Pub Date : 2023-12-01Epub Date: 2023-10-11DOI: 10.1080/09537104.2023.2264940
Joanne L Mitchell, Dalia Khan, Rekha H Rana, Neline Kriek, Amanda J Unsworth, Tanya Sage, Alexander P Bye, Michael Laffan, Susan Shapiro, Anjan Thakurta, Henri Grech, Karthik Ramasamy, Jonathan M Gibbins
Multiple myeloma (MM) and its precursor states, smoldering myeloma (SM) and monoclonal gammopathy of undetermined significance (MGUS) are associated with increased incidence of thrombosis, however the cause of this is unknown. Lenalidomide treatment of MM substantially improves patient survival, although significantly increases thrombotic risk by an unknown mechanism. This pilot study aimed to establish the impact of MM and its treatment with Lenalidomide on platelet function. We analyzed platelet function in MGUS, SM and MM compared to healthy controls. We report an increase in platelet reactivity in MGUS, SM, and MM where increases in fibrinogen binding, P-selectin exposure, altered receptor expression, elevated levels of aggregation and enhanced sensitivity to agonist stimulation were observed. We also demonstrate an increase in patient platelet reactivity post Lenalidomide treatment compared to pre-treatment. We show Lenalidomide treatment of platelets ex vivo increased reactivity that was associated with formation of larger thrombi at arterial shear rates but not venous shear rates. This study demonstrates a clear increase in platelet reactivity and prothrombotic potential in patients with MGUS, SM and MM which is elevated further upon treatment with Lenalidomide. Our observations suggest that more detailed studies are warranted to determine mechanisms of thrombotic complications to enable the development of new preventative strategies that specifically target platelets.
{"title":"Multiple myeloma and its treatment contribute to increased platelet reactivity.","authors":"Joanne L Mitchell, Dalia Khan, Rekha H Rana, Neline Kriek, Amanda J Unsworth, Tanya Sage, Alexander P Bye, Michael Laffan, Susan Shapiro, Anjan Thakurta, Henri Grech, Karthik Ramasamy, Jonathan M Gibbins","doi":"10.1080/09537104.2023.2264940","DOIUrl":"10.1080/09537104.2023.2264940","url":null,"abstract":"<p><p>Multiple myeloma (MM) and its precursor states, smoldering myeloma (SM) and monoclonal gammopathy of undetermined significance (MGUS) are associated with increased incidence of thrombosis, however the cause of this is unknown. Lenalidomide treatment of MM substantially improves patient survival, although significantly increases thrombotic risk by an unknown mechanism. This pilot study aimed to establish the impact of MM and its treatment with Lenalidomide on platelet function. We analyzed platelet function in MGUS, SM and MM compared to healthy controls. We report an increase in platelet reactivity in MGUS, SM, and MM where increases in fibrinogen binding, P-selectin exposure, altered receptor expression, elevated levels of aggregation and enhanced sensitivity to agonist stimulation were observed. We also demonstrate an increase in patient platelet reactivity post Lenalidomide treatment compared to pre-treatment. We show Lenalidomide treatment of platelets <i>ex vivo</i> increased reactivity that was associated with formation of larger thrombi at arterial shear rates but not venous shear rates. This study demonstrates a clear increase in platelet reactivity and prothrombotic potential in patients with MGUS, SM and MM which is elevated further upon treatment with Lenalidomide. Our observations suggest that more detailed studies are warranted to determine mechanisms of thrombotic complications to enable the development of new preventative strategies that specifically target platelets.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41210084","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}
Predicting the clinical course and allocating limited medical resources appropriately is crucial during the COVID-19 pandemic. Platelets are involved in microthrombosis, a critical pathogenesis of COVID-19; however, the role of soluble CLEC-2 (sCLEC-2), a novel platelet activation marker, in predicting the prognosis of COVID-19 remains unexplored. We enrolled 108 patients with COVID-19, hospitalized between January 2021 and May 2022, to evaluate the clinical use of sCLEC-2 as a predictive marker. sCLEC-2 levels were measured in plasma sampled on admission, as well as interleukin-6, cell-free DNA, von Willebrand factor, and thrombomodulin. We retrospectively classified the patients into two groups - those who required oxygenation during hospitalization (oxygenated group) and those who did not (unoxygenated group) - and compared their clinical and laboratory characteristics. The correlation between sCLEC-2 and the other parameters was validated. The sCLEC-2 level was significantly higher in the oxygenated group (188.8 pg/mL vs. 296.1 pg/mL). Multivariate analysis identified high sCLEC-2 levels (odds ratio per 10 pg/mL:1.25) as an independent predictor of oxygen therapy requirement. sCLEC-2 was positively correlated with cell-free DNA, supporting the association between platelet activation and neutrophil extracellular traps. In conclusion, sCLEC-2 is a clinically valuable marker in predicting oxygen therapy requirements for patients with COVID-19.
{"title":"High plasma soluble CLEC-2 level predicts oxygen therapy requirement in patients with COVID-19.","authors":"Saori Oishi, Makyo Ueda, Hirokazu Yamazaki, Nagaharu Tsukiji, Toshiaki Shirai, Yuna Naito, Masumi Endo, Ryohei Yokomori, Tomoyuki Sasaki, Katsue Suzuki-Inoue","doi":"10.1080/09537104.2023.2244594","DOIUrl":"10.1080/09537104.2023.2244594","url":null,"abstract":"<p><p>Predicting the clinical course and allocating limited medical resources appropriately is crucial during the COVID-19 pandemic. Platelets are involved in microthrombosis, a critical pathogenesis of COVID-19; however, the role of soluble CLEC-2 (sCLEC-2), a novel platelet activation marker, in predicting the prognosis of COVID-19 remains unexplored. We enrolled 108 patients with COVID-19, hospitalized between January 2021 and May 2022, to evaluate the clinical use of sCLEC-2 as a predictive marker. sCLEC-2 levels were measured in plasma sampled on admission, as well as interleukin-6, cell-free DNA, von Willebrand factor, and thrombomodulin. We retrospectively classified the patients into two groups - those who required oxygenation during hospitalization (oxygenated group) and those who did not (unoxygenated group) - and compared their clinical and laboratory characteristics. The correlation between sCLEC-2 and the other parameters was validated. The sCLEC-2 level was significantly higher in the oxygenated group (188.8 pg/mL vs. 296.1 pg/mL). Multivariate analysis identified high sCLEC-2 levels (odds ratio per 10 pg/mL:1.25) as an independent predictor of oxygen therapy requirement. sCLEC-2 was positively correlated with cell-free DNA, supporting the association between platelet activation and neutrophil extracellular traps. In conclusion, sCLEC-2 is a clinically valuable marker in predicting oxygen therapy requirements for patients with COVID-19.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10044853","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 : 2023-12-01DOI: 10.1080/09537104.2023.2222184
Kanakanagavalli Shravani Prakhya, Hemendra Vekaria, Daniёlle M Coenen, Linda Omali, Joshua Lykins, Smita Joshi, Hammodah R Alfar, Qing Jun Wang, Patrick Sullivan, Sidney W Whiteheart
Although the presence of glycogen in platelets was established in the 1960s, its importance to specific functions (i.e., activation, secretion, aggregation, and clot contraction) remains unclear. Patients with glycogen storage disease often present with increased bleeding and glycogen phosphorylase (GP) inhibitors, when used as treatments for diabetes, induce bleeding in preclinical studies suggesting some role for this form of glucose in hemostasis. In the present work, we examined how glycogen mobilization affects platelet function using GP inhibitors (CP316819 and CP91149) and a battery of ex vivo assays. Blocking GP activity increased glycogen levels in resting and thrombin-activated platelets and inhibited platelet secretion and clot contraction, with minimal effects on aggregation. Seahorse energy flux analysis and metabolite supplementation experiments suggested that glycogen is an important metabolic fuel whose role is affected by platelet activation and the availability of external glucose and other metabolic fuels. Our data shed light on the bleeding diathesis in glycogen storage disease patients and offer insights into the potential effects of hyperglycemia on platelets.
{"title":"Platelet glycogenolysis is important for energy production and function.","authors":"Kanakanagavalli Shravani Prakhya, Hemendra Vekaria, Daniёlle M Coenen, Linda Omali, Joshua Lykins, Smita Joshi, Hammodah R Alfar, Qing Jun Wang, Patrick Sullivan, Sidney W Whiteheart","doi":"10.1080/09537104.2023.2222184","DOIUrl":"10.1080/09537104.2023.2222184","url":null,"abstract":"<p><p>Although the presence of glycogen in platelets was established in the 1960s, its importance to specific functions (<i>i.e</i>., activation, secretion, aggregation, and clot contraction) remains unclear. Patients with glycogen storage disease often present with increased bleeding and glycogen phosphorylase (GP) inhibitors, when used as treatments for diabetes, induce bleeding in preclinical studies suggesting some role for this form of glucose in hemostasis. In the present work, we examined how glycogen mobilization affects platelet function using GP inhibitors (CP316819 and CP91149) and a battery of <i>ex vivo</i> assays. Blocking GP activity increased glycogen levels in resting and thrombin-activated platelets and inhibited platelet secretion and clot contraction, with minimal effects on aggregation. Seahorse energy flux analysis and metabolite supplementation experiments suggested that glycogen is an important metabolic fuel whose role is affected by platelet activation and the availability of external glucose and other metabolic fuels. Our data shed light on the bleeding diathesis in glycogen storage disease patients and offer insights into the potential effects of hyperglycemia on platelets.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10658951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9609392","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 : 2023-12-01DOI: 10.1080/09537104.2023.2237114
Smita Joshi, Kanakanagavalli Shravani Prakhya, Alexis N Smith, Harry Chanzu, Ming Zhang, Sidney W Whiteheart
Platelet secretion requires Soluble N-ethylmaleimide Sensitive Attachment Protein Receptors (SNAREs). Vesicle SNAREs/Vesicle-Associated Membrane Proteins (v-SNAREs/VAMPs) on granules and t-SNAREs in plasma membranes mediate granule release. Platelet VAMP heterogeneity has complicated the assessment of how/if each is used and affects hemostasis. To address the importance of VAMP-7 (V7), we analyzed mice with global deletions of V3 and V7 together or platelet-specific deletions of V2, V3, and global deletion of V7. We measured the kinetics of cargo release, and its effects on three injury models to define the context-specific roles of these VAMPs. Loss of V7 minimally affected dense and α granule release but did affect lysosomal release. V3-/-7-/- and V2Δ3Δ7-/- platelets showed partial defects in α and lysosomal release; dense granule secretion was unaffected. In vivo assays showed that loss of V2, V3, and V7 caused no bleeding or occlusive thrombosis. These data indicate a role for V7 in lysosome release that is partially compensated by V3. V7 and V3, together, contribute to α granule release, however none of these deletions affected hemostasis/thrombosis. Our results confirm the dominance of V8. When it is present, deletion of V2, V3, or V7 alone or in combination minimally affects platelet secretion and hemostasis.
{"title":"The complementary roles of VAMP-2, -3, and -7 in platelet secretion and function.","authors":"Smita Joshi, Kanakanagavalli Shravani Prakhya, Alexis N Smith, Harry Chanzu, Ming Zhang, Sidney W Whiteheart","doi":"10.1080/09537104.2023.2237114","DOIUrl":"10.1080/09537104.2023.2237114","url":null,"abstract":"<p><p>Platelet secretion requires Soluble N-ethylmaleimide Sensitive Attachment Protein Receptors (SNAREs). Vesicle SNAREs/Vesicle-Associated Membrane Proteins (v-SNAREs/VAMPs) on granules and t-SNAREs in plasma membranes mediate granule release. Platelet VAMP heterogeneity has complicated the assessment of how/if each is used and affects hemostasis. To address the importance of VAMP-7 (V7), we analyzed mice with global deletions of V3 and V7 together or platelet-specific deletions of V2, V3, and global deletion of V7. We measured the kinetics of cargo release, and its effects on three injury models to define the context-specific roles of these VAMPs. Loss of V7 minimally affected dense and α granule release but did affect lysosomal release. V3<sup>-/-</sup>7<sup>-/-</sup> and V2<sup>Δ</sup>3<sup>Δ</sup>7<sup>-/-</sup> platelets showed partial defects in α and lysosomal release; dense granule secretion was unaffected. <i>In vivo</i> assays showed that loss of V2, V3, and V7 caused no bleeding or occlusive thrombosis. These data indicate a role for V7 in lysosome release that is partially compensated by V3. V7 and V3, together, contribute to α granule release, however none of these deletions affected hemostasis/thrombosis. Our results confirm the dominance of V8. When it is present, deletion of V2, V3, or V7 alone or in combination minimally affects platelet secretion and hemostasis.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10564522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41210085","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 : 2023-12-01Epub Date: 2023-11-05DOI: 10.1080/09537104.2023.2267147
Alexis N Smith, Smita Joshi, Harry Chanzu, Hammodah R Alfar, Kanakanagavalli Shravani Prakhya, Sidney W Whiteheart
Platelets play many roles in the vasculature ensuring proper hemostasis and maintaining integrity. These roles are facilitated, in part, by cargo molecules released from platelet granules via Soluble NSF Attachment Protein Receptor (SNARE) mediated membrane fusion, which is controlled by several protein-protein interactions. Chaperones have been characterized for t-SNAREs (i.e. Munc18b for Syntaxin-11), but none have been clearly identified for v-SNAREs. α-Synuclein has been proposed as a v-SNARE chaperone which may affect SNARE-complex assembly, fusion pore opening, and thus secretion. Despite its abundance and that it is the only isoform present, α-synuclein's role in platelet secretion is uncharacterized. In this study, immunofluorescence showed that α-synuclein was present on punctate structures that co-stained with markers for α-granules and lysosomes and in a cytoplasmic pool. We analyzed the phenotype of α-synuclein-/- mice and their platelets. Platelets from knockout mice had a mild, agonist-dependent secretion defect but aggregation and spreading in vitro were unaffected. Consistently, thrombosis/hemostasis were unaffected in the tail-bleeding, FeCl3 carotid injury and jugular vein puncture models. None of the platelet secretory machinery examined, e.g. the v-SNAREs, were affected by α-synuclein's loss. The results indicate that, despite its abundance, α-synuclein has only a limited role in platelet function and thrombosis.
{"title":"α-Synuclein is the major platelet isoform but is dispensable for activation, secretion, and thrombosis.","authors":"Alexis N Smith, Smita Joshi, Harry Chanzu, Hammodah R Alfar, Kanakanagavalli Shravani Prakhya, Sidney W Whiteheart","doi":"10.1080/09537104.2023.2267147","DOIUrl":"10.1080/09537104.2023.2267147","url":null,"abstract":"<p><p>Platelets play many roles in the vasculature ensuring proper hemostasis and maintaining integrity. These roles are facilitated, in part, by cargo molecules released from platelet granules via <u>S</u>oluble <u>N</u>SF <u>A</u>ttachment <u>P</u>rotein <u>R</u>eceptor (SNARE) mediated membrane fusion, which is controlled by several protein-protein interactions. Chaperones have been characterized for t-SNAREs (<i>i.e</i>. Munc18b for Syntaxin-11), but none have been clearly identified for v-SNAREs. α-Synuclein has been proposed as a v-SNARE chaperone which may affect SNARE-complex assembly, fusion pore opening, and thus secretion. Despite its abundance and that it is the only isoform present, α-synuclein's role in platelet secretion is uncharacterized. In this study, immunofluorescence showed that α-synuclein was present on punctate structures that co-stained with markers for α-granules and lysosomes and in a cytoplasmic pool. We analyzed the phenotype of α-synuclein<sup>-/-</sup> mice and their platelets. Platelets from knockout mice had a mild, agonist-dependent secretion defect but aggregation and spreading <i>in vitro</i> were unaffected. Consistently, thrombosis/hemostasis were unaffected in the tail-bleeding, FeCl<sub>3</sub> carotid injury and jugular vein puncture models. None of the platelet secretory machinery examined, <i>e.g</i>. the v-SNAREs, were affected by α-synuclein's loss. The results indicate that, despite its abundance, α-synuclein has only a limited role in platelet function and thrombosis.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10629845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71485176","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 : 2023-12-01Epub Date: 2023-11-30DOI: 10.1080/09537104.2023.2287064
Qi Cai, Han Lin, Ping Guo
The hybrid-channel platelet counting method (PLT-H) is a new platelet counting technique proposed by Mindray of China. In this study, we aimed to evaluate the accuracy of this technique in various situations and its reliability in platelet transfusion decision-making. A total of 378 venous blood samples were tested. Using the immunological PLT counting method recommended by the International Council for Standardization in Hematology as the reference method (PLT-IRM), Passing-Bablok regression and Bland-Altman analysis were performed on the PLT-H results. The anti-interference performance of PLT-H under different interference levels was explored using intergroup comparisons, and confusion matrices were analyzed at various transfusion cutoff values. In the absence of interference, there was a strong correlation between PLT-H and PLT-IRM (r = 0.993, 95% CI: 0.990-0.996). Under various interference conditions, the correlation between PLT-H and PLT-IRM was between 0.963 and 0.992, with an average deviation of -14.56 to -2.02. The performance of PLT-H against interference did not change significantly with increasing levels of small RBCs, large PLTs, and RBC fragments (P = .5704, 0.0832, 0.9893). In low-value samples (PLT <100 × 109/L), the coefficient of variation (CV) for PLT-H was less than 7.6%, regardless of the presence or absence of interfering substances. In addition, there was a high agreement between PLT-H and PLT-IRM (ICC = 0.972). Confusion matrice analysis at each medical decision level showed similarity to methods using the fluorescence channel (PLT-O) and superiority to the impedance channel (PLT-I). Compared with PLT-I, PLT-H has higher accuracy in PLT counting, stronger anti-interference ability, better performance in low-value samples at no extra economic cost and can be more useful for platelet transfusion decision-making. PLT-H is a novel method for platelet counting that offers higher accuracy, providing physicians with the ability to make better medical decisions, particularly in cases where values are low, or interference is present. As it does not require additional reagents, it is highly likely to replace PLT-I and become the mainstream method for platelet counting in the future.
{"title":"Performance evaluation of PLT-H (hybrid-channel platelet) under various interferences and application studies for platelet transfusion decisions.","authors":"Qi Cai, Han Lin, Ping Guo","doi":"10.1080/09537104.2023.2287064","DOIUrl":"https://doi.org/10.1080/09537104.2023.2287064","url":null,"abstract":"<p><p>The hybrid-channel platelet counting method (PLT-H) is a new platelet counting technique proposed by Mindray of China. In this study, we aimed to evaluate the accuracy of this technique in various situations and its reliability in platelet transfusion decision-making. A total of 378 venous blood samples were tested. Using the immunological PLT counting method recommended by the International Council for Standardization in Hematology as the reference method (PLT-IRM), Passing-Bablok regression and Bland-Altman analysis were performed on the PLT-H results. The anti-interference performance of PLT-H under different interference levels was explored using intergroup comparisons, and confusion matrices were analyzed at various transfusion cutoff values. In the absence of interference, there was a strong correlation between PLT-H and PLT-IRM (<i>r</i> = 0.993, 95% CI: 0.990-0.996). Under various interference conditions, the correlation between PLT-H and PLT-IRM was between 0.963 and 0.992, with an average deviation of -14.56 to -2.02. The performance of PLT-H against interference did not change significantly with increasing levels of small RBCs, large PLTs, and RBC fragments (<i>P</i> = .5704, 0.0832, 0.9893). In low-value samples (PLT <100 × 10<sup>9</sup>/L), the coefficient of variation (CV) for PLT-H was less than 7.6%, regardless of the presence or absence of interfering substances. In addition, there was a high agreement between PLT-H and PLT-IRM (ICC = 0.972). Confusion matrice analysis at each medical decision level showed similarity to methods using the fluorescence channel (PLT-O) and superiority to the impedance channel (PLT-I). Compared with PLT-I, PLT-H has higher accuracy in PLT counting, stronger anti-interference ability, better performance in low-value samples at no extra economic cost and can be more useful for platelet transfusion decision-making. PLT-H is a novel method for platelet counting that offers higher accuracy, providing physicians with the ability to make better medical decisions, particularly in cases where values are low, or interference is present. As it does not require additional reagents, it is highly likely to replace PLT-I and become the mainstream method for platelet counting in the future.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138462152","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 : 2023-12-01Epub Date: 2023-12-05DOI: 10.1080/09537104.2023.2285446
Mila Kovacevic, Graziella Pompei, Vijay Kunadian
The older population represents a unique subset of patients due to a higher rate of comorbidities and risk factors, which can lead to a higher rate of ischemic and bleeding events. As a result, older adults are mainly underrepresented or excluded from randomized trials. Although the advancement in the percutaneous coronary intervention field with the development of new technologies, techniques, and potent antiplatelet therapy led to a reduction of ischemic risk, there is still a concern regarding bleeding hazards. Apart from the global utilization of less invasive trans-radial approach and proton pump inhibitors to reduce bleeding risk, proper tailoring of antiplatelet therapy in the older person is imperative. So far, several antiplatelet drugs have been introduced in different clinical scenarios, with dual antiplatelet therapy (combination of acetylsalicylic acid and P2Y12 inhibitor) recommended after percutaneous coronary intervention. The decision on the choice of antiplatelet drug and the DAPT duration is challenging and should be based on the relationship between ischemia and bleeding with the purpose of reducing ischemic events but not at the expense of increased bleeding complications. This is particularly important in the older population, where the evidence is obscure. The main objective of this review is to summarize the available evidence on contemporary antiplatelet therapy and different approaches of de-escalation strategies in older patients after percutaneous coronary intervention.
{"title":"Tailoring antiplatelet therapy in older patients with coronary artery disease.","authors":"Mila Kovacevic, Graziella Pompei, Vijay Kunadian","doi":"10.1080/09537104.2023.2285446","DOIUrl":"10.1080/09537104.2023.2285446","url":null,"abstract":"<p><p>The older population represents a unique subset of patients due to a higher rate of comorbidities and risk factors, which can lead to a higher rate of ischemic and bleeding events. As a result, older adults are mainly underrepresented or excluded from randomized trials. Although the advancement in the percutaneous coronary intervention field with the development of new technologies, techniques, and potent antiplatelet therapy led to a reduction of ischemic risk, there is still a concern regarding bleeding hazards. Apart from the global utilization of less invasive trans-radial approach and proton pump inhibitors to reduce bleeding risk, proper tailoring of antiplatelet therapy in the older person is imperative. So far, several antiplatelet drugs have been introduced in different clinical scenarios, with dual antiplatelet therapy (combination of acetylsalicylic acid and P2Y<sub>12</sub> inhibitor) recommended after percutaneous coronary intervention. The decision on the choice of antiplatelet drug and the DAPT duration is challenging and should be based on the relationship between ischemia and bleeding with the purpose of reducing ischemic events but not at the expense of increased bleeding complications. This is particularly important in the older population, where the evidence is obscure. The main objective of this review is to summarize the available evidence on contemporary antiplatelet therapy and different approaches of de-escalation strategies in older patients after percutaneous coronary intervention.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138482808","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 : 2023-12-01Epub Date: 2022-11-14DOI: 10.1080/09537104.2022.2139821
Talia Falcão Dalçóquio, Mayara Alves Dos Santos, Leandro Silva Alves, Flávia Bittar Brito Arantes, Larissa Ferreira-Santos, Maria Urbana Pinto Brandão Rondon, Remo Holanda M Furtado, Aline Gehlen Ferrari, Paulo Roberto Genestreti Rizzo, Rocio Salsoso, Andre Franci, Luciano Moreira Baracioli, Maria Janieire de Nazare Nunes Alves, Carlos Eduardo Negrão, José Carlos Nicolau
Exercise training (ET) can lower platelet reactivity in patients with cardiovascular risk factors. However, the effects of ET on platelet reactivity in higher-risk patients is unknown. The aim of this study was to evaluate the effects of ET on platelet reactivity in patients with recent myocardial infarction (MI). Ninety patients were randomly assigned 1 month post-MI to the intervention (patients submitted to a supervised ET program) or control group. All patients were on dual antiplatelet therapy (DAPT). Platelet reactivity by VerifyNow-P2Y12 (measured by P2Y12 reaction units - PRUs) test was determined at baseline and at the end of 14 ± 2 weeks of follow-up at rest (primary endpoint), and multiplate electrode aggregometry (MEA) adenosine diphosphate (ADP) and aspirin (ASPI) tests were performed immediately before and after the maximal cardiopulmonary exercise test (CPET) at the same time points (secondary endpoints). Sixty-five patients (mean age 58.9 ± 10 years; 73.8% men; 60% ST elevation MI) completed follow-up (control group, n = 31; intervention group, n = 34). At the end of the follow-up, the mean platelet reactivity was 172.8 ± 68.9 PRUs and 166.9 ± 65.1 PRUs for the control and intervention groups, respectively (p = .72). Platelet reactivity was significantly increased after the CPET compared to rest at the beginning and at the end of the 14-week follow-up (among the intervention groups) by the MEA-ADP and MEA-ASPI tests (p < .01 for all analyses). In post-MI patients on DAPT, 14 weeks of supervised ET did not reduce platelet reactivity. Moreover, platelet reactivity was increased after high-intensity exercise (ClinicalTrials.gov: NCT02958657; https://clinicaltrials.gov/ct2/show/NCT02958657).
{"title":"Effects of exercise on platelet reactivity after myocardial infarction: a randomized clinical trial.","authors":"Talia Falcão Dalçóquio, Mayara Alves Dos Santos, Leandro Silva Alves, Flávia Bittar Brito Arantes, Larissa Ferreira-Santos, Maria Urbana Pinto Brandão Rondon, Remo Holanda M Furtado, Aline Gehlen Ferrari, Paulo Roberto Genestreti Rizzo, Rocio Salsoso, Andre Franci, Luciano Moreira Baracioli, Maria Janieire de Nazare Nunes Alves, Carlos Eduardo Negrão, José Carlos Nicolau","doi":"10.1080/09537104.2022.2139821","DOIUrl":"10.1080/09537104.2022.2139821","url":null,"abstract":"<p><p>Exercise training (ET) can lower platelet reactivity in patients with cardiovascular risk factors. However, the effects of ET on platelet reactivity in higher-risk patients is unknown. The aim of this study was to evaluate the effects of ET on platelet reactivity in patients with recent myocardial infarction (MI). Ninety patients were randomly assigned 1 month post-MI to the intervention (patients submitted to a supervised ET program) or control group. All patients were on dual antiplatelet therapy (DAPT). Platelet reactivity by VerifyNow-P2Y<sub>12</sub> (measured by P2Y<sub>12</sub> reaction units - PRUs) test was determined at baseline and at the end of 14 ± 2 weeks of follow-up at rest (primary endpoint), and multiplate electrode aggregometry (MEA) adenosine diphosphate (ADP) and aspirin (ASPI) tests were performed immediately before and after the maximal cardiopulmonary exercise test (CPET) at the same time points (secondary endpoints). Sixty-five patients (mean age 58.9 ± 10 years; 73.8% men; 60% ST elevation MI) completed follow-up (control group, n = 31; intervention group, n = 34). At the end of the follow-up, the mean platelet reactivity was 172.8 ± 68.9 PRUs and 166.9 ± 65.1 PRUs for the control and intervention groups, respectively (p = .72). Platelet reactivity was significantly increased after the CPET compared to rest at the beginning and at the end of the 14-week follow-up (among the intervention groups) by the MEA-ADP and MEA-ASPI tests (p < .01 for all analyses). In post-MI patients on DAPT, 14 weeks of supervised ET did not reduce platelet reactivity. Moreover, platelet reactivity was increased after high-intensity exercise (ClinicalTrials.gov: NCT02958657; https://clinicaltrials.gov/ct2/show/NCT02958657).</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40474991","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 : 2023-12-01Epub Date: 2023-02-21DOI: 10.1080/09537104.2023.2170999
Adele Barlassina, Tomás José González-López, Nichola Cooper, Francesco Zaja
To establish pan-European consensus on tapering and discontinuing thrombopoietin receptor agonists (TPO-RAs) in patients with immune thrombocytopenia (ITP), we applied a three-step Delphi technique consisting of a one-to-one interview round and two online survey rounds. Three healthcare professionals (HCPs) from Italy, Spain, and the United Kingdom formed the Steering Committee (SC), which advised on study design, panelist selection, and survey development. A literature review also informed the development of the consensus statements. Likert scales were used to collect quantitative data on panelists' level of agreement. Twelve hematologists representing nine European countries assessed 121 statements spanning three categories: (1) patient selection; (2) tapering and discontinuation strategies; (3) post-discontinuation management. Consensus was reached on approximately half of the statements in each category (32.2%; 44.6%; 66%). Panelists agreed on patients' main selection criteria, patients' involvement in decision-making, tapering strategies, and follow-up criteria. Areas not reaching consensus were risk factors and predictors of successful discontinuation, monitoring intervals, and rates of successful discontinuation or relapse. This lack of consensus signals knowledge and practice gaps among European countries and suggests the need for the development of clinical practice guidelines that outline a pan-European, evidence-based approach to tapering and discontinuing TPO-RAs.
{"title":"European Delphi panel to build consensus on tapering and discontinuing thrombopoietin receptor agonists in immune thrombocytopenia.","authors":"Adele Barlassina, Tomás José González-López, Nichola Cooper, Francesco Zaja","doi":"10.1080/09537104.2023.2170999","DOIUrl":"10.1080/09537104.2023.2170999","url":null,"abstract":"<p><p>To establish pan-European consensus on tapering and discontinuing thrombopoietin receptor agonists (TPO-RAs) in patients with immune thrombocytopenia (ITP), we applied a three-step Delphi technique consisting of a one-to-one interview round and two online survey rounds. Three healthcare professionals (HCPs) from Italy, Spain, and the United Kingdom formed the Steering Committee (SC), which advised on study design, panelist selection, and survey development. A literature review also informed the development of the consensus statements. Likert scales were used to collect quantitative data on panelists' level of agreement. Twelve hematologists representing nine European countries assessed 121 statements spanning three categories: (1) patient selection; (2) tapering and discontinuation strategies; (3) post-discontinuation management. Consensus was reached on approximately half of the statements in each category (32.2%; 44.6%; 66%). Panelists agreed on patients' main selection criteria, patients' involvement in decision-making, tapering strategies, and follow-up criteria. Areas not reaching consensus were risk factors and predictors of successful discontinuation, monitoring intervals, and rates of successful discontinuation or relapse. This lack of consensus signals knowledge and practice gaps among European countries and suggests the need for the development of clinical practice guidelines that outline a pan-European, evidence-based approach to tapering and discontinuing TPO-RAs.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9348671","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}