Pub Date : 2022-03-14DOI: 10.1080/09537104.2022.2042234
Aleksander Siniarski, A. Gąsecka, Miłosz Starczyński, M. Banaszkiewicz, Szymon Darocha, A. Torbicki, M. Kurzyna, K. Filipiak, J. Nessler, G. Gajos
Abstract Prostacyclin (PGI2) analogues (epoprostenol, treprostonil, iloprost) are the cornerstone of pulmonary arterial hypertension (PAH) treatment. PGI2 analogues inhibit platelet reactivity, but their impact on coagulation and fibrinolysis parameters has not been elucidated. We compared platelet reactivity, thrombin generation, clot permeation, and lysis properties in patients with PAH treated with PGI2 analogues (n = 20) and those not receiving PGI2 analogues (n = 20). Platelet reactivity was lower in patients treated with PGI2 analogues, compared to the control group, as evaluated with arachidonic acid (ASPI), adenosine diphosphate (ADP), and thrombin receptor-activating peptide-6 (TRAP) tests (p = .009, p = .02, p = .007, respectively). In the subgroup analysis, both treprostinil and epoprostenol decreased platelet reactivity to the similar extent. There were no differences regarding thrombin generation, clot permeation, and lysis parameters in patients receiving and not receiving PGI2 analogues (p ≥ .60 for all). In the subgroup analysis, there were no differences regarding coagulation and fibrinolysis parameters between treprostinil, epoprostenol, and no PGI2 analogues. To conclude, patients with PAH treated with PGI2 analogues have reduced platelet reactivity, but similar clot formation and lysis parameters, compared to patients not receiving PGI2 analogues. Further randomized clinical trials are required to confirm these findings.
前列环素(PGI2)类似物(丙前列醇、曲前列醇、伊洛前列素)是肺动脉高压(PAH)治疗的基石。PGI2类似物抑制血小板反应性,但其对凝血和纤溶参数的影响尚未阐明。我们比较了接受PGI2类似物治疗的PAH患者(n = 20)和未接受PGI2类似物治疗的PAH患者(n = 20)的血小板反应性、凝血酶生成、血栓渗透和溶解特性。通过花生四烯酸(ASPI)、二磷酸腺苷(ADP)和凝血酶受体激活肽-6 (TRAP)试验评估,与对照组相比,接受PGI2类似物治疗的患者血小板反应性较低(p = 0.009, p = 0.02, p = 0.007)。在亚组分析中,treprostiil和epoprostenol降低血小板反应性的程度相似。在接受和未接受PGI2类似物治疗的患者中,凝血酶生成、血栓渗透和溶解参数没有差异(所有患者p≥0.60)。在亚组分析中,treprostiil、epoprostenol和无PGI2类似物在凝血和纤溶参数上没有差异。综上所述,与未接受PGI2类似物治疗的患者相比,接受PGI2类似物治疗的PAH患者血小板反应性降低,但凝块形成和溶解参数相似。需要进一步的随机临床试验来证实这些发现。
{"title":"Prostacyclin analogues decrease platelet aggregation but have no effect on thrombin generation, fibrin clot structure, and fibrinolysis in pulmonary arterial hypertension: PAPAYA coagulation","authors":"Aleksander Siniarski, A. Gąsecka, Miłosz Starczyński, M. Banaszkiewicz, Szymon Darocha, A. Torbicki, M. Kurzyna, K. Filipiak, J. Nessler, G. Gajos","doi":"10.1080/09537104.2022.2042234","DOIUrl":"https://doi.org/10.1080/09537104.2022.2042234","url":null,"abstract":"Abstract Prostacyclin (PGI2) analogues (epoprostenol, treprostonil, iloprost) are the cornerstone of pulmonary arterial hypertension (PAH) treatment. PGI2 analogues inhibit platelet reactivity, but their impact on coagulation and fibrinolysis parameters has not been elucidated. We compared platelet reactivity, thrombin generation, clot permeation, and lysis properties in patients with PAH treated with PGI2 analogues (n = 20) and those not receiving PGI2 analogues (n = 20). Platelet reactivity was lower in patients treated with PGI2 analogues, compared to the control group, as evaluated with arachidonic acid (ASPI), adenosine diphosphate (ADP), and thrombin receptor-activating peptide-6 (TRAP) tests (p = .009, p = .02, p = .007, respectively). In the subgroup analysis, both treprostinil and epoprostenol decreased platelet reactivity to the similar extent. There were no differences regarding thrombin generation, clot permeation, and lysis parameters in patients receiving and not receiving PGI2 analogues (p ≥ .60 for all). In the subgroup analysis, there were no differences regarding coagulation and fibrinolysis parameters between treprostinil, epoprostenol, and no PGI2 analogues. To conclude, patients with PAH treated with PGI2 analogues have reduced platelet reactivity, but similar clot formation and lysis parameters, compared to patients not receiving PGI2 analogues. Further randomized clinical trials are required to confirm these findings.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"33 1","pages":"1065 - 1074"},"PeriodicalIF":3.3,"publicationDate":"2022-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46890136","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}
Pub Date : 2022-03-14DOI: 10.1080/09537104.2022.2042233
Z. Wicik, P. Czajka, C. Eyileten, A. Fitas, M. Wolska, D. Jakubik, D. von Lewinski, H. Sourij, J. Siller-Matula, M. Postuła
Abstract MicroRNAs (miRNAs) are small, non-coding RNAs, able to regulate cellular functions by induction of mRNA degradation and post-transcriptional repression of gene expression. Platelets are the major source of circulating miRNAs, with significant regulatory potential on cardiovascular pathophysiology and other diseases. MiRNAs have been shown to modify the expression of platelet proteins, which influence the platelets reactivity. Circulating miRNAs can be determined from plasma, serum, or whole blood, and they can be used as diagnostic and prognostic biomarkers as well as therapeutic targets including cardiovascular diseases (CVDs). Herein, we present original results from bioinformatic analyses, which identified top 22 platelet-related miRNAs including hsa-miR-320a, hsa-miR-16-5p, hsa-miR-106a-5p, hsa-miR-320b, hsa-miR-15a-5p, hsa-miR-15b-5p, hsa-miR-195-5p, hsa-miR-92a-3p as widely involved in platelet reactivity and associated diseases, including CVDs, Alzheimer’s and cerebrovascular diseases, cancer and hypertension. Analysis focused on the identification of the highly regulatory targets shared between those miRNAs identified 43 of them. Best ranked genes associated with overall platelet activity and most susceptible for noncoding regulation were PTEN, PIK3R1, CREB1, APP, and MAPK1. Top targets also strongly associated with CVDs were VEGFA, IGF1, ESR1, BDNF, and PPARG. Top targets associated with other platelet-related diseases including cancer identified in our study were TP53, KRAS, and CCND1. The most affected pathways by top miRNAs and top targets included diseases of signal transduction by Growth Factor Receptors (GDFRs) and second messengers, platelet activation, signaling, and aggregation, signaling by VEGF, MAPK family signaling cascades, and signaling by Interleukins. Terms specific only for platelet-related miRNAs included coronary artery disease, platelet degranulation, and neutrophil degranulation, while for the top platelet-related genes it was Estrogen Signaling Receptor (ESR) mediated signaling, extra-nuclear estrogen signaling, and endometriosis. Our results show the novel features of platelet physiology and may provide a basis for further clinical studies focused on platelet reactivity. They also show in which aspects miRNAs can be promising biomarkers of platelet-related pathological processes.
{"title":"The role of miRNAs in regulation of platelet activity and related diseases - a bioinformatic analysis","authors":"Z. Wicik, P. Czajka, C. Eyileten, A. Fitas, M. Wolska, D. Jakubik, D. von Lewinski, H. Sourij, J. Siller-Matula, M. Postuła","doi":"10.1080/09537104.2022.2042233","DOIUrl":"https://doi.org/10.1080/09537104.2022.2042233","url":null,"abstract":"Abstract MicroRNAs (miRNAs) are small, non-coding RNAs, able to regulate cellular functions by induction of mRNA degradation and post-transcriptional repression of gene expression. Platelets are the major source of circulating miRNAs, with significant regulatory potential on cardiovascular pathophysiology and other diseases. MiRNAs have been shown to modify the expression of platelet proteins, which influence the platelets reactivity. Circulating miRNAs can be determined from plasma, serum, or whole blood, and they can be used as diagnostic and prognostic biomarkers as well as therapeutic targets including cardiovascular diseases (CVDs). Herein, we present original results from bioinformatic analyses, which identified top 22 platelet-related miRNAs including hsa-miR-320a, hsa-miR-16-5p, hsa-miR-106a-5p, hsa-miR-320b, hsa-miR-15a-5p, hsa-miR-15b-5p, hsa-miR-195-5p, hsa-miR-92a-3p as widely involved in platelet reactivity and associated diseases, including CVDs, Alzheimer’s and cerebrovascular diseases, cancer and hypertension. Analysis focused on the identification of the highly regulatory targets shared between those miRNAs identified 43 of them. Best ranked genes associated with overall platelet activity and most susceptible for noncoding regulation were PTEN, PIK3R1, CREB1, APP, and MAPK1. Top targets also strongly associated with CVDs were VEGFA, IGF1, ESR1, BDNF, and PPARG. Top targets associated with other platelet-related diseases including cancer identified in our study were TP53, KRAS, and CCND1. The most affected pathways by top miRNAs and top targets included diseases of signal transduction by Growth Factor Receptors (GDFRs) and second messengers, platelet activation, signaling, and aggregation, signaling by VEGF, MAPK family signaling cascades, and signaling by Interleukins. Terms specific only for platelet-related miRNAs included coronary artery disease, platelet degranulation, and neutrophil degranulation, while for the top platelet-related genes it was Estrogen Signaling Receptor (ESR) mediated signaling, extra-nuclear estrogen signaling, and endometriosis. Our results show the novel features of platelet physiology and may provide a basis for further clinical studies focused on platelet reactivity. They also show in which aspects miRNAs can be promising biomarkers of platelet-related pathological processes.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"33 1","pages":"1052 - 1064"},"PeriodicalIF":3.3,"publicationDate":"2022-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48982230","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}
Pub Date : 2022-03-09DOI: 10.1080/09537104.2022.2042236
C. Gutmann, M. Mayr
Abstract Platelets are essential mediators of physiological hemostasis and pathological thrombosis. Currently available tests and markers of platelet activation did not prove successful in guiding treatment decisions for patients with cardiovascular disease, justifying further research into novel markers of platelet reactivity. Platelets contain a variety of microRNAs (miRNAs) and are a major contributor to the extracellular circulating miRNA pool. Levels of platelet-derived miRNAs in the circulation have been associated with different measures of platelet activation as well as antiplatelet therapy and have therefore been implied as potential new markers of platelet reactivity. In contrast to the ex vivo assessment of platelet reactivity by current platelet function tests, miRNA measurements may enable assessment of platelet reactivity in vivo. It remains to be seen however, whether miRNAs may aid clinical diagnostics. Major limitations in the platelet miRNA research field remain the susceptibility to preanalytical variation, non-standardized sample preparation and data normalization that hampers inter-study comparisons. In this review, we provide an overview of the literature on circulating miRNAs as biomarkers of platelet activation, highlighting the underlying biology, the application in patients with cardiovascular disease and antiplatelet therapy and elaborating on technical limitations regarding their quantification in the circulation.
{"title":"Circulating microRNAs as biomarkers and mediators of platelet activation","authors":"C. Gutmann, M. Mayr","doi":"10.1080/09537104.2022.2042236","DOIUrl":"https://doi.org/10.1080/09537104.2022.2042236","url":null,"abstract":"Abstract Platelets are essential mediators of physiological hemostasis and pathological thrombosis. Currently available tests and markers of platelet activation did not prove successful in guiding treatment decisions for patients with cardiovascular disease, justifying further research into novel markers of platelet reactivity. Platelets contain a variety of microRNAs (miRNAs) and are a major contributor to the extracellular circulating miRNA pool. Levels of platelet-derived miRNAs in the circulation have been associated with different measures of platelet activation as well as antiplatelet therapy and have therefore been implied as potential new markers of platelet reactivity. In contrast to the ex vivo assessment of platelet reactivity by current platelet function tests, miRNA measurements may enable assessment of platelet reactivity in vivo. It remains to be seen however, whether miRNAs may aid clinical diagnostics. Major limitations in the platelet miRNA research field remain the susceptibility to preanalytical variation, non-standardized sample preparation and data normalization that hampers inter-study comparisons. In this review, we provide an overview of the literature on circulating miRNAs as biomarkers of platelet activation, highlighting the underlying biology, the application in patients with cardiovascular disease and antiplatelet therapy and elaborating on technical limitations regarding their quantification in the circulation.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"33 1","pages":"512 - 519"},"PeriodicalIF":3.3,"publicationDate":"2022-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47867452","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}
Pub Date : 2022-03-08DOI: 10.1080/09537104.2022.2026905
Lisa Blath, J. Martens, N. Rahe‐Meyer
Abstract Massive diffuse bleeding is still a problem in cardiovascular surgery. The first line treatment is platelet concentrate transfusion, although there is still insufficient information regarding efficacy, quantity, and timing. The objective of this prospective cohort study was to find out whether the amount of 4 apheresis platelet concentrates could reduce intraoperative bleeding and improve viscoelasticity and aggregometry. 10 patients were enrolled intraoperatively because of life-threatening diffuse bleeding after cardiopulmonary bypass and received 4 apheresis platelet concentrates back-to-back. The units were given every 5 minutes. After every unit, thromboelastometry, performed by ROTEM®, and aggregometry, performed by Multiplate®, were done together with Hematocrit, Hemoglobin, and Platelet Count. Hematocrit and Hemoglobin showed a statistically significant decrease of 14%, whereas Platelet Count showed a statistically significant increase of 205%. MCE-EXTEM increased statistically significant: 46%. There was no statistically significant increase in both ADP and COL results. Even a series of 4 platelet concentrates did not comprehensively improve both essential components of an adequate hemostasis: viscoelasticity and aggregation. Just the transfusion of platelet concentrates alone did not build a sufficient strategy improving hemostasis and reducing bleeding. A positive effect of surgical packing on stopping the bleeding could be seen.
{"title":"Efficacy of platelet transfusion in cardiac surgery","authors":"Lisa Blath, J. Martens, N. Rahe‐Meyer","doi":"10.1080/09537104.2022.2026905","DOIUrl":"https://doi.org/10.1080/09537104.2022.2026905","url":null,"abstract":"Abstract Massive diffuse bleeding is still a problem in cardiovascular surgery. The first line treatment is platelet concentrate transfusion, although there is still insufficient information regarding efficacy, quantity, and timing. The objective of this prospective cohort study was to find out whether the amount of 4 apheresis platelet concentrates could reduce intraoperative bleeding and improve viscoelasticity and aggregometry. 10 patients were enrolled intraoperatively because of life-threatening diffuse bleeding after cardiopulmonary bypass and received 4 apheresis platelet concentrates back-to-back. The units were given every 5 minutes. After every unit, thromboelastometry, performed by ROTEM®, and aggregometry, performed by Multiplate®, were done together with Hematocrit, Hemoglobin, and Platelet Count. Hematocrit and Hemoglobin showed a statistically significant decrease of 14%, whereas Platelet Count showed a statistically significant increase of 205%. MCE-EXTEM increased statistically significant: 46%. There was no statistically significant increase in both ADP and COL results. Even a series of 4 platelet concentrates did not comprehensively improve both essential components of an adequate hemostasis: viscoelasticity and aggregation. Just the transfusion of platelet concentrates alone did not build a sufficient strategy improving hemostasis and reducing bleeding. A positive effect of surgical packing on stopping the bleeding could be seen.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"33 1","pages":"987 - 997"},"PeriodicalIF":3.3,"publicationDate":"2022-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42561263","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}
Pub Date : 2022-02-28DOI: 10.1080/09537104.2022.2042238
T. Ueland, I. Hausberg, T. V. Mørtberg, T. Dahl, T. V. Lerum, A. Michelsen, T. Ranheim, Katerina Nezvalova Henriksen, A. Dyrhol-Riise, P. Holme, T. Aaløkken, O. Skjønsberg, A. Barratt-Due, M. Ahlén, P. Aukrust, B. Halvorsen
Abstract Thromboembolic events are frequent and associated with poor outcome in severe COVID-19 disease. Anti-PF4/polyanion antibodies are related to heparin-induced thrombocytopenia (HIT) and thrombus formation, but data on these antibodies in unselected COVID-19 populations are scarce. We assessed the presence of anti-PF4/polyanion antibodies in prospectively collected serum from an unselected cohort of hospitalized COVID-19 patients and evaluated if elevated levels could give prognostic information on ICU admission and respiratory failure (RF), were associated with markers of inflammation, endothelial activation, platelet activation, coagulation and fibrosis and were associated with long-term pulmonary CT changes. Five out of 65 patients had anti-PF4/polyanion reactivity with OD ≥0.200. These patients had more severe disease as reflected by ICU admission without any evidence of HIT. They also had signs of enhanced inflammation and fibrinogenesis as reflected by elevated ferritin and osteopontin, respectively, during the first 10 days of hospitalization. Increased ferritin and osteopontin persisted in these patients at 3 months follow-up, concomitant with pulmonary CT pathology. Our finding shows that the presence of anti-PF4/polyanion antibodies in unselected hospitalized COVID−19 patients was not related to HIT, but was associated with disease severity, inflammation, and pulmonary pathology after 3 months.
{"title":"Anti-PF4/polyanion antibodies in COVID-19 patients are associated with disease severity and pulmonary pathology","authors":"T. Ueland, I. Hausberg, T. V. Mørtberg, T. Dahl, T. V. Lerum, A. Michelsen, T. Ranheim, Katerina Nezvalova Henriksen, A. Dyrhol-Riise, P. Holme, T. Aaløkken, O. Skjønsberg, A. Barratt-Due, M. Ahlén, P. Aukrust, B. Halvorsen","doi":"10.1080/09537104.2022.2042238","DOIUrl":"https://doi.org/10.1080/09537104.2022.2042238","url":null,"abstract":"Abstract Thromboembolic events are frequent and associated with poor outcome in severe COVID-19 disease. Anti-PF4/polyanion antibodies are related to heparin-induced thrombocytopenia (HIT) and thrombus formation, but data on these antibodies in unselected COVID-19 populations are scarce. We assessed the presence of anti-PF4/polyanion antibodies in prospectively collected serum from an unselected cohort of hospitalized COVID-19 patients and evaluated if elevated levels could give prognostic information on ICU admission and respiratory failure (RF), were associated with markers of inflammation, endothelial activation, platelet activation, coagulation and fibrosis and were associated with long-term pulmonary CT changes. Five out of 65 patients had anti-PF4/polyanion reactivity with OD ≥0.200. These patients had more severe disease as reflected by ICU admission without any evidence of HIT. They also had signs of enhanced inflammation and fibrinogenesis as reflected by elevated ferritin and osteopontin, respectively, during the first 10 days of hospitalization. Increased ferritin and osteopontin persisted in these patients at 3 months follow-up, concomitant with pulmonary CT pathology. Our finding shows that the presence of anti-PF4/polyanion antibodies in unselected hospitalized COVID−19 patients was not related to HIT, but was associated with disease severity, inflammation, and pulmonary pathology after 3 months.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"33 1","pages":"640 - 644"},"PeriodicalIF":3.3,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41986683","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}
Pub Date : 2022-02-28DOI: 10.1080/09537104.2022.2042232
R. Dave, T. Geevar, G. Chellaiya, J. Mammen, Ramya Vijayan, Ashok Samuel, M. Gowri, S. Nair
Abstract Light transmission aggregometry (LTA) is the gold standard for the diagnosis of platelet function disorders (PFDs). The requirement of customized aggregometer, large blood volume, normal platelet count and processing within 4 hours of venipuncture for LTA makes platelet function testing inaccessible to wider population. Flow cytometric platelet activation test (PACT) may overcome these limitations. This study compares the performance of PACT with LTA, characterizes diagnostic patterns of PFDs on PACT and assesses the stability of PACT beyond 4 hours of venipuncture in controls (n = 5) at different temperature conditions. LTA and PACT were performed in 121 healthy controls and 66 patients with suspected PFD. PACT had excellent agreement (kappa = 0.93) with LTA and 94.1% sensitivity, 98.5% specificity. PACT had distinct patterns in Bernard Soulier Syndrome (n = 10), Glanzmann Thrombasthenia (n = 24), δ-granule disorder (n = 7), and other PFDs (n = 12). PACT could assess platelet function in patients (14%) with thrombocytopenia/lipemia wherein LTA was inconclusive. PACT was stable up to 24 hours in samples stored/transported at 2–8◦C. The results of utility and stability are only valid for the specific markers, agonist concentrations, and conditions investigated in this paper. PACT is a useful modality for the diagnosis of PFD, especially in children, thrombocytopenia cases or in the setup where an aggregometer is not readily available.
{"title":"Stability and utility of flow cytometric platelet activation tests: A modality to bridge the gap between diagnostic demand and supply","authors":"R. Dave, T. Geevar, G. Chellaiya, J. Mammen, Ramya Vijayan, Ashok Samuel, M. Gowri, S. Nair","doi":"10.1080/09537104.2022.2042232","DOIUrl":"https://doi.org/10.1080/09537104.2022.2042232","url":null,"abstract":"Abstract Light transmission aggregometry (LTA) is the gold standard for the diagnosis of platelet function disorders (PFDs). The requirement of customized aggregometer, large blood volume, normal platelet count and processing within 4 hours of venipuncture for LTA makes platelet function testing inaccessible to wider population. Flow cytometric platelet activation test (PACT) may overcome these limitations. This study compares the performance of PACT with LTA, characterizes diagnostic patterns of PFDs on PACT and assesses the stability of PACT beyond 4 hours of venipuncture in controls (n = 5) at different temperature conditions. LTA and PACT were performed in 121 healthy controls and 66 patients with suspected PFD. PACT had excellent agreement (kappa = 0.93) with LTA and 94.1% sensitivity, 98.5% specificity. PACT had distinct patterns in Bernard Soulier Syndrome (n = 10), Glanzmann Thrombasthenia (n = 24), δ-granule disorder (n = 7), and other PFDs (n = 12). PACT could assess platelet function in patients (14%) with thrombocytopenia/lipemia wherein LTA was inconclusive. PACT was stable up to 24 hours in samples stored/transported at 2–8◦C. The results of utility and stability are only valid for the specific markers, agonist concentrations, and conditions investigated in this paper. PACT is a useful modality for the diagnosis of PFD, especially in children, thrombocytopenia cases or in the setup where an aggregometer is not readily available.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"33 1","pages":"1043 - 1051"},"PeriodicalIF":3.3,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49453774","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}
Pub Date : 2022-02-17DOI: 10.1080/09537104.2021.1961710
Josiah Bote, Heather A Corkrey, Milka Koupenova
Influenza infection has long been associated with prothrombotic outcomes in patients and platelets are the blood component predominantly responsible for thrombosis. In this review, we outline what is known about influenza interaction with human platelets, virion internalization, and viral RNA sensing, and the consequent impact on platelet function. We further discuss activation of platelets by IgG-influenza complexes and touch upon mechanisms of environmental platelet activation that relate to prothrombotic outcomes in patients during infection.
{"title":"Human Platelets and Influenza Virus: Internalization and Platelet Activation.","authors":"Josiah Bote, Heather A Corkrey, Milka Koupenova","doi":"10.1080/09537104.2021.1961710","DOIUrl":"https://doi.org/10.1080/09537104.2021.1961710","url":null,"abstract":"<p><p>Influenza infection has long been associated with prothrombotic outcomes in patients and platelets are the blood component predominantly responsible for thrombosis. In this review, we outline what is known about influenza interaction with human platelets, virion internalization, and viral RNA sensing, and the consequent impact on platelet function. We further discuss activation of platelets by IgG-influenza complexes and touch upon mechanisms of environmental platelet activation that relate to prothrombotic outcomes in patients during infection.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"33 2","pages":"184-191"},"PeriodicalIF":3.3,"publicationDate":"2022-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8821732/pdf/nihms-1733872.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10740716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-02-17DOI: 10.1080/09537104.2021.2019695
Sidney W Whiteheart
While it is clear that platelets interact with viruses, the ramifications and mechanisms of those interactions are still being defined for each type of viral infection. HIV/AIDS+ represents a potentially unique example of how viremia affects platelets since the increasing efficacy of antiretroviral therapeutics (ART) has made it a chronic disease that increases the risk of cardiovascular disease. In this opinion article, we discuss some of the open questions about how platelets interact with HIV. What happens to a virion once it binds a platelet? What is the nature of virus-induced platelet activation? Are platelets a normal part of the immune response to viremia that has been co-opted to increase the spread of HIV? The answers to these and similar questions will help define how platelet-directed therapeutics might be used in treating HIV/AIDS+ patients.
{"title":"Platelet-HIV: interactions and their implications.","authors":"Sidney W Whiteheart","doi":"10.1080/09537104.2021.2019695","DOIUrl":"https://doi.org/10.1080/09537104.2021.2019695","url":null,"abstract":"<p><p>While it is clear that platelets interact with viruses, the ramifications and mechanisms of those interactions are still being defined for each type of viral infection. HIV/AIDS<sup>+</sup> represents a potentially unique example of how viremia affects platelets since the increasing efficacy of antiretroviral therapeutics (ART) has made it a chronic disease that increases the risk of cardiovascular disease. In this opinion article, we discuss some of the open questions about how platelets interact with HIV. What happens to a virion once it binds a platelet? What is the nature of virus-induced platelet activation? Are platelets a normal part of the immune response to viremia that has been co-opted to increase the spread of HIV? The answers to these and similar questions will help define how platelet-directed therapeutics might be used in treating HIV/AIDS<sup>+</sup> patients.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"33 2","pages":"208-211"},"PeriodicalIF":3.3,"publicationDate":"2022-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8881393/pdf/nihms-1766916.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9304805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-02-17DOI: 10.1080/09537104.2021.2020491
Matthew T Rondina
Platelets are increasingly recognized for their broad repertoire of activities spanning hemostatic, inflammatory, and immune continuums. In many cases, platelet functions cooperate to bridge these continuums, effectively triggering responses that may act collectively and catalytically to mediate thrombotic, inflammatory, and immune activities [1–3]. These cooperative responses have led to the creation of the term “immunothrombosis,” which emphasizes the closely woven interplay between inflammation, immunity, and thrombosis. As the second most common circulating blood cell, platelets are centrally positioned in the vasculature to trigger immunothrombosis. Platelets possess a repertoire of intracellular and stored molecules (often in granule compartments that can be secreted) and surface anchored receptors. The array of proteins, lipids, and RNAs possessed by platelets allow these small anucleate cells to sense and respond to diverse signals, including those generated during infectious settings. For example, platelets possess the RNA and/or protein for nearly all toll-like receptors (TLRs) [4,5]. TLRs are one of the several surface ligands allowing viruses to bind to platelets. In addition to TLRs, platelets also express other binding proteins, including β3 integrin, DC-SIGN, and FcRyIIA, which enable virions to bind to, engage with, and/or enter platelets. In addition to these receptor-mediated interactions, platelets may also actively take up virions through a variety of other mechanisms, including clathrin-mediated endocytosis (CME) and pinocytosis [6]. Often, more than one factor is required for internalization of viruses by platelets. Systemic agonists and pathogen particles generated as viruses enter their host and replicate may also be sensed or recognized by platelets, leading to downstream activation responses and signaldependent binding to, and communication with, leukocytes. These molecules include danger-associated molecular patterns (DAMPs; including HMGB1, S100 proteins, interleukin 1 [IL-1] family members, type interferons [IFN], and tumor necrosis factor alpha [TNF-α]) and pathogen associated molecular patterns (PAMPs; including nucleic acid motifs, ssRNA, dsRNA, and unmethylated CpG motifs). Platelets, once activated, are primed to interact and aggregate with leukocytes (e.g., heterotypic aggregation). Increased platelet–leukocyte interactions can be observed in patients infected with influenza, SARS-CoV-2, and dengue infection – among others [7–12]. These interactions can promote inflammatory cytokine synthesis (such as MCP-1, IL-1β, IL-8, and IL-10), neutrophil extracellular trap (NET) formation, and antigen-dependent T cell responses [3,13,14]. Platelets also secrete numerous molecules, such as platelet factor 4 (PF4), RANTES, and P-selectin, which may directly or indirectly mediate the pathogenesis of viral infections. The net effect of these interactions is generally thought to promote immunothrombosis, although the full range
{"title":"Editorial: special review series on viruses and platelets.","authors":"Matthew T Rondina","doi":"10.1080/09537104.2021.2020491","DOIUrl":"https://doi.org/10.1080/09537104.2021.2020491","url":null,"abstract":"Platelets are increasingly recognized for their broad repertoire of activities spanning hemostatic, inflammatory, and immune continuums. In many cases, platelet functions cooperate to bridge these continuums, effectively triggering responses that may act collectively and catalytically to mediate thrombotic, inflammatory, and immune activities [1–3]. These cooperative responses have led to the creation of the term “immunothrombosis,” which emphasizes the closely woven interplay between inflammation, immunity, and thrombosis. As the second most common circulating blood cell, platelets are centrally positioned in the vasculature to trigger immunothrombosis. Platelets possess a repertoire of intracellular and stored molecules (often in granule compartments that can be secreted) and surface anchored receptors. The array of proteins, lipids, and RNAs possessed by platelets allow these small anucleate cells to sense and respond to diverse signals, including those generated during infectious settings. For example, platelets possess the RNA and/or protein for nearly all toll-like receptors (TLRs) [4,5]. TLRs are one of the several surface ligands allowing viruses to bind to platelets. In addition to TLRs, platelets also express other binding proteins, including β3 integrin, DC-SIGN, and FcRyIIA, which enable virions to bind to, engage with, and/or enter platelets. In addition to these receptor-mediated interactions, platelets may also actively take up virions through a variety of other mechanisms, including clathrin-mediated endocytosis (CME) and pinocytosis [6]. Often, more than one factor is required for internalization of viruses by platelets. Systemic agonists and pathogen particles generated as viruses enter their host and replicate may also be sensed or recognized by platelets, leading to downstream activation responses and signaldependent binding to, and communication with, leukocytes. These molecules include danger-associated molecular patterns (DAMPs; including HMGB1, S100 proteins, interleukin 1 [IL-1] family members, type interferons [IFN], and tumor necrosis factor alpha [TNF-α]) and pathogen associated molecular patterns (PAMPs; including nucleic acid motifs, ssRNA, dsRNA, and unmethylated CpG motifs). Platelets, once activated, are primed to interact and aggregate with leukocytes (e.g., heterotypic aggregation). Increased platelet–leukocyte interactions can be observed in patients infected with influenza, SARS-CoV-2, and dengue infection – among others [7–12]. These interactions can promote inflammatory cytokine synthesis (such as MCP-1, IL-1β, IL-8, and IL-10), neutrophil extracellular trap (NET) formation, and antigen-dependent T cell responses [3,13,14]. Platelets also secrete numerous molecules, such as platelet factor 4 (PF4), RANTES, and P-selectin, which may directly or indirectly mediate the pathogenesis of viral infections. The net effect of these interactions is generally thought to promote immunothrombosis, although the full range","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"33 2","pages":"174-175"},"PeriodicalIF":3.3,"publicationDate":"2022-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8881311/pdf/nihms-1769166.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10736594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-02Epub Date: 2021-01-18DOI: 10.1080/09537104.2020.1859102
Ingrid Lindquist, Sven R Olson, Ang Li, Hanny Al-Samkari, Janice H Jou, Owen J T McCarty, Joseph J Shatzel
Thrombopoietin receptor agonists (TPO-RAs) can mitigate preprocedural thrombocytopenia in patients with chronic liver disease (CLD) however their effects on procedural outcomes is unclear. In this meta-analysis, we aimed to better define the efficacy, thrombotic risk and bleeding mitigation associated with the use of preoperative TPO-RAs in patients with CLD. We performed a systematic review and meta-analysis of randomized placebo-controlled clinical trials to assess the use of preprocedural TPO-RAs in patients with CLD, searching MEDLINE, EMBASE and the Cochrane library database. Six publications comprising eight randomized trials (1229 patients; 717 received TPO-RAs, 512 received placebo) and three unique TPO-RAs were retrieved. The majority of the included procedures were endoscopic. TPO-RAs were significantly more likely to result in a preoperative platelet count greater than 50 x 109/L (72.1% vs 15.6%, RR 4.8, 95% CI 3.6-6.4 p < .00001. NNT 1.8) and reduced the incidence of platelet transfusions (22.5% vs 67.8%, RR 0.33, 95% CI 0.3-0.4 p < .00001. NNT 2.2). Total periprocedural bleeding was decreased in patients who received TPO-RAs (11.6% vs 15.6%, RR 0.64, 95% CI 0.5-0.9 p = .01. NNT 24.7) and there was no increase in the rate of thrombosis (2.2% vs 1.8% RR 1.25, 95% CI 0.6-2.9 p = .60. NNH 211.1). In patients with CLD the use of preprocedural TPO-RAs resulted in significant increased platelet counts, and decreased the incidence of platelet transfusions as compared to placebo. TPO use likewise decreased the incidence of total periprocedural bleeding without increasing the rate of thrombosis.
促血小板生成素受体激动剂(TPO-RAs)可减轻慢性肝病(CLD)患者术前血小板减少症,但其对手术结果的影响尚不明确。在这项荟萃分析中,我们旨在更好地界定在 CLD 患者术前使用 TPO-RAs 的相关疗效、血栓风险和出血缓解情况。我们检索了 MEDLINE、EMBASE 和 Cochrane 图书馆数据库,对随机安慰剂对照临床试验进行了系统回顾和荟萃分析,以评估在 CLD 患者中使用术前 TPO-RAs 的情况。共检索到六篇出版物,包括八项随机试验(1229 例患者;717 例接受 TPO-RAs 治疗,512 例接受安慰剂治疗)和三项独特的 TPO-RAs。纳入的大多数手术都是内窥镜手术。TPO-RAs 使术前血小板计数大于 50 x 109/L 的可能性明显增加(72.1% vs 15.6%,RR 4.8,95% CI 3.6-6.4 p p = .01。NNT 24.7),血栓形成率没有增加(2.2% vs 1.8% RR 1.25,95% CI 0.6-2.9 p = .60。)与安慰剂相比,CLD 患者术前使用 TPO-RAs 可显著增加血小板计数,降低血小板输注的发生率。TPO的使用同样降低了围手术期出血的发生率,但没有增加血栓形成的发生率。
{"title":"The efficacy and safety of thrombopoietin receptor agonists in patients with chronic liver disease undergoing elective procedures: a systematic review and meta-analysis.","authors":"Ingrid Lindquist, Sven R Olson, Ang Li, Hanny Al-Samkari, Janice H Jou, Owen J T McCarty, Joseph J Shatzel","doi":"10.1080/09537104.2020.1859102","DOIUrl":"10.1080/09537104.2020.1859102","url":null,"abstract":"<p><p>Thrombopoietin receptor agonists (TPO-RAs) can mitigate preprocedural thrombocytopenia in patients with chronic liver disease (CLD) however their effects on procedural outcomes is unclear. In this meta-analysis, we aimed to better define the efficacy, thrombotic risk and bleeding mitigation associated with the use of preoperative TPO-RAs in patients with CLD. We performed a systematic review and meta-analysis of randomized placebo-controlled clinical trials to assess the use of preprocedural TPO-RAs in patients with CLD, searching MEDLINE, EMBASE and the Cochrane library database. Six publications comprising eight randomized trials (1229 patients; 717 received TPO-RAs, 512 received placebo) and three unique TPO-RAs were retrieved. The majority of the included procedures were endoscopic. TPO-RAs were significantly more likely to result in a preoperative platelet count greater than 50 x 10<sup>9</sup>/L (72.1% vs 15.6%, RR 4.8, 95% CI 3.6-6.4 <i>p</i> < .00001. NNT 1.8) and reduced the incidence of platelet transfusions (22.5% vs 67.8%, RR 0.33, 95% CI 0.3-0.4 <i>p</i> < .00001. NNT 2.2). Total periprocedural bleeding was decreased in patients who received TPO-RAs (11.6% vs 15.6%, RR 0.64, 95% CI 0.5-0.9 <i>p</i> = .01. NNT 24.7) and there was no increase in the rate of thrombosis (2.2% vs 1.8% RR 1.25, 95% CI 0.6-2.9 <i>p</i> = .60. NNH 211.1). In patients with CLD the use of preprocedural TPO-RAs resulted in significant increased platelet counts, and decreased the incidence of platelet transfusions as compared to placebo. TPO use likewise decreased the incidence of total periprocedural bleeding without increasing the rate of thrombosis.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"33 1","pages":"66-72"},"PeriodicalIF":3.3,"publicationDate":"2022-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286270/pdf/nihms-1657696.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10517737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}