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Immunological platelet transfusion refractoriness: current insights from mechanisms to therapeutics.Platelets Dec 2024Although there have been tremendous improvements in the production and storage of platelets, platelet transfusion refractoriness (PTR) remains a serious clinical issue... (Review)
Review
Although there have been tremendous improvements in the production and storage of platelets, platelet transfusion refractoriness (PTR) remains a serious clinical issue that may lead to various severe adverse events. The burden of supplying platelets is worsened by rising market demand and limited donor pools of compatible platelets. Antibodies against platelet antigens are known to activate platelets through FcγR-dependent or complement-activated channels, thereby rapidly eliminating foreign platelets. Recently, other mechanisms of platelet clearance have been reported. The current treatment strategy for PTR is to select appropriate and compatible platelets; however, this necessitates a sizable donor pool and technical assistance for costly testing. Consolidation of these mechanisms should be of critical significance in providing insight to establish novel therapeutics to target immunological platelet refractoriness. Therefore, the purposes of this review were to explore the modulation of the immune system over the activation and elimination of allogeneic platelets and to summarize the development of alternative approaches for treating and avoiding alloimmunization to human leukocyte antigen or human platelet antigen in PTR.
Topics: Humans; Platelet Transfusion; Blood Platelets; Thrombocytopenia; Antigens, Human Platelet; HLA Antigens
PubMed: 38314765
DOI: 10.1080/09537104.2024.2306983 -
Transfusion Jun 2021Platelet transfusion refractoriness (PTR), defined as an unsatisfactory post-transfusion platelet count increment, is a common complication of patients receiving...
Platelet transfusion refractoriness (PTR), defined as an unsatisfactory post-transfusion platelet count increment, is a common complication of patients receiving multiple transfusions. Different strategies are described in the management of PTR. In this work, we demonstrate the efficacy of the detection and identification of anti-HLA antibodies in the recipient using a threshold of 3000 mean fluorescence intensity (MFI), and the seek of donors not expressing HLA antigens against which the patient is immunized.
Topics: Adult; Aged; Blood Platelets; Female; HLA Antigens; Humans; Immunization; Isoantibodies; Male; Middle Aged; Platelet Count; Platelet Transfusion; Retrospective Studies; Young Adult
PubMed: 33709433
DOI: 10.1111/trf.16358 -
Transfusion Clinique Et Biologique :... Sep 2018Pathogen inactivation or reduction technologies for platelet components have been proposed to secure the microbial safety of this component, and particularly the... (Review)
Review
Pathogen inactivation or reduction technologies for platelet components have been proposed to secure the microbial safety of this component, and particularly the microbial contamination. Transfusion-transmitted bacterial infections were substantially reduced by additive steps applied at different levels of the transfusion chain, but still killed one recipient each year or every other year in a country like France. Besides, pathogen inactivation and reduction stand for eliminating most viral and protozoa infections persisting in the separated blood component. In addition, because those processes attack nucleic acids, they also aim at substantially alleviating the risk of Transfusion Associates Graft versus Host Disease, as they attack lymphocytes still comprises within the component. Meanwhile, pathogen inactivation or reduction may inflict some damages to the platelet components, that are shown to be additive to the "natural" storage lesions linked to ageing. While it is in general assumed that such processes do not expose transfused patients to an over-risk of bleeding, and are safe, this does not mean that there are no detrimental consequences in the patients, even if not ascribed to as serious. Two such effects are now discussed or debated: the first one is the possible increase in the demand of platelet component, and the other one could be a possible risk of alloimmunisation especially when treated platelets are aged (over 5 days). Three processes have been made available by the industry, that differ in their chemical and physical (ultraviolet light illumination) characteristics. Two processes are largely used (one nationwide in two European countries) and the third one is still under clinical evaluation. This short review endeavored to critically present the main features of the processes and of their implementation.
Topics: Blood; Blood Safety; Humans; Platelet Transfusion
PubMed: 30041847
DOI: 10.1016/j.tracli.2018.07.001 -
Transfusion Medicine Reviews Oct 2020Platelets are versatile cells which are capable of eliciting nonhemostatic immune functions, especially under inflammatory conditions. Depending on the specific setting,... (Review)
Review
Platelets are versatile cells which are capable of eliciting nonhemostatic immune functions, especially under inflammatory conditions. Depending on the specific setting, platelets may be either protective or pathogenic in acute lung injury and acute respiratory distress syndrome (ARDS). Their role in transfusion-related acute lung injury (TRALI) is less well defined; however, it has been hypothesized that recipient platelets and transfused platelets both play a pathogenic role in TRALI. Overall, despite conflicting findings, it appears that recipient platelets may play a pathogenic role in antibody-mediated TRALI; however, their contribution appears to be limited. It is imperative to first validate the involvement of recipient platelets by standardizing the animal models, methods, reagents, and readouts for lung injury and taking the animal housing environment into consideration. For the involvement of transfused platelets in TRALI, it appears that predominantly lipids such as ceramide in stored platelets are able to induce TRALI in animal models. These studies will also need to be validated, and moreover, the platelet-derived lipid-mediated mechanisms leading to TRALI will need to be investigated.
Topics: Animals; Blood Platelets; Humans; Platelet Transfusion; Transfusion-Related Acute Lung Injury
PubMed: 33036839
DOI: 10.1016/j.tmrv.2020.08.002 -
Blood Transfusion = Trasfusione Del... Mar 2016Platelet concentrates account for near 10% of all labile blood components but are responsible for more than 25% of the reported adverse events. Besides factors related... (Review)
Review
Platelet concentrates account for near 10% of all labile blood components but are responsible for more than 25% of the reported adverse events. Besides factors related to patients themselves, who may be particularly at risk of side effects because of their underlying illness, there are aspects of platelet collection and storage that predispose to adverse events. Platelets for transfusion are strongly activated by collection through disposal equipment, which can stress the cells, and by preservation at 22 °C with rotation or rocking, which likewise leads to platelet activation, perhaps more so than storage at 4 °C. Lastly, platelets constitutively possess a very large number of bioactive components that may elicit pro-inflammatory reactions when infused into a patient. This review aims to describe approaches that may be crucial to minimising side effects while optimising safety and quality. We suggest that platelet transfusion is complex, in part because of the complexity of the "material" itself: platelets are highly versatile cells and the transfusion process adds a myriad of variables that present many challenges for preserving basal platelet function and preventing dysfunctional activation of the platelets. The review also presents information showing--after years of exhaustive haemovigilance--that whole blood buffy coat pooled platelet components are extremely safe compared to the gold standard (i.e. apheresis platelet components), both in terms of acquired infections and of immunological/inflammatory hazards.
Topics: Blood Preservation; Blood Safety; Humans; Platelet Transfusion
PubMed: 26674828
DOI: 10.2450/2015.0042-15 -
ASAIO Journal (American Society For... Oct 2022Thrombocytopenia is common during extracorporeal membrane oxygenation (ECMO), and platelets are sometimes transfused to meet arbitrary goals. We performed a...
Thrombocytopenia is common during extracorporeal membrane oxygenation (ECMO), and platelets are sometimes transfused to meet arbitrary goals. We performed a retrospective cohort study of veno-arterial (VA) ECMO patients from a single academic medical center and explored the relationship between platelet transfusion and in-hospital mortality using multivariable logistic regression. One hundred eighty-eight VA ECMO patients were included in the study. Ninety-one patients (48.4%) were transfused platelets during ECMO. Patients who received platelet transfusion had more coronary artery disease, lower platelet counts at cannulation, higher predicted mortality, lower nadir platelet counts, more ECMO days, and more red blood cell (RBC) and plasma transfusion. Mortality was 19.6% for patients who received no platelets, 40.8% for patients who received 1-3 platelets, and 78.6% for patients who received 4 or more platelets ( P < 0.001). After controlling for confounding variables including baseline severity of illness, central cannulation, postcardiotomy status, RBC and plasma transfusion, major bleeding, and total ECMO days, transfusion of 4 or more platelets remained associated with in-hospital mortality; OR = 4.68 (95% CI = 1.18-27.28), P = 0.03. Our findings highlight the need for randomized controlled trials that compare different platelet transfusion triggers, so that providers can better understand when platelet transfusion is indicated in VA ECMO patients.
Topics: Blood Component Transfusion; Extracorporeal Membrane Oxygenation; Hospital Mortality; Humans; Plasma; Platelet Transfusion; Retrospective Studies
PubMed: 34967786
DOI: 10.1097/MAT.0000000000001643 -
Journal of the Royal College of... 1998The statement printed below was agreed at a consensus conference on platelet transfusion organised by the Royal College of Physicians of Edinburgh and held in Edinburgh...
The statement printed below was agreed at a consensus conference on platelet transfusion organised by the Royal College of Physicians of Edinburgh and held in Edinburgh in November 1997. We publish this statement at the request of the organising committee to bring it to the attention of physicians who do not read the haematological literature. The statement will also appear in the British Journal of Haematology in 1998 with the scientific evidence upon which it is based.
Topics: Blood Platelet Disorders; Contraindications; Humans; Platelet Transfusion; Practice Guidelines as Topic; Quality Control; United Kingdom
PubMed: 9597636
DOI: No ID Found -
Journal of Clinical Gastroenterology Jul 2012There exists uncertainty as to the optimal platelet values when managing patients with nonvariceal upper gastrointestinal (GI) bleeding. GOALS AND STUDY: A systematic... (Review)
Review
BACKGROUND
There exists uncertainty as to the optimal platelet values when managing patients with nonvariceal upper gastrointestinal (GI) bleeding. GOALS AND STUDY: A systematic review was carried out to determine the optimal approach when managing patients with thrombocytopenia in the setting of nonvariceal upper GI bleeding.
RESULTS
Eighteen of 803 potential articles were selected and reviewed, including 4 randomized controlled trials and 6 cohort studies. The only empirical clinical data available pertained to the management of hematology or oncology patients. There was no high-level evidence that determined the proper threshold of platelet transfusion specifically in GI bleeding. We were, therefore, limited to include principally consensus opinions, recommendations, and guidelines for platelet transfusion trigger as they apply to the treatment (including prophylaxis) of bleeding in general, with a paucity of data addressing major bleeding, let alone bleeding from a gastroenterologic origin. Randomized clinical trials were individually underpowered in allowing definitive conclusions, even though resulting recommendations were supported by similarly underpowered retrospective and prospective observational studies.
CONCLUSIONS
There exist a paucity of data to recommend optimal therapeutic platelet count targets in patients with active GI bleeding. Based principally on expert opinion recommendations, we propose a count of 50×10/L. Some professional associations have suggested in very specific clinical settings (postcardiopulmonary bypass surgery or central nervous system trauma) a higher value of up to 100×10/L. Properly designed randomized trials are required to more precisely address this important clinical question.
Topics: Gastrointestinal Hemorrhage; Humans; Platelet Transfusion; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Thrombocytopenia
PubMed: 22688143
DOI: 10.1097/MCG.0b013e31823d33e3 -
Frontiers in Immunology 2023Patients with hematological disorders and severe thrombocytopenia require extensive and iterative platelet transfusion support. In these patients, platelet transfusion... (Review)
Review
Patients with hematological disorders and severe thrombocytopenia require extensive and iterative platelet transfusion support. In these patients, platelet transfusion refractoriness represents a serious adverse transfusion event with major outcomes for patient care. Recipient alloantibodies against the donor HLA Class I antigens expressed at the cell surface of platelets result in a rapid removal of transfused platelets from the circulation and thus, therapeutic and prophylactic transfusion failure leading to a major bleeding risk. In this case, the only way to support the patient relies on the selection of HLA Class I compatible platelets, an approach restricted by the limited number of HLA-typed donors available and the difficulty of meeting the demand in an emergency. However, not all patients with anti-HLA Class I antibodies develop refractoriness to platelet transfusions, raising the question of the intrinsic characteristics of the antibodies and the immune-mediated mechanisms of platelet clearance associated with a refractory state. In this review, we examine the current challenges in platelet transfusion refractoriness and detail the key features of the antibodies involved that should be considered. Finally, we also provide an overview of future therapeutic strategies.
Topics: Humans; Platelet Transfusion; Isoantibodies; HLA Antigens; Thrombocytopenia; Blood Platelets
PubMed: 36845153
DOI: 10.3389/fimmu.2023.1125367 -
Haematologica Nov 2002
Topics: Hemorrhage; Humans; Platelet Transfusion; Practice Guidelines as Topic
PubMed: 12414336
DOI: No ID Found