Platelet Function Research Articles

Ingestion of the Non-Nutritive Sweetener Erythritol, but Not Glucose, Enhances Platelet Reactivity and Thrombosis Potential in Healthy Volunteers.

Although artificial and non-nutritive sweeteners are widely used and generally recognized as safe by the US and European Union regulatory agencies, there have been no clinical trials to assess either long-term cardiovascular disease risks or short-term cardiovascular disease-relevant phenotypes. Recent studies report that fasting plasma levels of erythritol, a commonly used sweetener, are clinically associated with heightened incident cardiovascular disease risks and enhance thrombosis potential in vitro and in animal models. Effects of dietary erythritol on thrombosis phenotypes in humans have not been examined. Using a prospective interventional study design, we tested the impact of erythritol or glucose consumption on multiple indices of stimulus-dependent platelet responsiveness in healthy volunteers (n=10 per group). Erythritol plasma levels were quantified with liquid chromatography tandem mass spectrometry. Platelet function at baseline and following erythritol or glucose ingestion was assessed via both aggregometry and analysis of granule markers released. Dietary erythritol (30 g), but not glucose (30 g), lead to a >1000-fold increase in erythritol plasma concentration (6480 [5930-7300] versus 3.75 [3.35-3.87] μmol/L; P<0.0001) and exhibited acute enhancement of stimulus-dependent aggregation responses in all subjects, agonists, and doses examined. Erythritol ingestion also enhanced stimulus-dependent release of the platelet dense granule marker serotonin (P<0.0001 for TRAP6 [thrombin activator peptide 6] and P=0.004 for ADP) and the platelet α-granule marker CXCL4 (C-X-C motif ligand-4; P<0.0001 for TRAP6 and P=0.06 for ADP). In contrast, glucose ingestion triggered no significant increases in stimulus-dependent release of either serotonin or CXCL4. Ingestion of a typical quantity of the non-nutritive sweetener erythritol, but not glucose, enhances platelet reactivity in healthy volunteers, raising concerns that erythritol consumption may enhance thrombosis potential. Combined with recent large-scale clinical observational studies and mechanistic cell-based and animal model studies, the present findings suggest that discussion of whether erythritol should be reevaluated as a food additive with the Generally Recognized as Safe designation is warranted. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04731363.

Biomedical application of TiO2NPs can cause arterial thrombotic risks through triggering procoagulant activity, activation and aggregation of platelets.

Titanium dioxide nanoparticles (TiO2NPs) are widely used in medical application. However, the relevant health risk has not been completely assessed, the potential of inducing arterial thrombosis (AT) in particular. Alterations in platelet function and susceptibility to arterial thrombosis induced by TiO2NPs were examined using peripheral blood samples from healthy adult males and an in vivo mouse model, respectively. Here, using human platelets (hPLTs) freshly isolated from health volunteers, we demonstrated TiO2NP treatment triggered the procoagulant activity of hPLTs through phosphatidylserine exposure and microvesicles generation. In addition, TiO2NP treatment increased the levels of glycoprotein IIb/IIIa and P-selectin leading to aggregation and activation of hPLTs, which were exacerbated by providing physiology-mimicking conditions, including introduction of thrombin, collagen, and high shear stress. Interestingly, intracellular calcium levels in hPLTs were increased upon TiO2NP treatment, which were crucial in TiO2NP-induced hPLT procoagulant activity, activation and aggregation. Moreover, using mice in vivo models, we further confirmed that TiO2NP treatment a reduction in mouse platelet (mPLT) counts, disrupted blood flow, and exacerbated carotid arterial thrombosis with enhanced deposition of mPLT. Together, our study provides evidence for an ignored health risk caused by TiO2NPs, specifically TiO2NP treatment augments procoagulant activity, activation and aggregation of PLTs via calcium-dependent mechanism and thus increases the risk of AT.

Prevention of ischemic stroke in old age

Stroke is one of the main causes of permanent disability and death and the risk increases with age. Primary and secondary prevention therefore have a high priority. The treatment of risk factors, such as high blood pressure, diabetes mellitus and hyperlipidemia is just as important as anticoagulation in atrial fibrillation, in addition to optimization of lifestyle and diet. Platelet function inhibitors play arole in the prophylaxis of recurrence, carotid surgery and stenting are used in selected patients. There is little study evidence for old people, individualized treatment planning takes functional status and comorbidities into account.

Volume Regulation and Non-Osmotic Volume of Individual Human Platelets Quantified by High-Speed Scanning Ion Conductance Microscopy.

Platelets are anucleate cells that play an important role in wound closure following vessel injury. Maintaining a constant platelet volume is critical for platelet function. For example, water-induced swelling can promote procoagulant activity and initiate thrombosis. However, techniques for measuring changes in platelet volume such as light transmittance or impedance techniques have inherent limitations as they only allow qualitative measurements or do not work on the single-cell level. Here, we introduce high-speed scanning ion conductance microscopy (HS-SICM) as a new platform for studying volume regulation mechanisms of individual platelets. We optimized HS-SICM to quantitatively image the morphology of adherent platelets as a function of time at scanning speeds up to 7 s/frame and with 0.1 fL precision. We demonstrate that HS-SICM can quantitatively measure the rapid swelling of individual platelets after a hypotonic shock and the following regulatory volume decrease (RVD). We found that the RVD of thrombin-, ADP-, and collagen-activated platelets was significantly reduced compared to non-activated platelets. Applying the Boyle van't Hoff relationship allowed us to extract the non-osmotic volume and volume fraction on a single-platelet level. Activation by thrombin or ADP, but not by collagen, resulted in a decrease of the non-osmotic volume, likely due to a release reaction, leaving the total volume unaffected.

The value of viscoelastic platelet function measurements with Sonoclot in patients with acute coronary syndrome undergoing percutaneous coronary intervention

PurposePlatelets play an important role in the pathogenesis of acute coronary syndrome (ACS), and adequate platelet inhibition is a cornerstone during invasive management with percutaneous coronary intervention (PCI). Despite this, pivotal role routine measurement of platelet function is not done. We aimed at using the using the Sonoclot device for measuring platelet activity and predicting outcome in patients with ACS undergoing PCI.MethodsThis was a cohort longitudinal study involving 50 patients who were admitted with ACS and undergoing emergent PCI in the critical care department at Cairo University from November 2020 to July 2021. Three parameters will be obtained: platelet function, ACT, and coagulation rate.ResultsAccording to the 1st parameter (platelet function), adequate platelet inhibition was achieved in 54% of our cases. To study the impact of this analysis, our population was classified into 2 groups (well-inhibited platelets vs. poorly inhibited platelets). The 2nd and 3rd parameters (ACT, CR) could separate our patients into 2 groups according to whether patients were well anticoagulated or not. Classification 1, well vs. poorly inhibited platelets, both groups were comparable. However, epicardial coronary flow (TIMI flow) and myocardial blush grade post-stenting were better in the well-inhibited platelets group. Classification 2, well vs. poor anticoagulation, there were no significant differences between the 2 groups.ConclusionAdequate platelet inhibition as measured by Sonoclot device can predict better outcomes in patients with ACS undergoing PCI.

Inhibition of RHOA activity preserves the survival and hemostasis function of long-term cold-stored platelets.

Thrombocytopenic patients require platelet transfusion to prevent and stop hemorrhage. Cold storage of platelets results in complex molecular lesions including changes in membrane microdomains that are recognized by host macrophages and hepatocyte counter-receptors, resulting in phagocytosis and clearance upon transfusion. For this reason, platelets are stored at room temperature, a method that confers increased risk of bacterial contamination. By applying signaling analysis as well as genetic and pharmacological approaches, we identified that the cold induced activation of RHOA GTPase is causal for the major hallmarks of platelet cold storage lesions. RHOA deficiency renders murine platelets insensitive to cold storage induced damage, and pharmacological inhibition by a RHOA activation inhibitor, R-G04, can prevent the cold storage induced lesions. RHOA inhibition prevents myosin activation and clathrin-independent formation and internalization of lipid rafts enriched in active glycosyltransferases as well as abnormal distribution of GpIbα. RHOA inhibition further prevents the metabolic reprogramming of cold induced storage lesions and allows the maintenance of glycolytic flux and mitochondrial dependent respiration. Importantly, human platelets transfused in mice after cold storage, in the presence of R-G04 or its more potent enantiomer S-G04, can circulate in vivo at similar levels as room-temperature stored platelets while retaining their hemostatic activity in vivo as assessed by bleeding time correction of aspirin-treated mice. Our studies provide a new mechanism based translational venue to prevent cold storage induced damage useful for human platelet transfusion in thrombocytopenic patients.

Why might cord blood be a better source of platelets for transfusion to neonates?

Thrombocytopenia (defined as a platelet count <150×109/L) is a common condition in preterm neonates and may occur in 18-35% of all infants admitted to the Neonatal Intensive Care Unit (NICU). Neonatal platelet functionality in terms of reactivity is often described as reduced compared to adults, even in healthy, term neonates. However, this platelet "hyporeactivity" does not correspond to a global functional impairment of the normal delicately balanced neonatal hemostatic system. The extent to which neonatal thrombocytopenia and platelet hyporeactivity contribute to the bleeding risk in preterm neonates remains unknown. Prophylactic platelet transfusions are often administered to them to reduce the risk of bleeding. However, recent literature indicates that adopting a higher platelet transfusion threshold than a lower one results in significantly higher death rates or major bleeding and can be harmful. Although the mechanism by which this occurs is not entirely clear, a mismatch between adult transfused platelets and the neonatal hemostatic system, as well as volume overload, are speculated to be potentially involved. Therefore, future research should consider novel transfusion products that may be more suitable for premature neonates. Blood products derived from umbilical cord blood (UCB) are promising, as they might perfectly match neonatal blood features. Here, we discuss the current knowledge about UCB-derived products, focusing on UCB-derived platelet concentrates and their potential for future clinical application. We will discuss how they may overcome the potential risks of transfusing adult-derived platelets to premature infants while maintaining efficacy.

Effect of toxins from different periodontitis-associated bacteria on human platelet function.

Periodontitis is caused by a dysbiosis of oral bacteria resulting in alveolar bone destruction and teeth loss. The role of platelets in pathogenesis of periodontitis is a subject of research. The release of toxins from periodontitis-associated bacteria may influence platelet function and contribute to the modulation of hemostatic or inflammatory responses. Therefore, we explored platelet function upon exposure to defined toxins: leukotoxin A from Aggregatibacter actinomycetemcomitans (LtxA), a synthetic version of the C14-Tri-LAN-Gly peptide from Fusobacterium nucleatum (C14), and lipopolysaccharides from Porphyromonas gingivalis (LPS). Light transmission aggregometry was performed after the addition of toxins to platelet-rich plasma in different doses. Flow cytometry was used to identify inhibitory effects of toxins by measuring phosphorylation of the vaso-dilator-stimulated phosphoprotein or to identify activating effects by the detection of CD62P expression. The release of chemokines derived from washed platelets was determined by immunoassays. Collagen-induced threshold aggregation values were diminished upon incubation with LtxA and C14, accompanied with an increase of vaso-dilator-stimulated phosphoprotein (VASP) phosphorylation, indicating platelet inhibition. In contrast, LPS did not affect aggregation but slightly enhanced CD62P expression under co-stimulation with low-dose thrombin pointing to slight platelet activation. The three toxins did not relevantly influence the secretion of chemokines. Although weak, the investigated toxins differently influenced human platelet function. LtxA and C14 mediated inhibitory effects, whereas LPS contributed to a slight activation of platelets. Further analysis of specific cellular responses mediated by bacterial toxins may render novel targets and suggestions for the treatment of periodontitis.

The Influence of Diabetes on Thrombotic Profiles and Outcomes on Patients with Peripheral Artery Disease

BackgroundElevated glycated hemoglobin (HbA1c) is associated with vascular complications, including arterial thrombosis post-revascularization. However, the objective relationship between levels of HbA1c and coagulation profiles has not been established. This study aims to determine the association between specific coagulation parameters and variations in HbA1c in patients undergoing lower extremity revascularization. MethodsPatients with Peripheral Artery Disease (PAD) undergoing revascularization were prospectively evaluated between December 2020 and July 2023. Patients were categorized based on their HbA1c levels, and their thromboelastography with platelet mapping (TEG-PM) results were compared at baseline, post-operatively day 1, 1 month, 3 months and 6 months. The parameters included Maximum Amplitude (MA) with both adenosine diphosphate (ADP) and arachidonic acid (AA), as well as ADP and AA percent aggregation indicating clot strength. The study further assessed the differences in these parameters between groups with varying HbA1c levels through the use of unpaired Student t test for pairwise analysis and Mann-Whitney U tests. ResultsAmong 830 samples, those with HbA1c above 6.5 demonstrated a significant increase in ADP MA (52.6 vs. 43.5, p<0.01), AA MA (36.6 vs. 29.65, p<0.05), clot strength without platelets ActF MA (activator F: 13.10 vs. 10.80, p<0.01), and heparin neutralized uninhibited clot strength from thrombin activation HKH MA (heparinized kaolin with heparinase: 61.10 vs. 57.70, p<0.01) values at baseline. Post-operatively, patients with HbA1c levels greater than 6.5 had higher median functional fibrinogen CFF FLEV levels (citrated functional fibrinogen: 40.95 vs. 371.35, p<0.05) and higher formation of fibrin in response to stimulation of thrombin by tissue factor CFF MA values (22.90 vs. 20.40, p<0.05) when measured within 36 hours of intervention, with these trends staying consistent during the 1-month follow-up visit. The trend analysis revealed a progressive increase in ADP MA values with rising HbA1c values, indicating a unit increase in the thrombotic risk relationship. Regression analysis showed a positive relationship between HbA1c and both ADP MA (a 2.261 unit increase for each unit increase in HbA1c) and AA MA. The R-square values indicate that HbA1c only explains a small percentage of the variance in these parameters, suggesting the confounding influence of other factors contributing to thrombosis. ConclusionElevated HbA1c levels appear to be associated with pro-thrombotic tendencies in clot dynamics as measured by TEG-PM, particularly in parameters related to platelet function. HbA1c explains a limited proportion of the variability in these measures, emphasizing the need for a comprehensive approach to evaluating clotting profiles in patients. This study lays the groundwork for further investigation into personalized antithrombotic strategies for patients with varying HbA1c levels.

Western Diet Modifies Platelet Activation Profiles in Male Mice

The correlation between obesity and cardiovascular disease has long been understood, yet scant investigations endeavored to determine the impact of an obesogenic diet on platelet activation or function. As platelets drive clot formation, the terminus of cardiovascular events, we aimed to elucidate the longitudinal effect of an obesogenic diet on platelet phenotype by assessing markers of platelet activation using flow cytometry. Male, weanling mice were fed either a Western diet (30% kcal sucrose, 40% kcal fat, 8.0% sodium) or Control diet (7% kcal sucrose, 10% kcal fat, 0.24% sodium). At 12, 16 and 20 weeks on diets, platelets were collected and stained to visualize glycoprotein Ibα (GPIbα), P-selectin and the conformationally active state of αIIbβ3 (a platelet specific integrin) after collagen stimulation. At all time points, a Western diet reduced GPIbα and αIIbβ3 expression in platelets broadly while P-selectin levels were unaffected. However, P-selectin was diminished by a Western diet in the GPIbα− subpopulation. Thus, a Western diet persistently primed platelets towards a blunted activation response as indicated by reduced active αIIbβ3 and P-selectin surface expression. This study provides a first look at the influence of diet on platelet activation and revealed that platelet activation is susceptible to dietary intervention.

Evaluation of an automated platelet aggregation method for detection of congenital or acquired platelet function defects.

Light transmission aggregometry (LTA) is the most widely used laboratory method for an initial screening of patients with a suspected platelet function defect (PFD), and its use has also been proposed for assessing the efficacy of antiplatelet treatment (APT). An automated LTA method has been developed by Sysmex (Kobe, Japan) on a routine coagulation analyzer (CS-2400), together with a new research parameter called PAL (platelet aggregation level) to evaluate patients on APT. We evaluated the performance of CS-2400 compared to a stand-alone lumi-dual-aggregometer device in the diagnosis of PFD and in assessing the efficacy of APT. For these purposes, the study population was represented by a cohort of 23 patients with a previous diagnosis of PFD and a cohort of 28 patients on APT. Compared to healthy volunteers, patients with PFD showed a statistically significant reduction (p<0.05) in the maximal %light transmission, irrespective of the agonist used, both with the CS-2400 and the lumi-dual-aggregometer. As regards PFD patients, CS-2400 was effective in identifying the more severe defects, with a good sensibility and specificity, but less effective in identifying milder forms of PFD, such as platelet secretion defects. Patients on APT showed a statistically significant (p=0.001) reduced median %light transmission and PAL scores compared to healthy controls. Thanks to this LTA technology, CS-2400, a routine coagulation analyzer widely available in routine laboratories, could prove useful for initial assessment of patients with a suspected PFD. Moreover, the PAL scores were a fairly accurate reflection of the platelet response to APT.

Interrogating a Compound Library in Search of an Inhibitor for TREM-like Transcript-1 to Fibrinogen Binding.

Cardiovascular disease (CVD) remains one of leading causes of death worldwide. Aberrant platelet function mediate fibrin(ogen) rich thrombi that lead to occlusive thrombi associated with mortality. The receptor, TREM-like transcript-1 (TLT-1), stored in the platelet a-granules and released upon platelet activation, binds fibrinogen and von Willebrand factor. Once it is released from platelets TLT-1 is a potential therapeutic target to prevent the thrombosis associated with CVD. Here we design an assay to screen a compound library of small molecules inhibitors. HEK-293 cells stably transfected with a full length human treml-1 construct were used to screen library of 800 compounds, for inhibition of TLT-1 to fibrinogen binding in an attachment assay using crystal violet staining. The possible cytotoxicity of the best compounds was determined via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide MTT and calcein AM staining assays. Here we demonstrate that the addition of TLT-1 to HEK-293 cells increases cell adhesion by more than 2-fold. We identified ~80 compounds that inhibit binding by more than 80%. We further tested the top compounds and confirmed that reduction of hTLT-1 to fibrinogen bound in the top compounds was not caused by cytotoxicity, as per colorimetric and fluorescent viability assays. Four compounds were identified as potential small molecule inhibitors one of which, BM-8372, demonstrated significant effect in platelet aggregation assays. Significance Statement TLT-1 is a key platelet receptor that binds fibrinogen and mediates clot formation The developed assay successfully screens 800 small molecules, pinpointing ~80 potent inhibitors that reduce TLT-1 binding by over 80%. Importantly, the study rigorously rules out cytotoxicity concerns, affirming the therapeutic potential of the identified compounds. By elucidating TLT-1's role and presenting promising inhibitors, this research offers a significant stride toward developing novel strategies to combat CVD-related thrombosis.

Initial Experience with the Derivo 2Heal Flow Diverter under Standard or Reduced-Dose Single Antiplatelet Therapy.

Flow diverters with surface modifications or coatings have been recently introduced to clinical practice with the expectation that they can reduce the rate of thromboembolic complications and residual aneurysms. The purpose of this study is to evaluate the utility of the Derivo 2Heal (D2H) device, a new fibrin and heparin-coated flow diverter. Patients treated by a single operator by using the D2H were retrospectively evaluated for demographic data, aneurysm characteristics, procedural variables, and follow-up data. All patients were treated by using a single D2H, monitored by platelet function testing and kept under single antiplatelet therapy with regular or half-dose clopidogrel or prasugrel after the procedure. Twenty patients with 26 aneurysms were treated. Three presented acutely with subarachnoid hemorrhage. Adjunctive devices were used in 6 patients. There were no technical failures and 2 periprocedural self-limited nonthrombotic minor adverse events. During follow-up, 1 of the acutely ruptured aneurysms reruptured, and 1 patient had a visual TIA. All patients were doing well clinically (19 with mRS of 0 and 1 with 1) at the last follow-up after discharge. The rates of total occlusion on very early angiographic (MRA/CTA or DSA, mean: 2.4 months), DSA (mean: 5.8 months), and midterm angiographic (mean: 14.5 months) follow-up for all versus uncoiled aneurysms were 68% versus 70%, 77.8% versus 90.0%, and 91.7% versus 90.1%, respectively. The absence of permanent neurologic deficits in the periprocedural period and favorable occlusion rates in this preliminary study suggest that the novel coating comprising fibrin and heparin may have the potential to increase the safety and efficacy of flow diversion and needs to be further studied by comparing the D2H device with its bare counterpart and other coated or surface-modified flow diverters.

Thromboelastogram and coagulation function index: relevance for female breast cancer.

Screening and postoperative intervention of breast tumors are critical for the effective diagnosis and treatment of disease development, and reliable diagnostic/screening methods become a key link. Thromboelastogram (TEG), routine platelet (PLT) count, and the coagulation function indicators in patients with different breast diseases were determined and analyzed to explore their predictive value in secondary bleeding disorders. A total of 131 patients with breast diseases, admitted to Jiangsu University Affiliated Hospital from January 2019 to December 2022, were selected as the research subjects. The detection items were analyzed using the receiver operating curve (ROC) after grouping for secondary bleeding disorders of patients with breast cancer. The reaction (R) and the coagulation (K) times were lower in the malignant breast disease group, while the coagulation angle (α), maximum amplitude (MA), coagulation index (CI), fibrinogen (FIB), and D-dimer (D-D) were higher than those in the benign breast disease group. The t-tests proved that the MA and FIB values were statistically significant (p < 0.05) in the benign and malignant breast disease groups. The R and K in patients with breast diseases were positively correlated with the activated partial thromboplastin time (aPTT) and D-D, but were negatively correlated with PLT. The α angle was negatively correlated with aPTT and D-D, but was positively correlated with PLT. The MA for PLT function was positively correlated with FIB and PLT. CI was negatively correlated with aPTT, thrombin time (TT), and D-D, but was positively correlated with PLT. ROC curve analysis showed that the CI and α angle had a significant predictive value, whereas the correlation of the other indicators was relatively low. Coagulation tests showed significant differences in patients with breast cancer, differing from those with benign breast diseases. TEG combined with conventional coagulation indicators is potentially valuable for the prediction of secondary bleeding disorders in patients with breast cancer.

Antiplatelet Therapy and Platelet Activity Testing for Neurointerventional Procedures

The management of antiplatelet medications in neurointerventional procedures remains a subject of considerable variability and debate. This review article explores the diverse clinical practices and the impact of different antiplatelet regimens and platelet activity testing on patient outcomes in neurointerventional treatments. While much of the evidence around antiplatelet therapies largely stems from randomized trials in cardiac and peripheral vascular diseases, their application in neurointerventional settings requires nuanced consideration. Various assays exist to assess individual platelet function, yet the optimal assay, thresholds, and agents remain uncertain due to interpatient variability in medication responsiveness. Expert consensus groups have attempted to standardize antiplatelet management, which is summarized for elective and emergent neurointerventional procedures. Clopidogrel, a commonly used antiplatelet, faces challenges such as genetic variability in metabolism and drug–drug interactions, impacting its effectiveness. Other agents, such as ticagrelor and prasugrel, offer alternatives with different mechanisms of action and potential advantages. Additionally, short‐acting intravenous P2Y 12 inhibitors, such as cangrelor, and glycoprotein IIb/IIIa inhibitors provide options for acute bridging therapy in neurointerventional cases. Despite advancements, significant gaps persist in understanding the optimal antiplatelet management for neurovascular procedures. While platelet function testing is commonly used, its clinical utility and standardization remain an area of investigation. This review underscores the need for further multicenter studies to delineate best practices and optimize patient outcomes in neurointerventional settings.

Pharmacodynamic Comparison of Two Aspirin Formulations in the Caribbean: The ARC Study.

This prospective, single-arm, crossover pharmacodynamic study assessed the effect of Bayer® low-dose enteric-coated aspirin 81mg tablets (LD EC-ASA) (Bayer AG, Leverkusen, North Rhine-Westphalia, Germany) compared to Vazalore® low-dose phospholipid-aspirin liquid-filled 81mg capsules (LD PL-ASA) (PLx Pharma Inc., Sparta, NJ, USA) on platelet reactivity with respect to aspirin reaction units (ARU). Forty-seven healthy volunteers were recruited. Platelet function was evaluated with the VerifyNow™ ARU assay (Werfen, Bedford, MA, USA) and assessed post-initiation of Bayer® LD EC-ASA daily for 14days, with a washout period of 28days, followed by Vazalore® LD PL-ASA daily for 14days, again followed by ARU testing. Participants on LD EC-ASA had a mean ARU score of 426, with 19.1% of participants having an ARU > 550; patients on LD PL-ASA derived a mean ARU score of 435, with 14.9% achieving an ARU > 550. There were no significant differences in aspirin resistance (ARU > 550) according to the formulation (Bayer® LD EC-ASA vs. Vazalore® LD PL-ASA) used. Aspirin resistance was independent of ethnicity regardless of the formulation used. In addition, there were no significant associations between body surface area (BSA) and Bayer® LD EC-ASA ARU value (p value 0.788) or Vazalore® LD PL-ASA ARU value (p value 0.477). No patients experienced any serious adverse events or treatment-emergent adverse events. There were no significant differences in aspirin resistance between Bayer® LD EC-ASA and Vazalore® LD PL-ASA. This dedicated pharmacodynamic study could potentially be informative and applicable for Trinidadian patients on dual antiplatelet therapy (DAPT). Further studies are required to confirm these exploratory findings. ClinicalTrials.gov identifier, NCT06228820, prospectively registered 1/18/2024.

RBCs regulate platelet function and hemostasis under shear conditions through biophysical and biochemical means

AbstractRed blood cells (RBCs) have been hypothesized to support hemostasis by facilitating platelet margination and releasing platelet-activating factors such as adenosine 5′-diphosphate (ADP). Significant knowledge gaps remain regarding how RBCs influence platelet function, especially in (patho)physiologically relevant hemodynamic conditions. Here, we present results showing how RBCs affect platelet function and hemostasis in conditions of anemia, thrombocytopenia, and pancytopenia and how the biochemical and biophysical properties of RBCs regulate platelet function at the blood and vessel wall interface and in the fluid phase under flow conditions. We found that RBCs promoted platelet deposition to collagen under flow conditions in moderate (50 × 103/μL) but not severe (10 × 103/μL) thrombocytopenia in vitro. Reduction in hematocrit by 45% increased bleeding in mice with hemolytic anemia. In contrast, bleeding diathesis was observed in mice with a 90% but not with a 60% reduction in platelet counts. RBC transfusion improved hemostasis by enhancing fibrin clot formation at the site of vascular injury in mice with severe pancytopenia induced by total body irradiation. Altering membrane deformability changed the ability of RBCs to promote shear-induced platelet aggregation. RBC-derived ADP contributed to platelet activation and aggregation in vitro under pathologically high shear stresses, as observed in patients supported by left ventricular assist devices. These findings demonstrate that RBCs support platelet function and hemostasis through multiple mechanisms, both at the blood and vessel wall interface and in the fluidic phase of circulation.

Kinetics and toxicity of nanoplastics in ex vivo exposed human whole blood as a model to understand their impact on human health

The ubiquitous presence of nanoplastics (NPLs) in the environment is considered of great health concern. Due to their size, NPLs can cross both the intestinal and pulmonary barriers and, consequently, their presence in the blood compartment is expected. Understanding the interactions between NPLs and human blood components is required. In this study, to simulate more adequate real exposure conditions, the whole blood of healthy donors was exposed to five different NPLs: three polystyrene NPLs of approximately 50 nm (aminated PS-NH2, carboxylated PS-COOH, and pristine PS- forms), together with two true-to-life NPLs from polyethylene terephthalate (PET) and polylactic acid (PLA) of about 150 nm. Internalization was determined in white blood cells (WBCs) by confocal microscopy, once the different main cell subtypes (monocytes, polymorphonucleated cells, and lymphocytes) were sorted by flow cytometry. Intracellular reactive oxygen species (iROS) induction was determined in WBCs and cytokine release in plasma. In addition, hemolysis, coagulation, and platelet activation were also determined. Results showed a differential uptake between WBC subtypes, with monocytes showing a higher internalization. Regarding iROS, lymphocytes were those with higher levels, which was observed for different NPLs. Changes in cytokine release were also detected, with higher effects observed after PLA- and PS-NH2-NPL exposure. Hemolysis induction was observed after PS- and PS-COOH-NPL exposure, but no effects on platelet functionality were observed after any of the treatments. To our knowledge, this is the first study comprehensively evaluating the bloodstream kinetics and toxicity of NPL from different polymeric types on human whole blood, considering the role played by the cell subtype and the NPLs physicochemical characteristics in the effects observed after the exposures.

Glanzmann Thrombasthenia – A Rare Case Report

Glanzmann thrombasthenia is a rare inherited bleeding disorder resulting from mutation in platelet membrane glycoprotein (GP) IIb or IIIa leading to impaired platelet function which is characterized by defective platelet aggregation and diminished clot retraction. Glanzmann thrombasthenia patients commonly visit to physician with features of bleeding. Here we discuss about the case of a 32-years-old young female presented with menorrhagia, ecchymosis and occasional gum bleeding. Her coagulation profile was in favor of Glanzmann thrombasthenia. This rare disease has a good outcome if early diagnosis and proper management can be ensured. Delta Med Col J. Jan 2021;9(2): 101-103

Stored platelet hemostatic phenotype and function is not altered when donors are on testosterone replacement therapy.

Critical shortages in the national blood supply have led to a re-evaluation of previously overlooked donor sources for blood products. As a part of that effort, red blood cells collected from therapeutic phlebotomy of donors on testosterone replacement therapy (TRT) have been conditionally approved for transfusion. However, platelets from TRT donors are not currently approved for use due to limited data on effects of supraphysiologic testosterone on recipient safety and platelet function. The objective of this study was to provide a comprehensive profile of phenotype and function in platelets from TRT and control donors. Platelets in plasma were collected from TRT and control donors (N = 10 per group; age- and sex-matched) and stored at room temperature for 7 days. On storage Day 1 (D1) and Day 7 (D7), platelet products were analyzed for platelet count, metabolic parameters (i.e., glucose, lactate, mitochondrial function), surface receptor expression, aggregation, thrombin generation, and thrombus formation under physiological flow conditions. TRT donor platelets were not significantly different than control donor platelets in terms of count, surface phenotype, metabolic function, ability to aggregate, thrombin generation, or ability to form occlusive thrombus under arterial flow regimes. Both groups were similar to each other by D7, but had significantly lost hemostatic function compared to D1. Platelets derived from donors undergoing TRT have similar phenotypic and functional profiles compared to those derived from control donors. This suggests that therapeutic phlebotomy of TRT donors may provide a useful source for platelet products.