología , Criopreservación/métodos , Humanos , Potencial de la Membrana Mitocondrial , Selectina-P/metabolismo , Fármacos Fotosensibilizantes/farmacología , Adhesividad Plaquetaria , Agregación Plaquetaria , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/metabolismo , Transfusión de Plaquetas , Proteómica
8.
Transfusion ; 51(3): 622-9, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20849406

RESUMEN

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.


Asunto(s)
Plaquetas/microbiología , Patógenos Transmitidos por la Sangre , Desinfección , Transfusión de Eritrocitos , Transfusión de Plaquetas , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Patógenos Transmitidos por la Sangre/aislamiento & purificación , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Transfusión de Plaquetas/efectos adversos , Transfusión de Plaquetas/métodos
9.
Transfusion ; 49(6): 1083-91, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19309473

RESUMEN

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.


Asunto(s)
Infecciones por Alphavirus/prevención & control , Virus Chikungunya/efectos de los fármacos , Virus Chikungunya/efectos de la radiación , Transfusión de Plaquetas/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Infecciones por Alphavirus/epidemiología , Donantes de Sangre , Niño , Preescolar , Femenino , Francia/epidemiología , Furocumarinas/farmacología , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Fotoquímica , Estudios Retrospectivos , Rayos Ultravioleta
10.
Transfusion ; 48(4): 697-705, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18194378

RESUMEN

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.


Asunto(s)
Plasma/efectos de los fármacos , Plasma/efectos de la radiación , Rayos Ultravioleta , Coagulación Sanguínea , Conservación de la Sangre/métodos , Europa (Continente) , Furocumarinas/farmacología , Humanos , Fotoquímica/métodos
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