Blood Platelet Function Research Articles

The Effect of Ketogenic Diet on Platelet Function in Children with Drug-Resistant Epilepsy

Abstract Background The ketogenic diet (KD) is a high-fat, adequate-protein, low-carbohydrate diet. As a special diet, the KD provides daily nutritional needs for children while controlling seizure and thus decreases the use of antiepileptic drugs. Several studies have reported pathological coagulation parameters and platelet abnormalities in patients treated with various antiseizure drugs (ASDs), especially for Valproic acid (VPA). The KD is frequently used in combination with antiepileptic drugs (AEDs), which may increase the risk of bleeding tendency, particularly with concomitant use of VPA or Topiramate. Objective To assess platelet count and function at baseline and six months after starting the KD in children with drug resistant epilepsy (DRE). Methods This prospective cohort study was conducted on 25 DRE children treated with KD for 6 months with age range of 4 months -14 years in the Children ‘s Hospital, Ain Shams University, Cairo, Egypt. They were assessed for anthropometric measurements, detailed medical history, history of bleeding symptoms, complete physical examination, neurological examination, and laboratory assessments as Complete Blood Count (CBC) and platelet function by ADP level at start and after 6 months of ketogenic diet treatment. Results There is no statistically significant change between platelet count and function initially and after 6 months of KD treatment, most of the patients (44%) were maintained on combination of Valproic acid and Levetiracetam and (40%) were maintained on triple therapy Valproic acid, Levetiracetam and Topiramate. Conclusion KD is an effective, safe, and tolerable therapy for children with DRE. No excessive bruising or other bleeding events were observed in any studied patient on KD.

Artificial blood for therapeutic and laboratory usage: Where do we stand?

The scarcity of blood for transfusion purposes has been widely acknowledged. Surgical therapeutic processes, war zones, and post-disaster treatments demand a huge amount of blood. Modern-day laboratories also require blood for bioengineering experimentation. Therefore, an artificially devised solution capable of mimicking the blood functions from biological and engineering relevance would be a noteworthy discovery of contemporary science. The experience drawn from discarded century-old blood substitutes has led us to technologically more advanced present-day solutions, which are better at carrying out the physiological functions of blood. Aiming at safety, stability, non-toxicity, and compatibility in terms of immuno-response, a remarkable number of substitutes are being tried to mimic the physiological properties and functions of red blood cells, platelets, plasma, and white blood cells. Despite significant efforts and time devoted, for transfusion, no product so far has been able to replace natural blood. This article puts together the important developments in blood substitutes that have evolved over the years, including substitutes for clinical as well as engineering requirements. It also points out the recent endeavors of synthesizing blood cells through modern synthetic routes. It has been highlighted that none of the blood substitutes have achieved the required efficacy so that they can be used in vivo. Finally, the emerging trends and future research needs have been stressed upon.

New light on changes in the number and function of blood platelets stimulated by cocoa and its products.

Hyperactivation of blood platelets, one of the causes of heart attack, and other cardiovascular diseases (CVDs), is influenced by various dietary components, including phenolic compounds from vegetables, fruits, teas, wines, cocoa and its products, including chocolate. The present paper sheds new light on the effect of cocoa and its products, especially dark chocolate, on the number and function of blood platelets, and the anti-platelet activity of their constituent phenolic compounds. A review was performed of papers identified in various electronic databases, including PubMed, Science Direct, Scopus, Web of Knowledge, and Google Scholar, with the aim of determining whether their anti-platelet activity may serve as part of a sweet strategy in countering CVDs. Various studies demonstrate that cocoa consumption, especially in the form of dark chocolate, with a high flavanol concentration, has anti-platelet activity and may play a significant role in cardioprotection; they also note that cocoa consumption may be a good strategy in diminishing cardiovascular risk, including hyperactivation of blood platelets.

Rapid and Nondestructive Evaluation of Platelet Function in Whole Blood by Microfluidic Deterministic Cytometry.

Platelet size is a determinant of platelet function. Here, a new microfluidic deterministic cytometry packed with S-shaped micropillars (S-MDC) was developed to rapidly and sensitively determine the apparent size (Dapp) of platelets, which was used to evaluate platelet function. The platelet Dapp in the diluted whole blood was rapidly and label-freely measured by S-MDC within 2 min under shear rates (0.4 mm/s) that mimicked physiological conditions. The level of CD62p on platelets scarcely changed before and after platelets went through the whole S-MDC, indicating that the platelet function was nondestructive. Notably, the human platelet Dapp determined before and after thrombin addition by S-MDC was highly coincident with the levels of CD62p on the platelet surface by flow cytometry (r = 0.819), revealing that the human platelet Dapp was available to assess the platelet activation state. In addition, the results of the rat platelet Dapp were consistent with myocardial injury of rats with myocardial ischemia before and after treatment with antiplatelet agents, suggesting that rat platelet Dapp can be used to reflect myocardial injury in vivo outcomes. These findings reveal that S-MDC is a promising technique for screening tests for a bleeding disorder, in addition to monitoring antiplatelet drugs.

Blood Coagulation and Platelet Function Are Impaired By the ARP2 p.R258G Variant in Mice

Introduction: Venous thromboembolism (VTE) displays significant heritability, yet the genes explaining this heritability are not completely characterized. We previously identified that tissue factor pathway inhibitor heterozygosity ( Tfpi+/−) on the homozygous F5L background ( F5L/L) produces a lethal perinatal thrombotic phenotype. Using a sensitized ENU mutagenesis screen, we discovered an autosomal dominant missense mutation in the Actr2 gene (p.R258G, Actr2G) that suppresses thrombosis and restores survival to F5L/LTfpi+/− mice. Inheritance of the Actr2Gmutation is associated with nearly complete suppression of the lethal F5L/LTfpi+/- phenotype. Actr2 codes for the ARP2 protein, an essential component of the ARP2/3 complex, which mediates actin cytoskeletal rearrangements during platelet activation. We hypothesized that the Actr2G variant affects blood coagulation and platelet function to reduce thrombosis. Methods: To investigate potential effects of the Actr2G mutation on the coagulation cascade, prothrombin time (PT), activated partial thromboplastin time (aPTT), and plasma-dependent thrombin generation assays (TGA) were used to evaluate clot formation. A mouse tail clip assay was used to measure bleeding time and quantify blood loss. Finally, platelets were assessed for functional defects using platelet spreading and aggregometry assays. Results: Actr2 +/Gplasma had significantly prolonged PT and aPTT compared to wild type controls (N>17, p<0.03). There was also a significant reduction in Actr2+/G thrombin peak height compared to wildtypes (N=10; p=0.03). Despite the delayed time to clot formation, Actr2+/G mice did not exhibit a bleeding phenotype and showed no significant differences in blood loss from tail clip assays. Activated Actr2+/G platelets exhibited reduced surface area and adhesion (N=5; p<0.02), as well as significant defects in collagen induced whole blood aggregation (N=10; p<0.02). Discussion: The results of the PT, aPTT and TGA indicate reduced thrombin generation potential, suggesting a defect in the common pathway of coagulation. This hypocoaguability may be due to a decrease in circulating procoagulant factors, or an increase in endogenous thrombin inhibitors. Both the significantly decreased aggregation and defective platelet spreading in the Actr2+/G mice indicate that Actr2+/G platelets are less responsive to agonists, a protective mechanism that contributes to overall thrombosis suppression. Conclusion: In summary, our studies demonstrate the pleiotropic effects that the Actr2G mutation exerts in suppressing thrombosis. The combination of altered plasma coagulation and platelet reactivity likely contribute to suppression of the F5L/LTfpi+/− phenotype. Defects in these actin-mediated processes precipitated by Actr2+/G are the likely root of the F5L/LTfpi+/- phenotype rescue, demonstrating the power of this gene in maintaining hemostatic balance. However, the combination of these thrombosis suppressing phenotypes is not significant enough to prolong the bleeding time in mice with the Actr2G mutation. Thus, our results suggest that targeting actin proteins such as ARP2 for novel antithrombotic drug therapies may have clinical applicability with limited effects on bleeding.

OMIP-097: High-parameter phenotyping of human platelets by spectral flow cytometry.

Using spectral flow cytometry, we developed a 16-color panel for analysis of platelet phenotype and function in human whole blood. The panel contains markers of clinical relevance and follows an optimized protocol for the high-parameter phenotyping of (phosphatidylserine positive) procoagulant platelets. Inclusion of established markers, such as CD62P and PAC-1, allows the subsetting of classic (proinflammatory and proaggregatory) phenotypes, while addition of novel markers, such as TLR9, allows the resolution of platelets with nonclassic functions. Multiple inducible (C3b, CD63, CD107a, CD154, and TLT-1) and constitutive (CD29, CD31, CD32, CD36, CD42a, CD61, and GPVI) markers are also measurable, and we demonstrate the use of automatic gating for platelet analysis. The panel is widely applicable to research and clinical settings and can be readily modified, should users wish to tailor the panel to more specific needs.

Phosphoinositides take a central stage in regulating blood platelet production and function

Blood platelets are produced by megakaryocytes through a complex program of differentiation and play a critical role in hemostasis and thrombosis. These anucleate cells are the target of antithrombotic drugs that prevent them from clumping in cardiovascular disease conditions. Platelets also significantly contribute to various aspects of physiopathology, including interorgan communications, healing, inflammation, and thromboinflammation. Their production and activation are strictly regulated by highly elaborated mechanisms. Among them, those involving inositol lipids have drawn the attention of researchers. Phosphoinositides represent the seven combinatorially phosphorylated forms of the inositol head group of inositol lipids. They play a crucial role in regulating intracellular mechanisms, such as signal transduction, actin cytoskeleton rearrangements, and membrane trafficking, either by generating second messengers or by directly binding to specific domains of effector proteins. In this review, we will explore how phosphoinositides are implicated in controlling platelet production by megakaryocytes and in platelet activation processes. We will also discuss the diversity of phosphoinositides in platelets, their role in granule biogenesis and maintenance, as well as in integrin signaling. Finally, we will address the discovery of a novel pool of phosphatidylinositol 3-monophosphate in the outerleaflet of the plasma membrane of human and mouse platelets.

The modulation of platelet function by growth hormone in growth hormone deficient Hypopituitary patients

BackgroundGrowth hormone deficiency (GHD) has been implicated in increased cardiovascular and cerebrovascular disease risk seen in hypopituitarism, however the mechanism remains speculative. We hypothesise that platelet abnormalities may play a contributory role. Herein we examined platelet behaviour in GHD hypopituitary patients, pre- and post-growth hormone (GH) replacement.MethodsThis study utilizes a physiological flow-based assay to quantify platelet function in whole blood from patient cohorts under arterial shear. Thirteen GH Naïve hypopituitary adults with GHD and thirteen healthy matched controls were studied. Patients were assessed before and after GH treatment. All other pituitary replacements were optimised before the study. In addition to a full endocrine profile, whole blood was labelled and perfused over immobilised von Willibrand factor (vWF). Seven parameters of dynamic platelet-vWF interactions were recorded using digital image microscopy and analysed by customised platelet tracking software.ResultsWe found a significantly altered profile of platelet-vWF interactions in GHD individuals compared to healthy controls. Specifically, we observed a marked increase in platelets shown to form associations such as tethering, rolling and adherence to immobilized vWF, which were reduced post GH treatment. Speed and distance platelets travelled across vWF was similar between controls and pre-therapy GHD patients, however, this was considerably increased post treatment. This may indicate reduced platelet signaling resulting in less stable adhesion of platelets post GH treatment.ConclusionsTaken together observed differences in platelet behaviour may contribute to an increased risk of thrombosis in GHD which can in part be reversed by GH therapy.

The oxylipin analog CS585 prevents platelet activation and thrombosis through activation of the prostacyclin receptor

AbstractCardiovascular disease remains the primary cause of morbidity and mortality globally. Platelet activation is critical for maintaining hemostasis and preventing the leakage of blood cells from the vessel. There has been a paucity in the development of new drugs to target platelet reactivity. Recently, the oxylipin 12(S)-hydroxy-eicosatrienoic acid (12-HETrE), which is produced in platelets, was shown to limit platelet reactivity by activating the prostacyclin receptor. Here, we demonstrated the synthesis of a novel analog of 12-HETrE, known as CS585. Human blood and mouse models of hemostasis and thrombosis were assessed for the ability of CS585 to attenuate platelet activation and thrombosis without increasing the risk of bleeding. Human platelet activation was assessed using aggregometry, flow cytometry, western blot analysis, total thrombus formation analysis system, microfluidic perfusion chamber, and thromboelastography. Hemostasis, thrombosis, and bleeding assays were performed in mice. CS585 was shown to potently target the prostacyclin receptor on the human platelet, resulting in a highly selective and effective mechanism for the prevention of platelet activation. Furthermore, CS585 was shown to inhibit platelet function in human whole blood ex vivo, prevent thrombosis in both small and large vessels in mouse models, and exhibit long-lasting prevention of clot formation. Finally, CS585 was not observed to perturb coagulation or increase the risk of bleeding in the mouse model. Hence, CS585 represents a new validated target for the treatment of thrombotic diseases without the risk of bleeding or off-target activation observed with other prostaglandin receptor agonists.

Comprehensive Approach to Developing Baseline Reference Ranges for Platelet Function

Background. Thrombocytopathies are topical issues of pediatrics. Platelet dysfunction clinically manifests as thrombotic and hemorrhagic events of various severity and location. Platelet function can be evaluated via aggregatometry. Specified parameters for aggregatometry can be used in pediatrics as a standard for evaluating platelet function in peripheral blood. There were no similar studies in children in Russian Federation.Objective. The aim of the study is — to justify the significance of reference ranges (RR) development for platelet aggregatometry in pediatrics.Methods. The study included 30 relatively healthy patients aged from 1 to 18 years. Laboratory tests included complete blood count via automatic hematological analyzer; platelet aggregation in whole blood was evaluated via impedance aggregometer; plasmic hemostasis component (Quick prothrombin), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen were evaluated on automatic coagulation analyzer; molecular genetic study of platelet genes polymorphisms was performed via real-time PCR. Several inducers were used to study platelet aggregation: thrombin receptor activating peptide (TRAP), adenosine diphosphate (ADP), arachidonic acid (ASPI). Instrumental methods included electrocardiography, ultrasound of abdomen, urinary system, and thyroid gland.Results. The study included 16 girls and 14 boys. The median age was 9.4, interquartile range (IQR) was 6.5; 14,1. RR for platelet aggregation indicators were determined for all aggregation inducers (thrombin, ADP, arachidonic acid) as a result of the study.Conclusion. The obtained data will allow to improve the diagnosis approach for platelet dysfunction regarding the established reference ranges. The results of further research may contribute in the development of the algorithm for controlling antiplatelet therapy in patients with contraindications or with genetically determined low sensitivity to thrombocyte aggregation inhibitors based on acetylsalicylic acid.

SARS-CoV-2 Spike Protein and Neutralizing Anti-Spike Protein Antibodies Modulate Blood Platelet Function

Several studies report elevated blood platelet activation and altered platelet count in COVID-19 patients, but the role of the SARS-CoV-2 spike protein in this process remains intriguing. Additionally, there is no data that anti-SARS-CoV-2 neutralizing antibodies (nAb) may attenuate spike protein activity toward blood platelets. Our results indicate that under in vitro conditions, the spike protein increased the collagen-stimulated aggregation of isolated platelets and induced the binding of vWF to platelets in ristocetin-treated blood. The spike protein also significantly reduced collagen- or ADP-induced aggregation or decreased GPIIbIIIa (fibrinogen receptor) activation in whole blood, depending on the presence of the anti-spike protein nAb. Our findings suggest that studies on platelet activation/reactivity in COVID-19 patients or in donors vaccinated with anti-SARS-CoV-2 and/or previously-infected COVID-19 should be supported by measurements of spike protein and IgG anti-spike protein antibody concentrations in blood.

Impact of Tyrosine Kinase Inhibitors Applied for First-Line Chronic Myeloid Leukemia Treatment on Platelet Function in Whole Blood of Healthy Volunteers In Vitro.

The tyrosine kinase inhibitors (TKIs) imatinib, dasatinib, bosutinib, and nilotinib are established for first-line treatment of chronic myeloid leukemia (CML) but may cause side effects such as bleeding and thrombotic complications. We investigated the impact of TKIs on platelet function ex vivo in anticoagulated whole blood (WB) samples from healthy adults by lumiaggregometry and PFA-100 test. Samples (n = 15 per TKI) were incubated for 30 minutes with TKI at therapeutically relevant final concentrations. Aggregation and ATP release were induced by collagen (1 µg/mL), arachidonic acid (0.5 mmol/L), and thrombin (0.5 U/mL). Imatinib, bosutinib, and nilotinib significantly increased collagen-induced aggregation compared with controls. In addition, for bosutinib and nilotinib, a significant increase in aggregation after induction with arachidonic acid was detected. ATP-release and PFA-100 closure times were not influenced significantly by these three TKI. In contrast, dasatinib demonstrated a concentration-dependent inhibition of collagen-induced aggregation and ATP release and a significant prolongation of the PFA-100 closure time with the collagen/epinephrine cartridge. Aggregation and ATP release by other agonists as well as closure time with the collagen/ADP cartridge were not influenced significantly. In conclusion, we clearly show a concentration-dependent inhibition of collagen-induced platelet function in WB by dasatinib confirming prior results obtained in platelet-rich plasma. Bosutinib and nilotinib exerted no impairment of platelet activation. On the contrary, both TKI showed signs of platelet activation. When comparing our results with existing data, imatinib in therapeutic relevant concentrations does not impair platelet function.

Only Subclinical Alterations in the Haemostatic System of People with Diabetes after COVID-19 Vaccination.

People with diabetes have an increased risk of experiencing adverse COVID-19 outcomes. COVID-19 vaccination is, therefore, highly recommended. However, people with diabetes have an inherently elevated risk of thrombotic events and the impact of the vaccination on the coagulation system in this patient population remains to be elucidated. The aim of this study was to investigate the impact of COVID-19 vaccination on the haemostatic system in people with type 1 or type 2 diabetes. We evaluated the effects of COVID-19 vaccination (BioNTech Pfizer, Moderna, AstraZeneca) on standard coagulation parameters, whole blood coagulation (Thrombelastometry), platelet function (impedance aggregation), and thrombin generation (calibrated automated thrombography) in people with type 1 diabetes mellitus (n = 41) and type 2 diabetes mellitus (n = 37). Blood sampling points were prior to vaccination and two weeks after the respective vaccination. Thrombelastometry measurements indicated moderately increased clot formation post-vaccination in people with type 1, as well as with type 2, diabetes: "Clot formation times" were significantly shorter, and both "maximum clot firmness" and "alpha angles" were significantly higher, as compared to the respective pre-vaccination values. Therefore, TEM parameters were not altered after vaccination in patients receiving ASA. Moreover, platelet aggregation was enhanced in people with type 1 diabetes, and plasma levels of D-Dimer were increased in people with type 2 diabetes, following COVID-19 vaccination. All other standard coagulation parameters, as well as thrombin generation, were not affected by the vaccination. The coagulation responses of people with diabetes to COVID-19 vaccination were only subclinical and comparable to those observed in healthy individuals. Our findings suggest that people with diabetes do not face an increased activation of the coagulation post-vaccination.

Bioactive food components and their inhibitory actions in multiple platelet pathways.

In addition to hemostasis and thrombosis, blood platelets are involved in various processes such as inflammation, infection, immunobiology, cancer metastasis, wound repair and angiogenesis. Platelets' hemostatic and non-hemostatic functions are mediated by the expression of various membrane receptors and the release of proteins, ions and other mediators. Therefore, specific activities of platelets responsible for the non-hemostatic disease are to be inhibited while leaving the platelet's hemostatic function unaffected. Platelets' anti-aggregatory property has been used as a primary criterion for antiplatelet drugs/bioactives; however, their non-hemostatic activities are not well known. This review describes the hemostatic and non-hemostatic function of human blood platelets and the modulatory effects of bioactive food components. PRACTICAL APPLICATIONS: In this review, we have discussed the antiplatelet effects of several food components. These bioactive compounds inhibit both hemostatic and non-hemostatic pathways involving blood platelet. Platelets have emerged as critical biological factors of normal and pathologic vascular healing and other diseases such as cancers and inflammatory and immune disorders. The challenge for therapeutic intervention in these disorders will be to find drugs and bioactive compounds that preferentially block specific sites implicated in emerging roles of platelets' complicated contribution to inflammation, tumour growth, or other disorders while leaving at least some of their hemostatic function intact.

Gestational Diabetes Melitus and Cord Blood Platelet Function Studied via the PFA-100 System.

Neonatal platelet hemostasis, although it has been well described over the recent years, remains elusive in specific patient populations, including neonates from high-risk pregnancies, such as those complicated with gestational diabetes mellitus (GDM). We aimed at evaluating the platelet function of neonates born to mothers with GDM using the platelet function analyzer (PFA-100). Cord blood samples were drawn from each subject and tested with two different agonists to provide two closure time (CT) values (collagen with epinephrine (COL/EPI) and collagen with adenosine diphosphate (COL/ADP)). A total of 84 and 118 neonates formed the GDM and the control group (neonates from uncomplicated pregnancies), respectively. COL/EPI CTs were prolonged in neonates from the GDM group compared to neonates from the control group, while no statistically significant difference of COL/ADP CTs was noted between the two groups, GDM and the control. Higher COL/ADP CTs were demonstrated in neonates born via cesarean section and in neonates with blood group O. A negative correlation between COL/ADP CT and gestational age, white blood cells (WBCs) and von Willebrand factor (VWF) activity was noted in neonates from the GDM group. In conclusion, neonates from the GDM group demonstrate a more hyporesponsive phenotype of their platelets, in comparison to the control neonates.

Effects of ex vivo blood anticoagulation and preanalytical processing time on the proteome content of platelets

BackgroundEx vivo assays of platelet function critically inform mechanistic and clinical hematology studies, where effects of divergent blood processing methods on platelet composition are apparent, but unspecified. ObjectiveHere, we evaluate how different blood anticoagulation options and processing times affect platelet function and protein content ex vivo. MethodsParallel blood samples were collected from healthy human donors into sodium citrate, acid citrate dextrose, EDTA or heparin, and processed over an extended time course for functional and biochemical experiments, including platelet proteome quantification with multiplexed tandem mass tag (TMT) labeling and triple quadrupole mass spectrometry (MS). ResultsEach anticoagulant had time‐dependent effects on platelet function in whole blood. For instance, heparin enhanced platelet agonist reactivity, platelet‐monocyte aggregate formation and platelet extracellular vesicle release, while EDTA increased platelet α‐granule secretion. Following platelet isolation, TMT‐MS quantified 3357 proteins amongst all prepared platelet samples. Altogether, >400 proteins were differentially abundant in platelets isolated from blood processed at 24 h versus 1 h post‐phlebotomy, including proteins pertinent to membrane trafficking and exocytosis. Anticoagulant‐specific effects on platelet proteomes included increased complement system and decreased α‐granule proteins in platelets from EDTA‐anticoagulated blood. Platelets prepared from heparinized blood had higher levels of histone and neutrophil‐associated proteins in a manner related to neutrophil extracellular trap (NET) formation and platelet:NET interactions in whole blood ex vivo. ConclusionOur results demonstrate that different anticoagulants routinely used for blood collection have varying effects on platelets ex vivo, where methodology‐associated alterations in platelet proteome may influence mechanistic, translational and biomarker studies.

The Role of Thromboelastography in Heparin Therapy for COVID-19 Patients

The 2019 coronavirus disease (COVID-19)-associated coagulopathy one of the significant complications often found in hospitalized COVID-19 patients. A hypercoagulable and prothrombotic state characterize coagulopathy with an increased risk of thrombotic events. Abnormal coagulation tests could predict bleeding risk, thrombosis, and disease severity. In addition to increasing the D-dimer, prolonged prothrombin time has decreased survival and increased treatment requirements. Based on laboratory findings, it was reported that 70% of patients with COVID-19 had disseminated intravascular coagulation (DIC) and 30% had thrombosis. Approximately 8% of patients with COVID-19 have hemorrhagic complications, the most common one is gastrointestinal bleeding. Variations in hypercoagulability and bleeding occur in COVID-19 patients. Therefore, the anticoagulant drug should be considered to minimize bleeding risk. An anti-bleeding agent for bleeding complications should be considered for the potential increase of coagulopathy. Thromboelastography (TEG) is a tool that is used to analyze the characteristics of viscoelastic clots, platelet function, and fibrinolysis in whole blood, providing a complete picture of the patient's coagulation status. From various therapeutic guidelines for COVID-19 patients, heparin is used as an anticoagulant drug to prevent thrombosis in COVID-19 patients. Starting from prophylactic doses to therapeutic doses, heparin is used to prevent the severity of COVID-19 patient course. The effect of coagulation on COVID-19 patients varies from no impact to hypercoagulation in TEG results.

The Role of Amino Acids in Endothelial Biology and Function.

The vascular endothelium acts as an important component of the vascular system. It is a barrier between the blood and vessel wall. It plays an important role in regulating blood vessel tone, permeability, angiogenesis, and platelet functions. Several studies have shown that amino acids (AA) are key regulators in maintaining vascular homeostasis by modulating endothelial cell (EC) proliferation, migration, survival, and function. This review summarizes the metabolic and signaling pathways of AAs in ECs and discusses the importance of AA homeostasis in the functioning of ECs and vascular homeostasis. It also discusses the challenges in understanding the role of AA in the development of cardiovascular pathophysiology and possible directions for future research.

Resveratrol Inhibits Metabolism and Affects Blood Platelet Function in Type 2 Diabetes.

Chronic hyperglycemia contributes to vascular complications in diabetes. Resveratrol exerts anti-diabetic and anti-platelet action. This study aimed to evaluate the effects of resveratrol on metabolism and the function of blood platelets under static and in in vitro flow conditions in patients with type 2 diabetes. Blood obtained from 8 healthy volunteers and 10 patients with type 2 diabetes was incubated with resveratrol and perfused over collagen-coated capillaries. Isolated blood platelets were incubated with resveratrol and activated by collagen to assess platelet function, metabolism, ATP release, TXA2 production, lipid peroxidation, and gluthatione content. In the type 2 diabetes group, plasma glucose and fructosamine concentrations were significantly higher than in the healthy group. In in vitro studies, collagen-induced thrombi formation in the blood of diabetic patients was 33% higher than in the healthy group. Resveratrol reduced thrombi by over 50% in the blood of healthy and diabetic patients. TXA2 production was 47% higher in diabetic platelets than in the healthy group. Resveratrol reduced TXA2 release by 38% in healthy platelets and by 79% in diabetic platelets. Resveratrol also reduced the activities of enzymes responsible for glycolysis and oxidative metabolism in the platelets of both groups. These data indicate that the resveratrol-induced inhibition of platelet metabolism and TXA2 release may lead to a reduction of platelet function and thrombus formation in patients with type 2 diabetes. Therefore, resveratrol may be beneficial to prevent vascular complications as a future complementary treatment in aspirin-resistant diabetic patients.

The Antioxidant, Anti-Platelet and Anti-Coagulant Properties of Phenolic Compounds, Associated with Modulation of Hemostasis and Cardiovascular Disease, and Their Possible Effect on COVID-19.

Patients affected by coronavirus disease 2019 (COVID-19) demonstrate a range of hemostasis dysfunctions, such as coagulation dysfunction and changes in blood platelet function, this being a major cause of death. These complications may also be associated with oxidative stress. Recently, various papers, including some reviews, have suggested that the use of dietary bioactive compounds, including phenolic compounds, may play a significant role in the treatment of COVID-19. However, while some phenolic compounds, such as curcumin, resveratrol, myricetin and scutellarian, have been found to have antiviral effects against COVID-19, recommendations regarding the use of such compounds to prevent or reduce the risk of CVDs during COVID-19 infection remain tentative. The present mini-review examines the antioxidant, anti-platelet and anticoagulant and antiviral activities of selected phenolic compounds and the possible implications for their use in treating CVDs associated with COVID-19. This review also examines whether these phenolic compounds can be promising agents in the modulation of hemostasis and CVDs during COVID-19. While their properties have been well documented in various in vitro and in vivo studies, particularly their positive role in the prophylaxis and treatment of CVDs, less is known regarding their prophylactic potential against CVDs during COVID-19, and no credible evidence exists for their efficiency in humans or animals. In such cases, no in vitro or in vivo studies are available. Therefore, it cannot be unequivocally stated whether treatment with these phenolic compounds offers benefits against CVDs in patients with COVID-19.