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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 Clinical Medicine Jul 2023The measurement and identification of plasma biomarkers can support the estimation of risk and diagnosis of deep vein thrombosis (DVT) associated with the use of a... (Review)
Review
BACKGROUND
The measurement and identification of plasma biomarkers can support the estimation of risk and diagnosis of deep vein thrombosis (DVT) associated with the use of a peripherally inserted central catheter (PICC).
OBJECTIVES
This systematic review and meta-analysis aimed to identify the association between the levels of potential biomarkers that reflect the activation of the blood system, long-term vascular complications, inflammatory system, and the occurrence of PICC-related DVT.
METHODS
Seven electronic databases (Embase, Web of Science, Medline, Scopus, Cinahl, Cochrane Central Register of Controlled Trials, and ERIC) were searched to identify literature published until December 2022. Studies were required to report: (I) adult and pediatric patients, outpatient or admitted to clinical, surgical, or ICU with PICC; (II) patients with PICC-related DVT and patients without PICC-related DVT as a comparator; and (III) at least one biomarker available. The Newcastle-Ottawa Scale was used to evaluate the quality of the studies. Study precision was evaluated by using a funnel plot for platelets level. We provided a narrative synthesis and meta-analysis of the findings on the biomarkers' outcomes of the studies. We pooled the results using random effects meta-analysis. The meta-analysis was conducted using Review Manager software v5.4. This systematic review is registered in PROSPERO (CRD42018108871).
RESULTS
Of the 3564 studies identified (after duplication removal), 28 were included. PICC-related DVT was associated with higher D-dimers (0.37 μg/mL, 95% CI 0.02, 0.72; = 0.04, I = 92%; for heterogeneity < 0.00001) and with higher platelets (8.76 × 10/L, 95% CI 1.62, 15.91; = 0.02, I = 41%; for heterogeneity = 0.06).
CONCLUSIONS
High levels of D-dimer and platelet were associated with DVT in patients with PICC. However, biomarkers such as APTT, fibrinogen, FDP, glucose, hemoglobin, glycated hemoglobin, INR, prothrombin time, prothrombin fragment 1.2, the thrombin-antithrombin complex, and WBC were not related to the development of DVT associated with PICC.
PubMed: 37445515
DOI: 10.3390/jcm12134480 -
Journal of Thrombosis and Thrombolysis Aug 2023Heparin-induced thrombocytopenia (HIT) occurs in approximately 3% of patients receiving heparinoids. About 30-75% of patients with type 2 of HIT develop thrombosis as a... (Meta-Analysis)
Meta-Analysis Review
Heparin-induced thrombocytopenia (HIT) occurs in approximately 3% of patients receiving heparinoids. About 30-75% of patients with type 2 of HIT develop thrombosis as a result of platelet activation. The most important clinical symptom is thrombocytopenia. Patients with severe COVID-19 are among those receiving heparinoids. This meta-analysis performed to picture the current knowledge and results of published studies in this field. Three search engines were searched and 575 papers were found. After evaluation, 37 articles were finally selected of which 13 studies were quantitatively analyzed. The pooled frequency rate of suspected cases with HIT in 13 studies with 11,241 patients was 1.7%. The frequency of HIT was 8.2% in the extracorporeal membrane oxygenation subgroup with 268 patients and 0.8% in the hospitalization subgroup with 10,887 patients. The coincidence of these two conditions may increase the risk of thrombosis. Of the 37 patients with COVID-19 and confirmed HIT, 30 patients (81%) were treated in the intensive care unit or had severe COVID-19. The most commonly used anticoagulants were UFH in 22 cases (59.4%). The median platelet count before treatment was 237 (176-290) x 10/µl and the median nadir platelet count was 52 (31-90.5) x 10/µl.
Topics: Humans; Heparin; Heparinoids; COVID-19; Thrombocytopenia; Anticoagulants; Thrombosis
PubMed: 37219826
DOI: 10.1007/s11239-023-02827-5 -
Seminars in Thrombosis and Hemostasis Apr 2024Cancer-associated thrombosis (CAT) is a major cause of both morbidity and mortality in cancer patients. Platelet count has been investigated as a predictor of CAT in... (Meta-Analysis)
Meta-Analysis
Cancer-associated thrombosis (CAT) is a major cause of both morbidity and mortality in cancer patients. Platelet count has been investigated as a predictor of CAT in various settings while knowledge on platelet activation parameters is sparse. This report provides a systematic review and meta-analysis on available literature on associations between platelet count and/or function and arterial and venous thrombosis in adult cancer patients. The review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. PubMed and Embase were searched up to March 2022. The National Heart, Lung, and Blood Institute's tools were used for quality assessment. In total, 100 studies were included which investigated the association between CAT and platelet count ( = 90), platelet indices ( = 19), and platelet function/activation markers ( = 13) in patients with solid cancers ( = 61), hematological cancers ( = 17), or mixed cancer types ( = 22). Eighty-one studies had venous thrombosis as their outcome measure, while 4 had arterial thrombosis and 15 studies had both. We found significantly elevated odds ratio of 1.50 (95% confidence interval: 1.19-1.88) for thrombosis with higher platelet counts. We saw a tendency toward an association between markers of platelet activation in forms of mean platelet volume and soluble P selectin and both arterial and venous thrombosis. Only one study investigated dynamic platelet function using flow cytometry. In conclusion, platelet count is associated with CAT across different cancer types and settings. Platelet function or activation marker analysis may be valuable in assisting thrombosis risk assessment in cancer patients but is sparsely investigated so far.
Topics: Adult; Humans; Thrombosis; Platelet Count; Venous Thrombosis; Neoplasms; Biomarkers
PubMed: 36921613
DOI: 10.1055/s-0043-1764381 -
Thrombosis Research Nov 2023Regular exercise training is essential in prevention and treatment of cardiovascular disease (CVD), yet the beneficial effects of exercise remain only partly explained....
INTRODUCTION
Regular exercise training is essential in prevention and treatment of cardiovascular disease (CVD), yet the beneficial effects of exercise remain only partly explained. Platelets play a key role in CVD and may be affected by regular exercise training. We aimed to systematically summarise studies investigating the effect of regular exercise training on platelet function in patients with CVD and in healthy individuals.
METHODS
Studies were identified by PubMed, Embase and Web of Science May 16, 2022. We selected studies investigating markers of platelet function in relation to regular exercise training in patients with CVD and in healthy individuals. Regular exercise was defined as exercise training for four weeks or more.
RESULTS
Of the included studies, 11 investigated patients with CVD and 29 were on healthy individuals. Studies were heterogeneous regarding design, study population and methodology, and the results were ambiguous. In total, 52 different markers of platelet function were investigated with platelet aggregation, soluble P-selectin, and thromboxane B (TXB) as the most frequently examined. When evaluating between-group changes after regular exercise, two studies found a reduced platelet aggregation in the exercise group whilst three studies did not find a difference between groups. With respect to TXB, three studies reported a reduction and two studies an increase in the exercise group. There were no between-group differences in the seven studies examining soluble P-selectin.
CONCLUSION
Regular exercise training has no clear impact on platelet function in patients with CVD or healthy individuals.
PROSPERO REGISTRATION
CRD42022350539.
Topics: Humans; P-Selectin; Cardiovascular Diseases; Platelet Aggregation; Blood Platelets; Exercise
PubMed: 36609119
DOI: 10.1016/j.thromres.2022.12.017 -
Clinical Rheumatology May 2023Platelet-rich plasma (PRP) has shown to be clinically effective in the treatment of knee osteoarthritis (OA). Notwithstanding, some inconsistences remain due to... (Meta-Analysis)
Meta-Analysis
Comparison of the clinical effectiveness of activated and non-activated platelet-rich plasma in the treatment of knee osteoarthritis: a systematic review and meta-analysis.
INTRODUCTION/OBJECTIVES
Platelet-rich plasma (PRP) has shown to be clinically effective in the treatment of knee osteoarthritis (OA). Notwithstanding, some inconsistences remain due to methodological differences in PRP preparation such as the use (or not) of activation strategies. We aimed to evaluate whether the use of non-activated PRP would be as effective as activated PRP in patients with knee OA.
METHOD
All randomized, placebo-controlled trials were identified through a search in MEDLINE, EMBASE, Scopus, and Web of Science up to June 2022. Pre- and post-injection pain and function scores were collected. The meta-analysis was conducted with a random-effects model and generic inverse variance method. Effect sizes were estimated using standardized mean differences (SMD).
RESULTS
Fourteen clinical trials involving 1292 subjects were included for meta-analysis. Exogenous activation of PRP revealed a significant pain relief (SMD, - 1.05 [95% CI - 1.58 to - 0.52]; p = 0.0001) and a significant functional improvement (SMD, - 1.21 [95% CI - 1.75 to - 0.67]; p < 0.0001) unlike studies describing the use of a non-activated PRP. The sensitivity analysis indicated that the effect size for both outcomes was not influenced by a single study.
CONCLUSIONS
The results of this systematic review suggest that the use of an exogenously activated PRP is more effective in improving both pain and functional scores in patients with knee OA. Key Points • Results from meta-analysis suggest that exogenously activated PRP is clinically more effective than non-activated PRP. • The use of an activated PRP was more frequently reported by the included studies. • The most frequent method for activation was the use of calcium chloride (CaCl).
Topics: Humans; Osteoarthritis, Knee; Treatment Outcome; Pain; Injections, Intra-Articular; Platelet-Rich Plasma; Hyaluronic Acid
PubMed: 36502442
DOI: 10.1007/s10067-022-06463-x -
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 -
Phytomedicine : International Journal... Jan 2023Cardiovascular disease is one of the most concerning chronic diseases in the world. Many studies have shown that platelet overactivation is a very important factor in...
BACKGROUND
Cardiovascular disease is one of the most concerning chronic diseases in the world. Many studies have shown that platelet overactivation is a very important factor in the occurrence and development of cardiovascular diseases. At present, the widely used antiplatelet drugs have some defects, such as drug resistance and adverse reactions.
PURPOSE
The purpose of this article is to summarize the main mechanisms and pathways of platelet activation, the main targets of antiplatelet aggregation, and the antiplatelet aggregation components of natural drugs and their mechanisms of action to provide new research ideas for the development and application of antiplatelet drugs.
STUDY DESIGN AND METHODS
In this review, we systematically searched the PubMed, Google Scholar, Web of Science, and CNKI databases and selected studies based on predefined eligibility criteria. We then assessed their quality and extracted data.
RESULTS
ADP, AA, THR, AF, collagen, SDF-1α, and Ca can induce platelet aggregation and trigger thrombosis. Natural drugs have a good inhibitory effect on platelet activation. More than 50 kinds of natural drugs and over 120 kinds of chemical compounds, including flavonoids, alkaloids, saponins, terpenoids, coumarins, and organic acids, have significantly inhibited platelet activation activity. The MAPK pathway, cGMP-PKG pathway, cAMP-PKA pathway, PI3K-AKT pathway, PTK pathway, PLC pathway, and AA pathway are the main mechanisms and pathways of platelet activation.
CONCLUSION
Natural drugs and their active ingredients have shown good activity and application prospects in anti-platelet aggregation. We hope that this review provides new research ideas for the development and application of antiplatelet drugs.
Topics: Humans; Platelet Aggregation Inhibitors; Phosphatidylinositol 3-Kinases; Platelet Activation; Platelet Aggregation; Blood Platelets; Cardiovascular Diseases
PubMed: 36347177
DOI: 10.1016/j.phymed.2022.154463 -
Turkish Journal of Anaesthesiology and... Oct 2022Thromboelastography and rotational thromboelastometry are the viscoelastic point of care devices that use whole blood samples to assess coagulation and fibrinolysis....
Role of Thromboelastography and Thromboelastometry in Predicting Risk of Hypercoagulability and Thrombosis in Critically Ill COVID-19 Patients: A Qualitative Systematic Review.
Thromboelastography and rotational thromboelastometry are the viscoelastic point of care devices that use whole blood samples to assess coagulation and fibrinolysis. These devices give information from initiation of the coagulation cascade, activation of clotting factors to fibrin cross-linking, and contribution of fibrinogen and platelet to clot strength and clot lysis. Viscoelastic point of care tests are well established in hypocoaguable states like trauma, cardiac surgery, liver transplantation, and their use in critical care settings with coronavirus disease 2019 (COVID-19) is not so well-known. We performed a systematic review of studies on thromboelastography and rotational thromboelastometry and their modifications to assess their role in critically ill patients with COVID-19. Inclusion criteria were any kind of studies using thromboelastography or rotational thromboelastometry during coronavirus disease critical illness published in English. Ninety-three articles, from December 1, 2019, to August 31, 2020, were identified in the initial search, out of which 12 articles (a total of 380 patients) satisfied the inclusion and exclusion criteria. Thromboelastography and rotational thromboelastometry were observed to detect the hypercoagulable changes and fibrinolysis shutdown associated with COVID-19. Hypercoagulability is associated with an increased risk of venous thrombosis and micro-thrombosis. This review identifies the role of thromboelastography and rotational thromboelastometry in studying the mechanisms contributing to coagulopathy and incidence of thrombosis in COVID-19.
PubMed: 36301281
DOI: 10.5152/TJAR.2021.21118 -
Seminars in Thrombosis and Hemostasis Jul 2023Pathogen reduction technologies (PRTs) such as Mirasol and Intercept were developed to eliminate transfusion-transmitted infections. The impact of PRTs on platelet...
Pathogen reduction technologies (PRTs) such as Mirasol and Intercept were developed to eliminate transfusion-transmitted infections. The impact of PRTs on platelet function during the storage period, their effect on platelet storage lesions, and the optimal storage duration following PRTs have not been clearly defined. The aim of this study was to systematically review the existing literature and investigate the impact of PRTs on functional alterations of PRT-treated platelets during the storage period. The authors identified 68 studies suitable to be included in this review. Despite the high heterogeneity in the literature, the results of the published studies indicate that PRTs may increase platelet metabolic activity, accelerate cell apoptosis, and enhance platelet activation, which can subsequently lead to a late exhaustion of activation potential and reduced aggregation response. However, these effects have a minor impact on platelet function during the early storage period and become more prominent beyond the fifth day of the storage period. Large in vivo trials are required to evaluate the effectiveness of PRT-treated platelets during the storage period and investigate whether their storage can be safely extended to more than 5 days, and up to the traditional 7-day storage period.
Topics: Humans; Blood Platelets; Platelet Activation; Blood Preservation; Platelet Transfusion
PubMed: 36252605
DOI: 10.1055/s-0042-1757897