Search Results (77)

Snake venoms are rich sources of bioactive molecules that modulate hemostasis and, among these, anticoagulant snake venom phospholipases A₂ (sPLA₂) are found in a range of snake venoms. Crotoxin (CTX), from the Crotalus durissus rattlesnake, is a heterodimeric PLA₂ complex, and literature has reported its mechanisms in anticoagulant activity. The present review revisits the biological roles of anticoagulant sPLA₂ and critically examines evidence on CTX in hemostatic regulation, aiming to clarify its mechanisms and therapeutic promise. CTX exerts anticoagulant activity via enzymatic hydrolysis of procoagulant phospholipids and direct interaction with coagulation factors, disrupting key complex assembly. It also counteracts inflammation-induced coagulation by modulating leukocyte- and endothelial-derived mediators, restoring balance among anticoagulant, procoagulant, and fibrinolytic pathways. Effects on platelet function appear comparatively modest, ranging from less potent pro-aggregatory activity to negligible aggregation. The dual anticoagulant and anti-inflammatory properties of CTX highlight its potential as a model for novel antithrombotic agents in hypercoagulable and inflammation-driven disorders, despite toxicological concerns that necessitate cautious pharmacological exploration. Full article

Sepsis is a clinical syndrome caused by abnormal host response to infection. Thrombocytopenia and platelet dysfunction are common findings in sepsis and associated with worse outcomes. The innate immune single-stranded RNA sensor, Toll-like Receptor-7 (TLR7), plays a key role in thrombocytopenia in sepsis. This study investigated whether TLR7 signaling also contributes to platelet dysfunction in sepsis, and whether the bioactivity of downstream inflammatory mediators, specifically extracellular vesicles (EVs), is impacted by the TLR7 signaling pathway. Sepsis was induced in wild-type (WT) and TLR7-deficient (TLR7^−/−) mice by cecal ligation and puncture. Blood was collected at twenty-four hours for platelet and plasma isolation, and platelet function was assessed using aggregation, adhesion, and calcium flux assays. EVs were isolated from plasma and used in vitro to evaluate their impact on platelet–leukocyte aggregate (PLA) formation. We found that septic platelets are highly activated and more adhesive, yet show markedly impaired aggregation and reduced calcium signaling, indicating functional exhaustion despite activation. Notably, mice lacking TLR7 maintained stronger platelet aggregation, enhanced adhesion, and preserved calcium release in the septic state compared to wild-type controls, suggesting a protective effect of TLR7 deficiency. Plasma EVs increased in abundance and size during sepsis and promoted clot and PLA formation in vitro. Notably, EV-mediated platelet activation was reduced with EVs derived from TLR7-deficient mice. Our results demonstrate that while sepsis drives persistent platelet activation and dysfunction, TLR7 deficiency preserves platelet function and modulates the pathogenic activity of EV-mediated platelet activation, highlighting TLR7 as a key regulator and potential therapeutic target in sepsis-induced platelet dysfunction. Full article

In reconstructive surgery, usage of different flaps is essential to cover tissue defects. Twisting, stretching or damaging the vascular pedicle may jeopardize the flaps’ viability. The aim of our experiment was to monitor tissue perfusion parameters of local versus rotated musculocutaneous flaps. In rats, musculus cutaneus maximus-based muscle–skin flaps were prepared bilaterally: one was sutured back to its original position, while the other flap was rotated to the ventral chest region (Flap group). In the Control group, flaps were not prepared. Tissue microcirculation was monitored intraoperatively, and on the 7th and 14th postoperative days. Blood samples were taken for testing hematological and hemorheological parameters. At the end of the observation period, biopsies were taken for biomechanical (tensile strengths) and histological investigations. We found that leukocyte and platelet counts significantly increased in the Flap group, while erythrocyte deformability decreased and aggregation increased. Although both local and rotated flaps survived and wound healing progressed well, in microcirculatory recordings, hypoperfusion and visible red blood cell aggregates were seen mostly in the rotated flaps. The rotated flaps were biomechanically weaker compared to local flaps or intact skin regions. This new model seems to be suitable for studying further flap pathophysiology focusing on tissue perfusion. Full article

Cigarette smoking is acknowledged as the most preventable risk factor for thrombogenesis-associated cardiovascular disease. Mice prenatally exposed to the thirdhand smoke (THS) form of tobacco exhibited a higher tendency to develop occlusive thrombosis, along with enhancement of several platelet functional responses. Our objective was to investigate whether prenatal (in utero) THS exposure impacts the platelet transcriptome, resulting in enhanced platelet functional responses, thereby underlying THS-associated thrombogenicity. Blood samples obtained from twenty male mice prenatally exposed to THS, along with an equal number of age-matched male mice exposed to clean air (CA) as a control, were divided into pools of five animals and used to prepare leukocyte and red blood cell-depleted platelets. RNA sequencing for mRNA and microRNA (miRNA) was utilized to analyze and compare the platelet expression profiles of the two exposure groups. RNA seq analyses revealed distinct changes in both gene expression and miRNA profiles, with 448 coding genes and 18 miRNAs significantly altered between the two groups. miRNA–mRNA interaction analysis highlighted 14 differentially expressed miRNAs that potentially target 120 of the differentially expressed genes in our data set. Interestingly, altered genes in miRNA–mRNA pairs were functionally enriched into pathways associated with platelet physiology, including platelet activation, signaling and aggregation, and cellular response to chemical stimuli. Our findings establish—for the first time—that prenatal exposure to THS modifies the platelet transcriptome, thereby rendering platelets hypersensitive to stimuli and more prone to thrombogenicity. Additionally, we illuminate the coordinated function of platelet miRNA and mRNA targets in mediating this response. Full article

Microfluidic methods are an important tool for studying the microrheology of blood and the mechanical properties of blood cells—erythrocytes, leukocytes, and platelets. In patients with diabetes, hypertension, obesity, sickle cell anemia, or cerebrovascular or peripheral vascular diseases, hemorheological alterations are commonly observed. These include increased blood viscosity and red blood cell (RBC) aggregation, along with reduced RBC deformability. Such disturbances significantly contribute to impaired microcirculation and microvascular perfusion. In blood vessels, abnormal hemorheological parameters can elevate resistance to blood flow, exert greater mechanical stress on the endothelial wall, and lead to microvascular complications. Among these parameters, erythrocyte deformability is a potential biomarker for diseases including diabetes, malaria, and cancer. This review highlights recent advances in microfluidic technologies for in vitro assays of RBC deformability and aggregation, as well as leukocyte aggregation and adhesion. It summarizes the core principles of microfluidic platforms and the experimental findings related to hemodynamic parameters. The advantages and limitations of each technique are discussed, and future directions for improving these devices are explored. Additionally, some aspects of the modeling of the microrheological properties of blood cells are considered. Overall, the described microfluidic systems represent promising tools for investigating erythrocyte mechanics and leukocyte behavior. Full article

Soluble CD40 ligand (sCD40L) is a molecule known for its thromboinflammatory properties and may act as a biomarker for platelet activation. Platelets are the principal producers of sCD40L, which is recognized for its impact on platelet function. However, its contribution to the platelet hyperreactivity observed in SARS-CoV-2 infection remains poorly understood. During viral infection, platelets function as crucial intermediaries, engaging with both viruses and leukocytes; and serve as a substantial source of inflammatory mediators, promoting thromboinflammation and immunothrombosis. While platelet hyperactivation is associated with the severity and mortality of COVID-19, the precise function of sCD40L in this setting remains inadequately defined. This study examined the role of platelet-derived sCD40L in platelet activation, aggregation, and thrombosis associated with COVID-19. Platelets from blood samples of 160 patients—102 with non-severe cases and 58 with severe cases—demonstrated heightened activation and aggregation, as well as elevated sCD40L release. In a mouse thrombosis model, sCD40L intensified thrombus development. These findings underscore the essential function of platelet-derived sCD40L in the pathophysiology of COVID-19 and endorse the therapeutic potential of targeting CD40L-mediated pathways to mitigate thromboinflammatory consequences. Full article

Hepatosplenomegaly can occur in extrahepatic diseases such as Philadelphia-negative chronic myeloproliferative neoplasms (MPNs), which may involve the liver and vasculature. In myelofibrosis, extramedullary hematopoiesis can be present in the liver, even within hepatic sinusoids. Liver biopsies in MPN patients have shown platelet aggregates obstructing these sinusoids. Both liver and spleen stiffness are significantly higher in myelofibrosis, correlating with the severity of bone marrow fibrosis. Spleen stiffness is also elevated in myelofibrosis and polycythemia Vera compared to essential thrombocythemia. MPNs are a leading cause of splanchnic vein thrombosis in the absence of cirrhosis or local malignancy, especially in the presence of the JAK2V617F mutation. This mutation promotes thrombosis through endothelial dysfunction and inflammation. It is found in endothelial cells, where it enhances leukocyte adhesion and upregulates thrombogenic and inflammatory genes. Hepatic sinusoidal microthromboses in MPNs may contribute to portal hypertension and liver dysfunction. MPN therapies can also affect liver function. While hepatocytolysis has been reported, agents such as Hydroxycarbamide and Ruxolitinib exhibit antifibrotic hepatic effects in experimental models. Overall, MPNs are linked to chronic inflammation, increased thrombotic risk—particularly splanchnic thrombosis—and atherogenesis. Full article

Background/Objectives: The analysis of the complete blood count (CBC)-derived inflammatory indexes across different histological subtypes of lung cancer supports the early detection of tumor-induced inflammation and has a good predictive value for severity in cancer patients. The main objective of this article was to assess the variations in CBC-derived inflammatory markers across different histologic subtypes of lung cancer, with the final goal of identifying specific predictors of severity for each histologic subtype of lung cancer. Methods: We conducted a retrospective descriptive study that included 202 patients diagnosed with lung carcinoma at the Clinical County Hospital Mureș. The analyzed parameters were as follows: the histological type, the stage of the tumor, patients’ general data, and associated comorbidities. In addition, nine CBC-derived inflammatory indexes, like the neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (d-NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), eosinophil-to-neutrophil ratio (ENR), eosinophil-to-monocyte ratio (EMR), systemic inflammatory index (SII), systemic inflammatory response index (SIRI), and aggregate index of systemic inflammation (AISI), were analyzed as predictors of severity and correlated with histologic findings. Results: The predictors of severity differed across the histologic subtypes. SIRI, d-NLR, and age were predictors of severity in adenocarcinoma patients, while the d-NLR, ENR, leukocyte, and neutrophil count predicted severity in squamous cell carcinoma. For SCLC patients, AISI, SIRI, SII, d-NLR, EMR, ENR, MLR, leukocyte count, lymphocyte count, neutrophil count, platelets count, COPD, smoking, and male gender were predictors for severity. Conclusions: Understanding the complexity and variations in the inflammatory response across different histologic types of lung cancer can personalize treatment regimens and target specific abnormal cellular lines, thus improving the outcome of this highly deadly condition. Full article

Background: This study aimed to investigate the effects of prostate tissue on platelet activation markers, primarily assessed through P-selectin expression, and to assess the formation of platelet–leukocyte aggregations in response to prostate tissue exposure. Furthermore, we compared platelet activation induced by prostate tissue homogenates with that induced by thrombin stimulation. These processes may play a role in the development of disseminated intravascular coagulation (DIC) following transurethral resection of the prostate (TURP). Methods: We collected prostate tissue samples from 12 patients undergoing TURP. The samples were homogenized and used to stimulate platelet-rich plasma in vitro. Flow cytometry was used to measure platelet P-selectin expression and platelet–leukocyte aggregation. Additionally, four experimental groups were established: (A) saline control, (B) thrombin stimulation, (C) phosphate-buffered saline (PBS) control, and (D) prostate tissue homogenate. Data were analyzed to assess the impact of prostate tissue and thrombin on platelet activation and platelet–leukocyte interactions. Results: Prostate tissue homogenates significantly increased platelet P-selectin expression and platelet–neutrophil aggregation compared with the control groups (p < 0.05). Overall, platelet–leukocyte aggregation was not significantly different between the thrombin and prostate tissue groups. However, prostate tissue exposure did not significantly affect platelet–monocyte and platelet–lymphocyte aggregations. Conclusions: Prostate tissue exposure during TURP induces platelet activation, particularly platelet P-selectin expression and platelet–neutrophil aggregation, suggesting a potential mechanism for DIC development. These findings highlight the importance of monitoring platelet activity in patients undergoing TURP and indicate that interventions targeting platelet P-selectin expression and platelet–neutrophil interactions may help mitigate DIC risk. Full article

An important area of health is health promotion. A healthy lifestyle supports health improvement and early prevention of chronic diseases. Stimulation of the body by cold water swimming and swimming in a swimming pool can lead to adaptive changes beneficial for the human cardiovascular system. Within the winter swimming season of 2023/2024, for a period of 5 months, from November to March, once a week, study participants (n = 30; n = 15 females and n = 15 males) from the Krakow Society of Winter Swimmers ‘Kaloryfer’ in Krakow (Poland) practiced winter swimming in cold water (4–5 °C) and swam in the sports pool of the University of Physical Culture in Krakow in water at a temperature of 28 °C. After a full season of winter swimming and swimming pool sessions, both males and females exhibited a tendency towards lower erythrocyte (p = 0.002), leukocyte (p < 0.001), and platelet counts (p < 0.001), as well as an increase in blood plasma viscosity (within normal limits) (p = 0.001), without any changes in blood aggregation or fibrinogen indicators. The remaining morphological indicators and the elongation index demonstrated only limited variation. Winter swimming induces positive changes in blood morphology and rheology. Full article

Background and Objectives: Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated, fibroinflammatory, multiorgan disease with an obscure pathogenesis. Findings indicating excessive platelet activation have been reported in systemic sclerosis, which is another autoimmune, multisystemic fibrotic disorder. The immune-mediated, inflammatory, and fibrosing intersections of IgG4-RD and systemic sclerosis raised a question about platelets’ role in IgG4-RD. Materials and Methods: By borrowing transcriptomic data from Nakajima et al. (GEO repository, GSE66465) we sought a platelet contribution to the pathogenesis of IgG4-RD. GEO2R and BRB-ArrayTools were used for class comparisons, and WebGestalt for functional enrichment analysis. During the selection of differentially expressed genes (DEGs), the translationally active but significantly low amount of platelet mRNA was specifically considered. The platelet-specific gene signature derived was used for cluster analysis of patient and control groups. Results: When IgG4-RD patients were compared with controls, 268 DEGs (204 with increased and 64 with decreased expression) were detected. Among these, a molecular signature of 22 platelet-specific genes harbored genes important for leukocyte–platelet aggregate formation (i.e., CLEC1B, GP1BA, ITGA2B, ITGB3, SELP, and TREML1) and extracellular matrix synthesis (i.e., CLU, PF4, PPBP, SPARC, and THBS1). Functional enrichment analysis documented significantly enriched terms related to platelets, including but not limited to “platelet reactivity”, “platelet degranulation”, “platelet aggregation”, and “platelet activation”. During clustering, the 22 gene signatures successfully discriminated IgG4-RD and the control and the IgG4-RD before and after treatment groups. Conclusions: Patients with IgG4-RD apparently display an activated platelet phenotype with a potential contribution to disease immunopathogenesis. If the platelets’ role is validated through further carefully designed research, the therapeutic potentials of selected conventional and/or novel antiplatelet agents remain to be evaluated in patients with IgG4-RD. Transcriptomics and/or proteomics research with platelets should take into account the relatively low amounts of platelet mRNA, miRNA, and protein. Secondary analysis of omics data sets has great potential to reveal new and valuable information. Full article

Backgrounds/Objectives: Abnormal platelet functions are associated with human morbidity and mortality. Platelets have emerged as critical regulators of numerous physiological and pathological processes beyond their established roles in hemostasis and thrombosis. Maintaining physiological platelet function is essential to hemostasis and preventing platelet-associated diseases such as cardiovascular disease, cancer metastasis, immune disorders, hypertension, diabetes, sickle cell disease, inflammatory bowel disease, sepsis, rheumatoid arthritis, myeloproliferative disease, and Alzheimer’s disease. Platelets become hyperactive in obesity, diabetes, a sedentary lifestyle, hypertension, pollution, and smokers. Platelets, upon activation, can trawl leukocytes and progenitor cells to the vascular sites. Platelets release various proinflammatory, anti-inflammatory, and angiogenic factors and shed microparticles in the circulation, thus promoting pathological reactions. These platelet-released factors also maintain sustained activation, further impacting these disease processes. Although the mechanisms are unknown, multiple stimuli induce platelet hyperreactivity but involve the early pathways of platelet activation. The exact mechanisms of how hyperactive platelets contribute to these diseases are still unclear, and antiplatelet strategies are inevitable for preventing these diseases. Reducing platelet function during the early stages could significantly impact these diseases. However, while this is potentially a worthwhile intervention, using antiplatelet drugs to limit platelet function in apparently healthy individuals without cardiovascular disease is not recommended due to the increased risk of internal bleeding, resistance, and other side effects. The challenge for therapeutic intervention in these diseases is identifying factors that preferentially block specific targets involved in platelets’ complex contribution to these diseases while leaving their hemostatic function at least partially intact. Since antiplatelet drugs such as aspirin are not recommended as primary preventives, it is essential to use alternative safe platelet inhibitors without side effects. Methods: A systematic search of the PUBMED database from 2000 to 2023 was conducted using the selected keywords: “functional foods”, “polyphenols”, “fatty acids”, “herbs”, fruits and vegetables”, “cardioprotective agents”, “plant”, “platelet aggregation”, “platelet activation”, “clinical and non-clinical trial”, “randomized”, and “controlled”. Results: Potent natural antiplatelet factors have been described, including omega-3 fatty acids, polyphenols, and other phytochemicals. Antiplatelet bioactive compounds in food that can prevent platelet hyperactivity and thus may prevent several platelet-mediated diseases, including cardiovascular disease. Conclusions: This narrative review describes the work during 2000–2023 in developing functional foods from natural sources with antiplatelet effects. Full article

Purpose: Physical activity induces numerous modifications in the morphological, rheological, and biochemical properties of blood. The purpose of this study was to evaluate changes in blood rheological and biochemical indicators among runners. Also, we assessed how the rheological and biochemical properties of blood in people who practised running characterised the range and direction of exercise modifications and allowed for the diagnosis of transient adaptive effects. Methods: This study included 12 athletes who regularly trained in middle- and long-distance running (6–8 times a week) and presented a high sports level (national and international class). The athletes performed a 30 min warm-up consisting of 15 min of jogging and exercises. After a 10 min rest, they completed a 3 km run with submaximal effort. Blood samples were collected at baseline and after the effort. Results: No statistically significant changes were revealed in erythrocyte, leukocyte, platelet, iron, ferritin, transferrin, erythropoietin, or C-reactive protein concentrations in the examined runners. The same applied to the elongation index at a shear stress within the range of 0.30–60.00 Pa, amplitude and total extent of aggregation, aggregation half-life, and aggregation index. A significant increase (within standard limits) was only observed in fibrinogen concentration after running. Conclusions: The lack of post-exercise changes in blood rheological and biochemical indicators in the investigated runners points at an efficient haemorheological system. This, in turn, reflects well-executed training and remarkably well-trained adaptive systems responsible for regeneration. Full article

Acute hyperglycemia is a transient increase in plasma glucose level (PGL) frequently observed in patients with ST-elevation myocardial infarction (STEMI). The aim of this review is to clarify the molecular mechanisms whereby acute hyperglycemia impacts coronary flow and myocardial perfusion in patients with acute myocardial infarction (AMI) and to discuss the consequent clinical and prognostic implications. We conducted a comprehensive literature review on the molecular causes of myocardial damage driven by acute hyperglycemia in the context of AMI. The negative impact of high PGL on admission recognizes a multifactorial etiology involving endothelial function, oxidative stress, production of leukocyte adhesion molecules, platelet aggregation, and activation of the coagulation cascade. The current evidence suggests that all these pathophysiological mechanisms compromise myocardial perfusion as a whole and not only in the culprit coronary artery. Acute hyperglycemia on admission, regardless of whether or not in the context of a diabetes mellitus history, could be, thus, identified as a predictor of worse myocardial reperfusion and poorer prognosis in patients with AMI. In order to reduce hyperglycemia-related complications, it seems rational to pursue in these patients an adequate and quick control of PGL, despite the best pharmacological treatment for acute hyperglycemia still remaining a matter of debate. Full article

Background and Objectives: Differentiation between brucella spondylodiscitis and Modic type I changes (MC1) includes difficulties. Hematological inflammatory indices (HII) such as neutrophil to lymphocyte ratio (NLR) and aggregate index of systemic inflammation (AISI) are suggested as indicators of inflammation and infection and have diagnostic, prognostic, and predictive roles in various diseases. This study aimed to evaluate differences between brucella spondylodiscitis and MC1 in terms of HII. Materials and Methods: Thirty-five patients with brucella spondylodiscitis and thirty-seven with MC1 were enrolled in the study. Brucella spondylodiscitis and MC1 were diagnosed by microbiological, serological, and radiological diagnostic tools. HII (NLR, MLR, PLR, NLPR, SII, SIRI, AISI) were derived from baseline complete blood count. Results: The two groups were similar for age (p = 0.579) and gender (p = 0.092), leukocyte (p = 0.127), neutrophil (p = 0.366), lymphocyte (p = 0.090), and monocyte (p = 0.756) scores. The Brucella spondylodiscitis group had significantly lower pain duration (p < 0.001), higher CRP and ESR levels (p < 0.001), and lower platelet count (p = 0.047) than the MC1 group. The two groups had similarity in terms of HII: NLR (p = 0.553), MLR (p = 0.294), PLR (p = 0.772), NLPR (p = 0.115), SII (p = 0.798), SIRI (p = 0.447), and AISI (p = 0.248). Conclusions: Increased HII can be used to differentiate infectious and non-infectious conditions, but this may be invalid in brucellosis. However, pain duration, CRP and ESR levels, and platelet count may be useful to distinguish brucella spondylodiscitis from MC1. Full article