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Gaceta Medica de Mexico 2021Estrogens that are used as contraceptives or in replacement therapy are associated with an increase in the risk for developing thrombosis, mainly during the first year...
BACKGROUND
Estrogens that are used as contraceptives or in replacement therapy are associated with an increase in the risk for developing thrombosis, mainly during the first year of treatment and in women with associated risk factors.
OBJECTIVE
To synthesize, characterize and identify the anticoagulant, antiplatelet aggregation and microvesicle-reducing effect of the new aminoestrogen Tyrame.
MATERIAL AND METHODS
CD1 strain mice were used, which had Tyrame (0, 1 and 2 mg/100 g) subcutaneously administered. At 24 h, a blood sample was obtained to determine whole-blood clotting time, microvesicles concentration and inhibitory effect on platelet aggregation.
RESULTS
Blood clotting time increased up to 1.5 times in comparison with the control. Platelet aggregation inhibition had different magnitude depending on the agonist agent employed, and was complete with collagen. Both effects had a dose-dependent relationship. The microvesicles decreased up to six times with respect to the control.
CONCLUSIONS
Tyrame reduces platelet aggregation and microvesicle formation, which emphasizes its potential therapeutic utility as an estrogen free of thrombotic effects.
Topics: Animals; Anticoagulants; Fibrinolytic Agents; Mice; Phenethylamines; Platelet Aggregation; Thrombosis
PubMed: 35108248
DOI: 10.24875/GMM.M21000621 -
BioMed Research International 2016Antipsychotic drugs (APDs) used to treat clinical psychotic syndromes cause a variety of blood dyscrasias. APDs suppress the aggregation of platelets; however, the...
Antipsychotic drugs (APDs) used to treat clinical psychotic syndromes cause a variety of blood dyscrasias. APDs suppress the aggregation of platelets; however, the underlying mechanism remains unknown. We first analyzed platelet aggregation and clot formation in platelets treated with APDs, risperidone, clozapine, or haloperidol, using an aggregometer and rotational thromboelastometry (ROTEM). Our data indicated that platelet aggregation was inhibited, that clot formation time was increased, and that clot firmness was decreased in platelets pretreated with APDs. We also examined the role two major adenosine diphosphate (ADP) receptors, P2Y1 and P2Y12, play in ADP-mediated platelet activation and APD-mediated suppression of platelet aggregation. Our results show that P2Y1 receptor stimulation with ADP-induced calcium influx was inhibited by APDs in human and rats' platelets, as assessed by in vitro or ex vivo approach, respectively. In contrast, APDs, risperidone and clozapine, alleviated P2Y12-mediated cAMP suppression, and the release of thromboxane A2 and arachidonic acid by activated platelets decreased after APD treatment in human and rats' platelets. Our data demonstrate that each APD tested significantly suppressed platelet aggregation via different mechanisms.
Topics: Animals; Antipsychotic Agents; Cells, Cultured; Humans; Male; Platelet Aggregation; Rats; Rats, Sprague-Dawley; Receptors, Purinergic P2Y1; Receptors, Purinergic P2Y12
PubMed: 27069920
DOI: 10.1155/2016/2532371 -
Wiener Klinische Wochenschrift Jan 2023Acute thrombotic complications as a key feature of accelerated atherothrombotic disease typically precipitate cardiovascular events and therefore strongly contribute to...
Acute thrombotic complications as a key feature of accelerated atherothrombotic disease typically precipitate cardiovascular events and therefore strongly contribute to cardiovascular morbidity and mortality in patients with diabetes. Inhibition of platelet aggregation can reduce the risk for acute atherothrombosis. The present article represents the recommendations of the Austrian Diabetes Association for the use of antiplatelet drugs in patients with diabetes according to current scientific evidence.
Topics: Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Diabetes Mellitus; Thrombosis; Austria; Blood Platelets
PubMed: 37101038
DOI: 10.1007/s00508-023-02168-6 -
PloS One 2014Thrombocytopenia is a serious issue connected with the pathogenesis of several human diseases including chronic inflammation, arthritis, Alzheimer's disease,...
Thrombocytopenia is a serious issue connected with the pathogenesis of several human diseases including chronic inflammation, arthritis, Alzheimer's disease, cardiovascular diseases (CVDs) and other oxidative stress-associated pathologies. The indiscriminate use of antibiotics and other biological drugs are reported to result in thrombocytopenia, which is often neglected during the treatment regime. In addition, augmented oxidative stress induced by drugs and pathological conditions has also been shown to induce thrombocytopenia, which seems to be the most obvious consequence of elevated rate of platelet apoptosis. Thus, blocking oxidative stress-induced platelet apoptosis would be of prime importance in order to negotiate thrombocytopenia and associated human pathologies. The current study presents the synthesis and platelet protective nature of novel ibuprofen derivatives. The potent anti-oxidant ibuprofen derivative 4f was selected for the study and the platelet protective efficacy and platelet aggregation inhibitory property has been demonstrated. The compound 4f dose dependently mitigates the oxidative stress-induced platelet apoptosis in both platelet rich plasma and washed platelets. The platelet protective nature of compound 4f was determined by assessing various apoptotic markers such as ROS generation, cytosolic Ca2+ levels, PS externalization, cytochrome C translocation, Caspase activation, mitochondrial membrane depolarization, cytotoxicity, LDH leakage and tyrosine phosphorylation of cytosolic proteins. Furthermore, compound 4f dose dependently ameliorated agonist induced platelet aggregation. Therefore, compound 4f can be estimated as a potential candidate in the treatment regime of pathological disorders associated with platelet activation and apoptosis. In addition, compound 4f can be used as an auxiliary therapeutic agent in pathologies associated with thrombocytopenia.
Topics: Apoptosis; Blood Platelets; Dose-Response Relationship, Drug; Humans; Ibuprofen; Oxidative Stress; Platelet Aggregation; Reactive Oxygen Species
PubMed: 25238069
DOI: 10.1371/journal.pone.0107182 -
Acta Pharmacologica Sinica May 2017The signal transducer and activator of transcription 3 (STAT3) plays a critical role in platelet functions. This study sought to understand the effects of the STAT3...
The signal transducer and activator of transcription 3 (STAT3) plays a critical role in platelet functions. This study sought to understand the effects of the STAT3 inhibitor SC99 on platelet activation and aggregation. Immunoblotting assays were applied to measure the effects of SC99 on the STAT3 signaling pathway. A ChronoLog aggregometer was used to evaluate platelet aggregation. A flow cytometer was used to evaluate P-selectin expression in the presence of SC99. AlamarBlue and Annexin-V staining were used to evaluate platelet viability and apoptosis, respectively. A fluorescence microscope was applied to analyze platelet spreading. SC99 inhibited the phosphorylation of JAK2 and STAT3 in human platelets but had no effects on the phosphorylation of AKT, p65 or Src, all of which are involved in platelet activation. Further studies revealed that SC99 inhibited human platelet aggregation induced by collagen and thrombin in a dose-dependent manner. SC99 inhibited thrombin-induced P-selectin expression and fibrinogen binding to single platelets. Moreover, SC99 inhibited platelet spreading on fibrinogen and clot retraction mediated by outside-in signaling. SC99 inhibited platelet aggregation in mice but it did not significantly prolong the bleeding time. Taken together, the present study revealed that SC99 inhibited platelet activation and aggregation as a STAT3 inhibitor. This agent can be developed as a promising treatment for thrombotic disorders.
Topics: Animals; Bleeding Time; Clot Retraction; Humans; Hydrazones; Mice, Inbred C57BL; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; STAT3 Transcription Factor; Signal Transduction
PubMed: 28260800
DOI: 10.1038/aps.2016.155 -
Journal of the American Heart... Jul 2020Background There are sex differences in the efficacy and safety of aspirin for the prevention of myocardial infarction and stroke. Whether this is explained by...
Background There are sex differences in the efficacy and safety of aspirin for the prevention of myocardial infarction and stroke. Whether this is explained by underlying differences in platelet reactivity and aspirin response remains poorly understood. Methods and Results Healthy volunteers (n=378 208 women) and patients with coronary artery disease or coronary artery disease risk factors (n=217 112 women) took aspirin for 4 weeks. Light transmittance aggregometry using platelet-rich plasma was used to measure platelet reactivity in response to epinephrine, collagen, and ADP at baseline, 3 hours after the first aspirin dose, and after 4 weeks of daily aspirin therapy. A subset of patients underwent pharmacokinetic and pharmacodynamic assessment with levels of salicylate and cyclooxygenase-1-derived prostaglandin metabolites and light transmittance aggregometry in response to arachidonic acid and after ex vivo exposure to aspirin. At baseline, women had increased platelet aggregation in response to ADP and collagen. Innate platelet response to aspirin, assessed with ex vivo aspirin exposure of baseline platelets, did not differ by sex. Three hours after the first oral aspirin dose, platelet aggregation was inhibited in women to a greater degree in response to epinephrine and to a lesser degree with collagen. After 4 weeks of daily therapy, despite higher salicylate concentrations and greater cyclooxygenase-1 inhibition, women exhibited an attenuation of platelet inhibition in response to epinephrine and ADP. Conclusions We observed agonist-dependent sex differences in platelet responses to aspirin. Despite higher cyclooxygenase-1 inhibition, daily aspirin exposure resulted in a paradoxical attenuation of platelet inhibition in response to epinephrine and ADP over time in women but not in men.
Topics: Adult; Aged; Aspirin; Case-Control Studies; Cohort Studies; Female; Humans; Male; Middle Aged; Platelet Aggregation; Platelet Aggregation Inhibitors; Sex Characteristics; Young Adult
PubMed: 32654613
DOI: 10.1161/JAHA.119.014726 -
Environmental Health and Preventive... Nov 2020Resveratrol has been shown to inhibit platelet aggregation. However, the mechanism for this action of resveratrol remains to be clarified. The purpose of this study was...
BACKGROUND
Resveratrol has been shown to inhibit platelet aggregation. However, the mechanism for this action of resveratrol remains to be clarified. The purpose of this study was to elucidate the Ca-related mechanism for the inhibitory action of resveratrol on platelet aggregation.
METHODS
Ca entry and subsequent aggregation of human platelets induced by different stimulants including thrombin, thapsigargin, and 1-oleoyl-2-acetylglycerol (OAG) were measured by the fluorescence method and light transmittance method, respectively. Each stimulant was added to a nominally Ca-free medium containing platelets, and then CaCl was added to the medium to induce Ca influx into platelets.
RESULTS
Thapsigargin-induced Ca entry into platelets and subsequent platelet aggregation were significantly inhibited in the presence of resveratrol at 6.25 μM or higher concentrations, while OAG-induced Ca entry and subsequent platelet aggregation were not affected by resveratrol at concentrations up to 50 μM. In the nominally Ca-free medium, thrombin induced a small transient increase in intracellular Ca concentrations, which was attenuated in the presence of resveratrol at 12.5 μM or higher concentrations. Thrombin-induced Ca entry into platelets and subsequent platelet aggregation were significantly inhibited in the presence of resveratrol at 12.5 μM or higher concentrations.
CONCLUSIONS
The results suggest that resveratrol inhibits thrombin-induced platelet aggregation through decreasing Ca release from its stores and inhibiting store-operated Ca influx into platelets.
Topics: Antioxidants; Calcium; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Resveratrol; Signal Transduction
PubMed: 33160329
DOI: 10.1186/s12199-020-00905-1 -
BMC Veterinary Research Nov 2015Feline platelets are prone to clumping after blood collection, rendering the determination of accurate platelet counts difficult for clinical laboratories and resulting...
BACKGROUND
Feline platelets are prone to clumping after blood collection, rendering the determination of accurate platelet counts difficult for clinical laboratories and resulting in a high incidence of pseudothrombocytopenia in feline haematology reports. No information is available about the kinetics of platelet aggregate formation in feline ethylenediaminetetraacetic acid blood and the course of platelet counts over a clinically relevant time period. The aim of the present study was to determine platelet counts in healthy cats over a time period of 24 h after blood collection at 9 time points; to assess potential effects of platelet aggregates, anaesthesia and bleeding conditions on feline platelets and white blood cell counts; and finally, to investigate if glucose concentration is associated with the presence of aggregates. From 30 clinically healthy cats, blood samples were analysed at 9 different time points using two different haematology instruments (using fluorescence and impedance-based flow cytometry) in the counting chamber and by blood smear evaluation.
RESULTS
Fourteen of the 30 samples were thrombocytopenic at one to 8 time points after collection as analysed on a fluorescence flow cytometry haematology analyser. At the 24-h timepoint, all thrombocytopenic samples had returned to normal platelet counts. Seventeen of the 30 samples showed platelet aggregates in the counting chamber. Significant differences in platelet counts were associated with the presence and size of aggregates and time since bleeding. No statistically significant differences in counts were found with regard to the quality of blood collection or the use of anaesthesia. Platelet aggregation and, therefore, pseudothrombocytopenia occurred in 57 % of the investigated samples at different time points.
CONCLUSION
For the first time, deaggregation of feline platelet aggregates could be demonstrated as a reversible effect of platelet aggregation. For clinical laboratories or veterinarians, it may be helpful to rerun feline samples with pseudothrombocytopenia to obtain a more reliable platelet count. The quality of blood collection seems not to be causative for platelet aggregation. Blood smear evaluation is absolutely indicated in cases when haematology instruments give PLT counts below the reference interval.
Topics: Animals; Blood Glucose; Blood Platelets; Cats; Kinetics; Platelet Aggregation
PubMed: 26542105
DOI: 10.1186/s12917-015-0590-7 -
Blood Sep 2016
Topics: Guanine Nucleotide Exchange Factors; Humans; Platelet Aggregation; rap1 GTP-Binding Proteins
PubMed: 27587867
DOI: 10.1182/blood-2016-07-719906 -
Annals of Palliative Medicine May 2020Multiple organ failure complicated by coagulation dysfunction is an important cause of death in patients with sepsis. This study aimed to explore the clinical...
BACKGROUND
Multiple organ failure complicated by coagulation dysfunction is an important cause of death in patients with sepsis. This study aimed to explore the clinical significance of platelet maximum aggregation rate (MAR) in patients with sepsis and explored the relationship between MAR and prognosis to support treatment decision-making.
METHODS
Blood samples from patients with sepsis (diagnosed according to the 2016 international diagnostic criteria for sepsis 3.0) treated between Sep 2017 and Apr 2018 were assessed. Patients were excluded if they had any other condition or treatment that may have affected platelet function in the previous 2 weeks. A control group of healthy subjects attending the physical examination center in the same period was also included. The MAR was measured using a whole blood platelet function analyzer (PL-12) using a range of different inducers of platelet aggregation, and normal saline. MAR was assessed in the healthy and septic groups, and survivors and non-survivors were compared in the sepsis group 28 days after treatment.
RESULTS
The MAR in the sepsis group was significantly lower than that seen in the healthy group (P<0.05 for all inducers). The MAR of patients with sepsis was negatively correlated with their Sequential Organ Failure Assessment (SOFA) scores. In the sepsis group, the MAR of non-survivors was significantly lower than that of the survivors (P<0.05 for all inducers).
CONCLUSIONS
The platelet MAR was significantly decreased in patients with sepsis and in non-survivors. These data may support treatment decision-making in patients with sepsis.
Topics: Biomarkers; Case-Control Studies; Humans; Multiple Organ Failure; Platelet Aggregation; Prognosis; Sepsis
PubMed: 32498524
DOI: 10.21037/apm.2020.04.12