PlateletsPub Date : 2024-12-01Epub Date: 2024-02-14DOI: 10.1080/09537104.2024.2315713
Kirk A Taylor
{"title":"Edi(torial) 2024: action plan for change and new initiatives.","authors":"Kirk A Taylor","doi":"10.1080/09537104.2024.2315713","DOIUrl":"10.1080/09537104.2024.2315713","url":null,"abstract":"","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2315713"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139730373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PlateletsPub Date : 2024-12-01Epub Date: 2024-05-22DOI: 10.1080/09537104.2024.2353582
Scott J Denardo, Pavlos P Vlachos, Brett A Meyers, Reza Babakhani-Galangashi, Lin Wang, Zejin Gao, James E Tcheng
{"title":"Translating proof-of-concept for platelet slip into improved antithrombotic therapeutic regimens.","authors":"Scott J Denardo, Pavlos P Vlachos, Brett A Meyers, Reza Babakhani-Galangashi, Lin Wang, Zejin Gao, James E Tcheng","doi":"10.1080/09537104.2024.2353582","DOIUrl":"10.1080/09537104.2024.2353582","url":null,"abstract":"<p><p>Platelets are central to thrombosis. Research at the intersection of biological and physical sciences provides proof-of-concept for shear rate-dependent platelet slip at vascular stenosis and near device surfaces. Platelet slip extends the observed biological \"slip-bonds\" to the boundary of functional gliding without contact. As a result, there is diminished engagement of the coagulation cascade by platelets at these surfaces. Comprehending platelet slip would more precisely direct antithrombotic regimens for different shear environments, including for percutaneous coronary intervention (PCI). In this brief report we promote translation of the proof-of-concept for platelet slip into improved antithrombotic regimens by: (1) reviewing new supporting basic biological science and clinical research for platelet slip; (2) hypothesizing the principal variables that affect platelet slip; (3) applying the consequent construct model in support of-and in some cases to challenge-relevant contemporary guidelines and their foundations (including for urgent, higher-risk PCI); and (4) suggesting future research pathways (both basic and clinical). Should future research demonstrate, explain and control platelet slip, then a paradigm shift for choosing and recommending antithrombotic regimens based on predicted shear rate should follow. Improved clinical outcomes with decreased complications accompanying this paradigm shift for higher-risk PCI would also result in substantive cost savings.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2353582"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Impact of pre-delivery medication treatment on delivery outcome in patients with primary immune thrombocytopenia: a cohort study.","authors":"Xue Xu, Mei-Ying Liang, Lin-Rui Zhao, Jian-Liu Wang, Xiao-Hui Zhang","doi":"10.1080/09537104.2024.2380366","DOIUrl":"https://doi.org/10.1080/09537104.2024.2380366","url":null,"abstract":"<p><strong>Background: </strong>Clinical research data showed a series of adverse events in the delivery period of primary immune thrombocytopenia (ITP) patients, including high cesarean section rate. Consensus report proposed that for patients with platelet count below 50 × 10<sup>9</sup>/L, prednisone or intravenous immunoglobulins (IVIg) can be given to raise the platelet count in third trimester in preparation for labor.</p><p><strong>Objectives: </strong>To evaluate the effect of low-dose prednisone or IVIg therapy on delivery outcomes in patients with ITP.</p><p><strong>Study design: </strong>This was a cohort study that included pregnant women with ITP from January 2017 to December 2022. Patients with platelet counts of (20-50) ×10<sup>9</sup>/L at the time of delivery (≥34 weeks) and who had not received any medication before were enrolled in the study. Patients were divided into the pre-delivery medication group (oral prednisone or IVIg) and untreated group according to their preferences. The differences in vaginal delivery rate, postpartum bleeding rate, and platelet transfusion volume between the two groups were compared using t-test, Wilcoxon rank-sum test, and χ2 test. Logistic regression analysis was used to identify the factors affecting vaginal delivery rate and postpartum bleeding rate, and multiple linear regression analysis was used to identify the factors affecting platelet transfusion volume.</p><p><strong>Results: </strong>During the study period, a total of 96 patients with ITP were enrolled, including 70 in the pre-delivery medication group and 26 in the untreated group. The platelet count of pre-delivery medication group was 54.8 ± 34.5 × 10<sup>9</sup>/L, which was significantly higher than that of untreated group 34.4 ± 9.0 × 10<sup>9</sup>/L (<i>p</i> = .004). The vaginal delivery rate of the medication group was higher than the untreated group [60.0% (42/70) vs. 30.8% (8/26), χ2 = 6.49, <i>p</i> = .013]. After adjusting for the proportion of multiparous women and gestational weeks, the results showed that medication therapy during the peripartum period was associated with vaginal delivery (OR = 4.937, 95% CI: 1.511-16.136, <i>p</i> = .008). The postpartum bleeding rates were 22.9% (16/70) and 26.9% (7/26) in the medication group and untreated group, respectively, with no significant difference between the two groups (χ2 = 0.17, <i>p</i> = .789), while the platelet transfusion volume was lower in the medication group than untreated group [(1.1 ± 1.0) vs. (1.6 ± 0.8) U].</p><p><strong>Conclusion: </strong>Pre-delivery medication therapy can increase vaginal delivery rate, reduce platelet transfusion volume, but does not decrease the incidence of postpartum hemorrhage.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2380366"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PlateletsPub Date : 2024-12-01Epub Date: 2024-02-05DOI: 10.1080/09537104.2024.2306983
Xiaoyu Chen, Yuhong Zhao, Yan Lv, Jue Xie
{"title":"Immunological platelet transfusion refractoriness: current insights from mechanisms to therapeutics.","authors":"Xiaoyu Chen, Yuhong Zhao, Yan Lv, Jue Xie","doi":"10.1080/09537104.2024.2306983","DOIUrl":"10.1080/09537104.2024.2306983","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2306983"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139692708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PlateletsPub Date : 2024-12-01Epub Date: 2024-02-12DOI: 10.1080/09537104.2024.2308635
Yujia Ye, Min Leng, Shengjie Chai, Lihong Yang, Longcheng Ren, Wen Wan, Huawei Wang, Longjun Li, Chaozhong Li, Zhaohui Meng
{"title":"Antiplatelet effects of the CEACAM1-derived peptide QDTT.","authors":"Yujia Ye, Min Leng, Shengjie Chai, Lihong Yang, Longcheng Ren, Wen Wan, Huawei Wang, Longjun Li, Chaozhong Li, Zhaohui Meng","doi":"10.1080/09537104.2024.2308635","DOIUrl":"10.1080/09537104.2024.2308635","url":null,"abstract":"<p><p>Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) restricts platelet activation via platelet collagen receptor GPVI/FcRγ-chain. In this study, screening against collagen-induced platelet aggregation was performed to identify functional CEACAM1 extracellular domain fragments. CEACAM1 fragments, including Ala-substituted peptides, were synthesized. Platelet assays were conducted on healthy donor samples for aggregation, cytotoxicity, adhesion, spreading, and secretion. Mice were used for tail bleeding and FeCl<sub>3</sub>-induced thrombosis experiments. Clot retraction was assessed using platelet-rich plasma. Extracellular segments of CEACAM1 and A1 domain-derived peptide QDTT were identified, while N, A2, and B domains showed no involvement. QDTT inhibited platelet aggregation. Ala substitution for essential amino acids (Asp139, Thr141, Tyr142, Trp144, and Trp145) in the QDTT sequence abrogated collagen-induced aggregation inhibition. QDTT also suppressed platelet secretion and \"inside-out\" GP IIb/IIIa activation by convulxin, along with inhibiting PI3K/Akt pathways. QDTT curtailed FeCl<sub>3</sub>-induced mesenteric thrombosis without significantly prolonging bleeding time, implying the potential of CEACAM1 A1 domain against platelet activation without raising bleeding risk, thus paving the way for novel antiplatelet drugs.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2308635"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139723746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PlateletsPub Date : 2024-12-01Epub Date: 2024-02-14DOI: 10.1080/09537104.2024.2313359
Aylin Balmes, Johanna G Rodríguez, Jan Seifert, Daniel Pinto-Quintero, Akif A Khawaja, Marta Boffito, Maike Frye, Andreas Friebe, Michael Emerson, Francesca Seta, Robert Feil, Susanne Feil, Tilman E Schäffer
{"title":"Role of the NO-GC/cGMP signaling pathway in platelet biomechanics.","authors":"Aylin Balmes, Johanna G Rodríguez, Jan Seifert, Daniel Pinto-Quintero, Akif A Khawaja, Marta Boffito, Maike Frye, Andreas Friebe, Michael Emerson, Francesca Seta, Robert Feil, Susanne Feil, Tilman E Schäffer","doi":"10.1080/09537104.2024.2313359","DOIUrl":"10.1080/09537104.2024.2313359","url":null,"abstract":"<p><p>Cyclic guanosine monophosphate (cGMP) is a second messenger produced by the NO-sensitive guanylyl cyclase (NO-GC). The NO-GC/cGMP pathway in platelets has been extensively studied. However, its role in regulating the biomechanical properties of platelets has not yet been addressed and remains unknown. We therefore investigated the stiffness of living platelets after treatment with the NO-GC stimulator riociguat or the NO-GC activator cinaciguat using scanning ion conductance microscopy (SICM). Stimulation of human and murine platelets with cGMP-modulating drugs decreased cellular stiffness and downregulated P-selectin, a marker for platelet activation. We also quantified changes in platelet shape using deep learning-based platelet morphometry, finding that platelets become more circular upon treatment with cGMP-modulating drugs. To test for clinical applicability of NO-GC stimulators in the context of increased thrombogenicity risk, we investigated the effect of riociguat on platelets from human immunodeficiency virus (HIV)-positive patients taking abacavir sulfate (ABC)-containing regimens. Our results corroborate a functional role of the NO-GC/cGMP pathway in platelet biomechanics, indicating that biomechanical properties such as stiffness or shape could be used as novel biomarkers in clinical research.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2313359"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139730374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PlateletsPub Date : 2024-12-01Epub Date: 2024-02-01DOI: 10.1080/09537104.2024.2304173
Ryan J Collinson, Lynne Wilson, Darren Boey, Zi Yun Ng, Bob Mirzai, Hun S Chuah, Rebecca Howman, Carolyn S Grove, Jacques A J Malherbe, Michael F Leahy, Matthew D Linden, Kathryn A Fuller, Wendy N Erber, Belinda B Guo
{"title":"Transcription factor 3 is dysregulated in megakaryocytes in myelofibrosis.","authors":"Ryan J Collinson, Lynne Wilson, Darren Boey, Zi Yun Ng, Bob Mirzai, Hun S Chuah, Rebecca Howman, Carolyn S Grove, Jacques A J Malherbe, Michael F Leahy, Matthew D Linden, Kathryn A Fuller, Wendy N Erber, Belinda B Guo","doi":"10.1080/09537104.2024.2304173","DOIUrl":"10.1080/09537104.2024.2304173","url":null,"abstract":"<p><p>Transcription factor 3 (TCF3) is a DNA transcription factor that modulates megakaryocyte development. Although abnormal TCF3 expression has been identified in a range of hematological malignancies, to date, it has not been investigated in myelofibrosis (MF). MF is a Philadelphia-negative myeloproliferative neoplasm (MPN) that can arise <i>de novo</i> or progress from essential thrombocythemia [ET] and polycythemia vera [PV] and where dysfunctional megakaryocytes have a role in driving the fibrotic progression. We aimed to examine whether TCF3 is dysregulated in megakaryocytes in MPN, and specifically in MF. We first assessed TCF3 protein expression in megakaryocytes using an immunohistochemical approach analyses and showed that TCF3 was reduced in MF compared with ET and PV. Further, the TCF3-negative megakaryocytes were primarily located near trabecular bone and had the typical \"MF-like\" morphology as described by the WHO. Genomic analysis of isolated megakaryocytes showed three mutations, all predicted to result in a loss of function, in patients with MF; none were seen in megakaryocytes isolated from ET or PV marrow samples. We then progressed to transcriptomic sequencing of platelets which showed loss of <i>TCF3</i> in MF. These proteomic, genomic and transcriptomic analyses appear to indicate that TCF3 is downregulated in megakaryocytes in MF. This infers aberrations in megakaryopoiesis occur in this progressive phase of MPN. Further exploration of this pathway could provide insights into TCF3 and the evolution of fibrosis and potentially lead to new preventative therapeutic targets.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2304173"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139672523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Development of an automated chemiluminescence enzyme immunoassay for the measurement of soluble C-type lectin-like receptor 2 (sCLEC-2) and molecular forms of sCLEC-2 measured in patient plasma.","authors":"Masahide Kawamura, Makyo Ueda, Shuhei Matsushita, Tomoyuki Sasaki, Hiroaki Furuyama, Tsutomu Hashimoto, Toshiaki Shirai, Fuminori Kazama, Katsue Suzuki-Inoue","doi":"10.1080/09537104.2024.2420949","DOIUrl":"https://doi.org/10.1080/09537104.2024.2420949","url":null,"abstract":"<p><p>Soluble CLEC-2 is anticipated to have various clinical applications as a novel biomarker for in vivo platelet activation, assessable using plasma obtained through routine sampling procedures. While sCLEC-2 has been measured using ELISA, we have developed a highly sensitive chemiluminescence enzyme immunoassay (CLEIA) reagent that can yield results in approximately 19 minutes. This study aims to assess its fundamental performance and explore the molecular forms of sCLEC-2 measured in patient samples. We examined the sensitivity, precision, linearity, influence of endogenous substances, residual platelets, as well as the correlation with the ELISA method, for the sCLEC-2 CLEIA reagent. The CLEIA method demonstrated sufficient sensitivity for levels observed in healthy donors, and its basic performance was satisfactory. It exhibited a strong correlation with the previously described ELISA method, with reference ranges that did not significantly differ from the ELISA data. The sCLEC-2 reference range for males was significantly higher than that for females. Since it is known that sCLEC-2 exists in shed form and microparticle form, we investigated molecular forms of sCLEC-2 measured by the CLEIA in in vitro-activated platelets and in patients' plasma using gel filtration. It is considered that the CLEIA method shows significantly stronger reactivity with the shed form compared to the microparticle form. Studies using gel filtration of patient samples also suggest that the shed form is being primarily measured. The sCLEC-2 CLEIA reagent exhibits robust performance and is promising for clinical applications.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2420949"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Relationship between thrombocytopenia and prognosis in children with septic shock: a retrospective cohort study.","authors":"Ruichen Zhang, Haixin Huang, Siwei Lu, Jian Chen, Dandan Pi, Hongxing Dang, Chengjun Liu, Feng Xu, Yue-Qiang Fu","doi":"10.1080/09537104.2024.2363242","DOIUrl":"https://doi.org/10.1080/09537104.2024.2363242","url":null,"abstract":"<p><p>Septic shock is a life-threatening disease worldwide often associated with thrombocytopenia. Platelets play a crucial role in bridging the gap between immunity, coagulation, and endothelial cell activation, potentially influencing the course of the disease. However, there are few studies specifically evaluating the impact of thrombocytopenia on the prognosis of pediatric patients. Therefore, the study investigates effects of early thrombocytopenia in the prognosis of children with septic shock. Pediatric patients with septic shock from 2015 to 2022 were included monocentrically. Thrombocytopenia was defined as a platelet count of <100 × 10<sup>9</sup>/L during the first 24 hours of septic shock onset. The primary outcome was the 28-day mortality. Propensity score matching was used to pair patients with different platelet counts on admission but comparable disease severity. A total of 419 pediatric patients were included in the analysis. Patients with thrombocytopenia had higher 28-day mortality (55.5% vs. 38.7%, <i>p</i> = .005) compared to patients with no thrombocytopenia. Thrombocytopenia was associated with reduced 28-PICU free days (median value, 0 vs. 13 days, <i>p</i> = .003) and 28-ventilator-free (median value, 0 vs. 19 days, <i>p</i> = .001) days. Among thrombocytopenia patients, those with platelet count ≤50 × 10<sup>9</sup>/L had a higher 28-day mortality rate (63.6% vs. 45%, <i>p</i> = .02). Multiple logistic regression showed that elevated lactate (adjusted odds ratio (OR) = 1.11; 95% confidence interval (CI): 1.04-1.17; <i>P</i> <0.001) and white blood cell (WBC) count (OR = 0.97; 95% CI: 0.95-0.99; <i>p</i> = .003) were independent risk factors for the development of thrombocytopenia. Thrombocytopenia group had increased bleeding events, blood product transfusions, and development of organ failure. In Kaplan-Meier survival estimates, survival probabilities at 28 days were greater in patients without thrombocytopenia (<i>p</i> value from the log-rank test, <i>p</i> = .004). There were no significant differences in the type of pathogenic microorganisms and the site of infection between patients with and without thrombocytopenia. In conclusion, thrombocytopenia within 24 hours of shock onset is associated with an increased risk of 28-day mortality in pediatric patients with septic shock.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2363242"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PlateletsPub Date : 2024-12-01Epub Date: 2024-12-16DOI: 10.1080/09537104.2024.2437241
Rachel E Lamerton, Samantha J Montague, Marisol Perez-Toledo, Steve P Watson, Adam F Cunningham
{"title":"Platelet aggregation responses to <i>Salmonella</i> Typhimurium are determined by host anti-<i>Salmonella</i> antibody levels.","authors":"Rachel E Lamerton, Samantha J Montague, Marisol Perez-Toledo, Steve P Watson, Adam F Cunningham","doi":"10.1080/09537104.2024.2437241","DOIUrl":"https://doi.org/10.1080/09537104.2024.2437241","url":null,"abstract":"<p><p>Invasive non-typhoidal <i>Salmonella</i> infections are responsible for >75 000 deaths/year and >500 000 cases/year globally. Seventy-five percent of these cases occur in Sub-Saharan Africa, an increasing number of which are from multi-drug resistant strains. Interactions between bacteria and platelets can lead to thrombus formation, which can be beneficial for control of infection (immunothrombosis), or harmful through uncontrolled inflammation and organ damage (thromboinflammation). It is unknown whether <i>Salmonella</i> Typhimurium can activate human platelets. To assess this, light transmission aggregometry was used to measure platelet activation by two different <i>Salmonella</i> Typhimurium strains in 26 healthy donors in platelet-rich plasma and washed platelets. In platelet-rich plasma, but not in washed platelets, <i>Salmonella</i> Typhimurium activated platelets in a donor- and strain-dependent manner mediated through the low affinity immune receptor FcγRIIA and the feedback agonists, ADP and thromboxane A<sub>2</sub>. Plasma swap studies between strong and weak responders demonstrated a plasma component was responsible for the variation between donors. Depletion of anti-<i>Salmonella</i> antibodies from plasma abolished <i>Salmonella-</i>induced platelet aggregation responses, and addition of polyclonal anti-<i>Salmonella</i> antibody allowed aggregation in washed platelets. Correlating levels of anti-<i>Salmonella</i> total IgG or the IgG1, IgG2, IgG3 and IgG4 subclasses to platelet responses revealed total IgG levels, rather than levels of individual subclasses, positively correlated with maximum platelet aggregation results, and negatively with lag times. Overall, we show that anti-<i>Salmonella</i> IgG antibodies are responsible for donor variation in platelet aggregation responses to <i>Salmonella</i> and mediate this activity through FcγRIIA.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2437241"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142838635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}