2,292 results on '"platelet reactivity"'
Search Results
2. Pharmacodynamic Comparison of Two Aspirin Formulations in the Caribbean: The ARC Study.
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Seecheran, Naveen, McCallum, Penelope, Grimaldos, Kathryn, Ramcharan, Priya, Kawall, Jessica, Katwaroo, Arun, Seecheran, Valmiki, Jagdeo, Cathy-Lee, Rafeeq, Salma, Seecheran, Rajeev, Quert, Abel Leyva, Ali, Nafeesah, Peram, Lakshmipathi, Khan, Shari, Ali, Fareed, Motilal, Shastri, Bhagwandass, Neal, Giddings, Stanley, Ramlackhansingh, Anil, and Sandy, Sherry
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PLATELET aggregation inhibitors , *BODY surface area , *VOLUNTEER recruitment , *ASPIRIN , *BLOOD platelets - Abstract
Introduction: This prospective, single-arm, crossover pharmacodynamic study assessed the effect of Bayer® low-dose enteric-coated aspirin 81 mg tablets (LD EC-ASA) (Bayer AG, Leverkusen, North Rhine-Westphalia, Germany) compared to Vazalore® low-dose phospholipid-aspirin liquid-filled 81 mg capsules (LD PL-ASA) (PLx Pharma Inc., Sparta, NJ, USA) on platelet reactivity with respect to aspirin reaction units (ARU). Methods: Forty-seven healthy volunteers were recruited. Platelet function was evaluated with the VerifyNow™ ARU assay (Werfen, Bedford, MA, USA) and assessed post-initiation of Bayer® LD EC-ASA daily for 14 days, with a washout period of 28 days, followed by Vazalore® LD PL-ASA daily for 14 days, again followed by ARU testing. Results: Participants on LD EC-ASA had a mean ARU score of 426, with 19.1% of participants having an ARU > 550; patients on LD PL-ASA derived a mean ARU score of 435, with 14.9% achieving an ARU > 550. There were no significant differences in aspirin resistance (ARU > 550) according to the formulation (Bayer® LD EC-ASA vs. Vazalore® LD PL-ASA) used. Aspirin resistance was independent of ethnicity regardless of the formulation used. In addition, there were no significant associations between body surface area (BSA) and Bayer® LD EC-ASA ARU value (p value 0.788) or Vazalore® LD PL-ASA ARU value (p value 0.477). No patients experienced any serious adverse events or treatment-emergent adverse events. Conclusions: There were no significant differences in aspirin resistance between Bayer® LD EC-ASA and Vazalore® LD PL-ASA. This dedicated pharmacodynamic study could potentially be informative and applicable for Trinidadian patients on dual antiplatelet therapy (DAPT). Further studies are required to confirm these exploratory findings. Trial Registration: ClinicalTrials.gov identifier, NCT06228820, prospectively registered 1/18/2024. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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3. Impact of proton pump inhibitor use on clinical outcomes in East Asian patients receiving clopidogrel following drug-eluting stent implantation.
- Author
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Kim, Ju Hyeon, Hong, Soon Jun, Cha, Jung-Joon, Lim, Subin, Joo, Hyung Joon, Park, Jae Hyoung, Yu, Cheol Woong, Ahn, Tae Hoon, Jeong, Young-Hoon, Kim, Byeong-Keuk, Chang, Kiyuk, Park, Yongwhi, Song, Young Bin, Ahn, Sung Gyun, Suh, Jung-Won, Lee, Sang Yeub, Cho, Jung Rae, Her, Ae-Young, Kim, Hyo-Soo, and Kim, Moo Hyun
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EAST Asians , *PROTON pump inhibitors , *PLATELET aggregation inhibitors , *PERCUTANEOUS coronary intervention , *GASTROINTESTINAL hemorrhage , *DRUG-eluting stents - Abstract
Background: Concomitant use of clopidogrel and proton pump inhibitor (PPI) is common, but PPI may reduce the antiplatelet effects of clopidogrel in patients undergoing percutaneous coronary intervention (PCI). We evaluated the impact of PPI use on clinical outcomes in post-PCI patients, by incorporating P2Y12 reaction unit (PRU) and CYP2C19 genotyping results. Methods: From a multicenter registry of patients who underwent PCI with drug-eluting stent implantation and received clopidogrel-based dual antiplatelet therapy (DAPT), patients who were prescribed a PPI at the time of PCI (PPI users) were compared to those who were not (non-users). The primary outcome included all-cause death, myocardial infarction, stent thrombosis, or cerebrovascular accident at 12 months. Major bleeding (Bleeding Academic Research Consortium [BARC] types 3–5) and gastrointestinal (GI) bleeding (BARC types 3–5) were important secondary outcomes. The adjusted outcomes were compared using a 1:1 propensity-score (PS) matching and competing risk analysis. Results: Of 13,160 patients, 2,235 (17.0%) were prescribed PPI, with an average age of 65.4 years. PPI users had higher on-treatment PRU levels than non-users. After PS matching, the primary outcome occurred in 51 patients who were PPI users (cumulative incidence, 4.7%) and 41 patients who were non-users (cumulative incidence, 3.7%; log-rank p = 0.27). In carriers of both CYP2C19 loss-of-function alleles, PPI use was linked to an increased risk of the primary outcome (hazard ratio, 3.22; 95% confidence interval, 1.18–8.78). The incidence of major bleeding and GI bleeding (BARC types 3–5) was comparable between PPI users and non-users in the PS-matched cohort. Conclusions: In post-PCI patients receiving clopidogrel-based DAPT, PPI use was not linked to an increased risk of adverse cardiac and cerebrovascular events, but there was a small but significant increase in on-treatment PRU. Future research using a more individualized approach would further elucidate these interactions and guide evidence-based clinical practices. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Platelet-fibrin clot strength and platelet reactivity predicting cardiovascular events after percutaneous coronary interventions.
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Kwon, Osung, Ahn, Jong-Hwa, Koh, Jin-Sin, Park, Yongwhi, Hwang, Seok Jae, Tantry, Udaya S, Gurbel, Paul A, Hwang, Jin-Yong, and Jeong, Young-Hoon
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PERCUTANEOUS coronary intervention ,MYOCARDIAL infarction ,MAJOR adverse cardiovascular events ,BLOOD platelets ,FIBRINOLYTIC agents ,PROGNOSIS - Abstract
Background and Aims Platelet-fibrin clot strength (PFCS) is linked to major adverse cardiovascular event (MACE) risk. However, the association between PFCS and platelet reactivity and their prognostic implication remains uncertain in patients undergoing percutaneous coronary intervention (PCI). Methods In PCI-treated patients (n = 2512) from registry data from January 2010 to November 2018 in South Korea, PFCS using thromboelastography and platelet reactivity using VerifyNow were measured. High PFCS (PFCS
High ) was defined as thromboelastography maximal amplitude ≥ 68 mm, and high platelet reactivity (HPR) was defined as >208 P2Y12 reaction units. Patients were stratified into four groups according to maximal amplitude and P2Y12 reaction unit levels: (i) normal platelet reactivity (NPR)-PFCSNormal (31.8%), (ii) HPR-PFCSNormal (29.0%), (iii) NPR-PFCSHigh (18.1%), and (iv) HPR-PFCSHigh (21.1%). Major adverse cardiovascular event (all-cause death, myocardial infarction, or stroke) and major bleeding were followed up to 4 years. Results High platelet reactivity and PFCSHigh showed an additive effect for clinical outcomes (log-rank test, P <.001). Individuals with NPR-PFCSNormal , NPR-PFCSHigh , HPR-PFCSNormal , and HPR-PFCSHigh demonstrated MACE incidences of 7.5%, 12.6%, 13.4%, and 19.3%, respectively. The HPR-PFCSHigh group showed significantly higher risks of MACE compared with the NPR-PFCSNormal group [adjusted hazard ratio (HRadj ) 1.89; 95% confidence interval (CI) 1.23–2.91; P =.004] and the HPR-PFCSNormal group (HRadj 1.60; 95% CI 1.12–2.27; P =.009). Similar results were observed for all-cause death. Compared with HPR-PFCSNormal phenotype, NPR-PFCSNormal phenotype was associated with a higher risk of major bleeding (HRadj 3.12; 95% CI 1.30–7.69; P =.010). Conclusions In PCI patients, PFCS and platelet reactivity demonstrated important relationships in predicting clinical prognosis. Their combined assessment may enhance post-PCI risk stratification for personalized antithrombotic therapy. [ABSTRACT FROM AUTHOR]- Published
- 2024
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5. Impact of proton pump inhibitor use on clinical outcomes in East Asian patients receiving clopidogrel following drug-eluting stent implantation
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Ju Hyeon Kim, Soon Jun Hong, Jung-Joon Cha, Subin Lim, Hyung Joon Joo, Jae Hyoung Park, Cheol Woong Yu, Tae Hoon Ahn, Young-Hoon Jeong, Byeong-Keuk Kim, Kiyuk Chang, Yongwhi Park, Young Bin Song, Sung Gyun Ahn, Jung-Won Suh, Sang Yeub Lee, Jung Rae Cho, Ae-Young Her, Hyo-Soo Kim, Moo Hyun Kim, Eun-Seok Shin, and Do-Sun Lim
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Clopidogrel ,Proton pump inhibitor ,Platelet reactivity ,Poor metabolizer ,Myocardial infarction ,Bleeding ,Medicine - Abstract
Abstract Background Concomitant use of clopidogrel and proton pump inhibitor (PPI) is common, but PPI may reduce the antiplatelet effects of clopidogrel in patients undergoing percutaneous coronary intervention (PCI). We evaluated the impact of PPI use on clinical outcomes in post-PCI patients, by incorporating P2Y12 reaction unit (PRU) and CYP2C19 genotyping results. Methods From a multicenter registry of patients who underwent PCI with drug-eluting stent implantation and received clopidogrel-based dual antiplatelet therapy (DAPT), patients who were prescribed a PPI at the time of PCI (PPI users) were compared to those who were not (non-users). The primary outcome included all-cause death, myocardial infarction, stent thrombosis, or cerebrovascular accident at 12 months. Major bleeding (Bleeding Academic Research Consortium [BARC] types 3–5) and gastrointestinal (GI) bleeding (BARC types 3–5) were important secondary outcomes. The adjusted outcomes were compared using a 1:1 propensity-score (PS) matching and competing risk analysis. Results Of 13,160 patients, 2,235 (17.0%) were prescribed PPI, with an average age of 65.4 years. PPI users had higher on-treatment PRU levels than non-users. After PS matching, the primary outcome occurred in 51 patients who were PPI users (cumulative incidence, 4.7%) and 41 patients who were non-users (cumulative incidence, 3.7%; log-rank p = 0.27). In carriers of both CYP2C19 loss-of-function alleles, PPI use was linked to an increased risk of the primary outcome (hazard ratio, 3.22; 95% confidence interval, 1.18–8.78). The incidence of major bleeding and GI bleeding (BARC types 3–5) was comparable between PPI users and non-users in the PS-matched cohort. Conclusions In post-PCI patients receiving clopidogrel-based DAPT, PPI use was not linked to an increased risk of adverse cardiac and cerebrovascular events, but there was a small but significant increase in on-treatment PRU. Future research using a more individualized approach would further elucidate these interactions and guide evidence-based clinical practices.
- Published
- 2024
- Full Text
- View/download PDF
6. Pharmacodynamic Comparison of Two Aspirin Formulations in the Caribbean: The ARC Study
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Naveen Seecheran, Penelope McCallum, Kathryn Grimaldos, Priya Ramcharan, Jessica Kawall, Arun Katwaroo, Valmiki Seecheran, Cathy-Lee Jagdeo, Salma Rafeeq, Rajeev Seecheran, Abel Leyva Quert, Nafeesah Ali, Lakshmipathi Peram, Shari Khan, Fareed Ali, Shastri Motilal, Neal Bhagwandass, Stanley Giddings, Anil Ramlackhansingh, and Sherry Sandy
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Aspirin ,Aspirin resistance ,Bayer® ,Vazalore® ,Platelet reactivity ,VerifyNow™ ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Introduction This prospective, single-arm, crossover pharmacodynamic study assessed the effect of Bayer® low-dose enteric-coated aspirin 81 mg tablets (LD EC-ASA) (Bayer AG, Leverkusen, North Rhine-Westphalia, Germany) compared to Vazalore® low-dose phospholipid-aspirin liquid-filled 81 mg capsules (LD PL-ASA) (PLx Pharma Inc., Sparta, NJ, USA) on platelet reactivity with respect to aspirin reaction units (ARU). Methods Forty-seven healthy volunteers were recruited. Platelet function was evaluated with the VerifyNow™ ARU assay (Werfen, Bedford, MA, USA) and assessed post-initiation of Bayer® LD EC-ASA daily for 14 days, with a washout period of 28 days, followed by Vazalore® LD PL-ASA daily for 14 days, again followed by ARU testing. Results Participants on LD EC-ASA had a mean ARU score of 426, with 19.1% of participants having an ARU > 550; patients on LD PL-ASA derived a mean ARU score of 435, with 14.9% achieving an ARU > 550. There were no significant differences in aspirin resistance (ARU > 550) according to the formulation (Bayer® LD EC-ASA vs. Vazalore® LD PL-ASA) used. Aspirin resistance was independent of ethnicity regardless of the formulation used. In addition, there were no significant associations between body surface area (BSA) and Bayer® LD EC-ASA ARU value (p value 0.788) or Vazalore® LD PL-ASA ARU value (p value 0.477). No patients experienced any serious adverse events or treatment-emergent adverse events. Conclusions There were no significant differences in aspirin resistance between Bayer® LD EC-ASA and Vazalore® LD PL-ASA. This dedicated pharmacodynamic study could potentially be informative and applicable for Trinidadian patients on dual antiplatelet therapy (DAPT). Further studies are required to confirm these exploratory findings. Trial Registration ClinicalTrials.gov identifier, NCT06228820, prospectively registered 1/18/2024.
- Published
- 2024
- Full Text
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7. Platelet Reactivity With Fentanyl, Morphine, or no Narcotic
- Published
- 2023
8. Different association of atherogenic index of plasma with the risk of high platelet reactivity according to the presentation of acute myocardial infarction
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Ki-Bum Won, Hyeon Jeong Kim, Jun Hwan Cho, Sang Yup Lee, Ae-Young Her, Byeong-Keuk Kim, Hyung Joon Joo, Yongwhi Park, Kiyuk Chang, Young Bin Song, Sung Gyun Ahn, Jung-Won Suh, Jung Rae Cho, Hyo-Soo Kim, Moo Hyun Kim, Do-Sun Lim, Sang-Wook Kim, Young-Hoon Jeong, and Eun-Seok Shin
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Plasma atherogenicity ,Platelet reactivity ,Acute myocardial infarction ,Prognosis ,Percutaneous coronary intervention ,Drug-eluting stents ,Medicine ,Science - Abstract
Abstract This study evaluated the association of atherogenic index of plasma (AIP) with platelet reactivity and clinical outcomes according to acute myocardial infarction (AMI). The composite of 3-year adverse outcomes of all-cause death, myocardial infarction, and cerebrovascular accident was evaluated in 10,735 patients after successful percutaneous coronary intervention with drug-eluting stents. AIP was defined as the base 10 logarithm of the ratio of triglyceride to high-density lipoprotein cholesterol concentration. High platelet reactivity (HPR) was defined as ≥ 252 P2Y12 reactivity unit. An increase of AIP (per-0.1 unit) was related to the decreased risk of HPR [odds ratio (OR) 0.97, 95% confidence interval (CI) 0.96–0.99; P = 0.001] in non-AMI patients, not in AMI patients (OR 0.98, 95% CI 0.96–1.01; P = 0.138). The HPR was associated with the increased risk of composite outcomes in both non-AMI and AMI patients (all-P
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- 2024
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9. Different association of atherogenic index of plasma with the risk of high platelet reactivity according to the presentation of acute myocardial infarction.
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Won, Ki-Bum, Kim, Hyeon Jeong, Cho, Jun Hwan, Lee, Sang Yup, Her, Ae-Young, Kim, Byeong-Keuk, Joo, Hyung Joon, Park, Yongwhi, Chang, Kiyuk, Song, Young Bin, Ahn, Sung Gyun, Suh, Jung-Won, Cho, Jung Rae, Kim, Hyo-Soo, Kim, Moo Hyun, Lim, Do-Sun, Kim, Sang-Wook, Jeong, Young-Hoon, and Shin, Eun-Seok
- Abstract
This study evaluated the association of atherogenic index of plasma (AIP) with platelet reactivity and clinical outcomes according to acute myocardial infarction (AMI). The composite of 3-year adverse outcomes of all-cause death, myocardial infarction, and cerebrovascular accident was evaluated in 10,735 patients after successful percutaneous coronary intervention with drug-eluting stents. AIP was defined as the base 10 logarithm of the ratio of triglyceride to high-density lipoprotein cholesterol concentration. High platelet reactivity (HPR) was defined as ≥ 252 P2Y12 reactivity unit. An increase of AIP (per-0.1 unit) was related to the decreased risk of HPR [odds ratio (OR) 0.97, 95% confidence interval (CI) 0.96–0.99; P = 0.001] in non-AMI patients, not in AMI patients (OR 0.98, 95% CI 0.96–1.01; P = 0.138). The HPR was associated with the increased risk of composite outcomes in both non-AMI and AMI patients (all-P < 0.05). AIP levels were not independently associated with the risk of composite outcomes in both patients with non-AMI and AMI. In conclusion, an inverse association between AIP and the risk of HPR was observed in patients with non-AMI. This suggests that the association between plasma atherogenicity and platelet reactivity may play a substantial role in the development of AMI. Trial registration: NCT04734028. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Body Weight Adjusted Clopidogrel Treatment in Patients With CORonary Artery Disease (BW-ACCORD)
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St. Antonius hospital Onderzoeksfonds, Ace pharmaceuticals, Allgen pharmaceuticals, and Jurriën M. ten Berg, MD, PhD, Prof. dr.
- Published
- 2023
11. The rapid change of shear rate gradient is beneficial to platelet activation
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Tiancong Zhang, Ling Liu, Xiaojing Huang, Xuemei Gao, Xuanrong Huan, Cui He, and Yuan Li
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Cardiovascular disease ,microfluidic chip ,PI3K/AKT signal pathway ,platelet reactivity ,shear gradient change rate ,von Willebrand factor activity ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
AbstractFluid shear plays a key role in hemostasis and thrombosis, and the purpose of this study was to investigate the effect of shear gradient change rate (SGCR) on platelet reactivity and von Willebrand factor (vWF) activity and its mechanism. In this study, we developed a set of microfluidic chips capable of generating different shear gradients and simulated the shear rate distribution in the flow field by COMSOL Multiphysics software. Molecular markers of platelet activation (P-selectin, activated GPIIb/IIIa, phosphatidylserine exposure, and monocyte-platelet aggregate formation) were analyzed by flow cytometry. Platelet aggregation induced by shear gradient was studied by a microfluidic experimental platform, and plasma vWF ristocetin cofactor (vWF: RCO) activity was investigated by flow cytometry. The expression of p-Akt was studied by Western blotting. The results showed that the faster the SGCR, the higher the expression of platelet p-Akt, and the stronger the platelet reactivity and vWF activity. This indicates that fluid shear stress can activate platelets and vWF in a shear gradient-dependent manner through the PI3K/AKT signal pathway, and the faster the SGCR, the more significant the activation effect.
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- 2024
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12. Remote intensive management to improve antiplatelet adherence in acute myocardial infarction: a secondary analysis of the randomized controlled IMMACULATE trial.
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Sim, Hui Wen, Koh, Karen W. L., Poh, Sock-Cheng, Chan, Siew Pang, Marchesseau, Stephanie, Singh, Devinder, Han, Yiying, Ng, Faclin, Lim, Eleanor, Prabath, Joseph F., Lee, Chi-Hang, Chen, Ruth, Carvalho, Leonardo, Tan, Sock-Hwee, Loh, Joshua P. Y., Tan, Jack W. C., Kuwelker, Karishma, Amanullah, R. M., Chin, Chee-Tang, and Yip, James W. L.
- Abstract
This study aim to investigate if remote intensive coaching for the first 6 months post-AMI will improve adherence to the twice-a-day antiplatelet medication, ticagrelor. Between July 8, 2015, to March 29, 2019, AMI patients were randomly assigned to remote intensive management (RIM) or standard care (SC). RIM participants underwent 6 months of weekly then two-weekly consultations to review medication side effects and medication adherence coaching by a centralized nurse practitioner team, whereas SC participants received usual cardiologist face-to-face consultations. Adherence to ticagrelor were determined using pill counting and serial platelet reactivity measurements for 12 months. A total of 149 (49.5%) of participants were randomized to RIM and 152 (50.5%) to SC. Adherence to ticagrelor was similar between RIM and SC group at 1 month (94.4 ± 0.7% vs. 93.6±14.7%, p = 0.537), 6 months (91.0±14.6% vs. 90.6±14.8%, p = 0.832) and 12 months (87.4±17.0% vs. 89.8±12.5%, p = 0.688). There was also no significant difference in platelet reactivity between the RIM and SC groups at 1 month (251AU*min [212–328] vs. 267AU*min [208–351], p = 0.399), 6 months (239AU*min [165–308] vs. 235AU*min [171–346], p = 0.610) and 12 months (249AU*min [177–432] vs. 259AU*min [182–360], p = 0.678). Sensitivity analysis did not demonstrate any association of ticagrelor adherence with bleeding events and major adverse cardiovascular events. RIM, comprising 6 months of intensive coaching by nurse practitioners, did not improve adherence to the twice-a-day medication ticagrelor compared with SC among patients with AMI. A gradual decline in ticagrelor adherence over 12 months was observed despite 6 months of intensive coaching. [ABSTRACT FROM AUTHOR]
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- 2024
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13. Platelet Reactivity in the Exacerbation of Psoriasis.
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Adamski, Piotr, Adamska, Urszula, Buszko, Katarzyna, Sikora, Joanna, and Czajkowski, Rafał
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BLOOD platelet aggregation , *BLOOD platelets , *PSORIASIS , *PLATELET count , *PLATELET function tests - Abstract
Background: Psoriasis is a chronic, inflammatory, immune-mediated disease with a specific cutaneous presentation. Increased platelet aggregation has been observed in patients with extensive psoriatic lesions. The aim of this study was to evaluate the clinical factors affecting platelet reactivity in patients with an exacerbation of psoriasis. Methods: This was a prospective, single-center, observational study, enrolling patients hospitalized for an aggravation of psoriasis. Enrolled patients underwent single platelet function testing with light transmission aggregometry on the first morning of hospitalization. Results: 120 patients were enrolled in the study. Of the compared subgroups, women had higher maximal platelet aggregation (MPA) than men (77% vs. 72%; p = 0.03), and those with BMIs < 25 kg/m2 showed higher platelet reactivity compared to subjects with BMIs ≥ 25 kg/m2 (75% vs. 73%; p = 0.02). There was a positive correlation between MPA and platelet count (r = 0.27; p < 0.01), as well as C-reactive protein concentration (r = 0.20; p = 0.03), while a negative correlation was observed with total cholesterol (r = −0.24; p = 0.01) and triglycerides (r = −0.30; p < 0.01). A two-step analysis based on multidimensional models with random effects revealed that every increase in the platelet count by 103/μL led to an increase in MPA by 0.07% (R2 = 0.07; p < 0.01), and an increase in triglycerides' concentration by 1 mg/dL was related to a reduction in MPA by 0.05% (R2 = 0.07; p < 0.01). Conclusions: The increased platelet reactivity observed in patients with psoriasis appears to be multifactorial and related to several clinical and laboratory features. Further research is warranted to put these findings into a clinical perspective. [ABSTRACT FROM AUTHOR]
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- 2024
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14. A novel machine learning model to predict high on-treatment platelet reactivity on clopidogrel in Asian patients after percutaneous coronary intervention.
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Ding, Lan-Ping, Li, Ping, Yang, Li-Rong, Pan, Mang-Mang, Zhou, Min, Zhang, Chi, Yan, Yi-Dan, Lin, Hou-Wen, Li, Xiao-Ye, and Gu, Zhi-Chun
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MACHINE learning ,PERCUTANEOUS coronary intervention ,ASIANS ,RECEIVER operating characteristic curves ,CLOPIDOGREL - Abstract
Background: Various genetic and nongenetic variables influence the high on-treatment platelet reactivity (HTPR) in patients taking clopidogrel. Aim: This study aimed to develop a novel machine learning (ML) model to predict HTPR in Chinese patients after percutaneous coronary intervention (PCI). Method: This cohort study collected information on 507 patients taking clopidogrel. Data were randomly divided into a training set (90%) and a testing set (10%). Nine candidate Machine learning (ML) models and multiple logistic regression (LR) analysis were developed on the training set. Their performance was assessed according to the area under the receiver operating characteristic curve, precision, recall, F1 score, and accuracy on the test set. Model interpretations were generated using importance scores by transforming model variables into scaled features and representing in radar plots. Finally, we established a prediction platform for the prediction of HTPR. Results: A total of 461 patients (HTPR rate: 19.52%) were enrolled in building the prediction model for HTPR. The XGBoost model had an optimized performance, with an AUC of 0.82, a precision of 0.80, a recall of 0.44, an F1 score of 0.57, and an accuracy of 0.87, which was superior to those of LR. Furthermore, the XGBoost method identified 7 main predictive variables. To facilitate the application of the model, we established an XGBoost prediction platform consisting of 7 variables and all variables for the HTPR prediction. Conclusion: A ML-based approach, such as XGBoost, showed optimum performance and might help predict HTPR on clopidogrel after PCI and guide clinical decision-making. Further validated studies will strengthen this finding. [ABSTRACT FROM AUTHOR]
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- 2024
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15. Platelet microRNAs as Potential Novel Biomarkers for Antiplatelet Therapy with P2Y 12 Inhibitors and Their Association with Platelet Function.
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Gumiężna, Karolina, Bednarek, Adrian, Sygitowicz, Grażyna, Maciejak-Jastrzębska, Agata, Baruś, Piotr, Hunia, Jaromir, Klimczak-Tomaniak, Dominika, Kochman, Janusz, Grabowski, Marcin, and Tomaniak, Mariusz
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PRASUGREL , *PLATELET aggregation inhibitors , *BLOOD platelets , *ACUTE coronary syndrome , *PERCUTANEOUS coronary intervention , *MICRORNA - Abstract
Introduction: Patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) require dual antiplatelet therapy (DAPT). However, the response to treatment can vary considerably. Certain platelet microRNAs (miRs) are suspected to predict DAPT response and influence platelet function. This study aimed to analyze selected miRs' expressions and compare them among patients treated with different P2Y12 inhibitors while assessing their association with platelet activity and turnover parameters. Materials and methods: We recruited 79 ACS patients post-PCI treated with clopidogrel, ticagrelor, or prasugrel, along with 18 healthy volunteers. Expression levels of miR-126-3p, miR223-3p, miR-21-5p, miR-197-3p, and miR-24-3p, as well as immature platelet fraction (IPF) and ADP-induced platelet reactivity, were measured and compared between groups. Results: Analyses revealed significantly lower expressions of miR-126-3p, miR-223-3p, miR-21-5p, and miR-197-3p in patients treated with ticagrelor, compared to clopidogrel (fold changes from −1.43 to −1.27, p-values from 0.028 to 0.048). Positive correlations were observed between platelet function and the expressions of miR-223-3p (r = 0.400, p = 0.019) and miR-21-5p (r = 0.423, p = 0.013) in patients treated with potent drugs. Additionally, miR-24-3p (r = 0.411, p = 0.012) and miR-197-3p (r = 0.333, p = 0.044) showed correlations with IPF. Conclusions: The identified platelet miRs hold potential as biomarkers for antiplatelet therapy. (ClinicalTrials.gov number, NCT06177587). [ABSTRACT FROM AUTHOR]
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- 2024
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16. Association of Age‐ and Body Mass Index‐Stratified High On‐Treatment Platelet Reactivity With Coronary Intervention Outcomes in East Asian Patients
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Jung‐Joon Cha, Seung‐Jun Lee, Jae Hyoung Park, Soon Jun Hong, Tae Hoon Ahn, Kiyuk Chang, Yongwhi Park, Young Bin Song, Sung Gyun Ahn, Jung‐Won Suh, Sang Yeub Lee, Jung Rae Cho, Ae‐Young Her, Young‐Hoon Jeong, Hyo‐Soo Kim, Moo Hyun Kim, Eun‐Seok Shin, Byeong‐Keuk Kim, and Do‐Sun Lim
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age ,body mass index ,clinical outcomes ,P2Y12 inhibitors ,percutaneous coronary intervention ,platelet reactivity ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Although age and body mass index (BMI) significantly affect platelet reactivity units and clinical outcomes after percutaneous coronary intervention, there are limited data on the relationship between high on‐treatment platelet reactivity (HPR) and clinical outcomes on age and BMI differences. Thus, we investigated the association of HPR with clinical outcomes according to age and BMI. Methods and Results The study analyzed 11 714 patients who underwent platelet function tests after percutaneous coronary intervention. The primary end point was the occurrence of major adverse cardiac and cerebrovascular events (MACCEs), whereas the secondary end point was major bleeding. HPR was defined as platelet reactivity units ≥252. Patients were categorized by age (22.6 kg/m2). Patients 22.6 kg/m2 had increases in MACCEs (adjusted HR, 1.387 [95% CI, 1.140–1.688]; P=0.001). No differences were shown in major bleeding. Conclusions HPR was linked to an increase in MACCEs or a decrease in major bleeding in patients after percutaneous coronary intervention, depending on age and BMI. This study is the first to observe that clinical outcomes in patients with HPR after percutaneous coronary intervention may vary based on age and BMI. Because the study is observational, the results should be viewed as hypothesis generating and emphasize the need for randomized clinical trials.
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- 2024
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17. Diabetes type 2: relationships between lysosomal exocytosis of circulating normal-sized platelets and in vitro ɑ-thrombin-evoked platelet responses
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Maria Edvardsson, Magnus Oweling, and Petter Järemo
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Annexin V ,αIIbβ3 activity ,lysosomal-associated membrane protein 1 ,platelets ,platelet reactivity ,Medicine - Abstract
AbstractBackground/objective Type 2 diabetes is a major risk factor for atherosclerotic disease. It is well agreed that the reactivity of diabetic platelets is increased but how platelet reactivity regulates is unknown. In our laboratory, density separated platelets have been investigated extensively and high- and low-density platelets circulate in an activated state. The density distribution of circulating platelets is altered in diabetes type 2 as well. We hypothesize that such platelets modify whole blood (WB) in vitro α-thrombin-evoked (10 μM/mL) activity in type 2 diabetes. Thus, the study aims to identify features of circulating normal-sized density subpopulations affecting whole blood (WB) platelet reactivity in type 2 diabetes.Patients and methods Patients with type 2 diabetes (n = 16) were enrolled. Their normal-sized platelets were divided into density subfractions (n = 16) using continuous polyvinylpyrrolidone-coated silica (Percoll™) gradients (density span, 1.090–1.040 kg/L) containing prostaglandin E1. The proportions (%) of such density-separated platelets expressing lysosomal-associated membrane protein 1 (LAMP-1) were analyzed using a flow cytometer. Further, determinations of WB ɑ-thrombin-evoked (10 U/mL) surface LAMP-1 (an assessment of lysosomal release), the fibrinogen (αIIbβ3) receptor activity, annexin V (binds to exposed membrane phosphatidylserine), and mitochondrial transmembrane potentials (an estimate of organelle integrity) were performed. Surface LAMP-1 expressions of individual normal-sized platelet density subpopulations were stratified into equal-sized groups (n = 2) depending on reactivity, as judged from the ɑ-thrombin-induced WB activity markers.Results With some exceptions, the proportion of normal-sized circulating platelets showing spontaneous LAMP-1 was strongly associated with WB ɑ-thrombin-evoked (10 U/mL) surface LAMP-1 and αIIbβ3 receptor activity. LAMP-1-expressing normal-sized platelets also displayed inverse associations with WB ɑ-thrombin-induced surface annexin V and mitochondrial damage, which are features of procoagulant platelets.Conclusions From the current descriptive work only involving type 2 diabetes, it is impossible to judge whether the findings are features of the disease or if they occur in healthy individuals as well. However, the study describes LAMP-1 expressing subpopulations of circulating normal-sized platelets that associate with WB α-thrombin (10 U/mL) responses in vitro. Increased proportions of such platelets induced lysosomal release and αIIbβ3 receptor activity, whereas lower proportions promoted WB agonist-induced procoagulant platelet creation. It is to hypothesize that the new described regulatory mechanism could in the future offer a possibility to influence platelet behavior in type 2 diabetes.Key messagesLysosomal exocytosis of circulating platelets influences reactivity, as determined by agonist-induced platelet reactions in vitroThus, the low release of lysosomes by normal-sized platelets in vivo increases agonist-evoked procoagulant platelet production.Higher lysosomal exocytosis of circulating normal-sized platelets promotes platelet aggregation and secretion.
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- 2023
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18. Integrating platelet reactivity in the age, creatinine and ejection fraction score to predict clinical outcomes following percutaneous coronary intervention in patients with chronic coronary syndrome: the PR-ACEF score
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Paolucci, Luca, Mangiacapra, Fabio, Viscusi, Michele Mattia, Sergio, Sara, Bressi, Edoardo, Colaiori, Iginio, Ricottini, Elisabetta, Cavallari, Ilaria, Nusca, Annunziata, Melfi, Rosetta, Ussia, Gian Paolo, and Grigioni, Francesco
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- 2024
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19. Effects of exercise on platelet reactivity after myocardial infarction: a randomized clinical trial.
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Falcão Dalçóquio, Talia, Alves dos Santos, Mayara, Silva Alves, Leandro, Brito Arantes, Flávia Bittar, Ferreira-Santos, Larissa, Pinto Brandão Rondon, Maria Urbana, Furtado, Remo Holanda M., Ferrari, Aline Gehlen, Rizzo, Paulo Roberto Genestreti, Salsoso, Rocio, Franci, Andre, Moreira Baracioli, Luciano, de Nazare Nunes Alves, Maria Janieire, Eduardo Negrão, Carlos, and Carlos Nicolau, José
- Subjects
- *
MYOCARDIAL infarction , *CLINICAL trials , *BLOOD platelets , *EXERCISE tests , *CARDIOVASCULAR diseases risk factors , *ADENOSINE diphosphate - Abstract
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 highintensity exercise (ClinicalTrials.gov: NCT02958657; https://clinicaltrials.gov/ct2/show/NCT02958657). [ABSTRACT FROM AUTHOR]
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- 2023
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20. Diabetes type 2: relationships between lysosomal exocytosis of circulating normal-sized platelets and in vitro ɑ-thrombin-evoked platelet responses.
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Edvardsson, Maria, Oweling, Magnus, and Järemo, Petter
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TYPE 2 diabetes ,BLOOD platelets ,BLOOD platelet aggregation ,EXOCYTOSIS ,MEMBRANE potential - Abstract
Type 2 diabetes is a major risk factor for atherosclerotic disease. It is well agreed that the reactivity of diabetic platelets is increased but how platelet reactivity regulates is unknown. In our laboratory, density separated platelets have been investigated extensively and high- and low-density platelets circulate in an activated state. The density distribution of circulating platelets is altered in diabetes type 2 as well. We hypothesize that such platelets modify whole blood (WB) in vitro α-thrombin-evoked (10 μM/mL) activity in type 2 diabetes. Thus, the study aims to identify features of circulating normal-sized density subpopulations affecting whole blood (WB) platelet reactivity in type 2 diabetes. Patients with type 2 diabetes (n = 16) were enrolled. Their normal-sized platelets were divided into density subfractions (n = 16) using continuous polyvinylpyrrolidone-coated silica (Percoll™) gradients (density span, 1.090–1.040 kg/L) containing prostaglandin E
1 . The proportions (%) of such density-separated platelets expressing lysosomal-associated membrane protein 1 (LAMP-1) were analyzed using a flow cytometer. Further, determinations of WB ɑ-thrombin-evoked (10 U/mL) surface LAMP-1 (an assessment of lysosomal release), the fibrinogen (αIIb β3) receptor activity, annexin V (binds to exposed membrane phosphatidylserine), and mitochondrial transmembrane potentials (an estimate of organelle integrity) were performed. Surface LAMP-1 expressions of individual normal-sized platelet density subpopulations were stratified into equal-sized groups (n = 2) depending on reactivity, as judged from the ɑ-thrombin-induced WB activity markers. With some exceptions, the proportion of normal-sized circulating platelets showing spontaneous LAMP-1 was strongly associated with WB ɑ-thrombin-evoked (10 U/mL) surface LAMP-1 and αIIb β3 receptor activity. LAMP-1-expressing normal-sized platelets also displayed inverse associations with WB ɑ-thrombin-induced surface annexin V and mitochondrial damage, which are features of procoagulant platelets. From the current descriptive work only involving type 2 diabetes, it is impossible to judge whether the findings are features of the disease or if they occur in healthy individuals as well. However, the study describes LAMP-1 expressing subpopulations of circulating normal-sized platelets that associate with WB α-thrombin (10 U/mL) responses in vitro. Increased proportions of such platelets induced lysosomal release and αIIb β3 receptor activity, whereas lower proportions promoted WB agonist-induced procoagulant platelet creation. It is to hypothesize that the new described regulatory mechanism could in the future offer a possibility to influence platelet behavior in type 2 diabetes. Lysosomal exocytosis of circulating platelets influences reactivity, as determined by agonist-induced platelet reactions in vitro Thus, the low release of lysosomes by normal-sized platelets in vivo increases agonist-evoked procoagulant platelet production. Higher lysosomal exocytosis of circulating normal-sized platelets promotes platelet aggregation and secretion. [ABSTRACT FROM AUTHOR]- Published
- 2023
- Full Text
- View/download PDF
21. Immature platelet fraction and immature platelet count as novel biomarkers of elevated platelet reactivity in NSTE-ACS patients receiving dual antiplatelet therapy.
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Gumiężna, Karolina, Bednarek, Adrian, Sygitowicz, Grażyna, Baruś, Piotr, Wiśniewska, Agnieszka, Klimczak-Tomaniak, Dominika, Kochman, Janusz, Opolski, Grzegorz, Grabowski, Marcin, and Tomaniak, Mariusz
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PLATELET count ,PLATELET aggregation inhibitors ,BLOOD platelets ,ACUTE coronary syndrome ,PERCUTANEOUS coronary intervention - Abstract
Background. Antiplatelet therapy is the cornerstone of treatment for patients presenting with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI). Some patients may not respond to such therapy adequately, which is associated with a greater risk of ischemic events. Reticulated platelets are the youngest, largest, and most active platelet subtype. They have been initially shown to be associated with an increased risk of cardiovascular (CV) events and increased platelet activity. Objectives. The aim of the presented study was to evaluate whether the immature platelet fraction (IPF) reflects the response to antiplatelet treatment in invasively managed ACS patients. Materials and methods. This prospective study enrolled ACS patients treated with PCI and dual antiplatelet therapy (DAPT) comprising acetylsalicylic acid (ASA) and clopidogrel or ticagrelor. In all patients, venous blood was collected within 24 h after the procedure. Platelet parameters were measured, including IPF using the Sysmex hematological analyzer and adenosine diphosphate (ADP)-induced platelet reactivity using the Multiplate® Analyzer. Results. A total of 108 patients were enrolled, including 62 with ST-segment elevation ACS (STE-ACS) and 46 with non-ST-segment elevation ACS (NSTE-ACS). Of them, 20.4% had diabetes mellitus, 26.9% had a history of MI and 59.2% of smoking. Spearman's correlation analysis demonstrated that higher IPF and immature platelet count (IPC) values are associated with increased ADP-induced platelet reactivity (respectively: rho = 0.387, 95% confidence interval (95% CI): 0.101-0.615, p = 0.008; and rho = 0.458, 95% CI: 0.185-0.666, p = 0.001) in NSTE-ACS but not in STE-ACS patients. Conclusions. Immature platelet count and IPF may be valuable markers of platelet activity in patients with NSTE-ACS treated invasively and receiving DAPT (ClinicalTrials.gov No. NCT06177587). [ABSTRACT FROM AUTHOR]
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- 2023
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22. Platelets as Potential Non-Traditional Cardiovascular Risk Factor—Analysis Performed in Healthy Donors.
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Szymańska, Patrycja, Luzak, Bogusława, Siarkiewicz, Przemysław, and Golański, Jacek
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CARDIOVASCULAR diseases risk factors , *BLOOD platelet aggregation , *LDL cholesterol , *REACTIVE oxygen species , *BODY mass index , *BLOOD platelets - Abstract
Abnormal lipid profile, increased glucose level, and elevated body weight are traditional cardiometabolic risk factors; however, the role of platelets in the development of cardiovascular disease (CVD) is increasingly being highlighted. The aim of this study was to select platelet-related parameters (non-genetic molecular and routine laboratory measurements) that may be associated with increased cardiovascular risk among healthy populations. We evaluated the level of platelet indices, platelet-based inflammatory markers, platelet reactivity parameters, and platelet reactive oxygen species (ROS) generation in relation to selected cardiometabolic risk factors. We noted the association between total cholesterol and LDL cholesterol with platelet aggregation and platelet ROS generation. We found the relationship between triglycerides, glucose, and body mass index with the relatively new multi-inflammatory indices (MII-1 and MII-3). Moreover, we noticed that the mean platelet volume-to-lymphocyte ratio in healthy subjects is not a good source of information about platelets and inflammation. We also highlighted that platelet-to-HDL-cholesterol ratio may be a promising prognostic cardiometabolic indicator. The association between platelet-related (especially molecular) and cardiometabolic parameters requires further research. However, the goal of this study was to shed light on the consideration of platelets as a non-traditional cardiovascular risk factor and a crucial element in identifying individuals at high-risk of developing CVD in the future. [ABSTRACT FROM AUTHOR]
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- 2023
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23. Association of lipoprotein(a) with intrinsic and on-clopidogrel platelet reactivity
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Kille, Alexander, Nührenberg, Thomas, Franke, Kilian, Valina, Christian M, Leibundgut, Gregor, Tsimikas, Sotirios, Neumann, Franz-Josef, and Hochholzer, Willibald
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Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Clinical Research ,Heart Disease ,Heart Disease - Coronary Heart Disease ,Cardiovascular ,Atherosclerosis ,Blood Platelets ,Clopidogrel ,Humans ,Lipoprotein(a) ,Percutaneous Coronary Intervention ,Platelet Aggregation ,Platelet Aggregation Inhibitors ,Platelet Function Tests ,Ticagrelor ,Ticlopidine ,Platelet reactivity ,Dual antiplatelet therapy ,Coronary arterial disease ,Percutaneous coronary intervention ,Riscfactor ,Clinical Sciences ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
Lipoprotein(a) [Lp(a)] is an independent, genetically determined, and causal risk factor for cardiovascular disease. Laboratory data have suggested an interaction of Lp(a) with platelet function, potentially caused by its interaction with platelet receptors. So far, the potential association of Lp(a) with platelet activation and reactivity has not been proven in larger clinical cohorts. This study analyzed intrinsic platelet reactivity before loading with clopidogrel 600 mg and on-treatment platelet reactivity tested 24 h following loading in patients undergoing elective coronary angiography. Platelet reactivity was tested by optical aggregometry following stimulation with collagen or adenosine diphosphate as well as by flow cytometry. Lp(a) levels were directly measured in all patients from fresh samples. The present analysis included 1912 patients. Lp(a) levels ranged between 0 and 332 mg/dl. There was a significant association of rising levels of Lp(a) with a higher prevalence of a history of ischemic heart disease (p
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- 2022
24. Diabetes and Thrombosis
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Schneider, David J., Toth, Peter P., Series Editor, Johnstone, Michael, editor, and Veves, Aristidis, editor
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- 2023
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25. Implication of diabetic status on platelet reactivity and clinical outcomes after drug-eluting stent implantation: results from the PTRG-DES consortium
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Ki-Hyun Jeon, Young-Hoon Jeong, In-Ho Chae, Byeong-Keuk Kim, Hyung Joon Joo, Kiyuk Chang, Yongwhi Park, Young Bin Song, Sung Gyun Ahn, Sang Yeub Lee, Jung Rae Cho, Ae-Young Her, Hyo-Soo Kim, Moo Hyun Kim, Do-Sun Lim, Eun-Seok Shin, Jung-Won Suh, and On Behalf of the PTRG-DES Consortium Investigators
- Subjects
Platelet reactivity ,Diabetes mellitus ,Stenting ,Hemoglobin A1c ,Insulin ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Background Diabetes mellitus (DM) is associated with thrombogenicity, clinically manifested with atherothrombotic events after percutaneous cutaneous intervention (PCI). This study aimed to investigate association between DM status and platelet reactivity, and their prognostic implication in PCI-treated patients. Methods The Platelet function and genoType-Related long-term Prognosis-Platelet Function Test (PTRG-PFT) cohort was established to determine the linkage of platelet function test (PFT) with long-term prognosis during dual antiplatelet therapy including clopidogrel in patients treated with drug-eluting stent (DES). We assessed platelet reactivity using VerifyNow and ‘high platelet reactivity (HPR)’ was defined as ≥ 252 P2Y12 reaction unit (PRU). Major adverse cardiac and cerebrovascular event (MACCE) was a composite of all-cause death, myocardial infarction, stent thrombosis or stroke. Results Between July 2003 and Aug 2018, DES-treated patients with available PFT were enrolled (n = 11,714). Diabetic patients demonstrated significant higher levels of platelet reactivity (DM vs. non-DM: 225.7 ± 77.5 vs. 213.6 ± 79.1 PRU, P
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- 2023
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26. Ticagrelor and Clopidogrel on Platelet Effects in Chinese Patients With Stable Coronary Artery Disease
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Yue LI, Professor
- Published
- 2022
27. Platelets and the Atherosclerotic Process: An Overview of New Markers of Platelet Activation and Reactivity, and Their Implications in Primary and Secondary Prevention.
- Author
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Nardin, Matteo, Verdoia, Monica, Cao, Davide, Nardin, Simone, Kedhi, Elvin, Galasso, Gennaro, van 't Hof, Arnoud W. J., Condorelli, Gianluigi, and De Luca, Giuseppe
- Subjects
- *
BLOOD platelet activation , *SECONDARY prevention , *BLOOD platelets , *CORONARY artery disease , *CORONARY arteries - Abstract
The key role played by platelets in the atherosclerosis physiopathology, especially in the acute setting, is ascertained: they are the main actors during thrombus formation and, thus, one of the major investigated elements related to atherothrombotic process involving coronary arteries. Platelets have been studied from different points of view, according with the technology advances and the improvement in the hemostasis knowledge achieved in the last years. Morphology and reactivity constitute the first aspects investigated related to platelets with a significant body of evidence published linking a number of their values and markers to coronary artery disease and cardiovascular events. Recently, the impact of genetics on platelet activation has been explored with promising findings as additional instrument for patient risk stratification; however, this deserves further confirmations. Moreover, the interplay between immune system and platelets has been partially elucidated in the last years, providing intriguing elements that will be basic components for future research to better understand platelet regulation and improve cardiovascular outcome of patients. [ABSTRACT FROM AUTHOR]
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- 2023
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28. Implication of diabetic status on platelet reactivity and clinical outcomes after drug-eluting stent implantation: results from the PTRG-DES consortium.
- Author
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Jeon, Ki-Hyun, Jeong, Young-Hoon, Chae, In-Ho, Kim, Byeong-Keuk, Joo, Hyung Joon, Chang, Kiyuk, Park, Yongwhi, Song, Young Bin, Ahn, Sung Gyun, Lee, Sang Yeub, Cho, Jung Rae, Her, Ae-Young, Kim, Hyo-Soo, Kim, Moo Hyun, Lim, Do-Sun, Shin, Eun-Seok, and Suh, Jung-Won
- Subjects
- *
BLOOD platelets , *PLATELET function tests , *PLATELET aggregation inhibitors , *MYOCARDIAL infarction , *TREATMENT effectiveness , *PROGNOSIS - Abstract
Background: Diabetes mellitus (DM) is associated with thrombogenicity, clinically manifested with atherothrombotic events after percutaneous cutaneous intervention (PCI). This study aimed to investigate association between DM status and platelet reactivity, and their prognostic implication in PCI-treated patients. Methods: The Platelet function and genoType-Related long-term Prognosis-Platelet Function Test (PTRG-PFT) cohort was established to determine the linkage of platelet function test (PFT) with long-term prognosis during dual antiplatelet therapy including clopidogrel in patients treated with drug-eluting stent (DES). We assessed platelet reactivity using VerifyNow and 'high platelet reactivity (HPR)' was defined as ≥ 252 P2Y12 reaction unit (PRU). Major adverse cardiac and cerebrovascular event (MACCE) was a composite of all-cause death, myocardial infarction, stent thrombosis or stroke. Results: Between July 2003 and Aug 2018, DES-treated patients with available PFT were enrolled (n = 11,714). Diabetic patients demonstrated significant higher levels of platelet reactivity (DM vs. non-DM: 225.7 ± 77.5 vs. 213.6 ± 79.1 PRU, P < 0.001) and greater prevalence of HPR compared to non-diabetic patients (38.1% vs. 32.0%, P < 0.001). PRU level and prevalence of HPR were significantly associated with insulin requirement and HbA1c level, as well as diabetic status. DM status and HPR phenotype had a similar prognostic implication, which showed the synergistic clinical impact on MACCE. Association between PRU level and MACCE occurrence seemed higher in diabetic vs. non-diabetic patients. In non-DM patients, HPR phenotype did not significantly increase the risk of MACCE (adjusted hazard ratio [HRadj]: 1.073; 95% confidence interval [CI]: 0.869–1.325; P = 0.511), whereas HPR was an independent determinant for MACCE occurrence among diabetic patients (HRadj: 1.507; 95% CI: 1.193–1.902; P < 0.001). Conclusion: The levels of on-clopidogrel platelet reactivity are determined by diabetic status and the severity of DM. In addition, HPR phenotype significantly increases the risk of MACCE only in diabetic patients. Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT04734028. [ABSTRACT FROM AUTHOR]
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- 2023
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29. Platelet Reactivity on ECMO: Role of VerifyNow.
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Mujahid, Omer Mohammed, Kapoor, Poonam Malhotra, Prakash, Mohit, Sharma, Pallavi, Badge, Mohanish, Choudhury, Minati, and Hote, Milind Padmakar
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BLOOD platelets ,BLOOD transfusion ,EXTRACORPOREAL membrane oxygenation ,ANTICOAGULANTS ,THROMBELASTOGRAPHY ,THROMBOLYTIC therapy ,PLATELET aggregation inhibitors ,FIBRINOGEN ,THROMBOCYTOPENIA - Abstract
Viscoelastic assays help in identifying disorders of clotting factors, platelet function, and detection of excessive fibrinolysis. Rotational thromboelastometry (ROTEM) assesses quantitative and qualitative aspects of whole blood coagulation which allows for the determination of the mechanism of hemostatic disturbance. This helps clinicians in targeting the correct blood component therapy transfusion. Now, using verify we aim to study platelet reactivity, VA ECMO which will reflect the platelet aggregation response to an aggregating agent like Aspirin and thus know the etiology of bleeding on VA ECMO, to know the right component therapy to be transfused with a Point of Care test. For extracorporeal membrane oxygenation, although the conventional laboratory tests are used to monitor anticoagulation on whole blood, viscoelastic tests reflect coagulation status like no other standard laboratory tests. They show the status of color propagation, formation, and stabilization. It was reported that platelet function was impaired over time in all parameters with different activators. [ABSTRACT FROM AUTHOR]
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- 2023
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30. On-treatment platelet reactivity through the thromboxane A2 or P2Y12 platelet receptor pathways is not affected by pelacarsen.
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Karwatowska-Prokopczuk, Ewa, Li, Lu, Yang, Jun, Witztum, Joseph L., and Tsimikas, Sotirios
- Abstract
Background: Pelacarsen decreases plasma levels of lipoprotein(a) [Lp(a)] and oxidized phospholipids (OxPL). It was previously reported that pelacarsen does not affect the platelet count. We now report the effect of pelacarsen on on-treatment platelet reactivity. Methods: Subjects with established cardiovascular disease and screening Lp(a) levels ≥60 mg per deciliter (~ ≥150 nmol/L) were randomized to receive pelacarsen (20, 40, or 60 mg every 4 weeks; 20 mg every 2 weeks; or 20 mg every week), or placebo for 6–12 months. Aspirin Reaction Units (ARU) and P2Y12 Reaction Units (PRU) were measured at baseline and the primary analysis timepoint (PAT) at 6 months. Results: Of the 286 subjects randomized, 275 had either an ARU or PRU test, 159 (57.8%) were on aspirin alone and 94 (34.2%) subjects were on dual anti-platelet therapy. As expected, the baseline ARU and PRU were suppressed in subjects on aspirin or on dual anti-platelet therapy, respectively. There were no significant differences in baseline ARU in the aspirin groups or in PRU in the dual anti-platelet groups. At the PAT there were no statistically significant differences in ARU in subjects on aspirin or PRU in subjects on dual anti-platelet therapy among any of the pelacarsen groups compared to the pooled placebo group (p > 0.05 for all comparisons). Conclusion: Pelacarsen does not modify on-treatment platelet reactivity through the thromboxane A
2 or P2Y12 platelet receptor pathways. [ABSTRACT FROM AUTHOR]- Published
- 2023
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- View/download PDF
31. The Perfect Valve.
- Author
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Webb, John G., Sathananthan, Janar, and Wood, David A.
- Abstract
[Display omitted] [ABSTRACT FROM AUTHOR]
- Published
- 2023
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32. Association of ADP-Induced Whole-Blood Platelet Aggregation with Serum Low-Density Lipoprotein Cholesterol in Patients with Coronary Artery Disease When Receiving Maintenance Ticagrelor-Based Dual Antiplatelet Therapy.
- Author
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Chyrchel, Bernadeta, Kruszelnicka, Olga, Wieczorek-Surdacka, Ewa, and Surdacki, Andrzej
- Subjects
- *
LDL cholesterol , *PLATELET aggregation inhibitors , *BLOOD platelet aggregation , *CORONARY artery disease , *ACUTE coronary syndrome - Abstract
The degree of platelet inhibition in patients undergoing dual antiplatelet therapy (DAPT) affects cardiovascular outcomes after acute coronary syndromes (ACS) and/or percutaneous coronary intervention. Our aim was to search for correlates of residual ex vivo platelet reactivity and circulating soluble P-selectin (sP-selectin), an index of in vivo platelet activation, in patients being treated by DAPT with ticagrelor. Adenosine diphosphate (ADP)-induced platelet aggregability (by multiple electrode aggregometry) and plasma sP-selectin were estimated in 62 stable post-ACS subjects (46 men and 16 women; mean age: 64 ± 10 years; 30 with type 2 diabetes (T2DM)) undergoing maintenance DAPT with ticagrelor and aspirin. These patients did not exhibit heart failure or other relevant coexistent diseases except for properly controlled T2DM, mild renal insufficiency, and hypertension. We also assessed this in 64 subjects on clopidogrel-based DAPT matched for age, sex, and T2DM status. ADP-induced platelet aggregation was below the optimal levels (190–460 arbitrary units (AU) * min) in most patients receiving ticagrelor-based DAPT, especially in those with below-median (<1.9 mmol/L) serum concentrations of low-density lipoprotein cholesterol (LDL-c) (128 ± 61 vs. 167 ± 73 AU * min for below-median and above-median LDL-c, respectively, p = 0.025). In contrast, platelet reactivity did not differ by LDL-c on clopidogrel-based DAPT (246 ± 101 vs. 268 ± 108 AU * min for below-median and above-median LDL-c, respectively, p > 0.4). Plasma sP-selectin was found to be unrelated to serum LDL-c when receiving DAPT with ticagrelor (p > 0.4) or clopidogrel (p > 0.8). In conclusion, our preliminary observational study suggests the association of lower residual ex vivo platelet aggregability with better LDL-c control in patients undergoing ticagrelor-based maintenance DAPT, which does not appear to be reflected by plasma sP-selectin. Whether the serum LDL-c level should be considered among the factors affecting the degree of platelet inhibition for those treated with ticagrelor-based DAPT needs to be investigated in larger studies. [ABSTRACT FROM AUTHOR]
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- 2023
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33. Altered platelet reactivity, coagulation, endothelial and inflammatory markers early after smoking cessation verified with cotinine plasma concentration.
- Author
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Ramotowski, Bogumił, Undas, Anetta, and Budaj, Andrzej
- Abstract
Background/Introduction: Cigarette smoking is a potent modifiable risk factor for coronary artery disease (CAD). However, little is known about alterations to prothrombotic state and platelet reactivity early after smoking cessation following percutaneous coronary interventions (PCI). Purpose: We investigated alterations to platelet reactivity, coagulation and markers of platelet, endothelial, inflammatory and coagulation activation in clopidogrel-treated patients with CAD after PCI before and after smoking cessation. Methods: Smoking patients aged 18 years or older at least 30 days after PCI were recruited and encouraged to quit the habit. At baseline and at 30 days, we measured platelet reactivity with VerifyNow system, thrombomodulin, P-selectin, platelet factor 4 (CXCL4/PF4), citrullinated histone H3 (H3cit) and cotinine level. Results: Among 117 patients, 84 patients (72%) at a median age of 60.5 years (40 [interquartile range 30–47] pack-years) completed a 30-day follow-up. At day 30, 30 (35.7%) patients stopped smoking with cotinine level < 50 ng/ml. Baseline characteristics were similar in both groups. In smoking quitters a change in platelet reactivity was larger (Δ platelet reactivity units (PRU) 19 [2, 43] vs. -6 [-32, 37], p = 0.018), along with a change in P-selectin concentration (-11.82 [-23.62, 1.34] vs. 7.19 [-14.24, 17.19] ng/ml, p = 0.005). Positive correlations was noticed between cotinine and both P-selectin (r = 0.23, p = 0.045) and CXCL4 (r = 0.27, p = 0.02). Conclusion: After smoking cessation in CAD patients following PCI an increase in platelet reactivity and a decrease in P-selectin levels were observed. The risk of thrombotic complications post PCI might be paradoxically enhanced among patients who stopped smoking. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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34. Low-dose of Ticagrelor and Standard-dose Clopidogrel on Platelet Effects in Chinese Patients With Stable CAD.
- Author
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Yue LI, Professor
- Published
- 2021
35. Platelet Reactivity in the Exacerbation of Psoriasis
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Piotr Adamski, Urszula Adamska, Katarzyna Buszko, Joanna Sikora, and Rafał Czajkowski
- Subjects
light transmission aggregometry ,platelet reactivity ,psoriasis ,Medicine - Abstract
Background: Psoriasis is a chronic, inflammatory, immune-mediated disease with a specific cutaneous presentation. Increased platelet aggregation has been observed in patients with extensive psoriatic lesions. The aim of this study was to evaluate the clinical factors affecting platelet reactivity in patients with an exacerbation of psoriasis. Methods: This was a prospective, single-center, observational study, enrolling patients hospitalized for an aggravation of psoriasis. Enrolled patients underwent single platelet function testing with light transmission aggregometry on the first morning of hospitalization. Results: 120 patients were enrolled in the study. Of the compared subgroups, women had higher maximal platelet aggregation (MPA) than men (77% vs. 72%; p = 0.03), and those with BMIs < 25 kg/m2 showed higher platelet reactivity compared to subjects with BMIs ≥ 25 kg/m2 (75% vs. 73%; p = 0.02). There was a positive correlation between MPA and platelet count (r = 0.27; p < 0.01), as well as C-reactive protein concentration (r = 0.20; p = 0.03), while a negative correlation was observed with total cholesterol (r = −0.24; p = 0.01) and triglycerides (r = −0.30; p < 0.01). A two-step analysis based on multidimensional models with random effects revealed that every increase in the platelet count by 103/μL led to an increase in MPA by 0.07% (R2 = 0.07; p < 0.01), and an increase in triglycerides’ concentration by 1 mg/dL was related to a reduction in MPA by 0.05% (R2 = 0.07; p < 0.01). Conclusions: The increased platelet reactivity observed in patients with psoriasis appears to be multifactorial and related to several clinical and laboratory features. Further research is warranted to put these findings into a clinical perspective.
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- 2024
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36. Corrigendum: The association between higher FFAs and high residual platelet reactivity among CAD patients receiving clopidogrel therapy
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Zehao Zhao, Shutong Dong, Tienan Sun, Kangning Han, Xin Huang, Meishi Ma, Shiwei Yang, and Yujie Zhou
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free fatty acids (FFA) ,coronary artery disease ,clopidogrel ,platelet reactivity ,thromboelastogram ,percutaneous coronary intervention ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2023
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37. Biomarkers of Thrombotic Status Predict Spontaneous Reperfusion in Patients With ST-Segment Elevation Myocardial Infarction.
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Kanji, Rahim, Gue, Ying X., Memtsas, Vassilios, Spencer, Neil H., and Gorog, Diana A.
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ST elevation myocardial infarction , *REPERFUSION , *MAJOR adverse cardiovascular events , *PERCUTANEOUS coronary intervention , *MYOCARDIAL infarction - Abstract
Spontaneous reperfusion, seen in ∼20% of patients with ST-segment elevation myocardial infarction (STEMI), manifests as normal epicardial flow in the infarct-related artery, with or without ST-segment resolution, before percutaneous coronary intervention (PCI). The drivers mediating this are unknown. The authors sought to relate spontaneous reperfusion to the thrombotic profile. In a prospective study, blood from STEMI patients (n = 801) was tested pre-PCI to assess in vitro , point-of-care, occlusion times (OT) and endogenous lysis times (LT). Spontaneous reperfusion was defined as infarct-related artery Thrombolysis In Myocardial Infarction flow grade 3 before PCI. Patients were followed for major cardiovascular events (death, myocardial infarction, or stroke). Spontaneous reperfusion was associated with a longer OT (435 seconds vs 366 seconds; P < 0.001) and a shorter LT (1,257 seconds vs 1,616 seconds; P < 0.001), lower troponin, and better left ventricular function. LT was superior to OT for predicting spontaneous reperfusion (area under the curve for LT: 0.707; 95% CI: 0.661-0.753; area under the curve for OT: 0.629; 95% CI: 0.581-0.677). Among patients with spontaneous reperfusion, those with complete, vs partial ST-segment resolution, had a longer OT (P = 0.002) and a shorter LT (P < 0.001). Spontaneous reperfusion was unrelated to clinical characteristics or pain-to-angiography times. Over 4 years, patients with spontaneous reperfusion experienced fewer major adverse cardiovascular events than those without (4.1% vs 10.6%; P = 0.013), especially in those with both spontaneous reperfusion and complete ST-segment resolution (1.5% vs 10.1%; P = 0.029). We demonstrate a novel hematological signature in STEMI patients with spontaneous reperfusion, namely, decreased platelet reactivity and faster endogenous fibrinolysis, relating to smaller infarcts and improved survival. This finding indicates a role for modulating thrombotic status early after STEMI onset, to facilitate spontaneous reperfusion and improve outcomes. [Display omitted] [ABSTRACT FROM AUTHOR]
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- 2023
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38. Clinical impact of high platelet reactivity in patients with atrial fibrillation and concomitant percutaneous coronary intervention on dual or triple antithrombotic therapy.
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Berteotti, M., Gori, A. M., Giusti, B., Fortini, A., Grossi, G., Ciardetti, N., Migliorini, A., Lotti, E., Valenti, R., Di Mario, C., Marchionni, N., and Marcucci, R.
- Abstract
High platelet reactivity (HPR) on clopidogrel is an established thrombotic risk factor after percutaneous coronary intervention (PCI). The introduction of more potent antiplatelet drugs has partially surpassed this issue. However, in the setting of concomitant atrial fibrillation (AF) and PCI clopidogrel is still the most adopted P2Y
12 inhibitor. In the present study all consecutive patients with history of AF discharged from our cardiology ward with dual (DAT) or triple (TAT) antithrombotic therapy after a PCI from April 2018 to March 2021 were enrolled in an observational registry. For all subjects, blood serum samples were collected and tested for platelet reactivity by arachidonic acid and ADP (VerifyNow system) and genotyping of the CYP2C19*2 loss-of-function polymorphism. We recorded at 3 and 12-months follow-up: (1) major adverse cardiac and cerebrovascular events (MACCE), (2) major hemorrhagic or clinically relevant non-major bleeding and (3) all-cause mortality. A total of 147 patients were included (91, 62% on TAT). In 93.4% of patients, clopidogrel was chosen as P2Y12 inhibitor. P2Y12 dependent HPR resulted an independent predictor of MACCE both at 3 and 12 months (HR 2.93, 95% C.I. 1.03 to 7.56, p = 0.027 and HR 1.67, 95% C.I. 1.20 to 2.34, p = 0.003, respectively). At 3-months follow-up the presence of CYP2C19*2 polymorphism was independently associated with MACCE (HR 5.21, 95% C.I. 1.03 to 26.28, p = 0.045). In conclusion, in a real-world unselected population on TAT or DAT, the entity of platelet inhibition on P2Y12 inhibitor is a potent predictor of thrombotic risk, suggesting the clinical utility of this laboratory evaluation for a tailored antithrombotic therapy in this high-risk clinical scenario. The present analysis was performed in patients with AF undergoing PCI on dual or triple antithrombotic therapy. At 1 year follow-up MACCE incidence was consistent, and it was not different in different antithrombotic pattern groups. P2Y12 dependent HPR was a potent independent predictor of MACCE both at 3- and 12-months follow-up. In the first 3 months after stenting the carriage of CYP2C19*2 allele was similarly associated with MACCE. Abbreviation: DAT, dual antithrombotic therapy; HPR, high platelet reactivity; MACCE, major adverse cardiac and cerebrovascular events; PRU, P2Y12 reactive unit; TAT, triple antithrombotic therapy. Created with BioRender.com. [ABSTRACT FROM AUTHOR]- Published
- 2023
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39. Impact of intravascular ultrasound parameters and platelet reactivity on primary patency after drug-coated balloon angioplasty for femoropopliteal artery disease.
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Okuno, Shota, Iida, Osamu, Takahara, Mitsuyoshi, Hata, Yosuke, Kurata, Naoya, Toyoshima, Taku, Asai, Mitsutoshi, Masuda, Masaharu, Okamoto, Shin, Ishihara, Takayuki, Nanto, Kiyonori, Kanda, Takashi, Tsujimura, Takuya, Matsuda, Yasuhiro, and Mano, Toshiaki
- Subjects
- *
INTRAVASCULAR ultrasonography , *TRANSLUMINAL angioplasty , *ARTERIAL diseases , *CHRONIC total occlusion , *BLOOD platelets - Abstract
Although the superiority of DCBs to uncoated balloon angioplasty for the treatment of femoropopliteal (FP) lesions has been demonstrated, the association of clinical factors, including anatomical features evaluated by intravascular ultrasound (IVUS) and platelet reactivity, with the loss of patency has not been systematically studied. The current prospective, observational study enrolled 160 consecutive patients (male 67.5%, mean age 74.7 ± 9.7 years) with 213 FP lesions treated with DCBs under IVUS evaluation. The platelet reactivity was measured in P2Y12 reaction units for all of the patients at the DCB treatment. The primary end point was primary patency at 12 months, while the secondary end points were freedom from target lesion revascularization (TLR), all-cause death, major target limb amputation and bleeding events at 12 months. Mean lesion length was 11.9 ± 9.4 cm and 34 (16.0%) were chronic total occlusions (CTOs). Thirty-four (16.0%) were severely calcified lesions. Primary patency by Kaplan–Meier estimate was 79.2% at 12 months, while the 12-month freedom from TLR, all-cause death and bleeding events were observed in 89.1%, 93.4% and 97.4%, respectively. There were no major target limb amputations through 12 months. Multivariate analysis showed that subintimal angioplasty for CTO lesions was a sole risk factor for loss of 12-month primary patency, while other IVUS parameters and platelet reactivity were not. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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40. HDL and Scavenger Receptor Class B Type I (SRBI)
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Yu, Hong, Crusio, Wim E., Series Editor, Dong, Haidong, Series Editor, Radeke, Heinfried H., Series Editor, Rezaei, Nima, Series Editor, Steinlein, Ortrud, Series Editor, Xiao, Junjie, Series Editor, and Zheng, Lemin, editor
- Published
- 2022
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41. Effects of exercise on platelet reactivity after myocardial infarction: a randomized clinical trial
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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, and José Carlos Nicolau
- Subjects
exercise training ,high-intensity exercise ,myocardial infarction ,platelet reactivity ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
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
- Published
- 2022
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42. Prostacyclin analogues decrease platelet aggregation but have no effect on thrombin generation, fibrin clot structure, and fibrinolysis in pulmonary arterial hypertension: PAPAYA coagulation
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Aleksander Siniarski, Aleksandra Gąsecka, Miłosz Starczyński, Marta Banaszkiewicz, Szymon Darocha, Adam Torbicki, Marcin Kurzyna, Krzysztof J. Filipiak, Jadwiga Nessler, and Grzegorz Gajos
- Subjects
fibrin clot ,fibrinolysis ,platelet reactivity ,prostacyclin analogues ,pulmonary arterial hypertension ,thrombin generation ,Diseases of the blood and blood-forming organs ,RC633-647.5 - 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.
- Published
- 2022
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43. The role of miRNAs in regulation of platelet activity and related diseases - a bioinformatic analysis
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Zofia Wicik, Pamela Czajka, Ceren Eyileten, Alex Fitas, Marta Wolska, Daniel Jakubik, Dirk von Lewinski, Harald Sourij, Jolanta M. Siller-Matula, and Marek Postula
- Subjects
bioinformatic analysis ,biomarker ,diagnosis ,mirna ,mirna-gene target interaction ,network ,platelet reactivity ,platelets ,prognosis ,Diseases of the blood and blood-forming organs ,RC633-647.5 - 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.
- Published
- 2022
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44. High platelet reactivity is a predictor of left ventricular remodelling in patients with acute myocardial infarction
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Masahiro Tsuji, Yusuke Kawai, Toru Miyoshi, Eisuke Saito, Kohei Kawamura, Tamaki Ono, Koji Tokioka, Tohru Ohe, Kazufumi Nakamura, and Hiroshi Ito
- Subjects
Myocardial infarction ,Left ventricular remodelling ,Platelet reactivity ,Inflammation ,Reverse remodelling ,Prasugrel ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Aims Acute myocardial infarction (AMI) is associated with left ventricular remodelling (LVR), which leads to progressive heart failure. Platelets play a pivotal role in promoting systemic and cardiac inflammatory responses during the complex process of myocardial wound healing or repair following AMI. This study aimed to investigate the impact of platelet reactivity immediately after primary percutaneous coronary intervention (PCI) on LVR in AMI patients with ST‐segment (STEMI) and non‐ST‐segment elevation (NSTEMI). Methods and results This prospective, single‐centre, observational study included 182 patients with AMI who underwent primary PCI (107 patient with STEMI and 75 patients with NSTEMI). Patients were administered a loading dose of aspirin plus prasugrel before the procedure, and platelet reactivity was assessed using the VerifyNow P2Y12 assay immediately after PCI. Echocardiography was performed before discharge and during the chronic phase (8 ± 3 months after discharge). LVR was defined as a relative ≥20% increase in left ventricular end‐diastolic volume index (LVEDVI). LVR in chronic phase was found in 34 patients (18.7%) whose platelet reactivity was significantly higher than those without LVR (259.6 ± 61.5 and 213.1 ± 74.8 P2Y12 reaction units [PRU]; P = 0.001). The occurrence of LVR did not differ between patients with STEMI and patients with NSTEMI (21.5% and 14.7%; P = 0.33). The optimal cut‐off value of platelet reactivity for discriminating LVR was ≥245 PRU. LVEDVI significantly decreased at chronic phase in patients without high platelet reactivity (
- Published
- 2022
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45. Mass cytometry of platelet-rich plasma: a new approach to analyze platelet surface expression and reactivity
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Melissa Klug, Kilian Kirmes, Jiaying Han, Olga Lazareva, Marc Rosenbaum, Giacomo Viggiani, Moritz von Scheidt, Jürgen Ruland, Jan Baumbach, Gianluigi Condorelli, Karl-Ludwig Laugwitz, Markus List, Isabell Bernlochner, and Dario Bongiovanni
- Subjects
mass cytometry ,platelet heterogeneity ,platelet reactivity ,platelets ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Mass cytometry (CyTOF) is a new technology that allows the investigation of protein expression at single cell level with high resolution. While several protocols are available to investigate leukocyte expression, platelet staining and analysis with CyTOF have been described only from whole blood. Moreover, available protocols do not allow sample storage but require fresh samples to be obtained, processed, and measured immediately. We provide a structured and reproducible method to stain platelets from platelet-rich plasma to study thrombocyte protein expression and reactivity using mass cytometry. With our method, it is possible to acquire a large number of events allowing deep bioinformatic investigation of platelet expression heterogeneity. Integrated in our protocol is also a previously established freezing protocol that allows the storage of stained samples and to delay their measurement. Finally, we provide a structured workflow using different platelet stimulators and a freely available bioinformatic pipeline to analyze platelet expression. Our protocol unlocks the potential of CyTOF analysis for studying platelet biology in health and disease.
- Published
- 2022
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46. SARS-CoV-2 Spike Protein and Neutralizing Anti-Spike Protein Antibodies Modulate Blood Platelet Function.
- Author
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Luzak, Boguslawa, Rozalski, Marcin, Przygodzki, Tomasz, Boncler, Magdalena, Wojkowska, Dagmara, Kosmalski, Marcin, and Watala, Cezary
- Subjects
- *
BLOOD platelet aggregation , *BLOOD platelets , *THROMBOPOIETIN receptors , *BLOOD platelet activation , *SARS-CoV-2 , *PLATELET count , *COVID-19 - Abstract
Several studies report elevated blood platelet activation and altered platelet count in COVID-19 patients, but the role of the SARS-CoV-2 spike protein in this process remains intriguing. Additionally, there is no data that anti-SARS-CoV-2 neutralizing antibodies (nAb) may attenuate spike protein activity toward blood platelets. Our results indicate that under in vitro conditions, the spike protein increased the collagen-stimulated aggregation of isolated platelets and induced the binding of vWF to platelets in ristocetin-treated blood. The spike protein also significantly reduced collagen- or ADP-induced aggregation or decreased GPIIbIIIa (fibrinogen receptor) activation in whole blood, depending on the presence of the anti-spike protein nAb. Our findings suggest that studies on platelet activation/reactivity in COVID-19 patients or in donors vaccinated with anti-SARS-CoV-2 and/or previously-infected COVID-19 should be supported by measurements of spike protein and IgG anti-spike protein antibody concentrations in blood. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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47. Transcription factors in megakaryocytes and platelets.
- Author
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Hengjie Yuan, Yafan Liu, Jianning Zhang, Jing-fei Dong, and Zilong Zhao
- Subjects
TRANSCRIPTION factors ,BLOOD platelets ,MEGAKARYOCYTES ,REGULATOR genes ,BLOOD coagulation ,PROTEIN synthesis - Abstract
Transcription factors bind promoter or regulatory sequences of a gene to regulate its rate of transcription. However, they are also detected in anucleated platelets. The transcription factors RUNX1, GATA1, STAT3, NFκB, and PPAR have been widely reported to play key roles in the pathophysiology of platelet hyper-reactivity, thrombosis, and atherosclerosis. These nontranscriptional activities are independent of gene transcription or protein synthesis but their underlying mechanisms of action remain poorly defined. Genetic and acquired defects in these transcription factors are associated with the production of platelet microvesicles that are known to initiate and propagate coagulation and to promote thrombosis. In this review, we summarize recent developments in the study of transcription factors in platelet generation, reactivity, and production of microvesicles, with a focus on non-transcriptional activities of selected transcription factors. [ABSTRACT FROM AUTHOR]
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- 2023
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48. Platelet Reactivity and Cardiovascular Mortality Risk in the LURIC Study.
- Author
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Berger, Martin, Dressel, Alexander, Kleber, Marcus E., März, Winfried, Hellstern, Peter, Marx, Nikolaus, and Schütt, Katharina
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- *
CARDIOVASCULAR diseases risk factors , *BLOOD platelets , *CORONARY artery disease , *CORONARY angiography , *GLUCOSE analysis - Abstract
Background: The clinical and prognostic implications of platelet reactivity (PR) testing in a P2Y12-inhibitor naïve population are poorly understood. Objectives: This explorative study aims to assess the role of PR and explore factors that may modify elevated mortality risk in patients with altered PR. Methods: Platelet ADP-induced CD62P and CD63 expression were measured by flow-cytometry in 1520 patients who were referred for coronary angiography in the Ludwigshafen Risk and Cardiovascular Health Study (LURIC). Results: High- and Low-platelet reactivity to ADP were strong predictors of cardiovascular and all-cause mortality and risk equivalent to the presence of coronary artery disease. (High platelet reactivity 1.4 [95% CI 1.1–1.9]; Low platelet reactivity: 1.4 [95% CI 1.0–2.0]). Relative weight analysis indicated glucose control (HbA1c), renal function ([eGFR]), inflammation (high-sensitive C-reactive protein [hsCRP]) and antiplatelet therapy by Aspirin as consistent mortality risk modifiers in patients with Low- and High-platelet reactivity. Pre-specified stratification of patients by risk modifiers HbA1c (<7.0%), eGFR (>60 mL/min/1.73 m2) and CRP (<3 mg/L) was associated with a lower mortality risk, however irrespective of platelet reactivity. Aspirin treatment was associated with reduced mortality in patients with high platelet reactivity only (p for interaction: 0.02 for CV-death [<0.01 for all-cause mortality]. Conclusions: Cardiovascular mortality risk in patients with High- and Low platelet reactivity is equivalent to the presence of coronary artery disease. Targeted glucose control, improved kidney function and lower inflammation are associated with reduced mortality risk, however independent of platelet reactivity. In contrast, only in patients with High-platelet reactivity was Aspirin treatment associated with lower mortality. [ABSTRACT FROM AUTHOR]
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- 2023
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49. Platelet reactivity expressed as a novel platelet reactivity score is associated with higher inflammatory state after coronary artery bypass grafting.
- Author
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Wilczyński, Mirosław, Krejca, Michał, Stepinski, Piotr, Rozalski, Marcin, and Golanski, Jacek
- Subjects
- *
CORONARY artery bypass , *CARDIOPULMONARY bypass , *INFLAMMATION , *BLOOD platelets , *MYOCARDIAL infarction , *BLOOD platelet aggregation , *ACUTE coronary syndrome , *MUCOCUTANEOUS lymph node syndrome - Abstract
Introduction: Despite therapy, patients operated using a cardiopulmonary bypass demonstrate increased platelet aggregation, which rebounds to above preoperative levels. The aim of the study was to test the interaction between platelet reactivity/activation and selected inflammatory markers in the post-operative period. Material and methods: In total, 103 patients with non-ST elevation acute coronary syndrome (NSTE-ACS) who were not eligible for percutaneous coronary interventions (PCI), and required urgent revascularization, were included. Platelet reactivity was measured using the PFA-100 platelet analyser, multiple electrode aggregometry, and was expressed as a novel platelet reactivity score (PRS). Patients were divided using their PRS scores into high platelet relativity or low platelet reactivity subgroups (HPR or LPR). Platelet basal activation was measured using immunoassays for soluble P-selectin and soluble CD40L. We measured high-sensitivity C-reactive protein (CRP), and used immunoassays for tumour necrosis factor α (TNF-α) and interleukin 6 (IL-6) as inflammation markers. Results: Significant differences between HPR and LPR groups were found for CRP (mg/l): 81.5 vs. 44.6, p < 0.02; and TNF-α (pg/l): 3.51 vs. 2.37, p < 0.02. A significant association was found between CRP, TNF-α, IL-6 and platelet reactivity (platelet reactivity score). Cohen's k showed: CRP = 0.49, p < 0.0001, TNF-α = 0.37, p < 0.002. Perioperative myocardial infarction and rhythm disturbances occurred more frequently in the high platelet reactivity group: 7 (16.3%) vs. 2 (3.3%), p < 0.04, and 9 (20.9%) vs. 4 (6.7%), p < 0.04, respectively. Conclusions: Inflammatory parameters CRP and TNF-α are strongly associated with platelet reactivity (expressed as PRS) in cardiopulmonary bypass graft patients. Platelet hyperreactivity in the early post-operative period combined with a systemic inflammatory state correlates with a higher risk of post-operative rhythm disturbances and myocardial infarction. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
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50. Growth Differentiation Factor 15 Is Associated with Platelet Reactivity in Patients with Acute Coronary Syndrome.
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Mutschlechner, David, Tscharre, Maximilian, Wadowski, Patricia P., Pultar, Joseph, Weikert, Constantin, Lee, Silvia, Eichelberger, Beate, Panzer, Simon, Perkmann, Thomas, and Gremmel, Thomas
- Subjects
- *
GROWTH differentiation factors , *ACUTE coronary syndrome , *BLOOD platelet aggregation , *BLOOD platelets , *ADENOSINE diphosphate - Abstract
Bleeding events in patients with acute coronary syndrome (ACS) are a risk factor for adverse outcomes, including mortality. We investigated the association of growth differentiation factor (GDF)-15, an established predictor of bleeding complications, with on-treatment platelet reactivity in ACS patients undergoing coronary stenting receiving prasugrel or ticagrelor. Platelet aggregation was measured by multiple electrode aggregometry (MEA) in response to adenosine diphosphate (ADP), arachidonic acid (AA), thrombin receptor-activating peptide (TRAP, a protease-activated receptor-1 (PAR-1) agonist), AYPGKF (a PAR-4 agonist) and collagen (COL). GDF-15 levels were measured using a commercially available assay. GDF-15 correlated inversely with MEA ADP (r = −0.202, p = 0.004), MEA AA (r = −0.139, p = 0.048) and MEA TRAP (r = −0.190, p = 0.007). After adjustment, GDF-15 was significantly associated with MEA TRAP (β = −0.150, p = 0.044), whereas no significant associations were detectable for the other agonists. Patients with low platelet reactivity in response to ADP had significantly higher GDF-15 levels (p = 0.005). In conclusion, GDF-15 is inversely associated with TRAP-inducible platelet aggregation in ACS patients treated with state-of-the-art antiplatelet therapy and significantly elevated in patients with low platelet reactivity in response to ADP. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
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