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Transfusion Medicine Reviews Oct 2023The optimal use of prophylactic platelet transfusion remains uncertain in a number of clinical scenarios. Platelet count thresholds have been established in patients... (Review)
Review
The optimal use of prophylactic platelet transfusion remains uncertain in a number of clinical scenarios. Platelet count thresholds have been established in patients with hematologic malignancies, yet thresholds backed by scientific data are limited or do not exist for many patient populations. Clinical scenarios involving transfusion thresholds for thrombocytopenic patients with critical illness, need for surgery or invasive procedures, or those involving specials populations like children and neonates, lack clear evidence for discerning favorable outcomes without undue risk related to platelet transfusion. In addition, while prophylactic platelet transfusions are administered with the goal of enhancing hemostasis, increasing evidence supports critical nonhemostatic roles for platelets related to innate and adaptive immunity, inflammation, and angiogenesis, which may impact patient responses and outcomes. Here we review several recent studies conducted in adult or pediatric patients that highlight the limitations in our current understanding of prophylactic platelet transfusion. Together, these studies underscore the need for additional research, especially in the form of robust randomized clinical trials and integrating additional parameters beyond the platelet count. Future research at the basic, translational, and clinical levels will best define the optimal role for prophylactic transfusion across the lifespan and its broader impact on health and disease.
Topics: Infant, Newborn; Adult; Humans; Child; Platelet Transfusion; Hemorrhage; Thrombocytopenia; Platelet Count; Blood Transfusion
PubMed: 37599188
DOI: 10.1016/j.tmrv.2023.150751 -
Platelets Dec 2023Extracellular vesicles (EVs) contain the characteristics of their cell of origin and mediate cell-to-cell communication. Platelet-derived extracellular vesicles (PEVs)... (Review)
Review
Extracellular vesicles (EVs) contain the characteristics of their cell of origin and mediate cell-to-cell communication. Platelet-derived extracellular vesicles (PEVs) not only have procoagulant activity but also contain platelet-derived inflammatory factors (CD40L and mtDNA) that mediate inflammatory responses. Studies have shown that platelets are activated during storage to produce large amounts of PEVs, which may have implications for platelet transfusion therapy. Compared to platelets, PEVs have a longer storage time and greater procoagulant activity, making them an ideal alternative to platelets. This review describes the reasons and mechanisms by which PEVs may have a role in blood transfusion therapy.
Topics: Humans; Blood Platelets; Platelet Transfusion; Extracellular Vesicles; Blood Transfusion
PubMed: 37578045
DOI: 10.1080/09537104.2023.2242708 -
Blood Reviews Nov 2023Platelet transfusion refractoriness due to HLA alloimmunization presents a significant medical problem, particularly among multiply transfused patients with hematologic... (Review)
Review
Platelet transfusion refractoriness due to HLA alloimmunization presents a significant medical problem, particularly among multiply transfused patients with hematologic malignancies and those undergoing hematopoietic stem cell transplants. HLA compatible platelet transfusions also impose significant financial burden on these patients. Recently, several novel mechanisms have been described in the development of HLA alloimmunization and platelet transfusion refractoriness. We review the history of platelet transfusions and mechanisms of HLA-sensitization and transfusion refractoriness. We also summarize advances in the diagnosis and treatment of platelet transfusion refractoriness due to HLA alloimmunization.
Topics: Humans; Platelet Transfusion; Isoantibodies; Thrombocytopenia; Blood Transfusion; Hematologic Neoplasms; Anemia, Hemolytic, Autoimmune; HLA Antigens; Blood Platelets
PubMed: 37805287
DOI: 10.1016/j.blre.2023.101135 -
Clinics in Laboratory Medicine Dec 2023Patients with MDS often suffer from anemia, and less often thrombocytopenia, and thus are a frequently transfused population. Red blood cell (RBC) transfusion may be... (Review)
Review
Patients with MDS often suffer from anemia, and less often thrombocytopenia, and thus are a frequently transfused population. Red blood cell (RBC) transfusion may be used to improve functional capacity and quality of life in this population, while platelet transfusion is typically used to decrease bleeding risk. Despite the frequency of transfusion in patients with MDS, there are few well-defined guidelines for RBC and platelet transfusion support in this patient population. Transfusion is not without risk-patients with MDS who are frequently transfused may develop alloantibodies to RBC antigens, which can lead to hemolytic transfusion reactions and delays in obtaining compatible RBCs. Regular communication between clinicians and blood bank physicians is crucial to ensure that patients with MDS receive the most appropriate blood products.
Topics: Humans; Erythrocytes; Quality of Life; Myelodysplastic Syndromes; Blood Transfusion; Erythrocyte Transfusion
PubMed: 37865510
DOI: 10.1016/j.cll.2023.07.002 -
Frontiers in Physiology 2023Dysfunction of the immune response is regarded as a prominent feature of neurological diseases, including neurodegenerative diseases, malignant tumors, acute... (Review)
Review
Dysfunction of the immune response is regarded as a prominent feature of neurological diseases, including neurodegenerative diseases, malignant tumors, acute neurotraumatic insult, and cerebral ischemic/hemorrhagic diseases. Platelets play a fundamental role in normal hemostasis and thrombosis. Beyond those normal functions, platelets are hyperactivated and contribute crucially to inflammation and immune responses in the central nervous system (CNS). Mitochondria are pivotal organelles in platelets and are responsible for generating most of the ATP that is used for platelet activation and aggregation (clumping). Notably, platelet mitochondria show marked morphological and functional alterations under heightened inflammatory/oxidative stimulation. Mitochondrial dysfunction not only leads to platelet damage and apoptosis but also further aggravates immune responses. Improving mitochondrial function is hopefully an effective strategy for treating neurological diseases. In this review, the authors discuss the immunomodulatory roles of platelet-derived mitochondria (PLT-mitos) in neurological diseases and summarize the neuroprotective effects of platelet mitochondria transplantation.
PubMed: 37719457
DOI: 10.3389/fphys.2023.1210509 -
Clinics in Perinatology Dec 2023Preterm neonates are a highly transfused patient group, with platelet transfusions being the second most transfused cellular blood component. Historically, however,... (Review)
Review
Preterm neonates are a highly transfused patient group, with platelet transfusions being the second most transfused cellular blood component. Historically, however, evidence to inform optimal platelet transfusion practice has been limited. In pediatrics, much of the evidence has been inferred from studies in adult patients, although neonatologists have generally applied more cautious and liberal platelet transfusion thresholds to mitigate the complications of intraventricular hemorrhage. A total of three randomized controlled trials have now been published comparing different platelet transfusion strategies in neonates.
Topics: Infant, Newborn; Adult; Humans; Child; Platelet Transfusion; Thrombocytopenia; Cerebral Hemorrhage
PubMed: 37866847
DOI: 10.1016/j.clp.2023.07.007 -
IScience Aug 2023Platelets play an important role in the pathogenesis of sepsis and platelet transfusion is a therapeutic option for sepsis patients, although the exact mechanisms have...
Platelets play an important role in the pathogenesis of sepsis and platelet transfusion is a therapeutic option for sepsis patients, although the exact mechanisms have not been elucidated so far. ITGA2B encodes the αIIb protein in platelets, and its upregulation in sepsis is associated with increased mortality rate. Here, we generated a (Q887X) knockin mouse, which significantly reduced ITGA2B expression of platelet and megakaryocyte. The decrease of ITGA2B level aggravated the death of septic mice. We analyzed the transcriptomic profiles of the platelets using RNA sequencing. Our findings suggest that ITGA2B upregulates PTPN6 in megakaryocytes via the transcription factors Nfkb1 and Rel. Furthermore, PTPN6 inhibits platelet apoptosis and necroptosis during sepsis by targeting the Ripk1/Ripk3/Mlkl and caspase-8 pathways. This prevents Kupffer cells from rapidly clearing activated platelets, and eventually maintains vascular integrity during sepsis. Our findings indicate a new function of ITGA2B in the regulation of platelet death during sepsis.
PubMed: 37554440
DOI: 10.1016/j.isci.2023.107414 -
Intensive Care Medicine Nov 2023Thrombocytopenia (platelet count < 150 × 10/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we...
PURPOSE
Thrombocytopenia (platelet count < 150 × 10/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients.
METHODS
We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses.
RESULTS
We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4-46.1) had thrombocytopenia; 23.4% (20-26) had thrombocytopenia at ICU admission, and 19.8% (17.6-22.2) developed thrombocytopenia during their ICU stay. Absence of acquired immune deficiency syndrome (AIDS), non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19-2.42).
CONCLUSION
Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic.
Topics: Adult; Humans; Male; Female; Middle Aged; Platelet Transfusion; Cohort Studies; Prospective Studies; Thrombocytopenia; Intensive Care Units; Hemorrhage; Retrospective Studies
PubMed: 37812225
DOI: 10.1007/s00134-023-07225-2 -
Research (Washington, D.C.) 2023Platelets are small, versatile blood cells that are critical for hemostasis/thrombosis. Local platelet accumulation is a known contributor to proinflammation in various...
Platelets are small, versatile blood cells that are critical for hemostasis/thrombosis. Local platelet accumulation is a known contributor to proinflammation in various disease states. However, the anti-inflammatory/immunosuppressive potential of platelets has been poorly explored. Here, we uncovered, unexpectedly, desialylated platelets (dPLTs) down-regulated immune responses against both platelet-associated and -independent antigen challenges. Utilizing multispectral photoacoustic tomography, we tracked dPLT trafficking to gut vasculature and an exclusive Kupffer cell-mediated dPLT clearance in the liver, a process that we identified to be synergistically dependent on platelet glycoprotein Ibα and hepatic Ashwell-Morell receptor. Mechanistically, Kupffer cell clearance of dPLT potentiated a systemic immunosuppressive state with increased anti-inflammatory cytokines and circulating CD4 regulatory T cells, abolishable by Kupffer cell depletion. Last, in a clinically relevant model of hemophilia A, presensitization with dPLT attenuated anti-factor VIII antibody production after factor VIII ( infusion. As platelet desialylation commonly occurs in daily-aged and activated platelets, these findings open new avenues toward understanding immune homeostasis and potentiate the therapeutic potential of dPLT and engineered dPLT transfusions in controlling autoimmune and alloimmune diseases.
PubMed: 37808178
DOI: 10.34133/research.0236 -
European Journal of Pediatrics Aug 2023Platelet transfusions (PTx) are the principal approach for treating neonatal thrombocytopenia, a common hematological abnormality affecting neonates, particularly... (Meta-Analysis)
Meta-Analysis Review
Platelet transfusions (PTx) are the principal approach for treating neonatal thrombocytopenia, a common hematological abnormality affecting neonates, particularly preterm infants. However, evidence about the outcomes associated with PTx and whether they provide clinical benefit or harm is lacking. The aim of this systematic review and meta-analysis is to assess the association between PTx in preterm infants and mortality, major bleeding, sepsis, and necrotizing enterocolitis (NEC) in comparison to not transfusing or using different platelet count thresholds for transfusion. A broad electronic search in three databases was performed in December 2022. We included randomized controlled trials, and cohort and case control studies of preterm infants with thrombocytopenia that (i) compared treatment with platelet transfusion vs. no platelet transfusion, (ii) assessed the platelet count threshold for PTx, or (iii) compared single to multiple PTx. We conducted a meta-analysis to assess the association between PTx and mortality, intraventricular hemorrhage (IVH), sepsis, and NEC and, in the presence of substantial heterogeneity, leave-one-out sensitivity analysis was performed. We screened 625 abstracts and 50 full texts and identified 18 reports of 13 eligible studies. The qualitative analysis of the included studies revealed controversial results as several studies showed an association between PTx in preterm infants and a higher risk of mortality, major bleeding, sepsis, and NEC, while others did not present a significant relationship. The meta-analysis results suggest a significant association between PTx and mortality (RR 2.4, 95% CI 1.8-3.4; p < 0.0001), as well as sepsis (RR 4.5, 95% CI 3.7-5.6; p < 0.0001), after a leave-one-out sensitivity analysis. There was also found a significant correlation between PTx and NEC (RR 5.2, 95% CI 3.3-8.3; p < 0.0001). As we were not able to reduce heterogeneity in the assessment of the relationship between PTx and IVH, no conclusion could be taken. Conclusion: Platelet transfusions in preterm infants are associated to a higher risk of death, sepsis, and NEC and, possibly, to a higher incidence of IVH. Further studies are needed to confirm these associations, namely between PTx and IVH, and to define the threshold from which PTx should be given with less harm effect. What is Known: • Platelet transfusions are given to preterm infants with thrombocytopenia either to treat bleeding or to prevent hemorrhage. • Lack of consensual criteria for transfusion. What is New: • A significant association between platelet transfusions and mortality, sepsis, and NEC.
Topics: Infant, Newborn; Humans; Infant, Premature; Hemorrhage; Enterocolitis, Necrotizing; Thrombocytopenia; Sepsis
PubMed: 37258776
DOI: 10.1007/s00431-023-05031-y