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International Journal of Molecular... Jun 2023Through a process termed , platelets cause thrombi to shrink and become more stable. After platelets are activated via inside-out signaling, glycoprotein αIIbβIII...
Through a process termed , platelets cause thrombi to shrink and become more stable. After platelets are activated via inside-out signaling, glycoprotein αIIbβIII binds to fibrinogen and initiates a cascade of intracellular signaling that ends in actin remodeling, which causes the platelet to change its shape. Clot retraction is also important for wound healing. Although the detailed molecular biology of clot retraction is only partially understood, various substances and physiological conditions modulate clot retraction. In this review, we describe some of the current literature pertaining to clot retraction modulators. In addition, we discuss compounds from , , and that diminish clot retraction and have numerous other health benefits. Caffeic acid and diindolylmethane, both common in plants and vegetables, likewise reduce clot retraction, as do all-trans retinoic acid (a vitamin A derivative), two MAP4K inhibitors, and the chemotherapeutic drug Dasatinib. Conversely, the endogenous anticoagulant Protein S (PS) and the matricellular protein secreted modular calcium-binding protein 1 (SMOC1) both enhance clot retraction. Most studies aiming to identify mechanisms of clot retraction modulators have focused on the increased phosphorylation of vasodilator-stimulated phosphoprotein and inositol 1,4,5-triphosphate receptor I and the decreased phosphorylation of various phospholipases (e.g., phospholipase A2 (PLA) and phosphatidylinositol-specific phospholipase Cγ2 (PLCγ), c-Jun N-terminal kinase, and (PI3Ks). One study focused on the decreased phosphorylation of Sarcoma Family Kinases (SFK), and others have focused on increased cAMP levels and the downregulation of inflammatory markers such as thromboxanes, including thromboxane A2 (TXA) and thromboxane B2 (TXB); prostaglandin A2 (PGE2); reactive oxygen species (ROS); and cyclooxygenase (COX) enzyme activity. Additionally, pregnancy, fibrinolysis, and the autoimmune condition systemic lupus erythematosus all seem to affect, or at least have some relation with, clot retraction. All the clot retraction modulators need in-depth study to explain these effects.
Topics: Blood Platelets; Clot Retraction; Phosphorylation; Platelet Aggregation; Signal Transduction
PubMed: 37445780
DOI: 10.3390/ijms241310602 -
Journal of the American Society of... Jul 2021Patients with CKD are at high risk for thrombotic and hemorrhagic complications. Abnormalities in platelet function are central to these complications, but reports on...
BACKGROUND
Patients with CKD are at high risk for thrombotic and hemorrhagic complications. Abnormalities in platelet function are central to these complications, but reports on platelet function in relation to CKD are conflicting, and vary from decreased platelet reactivity to normal or increased platelet responsiveness. The direct effects of uremic toxins on platelet function have been described, with variable findings.
METHODS
To help clarify how CKD affects platelet function, we conducted a systematic review and meta-analysis of platelet activity in CKD, with a focus on nondialysis-induced effects. We also performed an extensive literature search for the effects of individual uremic toxins on platelet function.
RESULTS
We included 73 studies in the systematic review to assess CKD's overall effect on platelet function in patients; 11 of them described CKD's effect on platelet aggregation and were included in the meta-analysis. Although findings on platelet abnormalities in CKD are inconsistent, bleeding time was mostly prolonged and platelet adhesion mainly reduced. Also, the meta-analysis revealed maximal platelet aggregation was significantly reduced in patients with CKD upon collagen stimulation. We also found that relatively few uremic toxins have been examined for direct effects on platelets ; analyses had varying methods and results, revealing both platelet-stimulatory and inhibitory effects. However, eight of the 12 uremic toxins tested in animal models mostly induced prothrombotic effects.
CONCLUSIONS
Overall, most studies report impaired function of platelets from patients with CKD. Still, a substantial number of studies find platelet function to be unchanged or even enhanced. Further investigation of platelet reactivity in CKD, especially during different CKD stages, is warranted.
PubMed: 33941607
DOI: 10.1681/ASN.2020101440 -
Journal of Community Hospital Internal... 2019: Clozapine is a second-generation antipsychotic used in refractory schizophrenia. Clozapine can lead to pulmonary embolism (PE) by various mechanisms including... (Review)
Review
: Clozapine is a second-generation antipsychotic used in refractory schizophrenia. Clozapine can lead to pulmonary embolism (PE) by various mechanisms including immobility, weight gain and increased platelet aggregation. : We performed a systematic review on published cases of PE associated with clozapine. : Comprehensive search of Medline, Embase and Cochrane library was done for relevant articles from inception until June 2017 : Total of 34 cases from 24 articles were included in the analysis. The mean age was 43.2 years with male predominance (63.6%). The mean dosage of clozapine was 281.4 mg daily. Duration of intake ranged from few days to many years. Nearly half of patients (47.82%) had no other co-morbidities for PE other than clozapine. For those reporting treatment, anticoagulation was chosen in 80%, thrombolysis in 10% and inferior vena cava filter placement in 5%. Mortality was 36.36% with three dying on presentation and an additional 9 dying during the follow-up period. Of the 18 patients in which follow-up data of clozapine were available, the drug was discontinued in 14 patients. : PE can occur at doses lower than usual dose of clozapine (300 mg daily). It is important to consider this association especially in patients with no other risk factors for PE.
PubMed: 31528276
DOI: 10.1080/20009666.2019.1627848 -
Clinical Neurology and Neurosurgery Sep 2023About 30 % of stroke patients have experienced unsuccessful reperfusion following endovascular therapy. Mechanical thrombectomy instruments may contribute to this by... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
About 30 % of stroke patients have experienced unsuccessful reperfusion following endovascular therapy. Mechanical thrombectomy instruments may contribute to this by stimulating platelet aggregation. Tirofiban is a selective and rapidly activated antagonist of the platelets nonpeptide glycoprotein IIb/IIIa receptors that can reversibly suppress platelet aggregation. But, data from the medical literature are conflicting regarding its safety and efficacy for stroke patients. Hence, this study was designed to assess the safety and efficacy of tirofiban in stroke patients.
METHODS
Five major databases (PubMed, Scopus, Web of Science, Embase, and Cochrane library) were searched till December 2022. The Cochrane tool was used for risk of bias assessment, and the RevMan 5.4 was utilized for data analysis.
RESULTS
Seven RCTs with 2088 stroke patients were included. Tirofiban significantly increased the number of patients with mRS 0 score after 90 days than control; RR= 1.39, 95 %CI [1.15, 1.69]; p = 0.0006. Additionally, it reduced the NIHSS score after seven days; MD= -0.60, 95 %CI [-1.14, -0.06]; p = 0.03. However, tirofiban increased the incidence of intracranial haemorrhage (ICH); RR= 1.22, 95 %CI [1.03, 1.44]; p = 0.02. Other assessed outcomes showed insignificant results.
CONCLUSIONS
Tirofiban was associated with a higher mRS 0 score after three months and a lower NIHSS score after seven days. However, it is associated with higher ICH. Multicentric trials are required to provide more convincing proof of its utility.
Topics: Humans; Tirofiban; Platelet Aggregation Inhibitors; Brain Ischemia; Treatment Outcome; Randomized Controlled Trials as Topic; Stroke; Intracranial Hemorrhages
PubMed: 37423089
DOI: 10.1016/j.clineuro.2023.107867 -
Medicine Dec 2023A systematic review and network meta-analysis (NMA) were conducted to explore the efficacy and safety of different antiplatelet or anticoagulation drugs in chronic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A systematic review and network meta-analysis (NMA) were conducted to explore the efficacy and safety of different antiplatelet or anticoagulation drugs in chronic coronary syndromes patients.
METHODS
Electronic databases (Pubmed, Embase and Cochrane databases) were systematically searched to identify randomized controlled trials evaluating different antiplatelet or anticoagulation drugs (aspirin, aspirin + clopidogrel, aspirin + clopidogrel + cilostazol, clopidogrel/prasugrel + aspirin, aspirin + rivaoxaban 2.5 mg, aspirin + ticagrelor 60 mg, aspirin + ticagrelor 90 mg, clopidogrel or rivroxaban 5 mg) versus placebo for treatment chronic coronary syndromes patients. Outcomes included major adverse cardiovascular events, all cause death, major bleeding and myocardial infarction. A random-effect Bayesian NMA was conducted for outcomes of interest, and results were presented as odds ratios (ORs) and 95% credible intervals. The NMA was performed using R Software with a GeMTC package. A Bayesian NMA was performed and relative ranking of agents was assessed using surface under the cumulative ranking probabilities.
RESULTS
Ten randomized controlled trials met criteria for inclusion and finally included in this NMA. In head-to-head comparison, no significant difference was observed between all antithrombotic treatment strategies with respect to primary endpoint of major adverse cardiovascular events. In head-to-head comparison, no significant difference was observed between all antithrombotic treatment strategies with respect to all cause death. Clopidogrel/prasugrel + aspirin (OR = 3.8, 95% credible intervals [CrI]: 1.3-12.0, P < .05) and aspirin + rivaroxaban 2.5 mg (OR = 3.1, 95%CrI: 1.1-9.5, P < .05) was associated with an increase of the major bleeding. Compared with aspirin alone, aspirin + clopidogrel (OR = 0.42, 95%CrI: 0.22-0.76, P < .05) and aspirin + ticagrelor 90 mg (OR = 0.42, 95%CrI: 0.17-0.95, P < .05) was associated with a decrease of the myocardial infarction.
CONCLUSIONS
Myocardial infarction was significantly lower when adding clopidogrel or ticagrelor 90 mg to aspirin than those in the aspirin alone group. However, clopidogrel/prasugrel and rivaroxaban 2.5 mg was associated with an increase of the major bleeding than aspirin alone.
Topics: Humans; Clopidogrel; Platelet Aggregation Inhibitors; Ticagrelor; Prasugrel Hydrochloride; Rivaroxaban; Network Meta-Analysis; Bayes Theorem; Fibrinolytic Agents; Aspirin; Myocardial Infarction; Hemorrhage; Anticoagulants; Acute Coronary Syndrome; Treatment Outcome
PubMed: 38050293
DOI: 10.1097/MD.0000000000036429 -
Behavioural Neurology 2022There have been speculation and research linking migraine with abnormalities of platelet aggregation and activation. The role of the P2Y12 platelet inhibitor in the... (Meta-Analysis)
Meta-Analysis Review
There have been speculation and research linking migraine with abnormalities of platelet aggregation and activation. The role of the P2Y12 platelet inhibitor in the treatment of migraine has not been established. We aim to evaluate the efficacy of the platelet P2Y12 inhibitor in the treatment of migraine and prevention of new-onset migraine headache (MHA) following transcatheter atrial septal defect closure (ASDC). We searched the PubMed, Web of Science, and Cochrane Library databases for relevant studies. The primary outcomes were the headache responder rate and the rate of new-onset migraine attacks following ASDC. Four studies for a total of 262 migraine patients with or without patent foramen ovale (PFO) and three studies involving 539 patients with antiplatelet treatment in the prevention of new-onset migraine following ASDC were included. The pooled responder rate of the P2Y12 inhibitor for migraine was 0.64 (95% CI: 0.43 to 0.81). For patients who underwent ASDC, the use of antiplatelet regimens including the P2Y12 inhibitor, compared with regimens excluding P2Y12 inhibitor, resulted in a lower rate of new-onset migraine (OR: 0.41, 95% CI: 0.22 to 0.77, = 0.005). We concluded that the P2Y12 platelet inhibitor may have a primary prophylactic role in migraine patients with or without PFO and prevent new-onset MHA after ASDC. The responsiveness of the P2Y12 inhibitor could help select candidates who would benefit from PFO closure. It warrants further large-scale research to explore the role of the P2Y12 inhibitor, particularly in a proportion of migraine patients.
Topics: Cardiac Catheterization; Foramen Ovale, Patent; Humans; Migraine Disorders; Platelet Aggregation Inhibitors
PubMed: 35355664
DOI: 10.1155/2022/2118740 -
Iranian Journal of Medical Sciences Nov 2022Platelet aggregation is a crucial mechanism in the progression of atherothrombotic events. This systematic review aims to introduce the plants studied in healthy people... (Review)
Review
BACKGROUND
Platelet aggregation is a crucial mechanism in the progression of atherothrombotic events. This systematic review aims to introduce the plants studied in healthy people as the primary prevention to inhibit platelet aggregation. We also discuss possible mechanisms that are involved in the inhibition of platelet aggregation.
METHODS
A systematic search on the electronic medical databases from 1970 to February 2020 was performed. The selected keywords were: "herb", "plant", "platelet aggregation", "platelet activation", "clinical trial", "randomized" and "controlled".
RESULTS
The result of the initial search was a pool of 136 articles. After initial abstract reviewing, there were 55 relevant articles. Finally, 28 eligible records fulfilled our inclusion criteria to enter the qualitative synthesis process.
CONCLUSION
Out of the 10 plants evaluated in the clinical trials, nine had inhibitory effects on platelet aggregation. Most of the reviewed plants, including tomato ( L), garlic (), kiwifruit (), cacao (), grape (), ginkgo (), flaxseed (), sea buckthorn berry (), and argan () could be potential sources for the primary prevention of atherothrombotic events at an appropriate dosage. Finally, we do not consider phytoceuticals as a replacement for the guideline-directed medical treatment. Large randomized double-blind clinical trials are required to evaluate the anti-platelet characteristics of these plants for the adjuvant primary prevention of cardiovascular disease.
Topics: Humans; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Platelet Aggregation; Ginkgo biloba; Garlic; Hippophae; Primary Prevention
PubMed: 36380973
DOI: 10.30476/IJMS.2021.91328.2247 -
European Journal of Vascular and... Mar 2022The aim was to enhance understanding of the role of platelet biomarkers in the pathogenesis of vascular events and risk stratifying patients with asymptomatic or... (Review)
Review
OBJECTIVE
The aim was to enhance understanding of the role of platelet biomarkers in the pathogenesis of vascular events and risk stratifying patients with asymptomatic or symptomatic atherosclerotic carotid stenosis.
DATA SOURCES
Systematic review conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.
REVIEW METHODS
A systematic review collated data from 1975 to 2020 on ex vivo platelet activation and platelet function/reactivity in patients with atherosclerotic carotid stenosis.
RESULTS
Forty-three studies met the inclusion criteria; the majority included patients on antiplatelet therapy. Five studies showed increased platelet biomarkers in patients with ≥ 30% asymptomatic carotid stenosis (ACS) vs. controls, with one neutral study. Preliminary data from one study suggested that quantification of "coated platelets" in combination with stenosis severity may aid risk stratification in patients with ≥ 50% - 99% ACS. Platelets were excessively activated in patients with ≥ 30% symptomatic carotid stenosis (SCS) vs. controls (≥ 11 positive studies and one neutral study). Antiplatelet-High on Treatment Platelet Reactivity (HTPR), previously called "antiplatelet resistance", was observed in 23% - 57% of patients on aspirin, with clopidogrel-HTPR in 25% - 100% of patients with ≥ 50% - 99% ACS. Aspirin-HTPR was noted in 9.5% - 64% and clopidogrel-HTPR in 0 - 83% of patients with ≥ 50% SCS. However, the data do not currently support the use of ex vivo platelet function/reactivity testing to tailor antiplatelet therapy outside of a research setting. Platelets are excessively activated (n = 5), with increased platelet counts (n = 3) in recently symptomatic vs. asymptomatic patients, including those without micro-emboli on transcranial Doppler (TCD) monitoring (n = 2). Most available studies (n = 7) showed that platelets become more reactive or activated following carotid endarterectomy or stenting, either as an acute phase response to intervention or peri-procedural treatment.
CONCLUSION
Platelets are excessively activated in patients with carotid stenosis vs. controls, in recently symptomatic vs. asymptomatic patients, and may become activated/hyper-reactive following carotid interventions despite commonly prescribed antiplatelet regimens. Further prospective multicentre studies are required to determine whether models combining clinical, neurovascular imaging, and platelet biomarker data can facilitate optimised antiplatelet therapy in individual patients with carotid stenosis.
Topics: Aspirin; Biomarkers; Blood Platelets; Carotid Stenosis; Humans; Platelet Aggregation Inhibitors; Stroke
PubMed: 35181225
DOI: 10.1016/j.ejvs.2021.10.045 -
The Cochrane Database of Systematic... Jan 2022In people with acute ischaemic stroke, platelets become activated and can cause blood clots to form and block an artery in the brain, resulting in damage to part of the... (Review)
Review
BACKGROUND
In people with acute ischaemic stroke, platelets become activated and can cause blood clots to form and block an artery in the brain, resulting in damage to part of the brain. Such damage gives rise to the symptoms of stroke. Antiplatelet therapy might reduce the volume of brain damaged by ischaemia and also reduce the risk of early recurrent ischaemic stroke, thereby reducing the risk of early death and improving long-term outcomes in survivors. However, antiplatelet therapy might also increase the risk of fatal or disabling intracranial haemorrhage.
OBJECTIVES
To assess the efficacy and safety of immediate oral antiplatelet therapy (i.e. started as soon as possible and no later than two weeks after stroke onset) in people with acute presumed ischaemic stroke.
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, and two trials registers, and performed forward reference/cited reference searching in August 2020.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing oral antiplatelet therapy (started within 14 days of the stroke) with control in people with definite or presumed ischaemic stroke.
DATA COLLECTION AND ANALYSIS
Two review authors independently applied the inclusion criteria and assessed trial quality. For the included trials, they extracted and cross-checked the data. They assessed risk of bias of each study using the Risk of Bias 1 (RoB1) tool and overall certainty of the evidence for each outcome using the GRADE approach.
MAIN RESULTS
We included 11 studies involving 42,226 participants. Three new trials have been added since the last update (743 participants). As per the previous version of this review, two trials testing aspirin 160 mg to 300 mg once daily, started within 48 hours of onset, contributed 96% of the data. The risk of bias was low. The maximum follow-up was six months. With treatment, there was a decrease in death or dependency at the end of follow-up (odds ratio (OR) 0.95, 95% confidence interval (CI) 0.91 to 0.99; 7 RCTs, 42,034 participants; moderate-certainty evidence). For every 1000 people treated with aspirin, 13 people would avoid death or dependency (number needed to treat for an additional beneficial outcome 79).
AUTHORS' CONCLUSIONS
Antiplatelet therapy with aspirin 160 mg to 300 mg daily, given orally (or by nasogastric tube or per rectum in people who cannot swallow) and started within 48 hours of onset of presumed ischaemic stroke, significantly decreased death and dependency, and reduced the risk of early recurrent ischaemic stroke without a major risk of early haemorrhagic complications; long-term outcomes were improved.
Topics: Aspirin; Brain Ischemia; Humans; Ischemic Stroke; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stroke
PubMed: 35028933
DOI: 10.1002/14651858.CD000029.pub4 -
Brain and Behavior Oct 2022We aimed to investigate the prescription of antithrombotic drugs (including anticoagulants and antiplatelets) and medication adherence after stroke. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
We aimed to investigate the prescription of antithrombotic drugs (including anticoagulants and antiplatelets) and medication adherence after stroke.
METHODS
We performed a systematic literature search across MEDLINE and Embase, from January 1, 2015, to February 17, 2022, to identify studies reporting antithrombotic medications (anticoagulants and antiplatelets) post stroke. Two people independently identified reports to include, extracted data, and assessed the quality of included studies according to the Newcastle-Ottawa scale. Where possible, data were pooled using random-effects meta-analysis.
RESULTS
We included 453,625 stroke patients from 46 studies. The pooled proportion of prescribed antiplatelets and anticoagulants among patients with atrial fibrillation (AF) was 62% (95% CI: 57%-68%), and 68% (95% CI: 58%-79%), respectively. The pooled proportion of patients who were treated according to the recommendation of guidelines of antithrombotic medications from four studies was 67% (95% CI: 41%-93%). It was reported that 11% (95% CI: 2%-19%) of patients did not receive antithrombotic medications. Good adherence to antiplatelet, anticoagulant, and antithrombotic medications was 78% (95% CI: 67%-89%), 71% (95% CI: 57%-84%), and 73% (95% CI: 59%-86%), respectively.
CONCLUSION
In conclusion, we found that less than 70% of patients were prescribed and treated according to the recommended guidelines of antithrombotic medications, and good adherence to antithrombotic medications is only 73%. Prescription rate and good adherence to antithrombotic medications still need to be improved among stroke survivors.
Topics: Anticoagulants; Fibrinolytic Agents; Humans; Platelet Aggregation Inhibitors; Prescriptions; Stroke; Survivors
PubMed: 36067030
DOI: 10.1002/brb3.2752