Relation of platelet aggregation and fibrinogen levels to advancing age in aspirin- and thienopyridine-treated patients

Koltai, Katalin; Fehér, Gergely; Kenyeres, Péter; Lenart, I; Alexy, Tamás; Horváth, Beáta; Márton, Zsolt; Késmárky, Gábor; Tóth, Kálmán

doi:10.3233/ch-2008-1140

Cited by 11 publications

(5 citation statements)

References 26 publications

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“…Fifth, it should be emphasized that ICH during antiplatelet treatment occurs typically in elderly and comorbid patients, whereas animals used in this study were young and healthy. Age has to be considered as a relevant confounder in this context, because several investigations showed an age-related increase in platelet aggregation even under treatment with ASA or ASA + clopidogrel (Franchini, 2006;Koltai et al, 2008). Finally, it is also important to mention that we determined hematoma volumes at one time point only, i.e., 24 hours after ICH induction.…”

Section: Discussionmentioning

confidence: 99%

Antiplatelet Pretreatment does not Increase Hematoma Volume in Experimental Intracerebral Hemorrhage

Lauer

Schlunk

Cott

et al. 2011

J Cereb Blood Flow Metab

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While oral anticoagulants are associated with greater hematoma expansion and higher mortality rates in patients with intracerebral hemorrhage (ICH), there is ongoing discussion whether pretreatment with antiplatelet drugs also worsens prognosis. Using an experimental model of ICH, we investigated the effects of antiplatelet pretreatment on hematoma volume and functional outcome. CD-1 mice were treated with acetyl-salicylic acid (ASA, 60 mg/kg per 24 hours), clopidogrel (22.5 mg/kg per 24 hours), or both (ASA + clopidogrel) through drinking water for 3 days (n = 20 per group). Thereafter, platelet aggregation was found to be significantly reduced. Untreated mice and mice pretreated with warfarin served as controls. A stereotactic injection of collagenase into the right striatum was used to induce ICH. Twenty-four hours after ICH induction, hematoma volume was measured to be 15.0±4.4 lL in controls, 14.1±5.3 lL in ASA mice, 16.8±5.1 lL in clopidogrel mice, and 16.4 ± 5.1 lL in ASA + clopidogrel animals. These differences were not statistically significant. However, mice pretreated with warfarin revealed largely increased hematoma volumes (25.0 ± 7.4 lL versus controls, P = 0.001). Neurologic outcome was not different between antiplateletpretreated animals and untreated controls. Our results suggest that plasmatic coagulation rather than platelet function is the most critical element for preventing hematoma expansion in acute ICH. Future therapeutic strategies may take these findings into account.

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Section: Discussionmentioning

confidence: 99%

Antiplatelet Pretreatment does not Increase Hematoma Volume in Experimental Intracerebral Hemorrhage

Lauer

Schlunk

Cott

et al. 2011

J Cereb Blood Flow Metab

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“…Хотя в работе N. Tang et al на большой выборке здоровых 9376 мужчин и 4984 женщин в широком возрастном диапазоне (до 40 и старше 70 лет) было показано отсутствие различий в ADP-индуцированной агрегации тромбоцитов между возрастными подгруппами [43]. Более того, имеются работы, демонстрирующие отсутствие влияния возраста на эффективность тиенопиридинов у пациентов с ИБС [44]. В нашем исследовании пациенты группы ВОРТ были моложе на несколько лет по сравнению с другими группами, и возраст вошел в модель для прогнозирования ВОРТ со знаком минус, хотя мы не включали в исследование пациентов старше 74 лет.…”

Section: рисунок 2 -Roc-кривая модели; Auc -площадь под Roc-кривой Fi...unclassified

“…Рост концентрации фибриногена в плазме, даже в пределах референсных значений, коррелирует с увеличением риска сердечно-сосудистых осложнений [48]. Согласно некоторым литературным данным, не было обнаружено связи между агрегацией тромбоцитов и уровнем фибриногена у пациентов, получавших 75 мг клопидогрела либо 500 мг тиклопидина [44], либо получавших тикагрелор или прасугрель [49]. В нашей работе уровень фибриногена достоверно не различался между исследуемыми группами, однако данный показатель со знаком минус вошел в модель для определения риска НОРТ.…”

Section: рисунок 2 -Roc-кривая модели; Auc -площадь под Roc-кривой Fi...unclassified

Determinants of High and Low Platelet Residual Reactivity on Day 1-2 of Myocardial Infarction When Taking Clopidogrel

Pronko,

Snezhitskiy,

Kapytski

2023

Journal GrGMU

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The aim of the study was to determine the clinical and laboratory factors that determine high and low platelet reactivity in patients taking clopidogrel on day 1-2 of myocardial infarction (MI). Material and Methods. A total of 405 patients (322 men and 83 women) with MI aged 31 to 74 years were examined. Group 1 included patients with low residual platelet reactivity (LRPR) – 89 people, group 2 consisted of patients with optimal platelet reactivity (OPR) – 223 people, group 3 was composed of patients with high residual platelet reactivity (HRPR) – 93 people. Platelet aggregation was assessed on a Multiplate impedance aggregometer (Germany) with several aggregation inducers. A blood test and a study of morphometric parameters of platelets were performed by the cytoflow method on an automated hematology analyzer Sysmex XS-500i (Japan). The study of the level of soluble CD40 ligand (sСD40L) and sP-selectin was performed in 140 patients, von Willebrand factor (VWF) and endothelin-1 were assessed in 150 people on the enzyme immunoassay analyzer Sunrise (TECAN, Austria) using Fine Biotech kits (China). All studies were performed upon admission to the hospital on day 1-2 of MI (at least 12 hours after the administration of a loading dose of clopidogrel). Results. A one-way linear regression analysis identified the following factors that independently affect the value of the ADP-test: age (β=-0.21, 95% CI: -0.42 – -0.0095; p=0.04); total cholesterol (β=1.4, 95% CI: 0.26–2.56; p=0.04); white blood cell count (β= 0.57, 95% CI: 0.003–1.14; p=0.049); hemoglobin (β=-0.16, 95% CI: -0.27 – -0.044; p=0.0067); platelet count (β=1.4, 95% CI: 0.26 – 2.56; p=0.04); PCT (β=76.8, 95% CI: 41.5 – 112.1; p=0.000024); TRAP-test (β=0.4, 95% CI: 0.33–0.46; p<0.000001); CD40L (β=0.044, 95% CI: 0.013–0.074; p=0.005); sP-selectin (β=2.3, 95% CI: 0.63 – 3.97; p=0.007); VWF (β=0.06, 95% CI: 0.016 – 0.11; p=0.0085). To determine the probability of HRPR developing a binary logistic regression model was constructed based on the observational data of a sample of 398 patients, which included the following indicators: age, white blood cell count, mean platelet volume (MPV) and platelet distribution width (PDW) values, results of TRAP-test and the level of creatinine. At the probability cut-off p=0.4746, the sensitivity of the constructed model was 74.2%, specificity - 74.1%, classification accuracy – 74.1%, the area under the ROC-curve – 0.795 (CI: 0.745 – 0.844). To determine the probability of developing LRPR, a binary logistic regression model was constructed based on the observational data of 143 patients, which included the following indicators: the number of leukocytes, MPV and TRAP-test values, fibrinogen and VWF levels. With a probability cut-off p=0.5589, the sensitivity of this model was 84.6%, specificity – 77.8%, classification accuracy – 79.0%, the area under the ROC-curve – 0.826 (CI: 0.747 – 0.905). Conclusion. On days 1-2 of MI, 22% of patients with an excessive response to clopidogrel and 23% with an insufficient response to clopidogrel were identified. The determinants of HRPR are age, white blood cell count, MPV, PDW, TRAP-test and creatinine levels. The determinants of LRPR are white blood cell count, MPV values, spontaneous platelet aggregation, detected by the TRAP-test, the level of fibrinogen and VWF.

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“…Aggregation measurements: the epinephrine-induced platelet aggregation was studied by CARAT TX4 optical aggregometer (Carat Diagnostics Ltd, Budapest, Hungary at 37 ºC based on Born' method (Born, 1962;Koltai et al,2008).…”

Section: Upper Gastrointestinal Tract Complications (Ugic) (Peptic Ulmentioning

confidence: 99%

Capsaicin is a New Gastrointestinal Mucosal Protecting Drug Candidate in Humans — Pharmaceutical Development and Production Based on Clinical Pharmacology

Mózsik¹,

Past²,

Habon³

et al. 2014

Capsaicin - Sensitive Neural Afferentation and the Gastrointestinal Tract: From Bench to Bedside

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applications of these drugs are contraindicated from the points of gastroenterologist. 4. We earlier proved clearly that the small doses of capsaicin (given orally in doses of nanogram to microgram / kg in animal experiments and 200 to 800 µg in human observations) prevents the aspirin, indomethacin (a mixed COX-1 and COX-2 inhibitor)-induced gastrointestinal mucosal damage. Aims: 1. The development and pharmaceutically production of the planned production of new gastrointestinal mucosal protective drug (capsaicin alone and/or capsaicin in combination with different nonsteroidal anti-inflammatory drugs) for the use in human healthy beings and in patients. 2. For the development and production of a new drug, we had to respect the following aspects: a. the knowledge of the chemical composition of natural origin capsaicin(oids); b. problems of the analytical measurements of capsaicin(oids) in the biological samples (in animals and humans); c. correct and complete preclinical dossier; d. correct dossier of acute and chronic toxicological studies with capsaicin (including the different tests) in two speciments of animal experiments; e. existence of a complete drug master file (DMF); f. the exclusion of pesticides, fusariums, aflatoxin and other toxicological agents (which are used during the plant cultivation in the different countries) from the capsaicin(oids) preparations used for drug production; g. to collect the necessary permissions from the different international and national authrorities before starting of pharmaceutical production of drug alone or in combinations; h. different pharmaceutical controlling measurements and other pharmaceutical aspects of planned drug or drug combinations (such as stability, drug preparation, different pharmaceutical technologies, etc.); i. preparation of different protocols for human human phase examinations (especially for human phase I.); j. to receive the permissions from the the different national authorities to carried out the prepared protocols before starting of the classical pharmacological studies; k. to gather the necessary numbers of experts from the very different scientific fields, who are able to solve all of above mentioned scientific, pharmaceutical, research problems (in animal experiments and in human observations); l. to find accredited institutes to perform human clinical pharmacological (phase) examinations. 2. When we solved all of above scientific problems, the human phase I. examinations with capsaicin alone and with combination+aspirin and capsaicin+diclofenac, the human phase I. examinations were in the

show abstract

Relation of platelet aggregation and fibrinogen levels to advancing age in aspirin- and thienopyridine-treated patients

Cited by 11 publications

References 26 publications

Antiplatelet Pretreatment does not Increase Hematoma Volume in Experimental Intracerebral Hemorrhage

Antiplatelet Pretreatment does not Increase Hematoma Volume in Experimental Intracerebral Hemorrhage

Determinants of High and Low Platelet Residual Reactivity on Day 1-2 of Myocardial Infarction When Taking Clopidogrel

Capsaicin is a New Gastrointestinal Mucosal Protecting Drug Candidate in Humans — Pharmaceutical Development and Production Based on Clinical Pharmacology

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