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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 -
European Journal of Pediatrics Aug 2023Platelet transfusions (PTx) are the principal approach for treating neonatal thrombocytopenia, a common hematological abnormality affecting neonates, particularly... (Meta-Analysis)
Meta-Analysis Review
Platelet transfusions (PTx) are the principal approach for treating neonatal thrombocytopenia, a common hematological abnormality affecting neonates, particularly preterm infants. However, evidence about the outcomes associated with PTx and whether they provide clinical benefit or harm is lacking. The aim of this systematic review and meta-analysis is to assess the association between PTx in preterm infants and mortality, major bleeding, sepsis, and necrotizing enterocolitis (NEC) in comparison to not transfusing or using different platelet count thresholds for transfusion. A broad electronic search in three databases was performed in December 2022. We included randomized controlled trials, and cohort and case control studies of preterm infants with thrombocytopenia that (i) compared treatment with platelet transfusion vs. no platelet transfusion, (ii) assessed the platelet count threshold for PTx, or (iii) compared single to multiple PTx. We conducted a meta-analysis to assess the association between PTx and mortality, intraventricular hemorrhage (IVH), sepsis, and NEC and, in the presence of substantial heterogeneity, leave-one-out sensitivity analysis was performed. We screened 625 abstracts and 50 full texts and identified 18 reports of 13 eligible studies. The qualitative analysis of the included studies revealed controversial results as several studies showed an association between PTx in preterm infants and a higher risk of mortality, major bleeding, sepsis, and NEC, while others did not present a significant relationship. The meta-analysis results suggest a significant association between PTx and mortality (RR 2.4, 95% CI 1.8-3.4; p < 0.0001), as well as sepsis (RR 4.5, 95% CI 3.7-5.6; p < 0.0001), after a leave-one-out sensitivity analysis. There was also found a significant correlation between PTx and NEC (RR 5.2, 95% CI 3.3-8.3; p < 0.0001). As we were not able to reduce heterogeneity in the assessment of the relationship between PTx and IVH, no conclusion could be taken. Conclusion: Platelet transfusions in preterm infants are associated to a higher risk of death, sepsis, and NEC and, possibly, to a higher incidence of IVH. Further studies are needed to confirm these associations, namely between PTx and IVH, and to define the threshold from which PTx should be given with less harm effect. What is Known: • Platelet transfusions are given to preterm infants with thrombocytopenia either to treat bleeding or to prevent hemorrhage. • Lack of consensual criteria for transfusion. What is New: • A significant association between platelet transfusions and mortality, sepsis, and NEC.
Topics: Infant, Newborn; Humans; Infant, Premature; Hemorrhage; Enterocolitis, Necrotizing; Thrombocytopenia; Sepsis
PubMed: 37258776
DOI: 10.1007/s00431-023-05031-y -
Cureus Oct 2023Adhesive capsulitis (AC) is a common cause of shoulder pain seen in 3%-5% of the population. Platelet-rich plasma (PRP) is platelet-rich blood with pro-inflammatory and... (Review)
Review
Adhesive capsulitis (AC) is a common cause of shoulder pain seen in 3%-5% of the population. Platelet-rich plasma (PRP) is platelet-rich blood with pro-inflammatory and anti-inflammatory properties that has been proposed as a treatment option for patients with AC. The purpose of this study was to analyze outcomes of range of motion (ROM) and subjective outcomes, including the visual analog scale (VAS), disability of arm, shoulder, and hand (DASH), and shoulder pain and disability index (SPADI) scores. PubMed, Embase, and Cochrane databases were searched, and manuscripts were screened using defined preferred reporting items for systematic reviews and meta-analyses (PRISMA) criteria. Two reviewers independently screened articles for inclusion/exclusion using PICOS criteria and extracted data regarding ROM and subjective outcome scores. Nineteen total articles were included. Eleven of the 19 studies recorded ROM as a dependent variable. All articles reported improved ROM with PRP injection when compared to baseline. When recording degrees of shoulder ROM in different planes at the latest follow-up, there were a total of 67 comparative data points for PRP vs. control. Of the 67 comparisons, 62 (93%) had a larger final ROM in the PRP group. VAS scores were reported in 16 of the 19 studies, DASH scores were reported in eight of the 19 articles, and SPADI scores were reported in seven of the 19 articles. VAS, DASH, and SPADI scores were all superior in the PRP group compared to the control. Two studies reported the same final VAS score, but the PRP groups had a larger overall improvement. Of the studies that reported objective ROM outcomes, the PRP group had greater ROM at the longest follow-up compared to control in the vast majority of comparisons. For the studies that reported subjective outcomes, all patients that received PRP had a decrease in VAS pain scores and an improvement in DASH and SPADI questionnaires.
PubMed: 37808592
DOI: 10.7759/cureus.46580 -
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 -
Annals of the Academy of Medicine,... Apr 2021Coronavirus disease 2019 (COVID-19)-induced coagulopathy (CIC) has been widely reported in the literature. However, the spectrum of abnormalities associated with CIC has... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Coronavirus disease 2019 (COVID-19)-induced coagulopathy (CIC) has been widely reported in the literature. However, the spectrum of abnormalities associated with CIC has been highly variable.
METHODS
We conducted a systematic review of the literature (until 1 June 2020) to assess CIC and disease severity during the early COVID-19 pandemic. Primary outcomes were pooled mean differences in platelet count, D-dimer level, prothrombin time, activated partial thromboplastin time (aPTT) and fibrinogen level between non-severe and severe patients, stratified by degree of hypoxaemia or those who died. The risk factors for CIC were analysed. Random-effects meta-analyses and meta-regression were performed using R version 3.6.1, and certainty of evidence was rated using the Grading of Recommendation, Assessment, Development, and Evaluation approach.
RESULTS
Of the included 5,243 adult COVID-19 patients, patients with severe COVID-19 had a significantly lower platelet count, and higher D-dimer level, prothrombin time and fibrinogen level than non-severe patients. Pooled mean differences in platelet count (-19.7×109/L, 95% confidence interval [CI] -31.7 to -7.6), D-dimer level (0.8μg/mL, 95% CI 0.5-1.1), prothrombin time (0.4 second, 95% CI 0.2-0.6) and fibrinogen level (0.6g/L, 95% CI 0.3-0.8) were significant between the groups. Platelet count and D-dimer level were significant predictors of disease severity on meta-regression analysis. Older men had higher risks of severe coagulopathic disease.
CONCLUSION
Significant variability in CIC exists between non-severe and severe patients, with platelet count and D-dimer level correlating with disease severity. Routine monitoring of all coagulation parameters may help to assess CIC and decide on the appropriate management.
Topics: Adult; Aged; Blood Coagulation Disorders; COVID-19; Humans; Male; Pandemics; Prothrombin Time; SARS-CoV-2
PubMed: 33990820
DOI: 10.47102/annals-acadmedsg.2020420 -
International Journal of Molecular... Nov 2017Current biological treatments for non-healing wounds aim to address the common deviations in healing mechanisms, mainly inflammation, inadequate angiogenesis and reduced... (Review)
Review
Current biological treatments for non-healing wounds aim to address the common deviations in healing mechanisms, mainly inflammation, inadequate angiogenesis and reduced synthesis of extracellular matrix. In this context, regenerative medicine strategies, i.e., platelet rich plasmas and mesenchymal stromal cell products, may form part of adjuvant interventions in an integral patient management. We synthesized the clinical experience on ulcer management using these two categories of biological adjuvants. The results of ten controlled trials that are included in this systematic review favor the use of mesenchymal stromal cell based-adjuvants for impaired wound healing, but the number and quality of studies is moderate-low and are complicated by the diversity of biological products. Regarding platelet-derived products, 18 controlled studies investigated their efficacy in chronic wounds in the lower limb, but the heterogeneity of products and protocols hinders clinically meaningful quantitative synthesis. Most patients were diabetic, emphasizing an unmet medical need in this condition. Overall, there is not sufficient evidence to inform routine care, and further clinical research is necessary to realize the full potential of adjuvant regenerative medicine strategies in the management of chronic leg ulcers.
Topics: Humans; Leg Ulcer; Platelet-Rich Plasma; Wound Healing
PubMed: 29182584
DOI: 10.3390/ijms18122561 -
The Journal of International Medical... Jan 2022This meta-analysis evaluated the association between the mean platelet volume (MPV) and polycystic ovary syndrome (PCOS). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This meta-analysis evaluated the association between the mean platelet volume (MPV) and polycystic ovary syndrome (PCOS).
METHODS
A systematic literature search using PubMed, EMBASE, and Web of Science databases until June 2021 was conducted. Pooled standardized mean differences (SMD) and 95% confidence intervals (CI) were determined using a random effects model.
RESULTS
Ten studies involving 866 women with PCOS and 548 age- and body mass index-matched women without PCOS were included. The MPV was significantly increased in women with PCOS compared with non-PCOS women (SMD = 0.43, 95% CI = 0.13-0.72). Subgroup analyses showed that this trend was consistent in cross-sectional studies (SMD = 0.44, 95% CI = 0.03-0.86) and in Turkish women (SMD = 0.46, 95% CI = 0.13-0.79). Meta-regression analysis revealed a marginally positive correlation between the MPV and the homoeostasis model assessment of insulin resistance in women with PCOS. The sensitivity analysis showed that the effect estimate was robust and stable, and publication bias was not evidenced in the pooled analysis.
CONCLUSIONS
This meta-analysis revealed that women with PCOS have a significantly increased MPV than women without PCOS, which is probably associated with insulin resistance.INPLASY registration number: INPLASY2021100021.
Topics: Body Mass Index; Cross-Sectional Studies; Female; Humans; Insulin Resistance; Mean Platelet Volume; Polycystic Ovary Syndrome
PubMed: 34986678
DOI: 10.1177/03000605211067316 -
Neonatology 2015Several cohort studies have shown an association between low platelet counts in the first day(s) of life and patent ductus arteriosus (PDA) in preterm infants. However,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several cohort studies have shown an association between low platelet counts in the first day(s) of life and patent ductus arteriosus (PDA) in preterm infants. However, these results have not been confirmed by other studies.
OBJECTIVE
To perform a meta-analysis of all the studies addressing the relationship between platelet counts in the first day(s) of life and PDA in preterm infants.
METHODS
PubMed/MEDLINE and EMBASE were searched from their inception until December 2014. Results from 11 cohort studies involving 3,479 preterm infants (gestational age <32 weeks) were pooled using random-effects modeling.
RESULTS
Meta-analysis showed a significant positive association between PDA and platelet counts <150 × 10(9)/l [6 studies, risk ratio (RR) = 1.215, 95% CI: 1.027-1.436], between PDA and platelet counts <100 × 10(9)/l (5 studies, RR = 1.255, 95% CI: 1.034-1.525), and between significant PDA (SPDA) and platelet counts <100 × 10(9)/l (5 studies, RR = 1.254, 95% CI: 1.021-1.540). The association between SPDA and platelet counts <150 × 10(9)/l was not statistically significant (6 studies, RR = 1.289, 95% CI: 0.925-1.795). Pooled standard differences in mean platelet counts between infants with and without PDA/SPDA were not statistically different.
CONCLUSION
This meta-analysis reveals a marginal but significant association between low platelet counts in the first day(s) of life and PDA/SPDA in very preterm infants. This association needs to be confirmed in prospective studies.
Topics: Ductus Arteriosus, Patent; Gestational Age; Humans; Infant, Extremely Premature; Infant, Newborn; Platelet Count; Risk Factors
PubMed: 26159239
DOI: 10.1159/000431281 -
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 -
Skin Research and Technology : Official... Sep 2023To critically assess the effect and safety of platelet-rich plasma (PRP) in chronic wounds and vitiligo.
OBJECTIVE
To critically assess the effect and safety of platelet-rich plasma (PRP) in chronic wounds and vitiligo.
METHODS
A systematic literature searching was performed. Results were expressed as weight mean difference (WMD) or risk ratio (RR) with 95% confidence intervals (CIs). Pooled estimates were performed using a fixed-effects model or random-effects model, depending on the heterogeneity among studies.
RESULTS
A total of 27 studies were included in this meta-analysis. In patients with chronic diabetic ulcers, PRP significantly increased proportion of complete wound healing, percentage of wound area healed, and shortened the complete wound healing. In venous ulcers, PRP improved the epithelialized area and percentage of wound area healed. In vitiligo, PRP had better results in degree of improvement and mean repigmentation than controls. Regarding the safety profile, PRP did not increase the risk of infection in patients with chronic diabetic ulcers. Meta-regression revealed that source of PRP and preparation method of PRP significantly affected the proportion of complete wound healing, whereas age, gender, country, duration of wound, and wound size had no impact on this outcome.
CONCLUSION
PRP is effective and safe, and can be used as a potential therapeutic adjunct or alternative treatment in chronic wounds of multiple etiologies and vitiligo.
PubMed: 37753680
DOI: 10.1111/srt.13444