-
BMC Medicine Nov 2020Antiretroviral therapy (ART) alters platelet reactivity, and as a consequence, patients living with HIV may be at an increased risk of cardiovascular disease (CVD). The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antiretroviral therapy (ART) alters platelet reactivity, and as a consequence, patients living with HIV may be at an increased risk of cardiovascular disease (CVD). The current evidence on platelet activation levels in patients with HIV remains inconclusive. We therefore aimed to systematically synthesise evidence on the association of platelet activation in HIV-infected patients on successful treatment.
METHODS
Electronic databases were searched from inception until November 2019. Studies were included if the primary or secondary outcome of the study was to assess platelet activation in HIV-infected patients on ART. The primary outcome of this review included the levels of platelet activation. The pooled effect estimates were calculated using a random-effects meta-analysis model.
RESULTS
We identified 30 studies comprising of 2325 participants. The pooled estimates showed elevated levels of platelet activation in treatment-naïve HIV-infected patients compared to uninfected controls (Hedges' g 2.00 [95%CI 1.05, 2.94]; z = 4.12, p < 0.0001). These remained elevated despite successful ART (Hedges' g 2.05 [95%CI 0.58, 3.52]; z = 2.71, p = 0.0067).
CONCLUSION
The levels of platelet activation are elevated in treatment-naïve HIV-infected patients, and these persist during successful ART. Further studies should assess the clinical relevance of monitoring the levels of platelet activation in HIV-infected patients on ART.
Topics: Anti-Retroviral Agents; Cardiovascular Diseases; HIV Infections; Humans; Platelet Activation
PubMed: 33203400
DOI: 10.1186/s12916-020-01801-9 -
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 -
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 -
British Journal of Clinical Pharmacology Nov 2014Platelets play an important role in cardiovascular disease, and β-blockers are often prescribed for cardiovascular disease prevention. β-Blockers may directly affect... (Meta-Analysis)
Meta-Analysis Review
AIMS
Platelets play an important role in cardiovascular disease, and β-blockers are often prescribed for cardiovascular disease prevention. β-Blockers may directly affect platelet aggregation, because β-adrenergic receptors are present on platelets. There is uncertainty about the existence and magnitude of an effect of β-blockers on platelet aggregation. The aim of this study was to perform a systematic review and meta-analysis of the effect of β-blockers on platelet aggregation.
METHODS
MEDLINE and EMBASE were searched until April 2014. Two reviewers independently performed data extraction and risk of bias assessment. Type of β-blocker, population, treatment duration and platelet aggregation were extracted. Standardized mean differences were calculated for each study and pooled in a random-effects meta-analysis.
RESULTS
We retrieved 31 studies (28 clinical trials and three observational studies). β-Blockers decreased platelet aggregation (standardized mean difference -0.54, 95% confidence interval -0.85 to -0.24, P < 0.0001). This corresponds to a reduction of 13% (95% confidence interval 8-17%). Nonselective lipophilic β-blockers decreased platelet aggregation more than selective nonlipophilic β-blockers.
CONCLUSIONS
Clinically used β-blockers significantly reduce platelet aggregation. Nonselective lipophilic β-blockers seem to reduce platelet aggregation more effectively than selective nonlipophilic β-blockers. These findings may help to explain why some β-blockers are more effective than others in preventing cardiovascular disease.
Topics: Adrenergic beta-Antagonists; Cardiovascular Diseases; Clinical Trials as Topic; Humans; Observational Studies as Topic; Platelet Aggregation
PubMed: 24730697
DOI: 10.1111/bcp.12404 -
Orthopaedic Journal of Sports Medicine Apr 2020Platelet-rich plasma (PRP) has wide applications in orthopaedic care. Its beneficial effects are attributed to the growth factor profile from the platelet secretome. In... (Review)
Review
BACKGROUND
Platelet-rich plasma (PRP) has wide applications in orthopaedic care. Its beneficial effects are attributed to the growth factor profile from the platelet secretome. In theory, these effects would be diminished by medications that inhibit platelet activation and/or the subsequent release of growth factors.
PURPOSE
To determine whether commonly used antiplatelets, nonsteroidal anti-inflammatory drugs (NSAIDs), or anticoagulant medications affect platelet growth factor release in PRP.
STUDY DESIGN
Systematic review; Level of evidence, 2.
METHOD
A systematic review of the literature related to antiplatelet, anti-inflammatory, and anticoagulant drugs was performed following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We used the Downs and Black objective quality scoring system. The literature search consisted of PubMed and Cochrane Library databases. Search terms consisted of 1 item selected from "platelet-rich plasma," "platelet-derived growth factor," and "platelet-rich plasma AND growth factor" combined with 1 item from "antiplatelet," "aspirin," "anticoagulant," and "NSAID." Only studies published within the past 25 years were included.
RESULTS
A total of 15 studies met the inclusion criteria: 7 studies detected no significant decrease in growth factors or mitogenesis, whereas 6 detected a decrease with antiplatelet agents, 1 detected mixed results with an antiplatelet agent, and 1 had mixed results with an antiplatelet agent/vasodilator. In terms of PRP activation, all 3 studies assessing collagen, the 2 studies analyzing adenosine diphosphate alone, and the 1 study investigating arachidonic acid found a decrease in growth factor concentration.
CONCLUSION
Antiplatelet medications may decrease the growth factor release profile in a cyclooxygenase 1- and cyclooxygenase 2-dependent manner. Eight of 15 studies found a decrease in growth factors or mitogenesis. However, more studies are needed to comprehensively understand antiplatelet effects on the PRP secretome.
PubMed: 32426401
DOI: 10.1177/2325967120912841 -
Aging Jul 2021Platelet activation plays an important role in the progression of pulmonary embolism (PE). Mean platelet volume (MPV) can serve as a marker of platelet activity in... (Meta-Analysis)
Meta-Analysis
Platelet activation plays an important role in the progression of pulmonary embolism (PE). Mean platelet volume (MPV) can serve as a marker of platelet activity in patients with PE. Many studies have reported different results regarding the relationship. Therefore, we aimed to perform a systematic review and meta-analysis to evaluate the relationship between MPV and PE. Two reviewers independently searched relevant articles in databases from inception to April 21, 2021 and identified all studies on MPV and PE as the outcomes of interest. Further, we selected studies meeting the criteria and extracted the data. Of the 2505 publications identified, we included 18 studies after screening. Results showed MPV was significantly higher in patients with PE (0.83 fL, 95% CI: 0.38-1.28, P<0.001) than in controls. The mean difference in MPV between those who died and survivors of PE was 1.23 fL (95% CI: 0.96-1.51, P<0.001). Hence, an increased MPV is associated with PE. MPV could be a useful tool to predict the occurrence and death risk of PE together with other risk factors.
Topics: Biomarkers; Humans; Mean Platelet Volume; Platelet Activation; Predictive Value of Tests; Prognosis; Pulmonary Embolism
PubMed: 34214051
DOI: 10.18632/aging.203205 -
Medicine Dec 2021The relationship between platelet-associated parameters and psoriasis has been controversial. The purpose of our meta-analysis was to assess whether platelet count,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The relationship between platelet-associated parameters and psoriasis has been controversial. The purpose of our meta-analysis was to assess whether platelet count, platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), and platelet distribution width (PDW) are associated with psoriasis.
METHODS
We performed a thorough documentation retrieval via PubMed, EMBASE, and Web of Science until June 2021. Pooled standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated using a random-effects model.
RESULTS
Overall, 22 studies involving 1749 patients with psoriasis and 1538 healthy controls were selected for the meta-analysis. The outcomes showed that platelet count presented non-significant differences between psoriatic patients and normal individuals (SMD = 0.12, 95% CI = -0.07 to 0.32, P = .210), while PLR (SMD = 0.28, 95% CI = 0.03-0.53, P = .031), MPV (SMD = 0.55, 95% CI = 0.30-0.79, P < .001), and PDW (SMD = 0.29, 95% CI = 0.03-0.55, P = .027) were remarkably greater in the psoriatic patients than in the healthy individuals, and similar results were found in subgroup analyses. The analytical results of susceptibility revealed that the outcomes were robust, and no evidence of substantial publication bias was identified.
CONCLUSION
Patients with psoriasis present significantly higher PLR, MPV, and PDW than healthy individuals, suggesting that psoriasis is accompanied by low-grade systemic inflammation and platelet activation.
Topics: Biomarkers; Blood Platelets; Health Status; Humans; Lymphocyte Count; Mean Platelet Volume; Platelet Count; Psoriasis
PubMed: 34918687
DOI: 10.1097/MD.0000000000028234 -
Thrombosis and Haemostasis Jun 2022Cardiovascular disease, in particular due to arterial thrombosis, is a leading cause of mortality and morbidity, with crucial roles of platelets in thrombus formation....
Cardiovascular disease, in particular due to arterial thrombosis, is a leading cause of mortality and morbidity, with crucial roles of platelets in thrombus formation. For multiple plant-derived phytochemicals found in common dietary components, claims have been made regarding cardiovascular health and antiplatelet activities. Here we present a systematic overview of the published effects of common phytochemicals, applied in vitro or in nutritional intervention studies, on agonist-induced platelet activation properties and platelet signaling pathways. Comparing the phytochemical effects per structural class, we included general phenols: curcuminoids (e.g., curcumin), lignans (honokiol, silybin), phenolic acids (caffeic and chlorogenic acid), derivatives of these (shikimic acid), and stilbenoids (isorhapontigenin, resveratrol). Furthermore, we evaluated the flavonoid polyphenols, including anthocyanidins (delphinidin, malvidin), flavan-3-ols (catechins), flavanones (hesperidin), flavones (apigenin, nobiletin), flavonols (kaempferol, myricetin, quercetin), and isoflavones (daidzein, genistein); and terpenoids including carotenes and limonene; and finally miscellaneous compounds like betalains, indoles, organosulfides (diallyl trisulfide), and phytosterols. We furthermore discuss the implications for selected phytochemicals to interfere in thrombosis and hemostasis, indicating their possible clinical relevance. Lastly, we provide guidance on which compounds are of interest for further platelet-related research.
Topics: Blood Platelets; Flavonoids; Hemostasis; Humans; Phenols; Phytochemicals; Thrombosis
PubMed: 34715717
DOI: 10.1055/a-1683-5599 -
Critical Care (London, England) Aug 2018Platelets (PLTs) are usually stored for up to 5 days prior to transfusion, although in some blood services the storage period is extended to 7 days. During storage,...
BACKGROUND
Platelets (PLTs) are usually stored for up to 5 days prior to transfusion, although in some blood services the storage period is extended to 7 days. During storage, changes occur in both PLT and storage medium, which may lead to PLT activation and dysfunction. The clinical significance of these changes remains uncertain.
METHODS
We performed a systematic review to assess the association between PLT storage time and clinical or transfusion outcomes in patients receiving allogeneic PLT transfusion. We searched studies published in English between January 2000 and July 2017 identified from MEDLINE, Embase, PubMed and the Cochrane Libraries.
RESULTS
Of the 18 studies identified, five included 4719 critically ill patients (trauma, post-cardiac surgery and a heterogeneous population of critically ill patients) and 13 included 8569 haematology patients. The five studies in critically ill patients were retrospective and did not find any association between PLT storage time when PLTs were stored for up to 5 days and mortality. There was also no association between older PLTs and sepsis in the two largest studies (n = 4008 patients). Of the 13 studies in haematology patients, seven analysed prolonged storage time up to 6.5 or 7 days. Administration of fresh PLTs (less than 2 or 3 days) was associated with a significant increase in corrected count increment (CCI) compared to older PLTs in seven of the eight studies analysing this outcome. One single centre retrospective study found an increase in bleeding events in patients receiving older PLTs.
CONCLUSIONS
PLT storage time does not appear to be associated with clinical outcomes, including bleeding, sepsis or mortality, in critically ill patients or haematology patients. The freshest PLTs (less than 3 days) were associated with a better CCI, although there was no impact on bleeding events, questioning the clinical significance of this association. However, there is an absence of evidence to draw definitive conclusions, especially in critically ill patients.
Topics: Blood Platelets; Critical Illness; Drug Storage; Humans; Platelet Transfusion; Treatment Outcome
PubMed: 30077181
DOI: 10.1186/s13054-018-2114-x -
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