RESUMEN
The impact of the biophysical environment on the platelet storage lesion (PSL) has mainly focused on reduced temperature storage, overlooking the significance of storage-induced shear stress. Shear stress in platelet storage refers to the frictional force acting parallel to the bag surface and exists solely through the implementation of agitation. This study investigates whether minimizing exposure to agitation-induced shear stress can alleviate the unexplained loss of function in stored platelet concentrates for neonatal transfusion (neonatal PCs). Using particle tracking analysis, fluid motion was measured in neonatal and adult platelet storage bags under agitation frequencies ranging from 20-60 rpm. Platelets stored at 20-60 rpm agitation over 8 days were examined by biochemical analysis, aggregation, and expression of activation markers. Results indicate that neonatal PCs experience significantly higher storage-induced shear stress compared to adult doses, leading to reduced functionality and increased activation from day 2 of storage. Adjusting the neonatal PC agitation frequency to 20 rpm improved functionality in early storage, while 40 rpm maintains this improvement throughout storage with reduced activation, compared to 60 rpm storage. This study confirms that small volume PC storage for neonatal use contributes to the PSL through the induction of shear stress, suggesting further evaluation of the recommended agitation frequency for neonatal PCs or postponement of the production of neonatal PCs until requested for neonatal transfusion.
Context Approximately 15% of all neonates and up to 50% of critically ill newborns, present with low platelet counts, and will require platelet transfusion support.Platelet concentrates stored for neonatal transfusion have previously shown an accelerated reduction in quality during storage compared to platelet concentrates stored for adult transfusion and therefore may not provide as effective a therapeutic product.The current study hypothesized this loss of function over storage (known as the platelet storage lesion) to be a result of shear stress induced by agitation, exacerbated by the use of smaller bags in the neonatal preparation.Findings Our findings show that storage of platelet concentrates as smaller bags suitable for neonatal transfusion accelerates the platelet storage lesion, which experience a 4-fold greater shear stress than the adult preparation.The shear stress experienced by platelet concentrates stored for neonatal transfusion could be reduced by reducing the speed of agitation, thereby reducing the extent of the platelet storage lesion.Impact This study provides evidence that small volume storage promotes shear stress in platelet concentrates stored for neonatal transfusion, and optimizing storage conditions to reduce the shear stress induced by agitation can help to offset the platelet storage lesion.Further evaluation is required to establish a recommended agitation frequency for platelet concentrates stored for neonatal transfusion. An alternative strategy might include postponement of the production of platelet concentrates for neonatal transfusion until a neonatal transfusion is requested.
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Plaquetas , Conservación de la Sangre , Humanos , Plaquetas/metabolismo , Recién Nacido , Conservación de la Sangre/métodos , Transfusión de Plaquetas/métodos , AdultoRESUMEN
BACKGROUND: New blood products are considered for treatment of patients with major hemorrhage. The aim of this report is to describe the current transfusion practices in Europe for patients with major hemorrhage and explore the need for new or modified blood products to ensure prehospital and in-hospital blood supply. STUDY DESIGN AND METHOD: The European Blood Alliance (EBA) Working Group on Innovation and New Blood Products' subgroup on major hemorrhage performed a survey among the EBA member states. RESULTS: The response rate was 58% (17 responses from 15 of the 26 EBA member states). Of these, sixteen (94%) provide massive transfusion packages (MTPs) with balanced ratio of red blood cells and plasma. Seven of the respondents included platelets from the start of treatment. Eleven (65%) provide prehospital blood products, mainly red cell concentrates or dried and/or thawed plasma with 5 days of extended storage. Two countries provide prehospital whole blood. Twelve respondents (71%) saw a need for implementation of new or modified blood components in their institution. The top three priorities were whole blood (12 of 12, 100%), dried plasma (8 of 12, 67%), and cold-stored platelets (7 of 12, 58%). DISCUSSION: Current national guidelines for use of blood products in patients with major hemorrhage in Europe agree on the use of balanced transfusion, however the timing and source of platelets differ. Blood products for prehospital transfusion are available in several European countries. An interest in new or modified blood products for patients with major hemorrhage was observed, especially for whole blood.
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Transfusión Sanguínea , Hemorragia , Humanos , Hemorragia/terapia , Transfusión de Componentes Sanguíneos , Plaquetas , Europa (Continente)RESUMEN
When platelet concentrates (PCs) were first introduced in the 1960s as a blood component therapy, they were stored in the cold. As platelet transfusion became more important for the treatment of chemotherapy-induced thrombocytopenia, research into ways to increase supply intensified. During the late 1960s/early 1970s, it was demonstrated through radioactive labeling of platelets that room temperature platelets (RTP) had superior post-transfusion recovery and survival compared with cold-stored platelets (CSP). This led to a universal switch to room temperature storage, despite CSP demonstrating superior hemostatic effectiveness upon being transfused. There has been a global resurgence in studies into CSP over the last two decades, with an increase in the use of PC to treat acute bleeding within hospital and pre-hospital care. CSP demonstrate many benefits over RTP, including longer shelf life, decreased bacterial risk and easier logistics for transport, making PC accessible in areas where they have not previously been, such as the battlefield. In addition, CSP are reported to have greater hemostatic function than RTP and are thus potentially better for the treatment of bleeding. This review describes the history of CSP, the functional and metabolic assays used to assess the platelet storage lesion in PC and the current research, benefits and limitations of CSP. We also discuss whether the application of new technology for studying mitochondrial and glycolytic function in PC could provide enhanced understanding of platelet metabolism during storage and thus contribute to the continued improvements in the manufacturing and storage of PC.
What is the context? To transition into an activated state, platelets require a highly efficient source of energy that is met through the production of ATP this is referred to as "platelet bioenergetics"Platelets can be removed from healthy donors and used to make platelet concentrates for clinical usePlatelet concentrates are used clinically either therapeutically (to halt bleeding) or prophylactically (to prevent bleeding in patients with low platelet counts)They are stored at room temperature (2024oC) with constant gentle agitation, in packs that allow gas exchange and have a 7-day shelf life in some jurisdictionsStoring platelets in the cold (26oC) has historically been shown to improve their ability to halt bleedingWhat is new? There is a renewed interest in cold stored platelets for use in actively bleeding patientsThere are benefits to cold-storing platelets over room temperature storageCold stored platelets are licensed in the US and Norway for certain indications for 14 daysWhat is next? Cold stored platelets have the potential to improve logistics of clinical supply of platelets, enable supply of platelet concentrates where access is currently limited, such as pre-hospital care and on the battlefield and provide improved hemostatic effects for bleeding patients.New research measuring the bioenergetic profiles of cold stored platelets could advance understanding of metabolism in cold stored platelets and support decisions on their re-introduction on a wider scale.
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Plaquetas , Conservación de la Sangre , Humanos , Plaquetas/metabolismo , Frío , Transfusión de Plaquetas , Hemorragia/etiología , Hemorragia/terapia , Hemorragia/metabolismo , Metabolismo EnergéticoAsunto(s)
Plaquetas , Conservación de la Sangre , Humanos , Soluciones , Concentración de Iones de HidrógenoRESUMEN
BACKGROUND AND OBJECTIVES: DEHP, di(2-ethylhexyl) phthalate, is the most common member of the class of ortho-phthalates, which are used as plasticizers. The Medical Device Regulation has restricted the use of phthalates in medical devices. Also DEHP has been added to the Annex XIV of REACH, "Registration, Evaluation, Authorisation and Restriction of Chemicals" due to its endocrine disrupting properties to the environment. As such, the sunset date for commercialisation of DEHP-containing blood bags is May 27th 2025. There are major concerns in meeting this deadline as these systems have not yet been fully validated and/or CE-marked. Also, since DEHP is known to affect red cell quality during storage, it is imperative to transit to non-DEHP without affecting blood product quality. Here, EBA members aim to establish common grounds on the evaluation and assessment of blood components collected, prepared and stored in non-DEHP devices. MATERIALS AND METHODS: Based on data as well as the input of relevant stakeholders a rationale for the validation of each component was composed. RESULTS: The red cell components will require the most extensive validation as their quality is directly affected by the absence of DEHP, as opposed to platelet and plasma components. CONCLUSION: Studies in the scope of evaluating the quality of blood products obtained with non-DEHP devices, under the condition that they are carried out according to these recommendations, could be used by all members of the EBA to serve as scientific support in the authorization process specific to their jurisdiction or for their internal validation use.
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Dietilhexil Ftalato , Ácidos Ftálicos , Humanos , Conservación de la Sangre , PlastificantesRESUMEN
BACKGROUND AND OBJECTIVES: An observed decline in end-of-storage pH in plateletpheresis-derived platelet concentrates for neonatal use suspended in 100% autologous plasma was expected to be reversed by the addition of a platelet additive solution, (PAS)-E, increasing unit volume by approximately 20%. This study determined the impact on other in vitro storage parameters to ensure the expected increase in pH did not mask an adverse impact on component quality. STUDY DESIGN AND METHODS: For each replicate, one of a pair from a double adult dose plateletpheresis collection had approximately 50 ml of PAS-E added on Day 3 of storage. Its unmodified twin served as a control. Each adult dose was split into four neonatal storage packs and tested on Days 3, 6, 7 and 8. Three of 12 replicates were from donors with a history of low pH at end of storage and reflected the worst-case scenario for the new components. A further experiment evaluated whether any differences were simply due to the increased unit volume. RESULTS: In the nine randomly selected collections, pH on Day 8 was approximately 0.4 units higher in the test units. Platelet activation tended to be lower, with CD62P surface expression on Day 8 of 54.6 ± 9.9% compared to 65.8 ± 10.7% for controls (p < 0.001). Test units from donors with historically low pH retained pH22°C levels above 6.8 compared to controls (<6.4 on Day 8). CONCLUSION: The addition of 20% PAS-E by volume increased the buffering capacity of the units whilst maintaining other in vitro storage characteristics.
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Plaquetas , Conservación de la Sangre , Plaquetas/metabolismo , Humanos , Recién Nacido , Plasma , Activación Plaquetaria , PlaquetoferesisRESUMEN
BACKGROUND: Serological assays for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) have roles in seroepidemiology, convalescent plasma-testing, antibody durability and vaccine studies. Currently, SARS-CoV-2 serology is performed using serum/plasma collected by venepuncture. Dried blood spot (DBS) testing offers significant advantages as it is minimally invasive, avoids venepuncture with specimens being mailed to the laboratory. METHODS: A pathway utilizing a newborn screening laboratory infrastructure was developed using an enzyme-linked immunosorbent assay to detect IgG antibodies against the receptor-binding domain of the SARS-CoV-2 spike protein in DBS specimens. Paired plasma and DBS specimens from SARS-CoV-2 antibody-positive and -negative subjects and polymerase chain reaction positive subjects were tested. DBS specimen stability, effect of blood volume and punch location were also evaluated. RESULTS: DBS specimens from antibody-negative (n = 85) and -positive (n = 35) subjects and polymerase chain reaction positive subjects (n = 11) had a mean (SD; range) optical density (OD) of 0.14 (0.046; 0.03-0.27), 0.98 (0.41; 0.31-1.64) and 1.12 (0.37; 0.49-1.54), respectively. An action value OD >0.28 correctly assigned all cases. The weighted Deming regression for comparison of the DBS and the plasma assay yielded: y = 0.004041 + 1.005x, r = 0.991, Sy/x 0.171, n = 82. Extraction efficiency of antibodies from DBS specimens was >99%. DBS specimens were stable for at least 28 days at ambient room temperature and humidity. CONCLUSIONS: SARS-CoV-2 IgG receptor-binding domain antibodies can be reliably detected in DBS specimens. DBS serological testing offers lower costs than either point of care or serum/plasma assays that require patient travel, phlebotomy and hospital/clinic resources; the development of a DBS assay may be particularly important for resource poor settings.