Search Results (3,212)

Hemostasis depends on the coordinated interaction between platelets, coagulation factors, endothelium, and shear forces. Current point-of-care (POC) assays evaluate isolated components of haemostasis or operate under nearly static conditions, limiting their ability to reproduce physiological thrombus formation. In this study, we performed the technical validation of Smart Clot, a fully automated, microfluidic POC platform that quantifies platelet aggregation, fibrin formation, and total thrombus growth under controlled arterial shear using unmodified whole blood. Recalcified citrated blood was perfused over collagen at $\dot{\gamma }$_w = 300 s⁻¹. Dual-channel epifluorescence microscopy acquired platelet and fibrin(ogen) signals at 1 frame per second. Integrated Density time-series were fitted with a five-parameter logistic model; first derivatives and their integrals yielded standardized pseudo-volumes for platelets, fibrin(ogen), and total thrombus. Sixty-two healthy donors established reference distributions; one-hundred-thirteen patients on antithrombotic therapy assessed pharmacodynamic sensitivity. Platelet-derived parameters were approximately normally distributed, whereas fibrin(ogen) and total thrombus values followed log-normal patterns. Anticoagulants and antiplatelet agents produced graded, mechanism-consistent inhibition of all thrombus components. Cardiopulmonary bypass samples showed profound but transient suppression of platelet and fibrin activity. Across activity ranges, multiple statistical assessments supported high analytical repeatability. Smart Clot provides rapid, reproducible, flow-aware quantification of platelet–fibrin dynamics, capturing pharmacological modulation and peri-operative impairment with high sensitivity. These results support its potential as a next-generation POC assay for physiological hemostasis assessment. Full article

Therapeutic plasma exchange is a procedure in which plasma is removed and replaced with another fluid to correct blood abnormalities. There is growing evidence of its benefit in certain clinical conditions, including thrombotic thrombocytopenic purpura, hematological diseases, and immune-mediated neurological disorders. Therapeutic plasma exchange prescription includes the choice of technique (centrifugation or membrane filtration) and the choice of vascular access, as well as the total plasma volume to be exchanged, the type of replacement fluid, the number and frequency of sessions, and the method of anticoagulation. These patients may be critically ill and undergo this technique in an intensive care unit, where the intensivist manages the procedure independently or in collaboration with other specialists. We aim to make an easy-to-follow general prescription of this procedure, by offering a practical revision that empowers physicians, such as non-autonomous intensivists, to autonomously prescribe and manage this procedure, reducing delays in initiating treatment and addressing complications. Full article

Inflammatory bowel disease (IBD) is associated with an increased risk of venous thromboembolic events (VTEs) and a moderate risk of arterial cardiovascular events. This varies with inflammatory activity and acute-care exposure, with pathophysiological data supporting a thromboinflammatory phenotype in which intestinal inflammation influences systemic vascular homeostasis through innate immune activation, coagulation–platelet crosstalk, endothelial dysfunction, impaired fibrinolysis, and immunothrombosis. Clinically, prevention and management should be integrated into routine care and anchored in sustained, steroid-sparing disease control, combined with guideline-based in-hospital thromboprophylaxis and standard cardiovascular prevention. Decisions regarding anticoagulant therapy after VTEs should follow established principles while recognizing that recurrence prevention depends not only on anticoagulant choice but also on minimizing repeated inflammatory and treatment-related risk exposures. Cardiovascular risk assessment and optimization of modifiable factors should be considered before therapy escalation or treatment switching. Future advances will likely come from more personalized risk assessment across dynamic high-risk windows and from adjunctive, mechanism-informed strategies targeting key nodes of the gut–vascular interface and immunothrombosis. Full article

The introduction of direct oral anticoagulants (DOACs), particularly factor Xa (FXa) inhibitors, has transformed the prevention and treatment of thromboembolic events. These agents have largely replaced vitamin K antagonists across most indications due to their predictable pharmacokinetics, reduced rates of intracranial bleeding, and overall ease of use. Nevertheless, a substantial residual bleeding risk remains, particularly gastrointestinal bleeding and clinically relevant non-major bleeding in elderly, frail, or polymedicated patients. Furthermore, the management of patients with severe renal dysfunction, active cancer, especially gastrointestinal or genitourinary malignancies and those requiring complex pharmacological regimens, continues to pose significant challenges. These limitations have intensified interest in targeting earlier steps of the coagulation cascade, specifically factor XI (FXI) and its activated form (FXIa). FXI occupies a unique mechanistic position: it contributes substantially to pathological thrombosis while playing only a limited role in physiological hemostasis. Genetic, observational, and mechanistic evidence consistently demonstrates that FXI deficiency confers protection against venous thromboembolism and cardiovascular events while causing minimal spontaneous bleeding. This biological paradigm has catalyzed the development of novel FXI/FXIa inhibitors, including small-molecule agents (asundexian, milvexian) and biological therapies (abelacimab). Clinical trials such as AXIOMATIC-TKR, PACIFIC-AF, and OCEANIC-AF, and ongoing programmes including ASTER and MAGNOLIA suggest that FXI inhibition may preserve antithrombotic efficacy while substantially reducing bleeding risk. This review summarizes the current landscape of oral FXa inhibitors, outlines the biological rationale for FXI/FXIa inhibition, and discusses the evolving clinical evidence supporting what may represent the next major advance in anticoagulant therapy. Full article

Dorsal vein thrombophlebitis, or penile Mondor disease, is a rare benign penile condition presenting with cord-like induration at the dorsum of the penis. This induration is caused by an isolated thrombosis of the dorsal superficial vein of the penis. As symptoms are not typical and many patients are asymptomatic, it is often underdiagnosed. Causes include trauma, infection, sexual activity, genital surgery, and cancer. Differential diagnosis includes Peyronie’s disease and sclerosing lymphangitis, and diagnosis remains crucial as it facilitates the treatment plan and reassures the patient. Treatment consists of conservative measures, such as oral nonsteroidal anti-inflammatory medications (NSAIDs) and anticoagulation, and surgical management, with excision of the thrombosed vein. We present a case report of penile Mondor disease following circumcision, with the aim to provide educational ultrasound images of this rare entity. The patient, 32 years old, on the sixth postoperative day, developed a cord-like induration, along with pain, at the dorsum of the penis. Physical examination revealed a cord-like mass on the dorsal aspect of the penis. Penile triplex demonstrated a lack of endoluminal flow signals of the superficial dorsal veins, which were uncompressible. Triplex of the femoral and iliac veins showed no sign of thrombosis. Clinical presentation, along with imaging findings, facilitated the diagnosis of Mondor disease. The patient was treated conservatively with sexual abstinence and NSAIDs, and 6 weeks after the presentation, the patient was asymptomatic, without evidence of the disease in clinical examination. Full article

Coagulation is a physiological process necessary to achieve homeostasis. Many pathologies lead to spontaneous activation of the coagulation pathways and increase the risk of venous thrombosis (e.g., atrial fibrillation, orthopaedic surgery, cancer). Therefore, a lot of patients need anticoagulant drugs as preventive or curative treatment. In general, older molecules (unfractionated heparin, low-molecular-weight heparins, vitamin K antagonists) have good efficacy. Still, their adverse reactions, increased risk of bleeding, or difficult administration led to low adherence to treatment and had even limited their use. Recently, new molecules were authorised to improve patient adherence to treatment, mainly formulated for oral administration (e.g., dabigatran, rivaroxaban, apixaban, etc.). This therapeutic approach has a low risk of bleeding and does not require special monitoring by laboratory tests. Also, new anticoagulants for patients with heparin-induced thrombocytopenia (e.g., argatroban, lepirudin, bivalirudin, etc.) were obtained. Moreover, reversal agents for the new anticoagulant molecules used in overdoses or in situations where immediate cessation of the anticoagulant effect is required (e.g., emergency surgery) were studied, some of them being authorised on the pharmaceutical market. This narrative review aims to provide a pharmacological and therapeutic overview of anticoagulant drugs, underlining their implementation and limitations. Full article

Background: Direct oral anticoagulants (DOACs) are now the preferred anticoagulant over vitamin K antagonists for patients with atrial fibrillation (AF) and venous thromboembolism (VTE). Variability in drug exposure raises concerns about bleeding and thrombotic events, highlighting the potential value of therapeutic drug monitoring (TDM). Methods: This systematic review and meta-analysis conducted a systematic search of PubMed, Embase, Web of Science, Scopus, Cochrane Library, and ClinicalTrials.gov (from inception to May 2025) and identified studies reporting DOAC levels and clinical outcomes. Two reviewers independently performed screening, data extraction, and risk-of-bias assessment (RoB 2.0, Newcastle–Ottawa Scale). Random-effects meta-analytical models generated pooled estimates, with meta-regression exploring potential sources of variability (DOAC type, drug levels) and exposure–response relationships. Results: Nineteen studies comprising 5770 patients were included in the review. The pooled event rates were 8% for major bleeding (95% CI: 0.05–0.11), 7% for thrombotic events (95% CI: 0.05–0.09), and 3% for mortality (95% CI: 0.03–0.04). Heterogeneity was substantial for bleeding and thrombotic events (I² = 95.6% and 87.3%, respectively) but negligible for mortality (I² = 0%). Meta-regression analyses showed no significant association between mean DOAC concentration and either major bleeding (β = −0.00021, p = 0.35, Adj R² ≈ 0%) or thrombotic events (β = 0.00005, p = 0.78, Adj R² ≈ 0%), indicating that variations in measured plasma levels did not meaningfully explain event rate differences across studies. Conclusions: In this systematic review and meta-analysis, measured DOAC concentrations show limited and inconsistent association with clinical outcomes. While the present synthesis does not demonstrate a statistically robust linear correlation between DOAC plasma concentrations and adverse outcomes, it highlights the multifactorial determinants of bleeding and thrombosis risk underscores the potential value of selective TDM in individualized care. Further prospective, standardized studies are needed to define clinically actionable thresholds and to validate TDM-guided strategies that optimize the delicate balance between safety and efficacy in DOAC therapy. Full article

The administration of various medications can induce bone loss as an adverse effect and may result in drug-induced osteoporosis, an important and clinically relevant form of secondary osteoporosis associated with an increased fracture risk. This review summarizes the skeletal effects of selected commonly used drugs with respect to bone metabolism, bone mineral density, and fracture outcomes. Medications may exert direct effects on osteoblasts and/or osteoclasts, leading to impaired bone remodeling and reduced bone mass. Alternatively, indirect mechanisms may contribute to skeletal damage, including disturbances in calcium and vitamin D metabolism with subsequent secondary hyperparathyroidism, as well as therapy-induced hypogonadism. Drug classes frequently associated with drug-induced osteoporosis during long-term use include glucocorticoids, aromatase inhibitors, androgen-deprivation therapy, thyroxine, proton pump inhibitors, anticoagulants (heparin and vitamin K antagonists), antidepressants, neuroleptics, and thiazolidinediones. Importantly, this overview represents a selection of relevant agents and does not aim to provide an exhaustive list. When prescribing potentially bone-damaging medications over extended periods, particularly in older individuals, bone health should be proactively considered. Evaluation should include laboratory assessment, fracture risk estimation (e.g., FRAX^®), and bone mineral density measurement when appropriate. Adequate calcium and vitamin D intake should be ensured, and guideline-based osteoporosis therapy initiated when indicated. Full article

Background/Objectives: This study aimed to identify risk factors for postoperative wound infections and healing disorders in patients with brain tumors, based on a large, single-center analysis, and to establish an evidence-based foundation for prevention. Methods: A retrospective analysis was conducted on 1480 patients who underwent intracranial tumor resection in our department over a ten-year period, without the influence of anticoagulant or antiplatelet medication. Potential predictors of wound healing disorders were evaluated, focusing on demographic variables and pre-existing conditions. Results: Among the 1480 patients, postoperative wound infections occurred in 47 cases, corresponding to a cumulative incidence of 3.17%. Platelet count (p = 0.018) and partial thromboplastin time (p = 0.011) emerged as potential risk factors for postoperative wound infections. Length of hospital stay appeared as a distinct outcome-associated marker in cases of postoperative wound infection (p = 0.018). In contrast, demographic characteristics (age, sex, blood type), comorbidities (hypertension, diabetes mellitus, cardiovascular disease, kidney disease, chronic inflammatory conditions), and other surgical or laboratory parameters showed no significant association with wound healing disorders. Conclusions: In patients with brain tumors undergoing surgery without the influence of anticoagulant or antiplatelet therapy, most demographic factors, common comorbidities, and selected laboratory parameters were not associated with an increased risk of postoperative wound infections. Awareness of the identified risk factors may help guide preventive strategies and nursing care. Full article

The traditional Chinese medicinal herb Gynura segetum is increasingly recognized for its hepatotoxic potential, primarily attributed to its pyrrolizidine alkaloid (PA) content. PAs are a leading cause of herb-induced liver injury (HILI) in China and are strongly linked to hepatic sinusoidal obstruction syndrome (HSOS). This review systematically summarizes the pathogenesis, diagnostic advancements, and therapeutic strategies for PA-induced HSOS. Molecular mechanisms of PA metabolism are detailed, encompassing cytochrome P450-mediated bioactivation and the subsequent formation of pyrrole–protein adducts, which trigger sinusoidal endothelial cell injury and hepatocyte apoptosis. Advances in diagnostic criteria, including the Nanjing Criteria and the Roussel Uclaf Causality Assessment Method (RUCAM)-integrated Drum Tower Severity Scoring System, are discussed. Furthermore, emerging biomarkers, such as circulating microRNAs and pyrrole–protein adducts, are examined. Imaging modalities, such as contrast-enhanced computed tomography (CT) and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) magnetic resonance imaging (MRI), have evolved from descriptive tools into quantitative and prognostic instruments. Therapeutic approaches have evolved from supportive care to precision interventions, including anticoagulation, transjugular intrahepatic portosystemic shunt (TIPS), and autophagy-modulating agents. A comprehensive literature review, utilizing databases such as PubMed and Web of Science, was conducted to summarize progress since the introduction of the “Nanjing Guidelines”. Ultimately, this review underscores the critical need for integrated diagnostic and therapeutic frameworks, alongside enhanced public awareness and regulatory oversight, to effectively mitigate PA-related liver injury. Full article

The natural polypeptide drug hirudin, a direct thrombin inhibitor, exhibits potent anticoagulant, anti-myocardial fibrotic, and anti-inflammatory effects in the treatment of cardiovascular diseases (CVD), but its clinical application remains limited by its low bioavailability, insufficient targeting capability, and bleeding risk. In recent years, the development of nanotechnology has enabled peptide drug delivery systems to demonstrate substantial promise in medical practice. Significant progress has been made in overcoming limitations and enhancing therapeutic efficacy against CVD through the use of Hirudin-based drug delivery systems by addressing drug stability in vivo, improving targeting ability, and ultimately achieving responsive release. This paper systematically reviews the mechanisms of action, clinical applications, and novel delivery strategies of the peptide drug hirudin in the treatment of CVD, with a particular focus on recent advances in hirudin-based drug delivery systems, and it also looks forward to future research directions for hirudin delivery systems, including the development of scalable intelligent carriers, the construction of real-time feedback systems, and the establishment of standardized in vitro and in vivo evaluation systems, aiming to present novel strategies for safe and efficient treatment of CVD. Full article

Proteoglycans are macromolecules consisting of a core protein and one or more glycosaminoglycan side chains. Proteoglycans synthesized by vascular endothelial cells modulate various functions such as anticoagulant activity and vascular permeability. We previously reported that some heavy metals interfere with proteoglycan expression, and that organic–inorganic hybrid molecules, such as metal complexes and organometallic compounds, serve as useful tools to analyze proteoglycan synthesis mechanisms. However, the effects of metal compounds lacking electrophilicity on proteoglycan synthesis remain unclear. Au₂₅(SG)₁₈, a nanoscale gold cluster consisting of a metal core protected by gold–glutathione complexes, exhibits extremely low intramolecular polarity. In this study, we investigated the effect of Au₂₅(SG)₁₈ on proteoglycan synthesis in vascular endothelial cells. Au₂₅(SG)₁₈ accumulated significantly in vascular endothelial cells at low cell density and suppressed the expression of perlecan, a major heparan sulfate proteoglycan in cells, by inactivating ADP-ribosylation factor 6 (Arf6). Additionally, Au₂₅(SG)₁₈ reduced the expression of biglycan, a small dermatan sulfate proteoglycan, in vascular endothelial cells at low cell density; however, the underlying mechanisms remain unclear. Overall, our findings suggest that organic–inorganic hybrid molecules regulate the activity of Arf6-mediated protein transport to the extracellular space and that perlecan is regulated through this mechanism, highlighting the importance of Arf6-mediated extracellular transport for maintaining vascular homeostasis. Full article

Background/Objective: Ketorolac is an effective alternative and addition to opioids for postoperative pain control; however, there is concern of perioperative bleeding risk with its use. Within gynecology, this risk has not yet been explored in the context of hysterectomy. This study aimed to evaluate the risk of postoperative bleeding complications with ketorolac administration in the context of hysterectomy. Methods: This was a retrospective cohort study that included all patients who underwent hysterectomy for benign indications between 2015 and 2024 at a quaternary care academic hospital. Inclusion criteria were any type of hysterectomy during the study period, while exclusion criteria were malignancy and peripartum status. Complication data for up to thirty days post operation were collected. Multivariable regression analysis, including age, American Society of Anesthesiology category, use of celecoxib before surgery, anticoagulant treatment, uterus size, surgical approach, increased surgical complexity, and lysis of adhesions, was performed to identify the adjusted odds of postoperative bleeding complications. The primary outcome was a composite of any postoperative bleeding complications by use of postoperative ketorolac, including postoperative transfusion, readmission, or reoperation for bleeding. Results: In total, 4236 patients underwent hysterectomy for benign indications during our study period, of which 76% (n = 3236) received ketorolac postoperatively. The composite postoperative bleeding rate was lower in the ketorolac group (2.1% vs. 4.1%, p = 0.001). There was no association between ketorolac use and risk of postoperative bleeding in multivariable regression analysis (aOR 1.02, 95% CI 0.36–2.88). There was no difference in overall intraoperative or perioperative complications (p = 0.070 for both). Major perioperative complications were less likely in the ketorolac group (p = 0.046). Additionally, there were no differences in postoperative complications except for ileus, which was less likely in the ketorolac group (p = 0.034). Conclusions: Ketorolac administration was not associated with a higher risk of bleeding complications after hysterectomy, including when celecoxib was used preoperatively as part of an enhanced recovery protocol. It may safely be administered as an opioid-sparing pain medication in this setting. Full article

Background/Objectives: The underlying molecular mechanisms of deep vein thrombosis (DVT), which continues to be a major global public health concern, remain unclear. A key component of anticoagulant therapy, heparin (HP) interacts with heparin-binding growth factors including pleiotrophin (PTN) and midkine (MK), both of which have basic amino acid-rich domains that have a strong affinity for HP. The purpose of this study was to determine if changes in the levels of circulating HP, MK, and PTN are linked to the onset of acute DVT. Methods: Thirty patients diagnosed with acute DVT by venous Doppler ultrasonography (VDU) and 28 healthy controls with normal VDU findings were enrolled. Serum HP, MK, and PTN concentrations were measured using ELISA. In DVT patients, blood samples were obtained before and after routine subcutaneous low-molecular-weight heparin treatment; controls provided a single blood sample. ROC curve analysis was used to assess diagnostic performance. Results: Prior to treatment, patients with acute DVT exhibited significantly lower serum HP levels (p < 0.05) and significantly higher MK and PTN levels compared with healthy controls (both p < 0.05). Following heparin administration, serum HP levels increased significantly (p < 0.05), while MK and PTN levels showed a decreasing trend that did not reach statistical significance (p > 0.05). ROC curve analysis demonstrated limited diagnostic performance for HP (sensitivity 10.3%, specificity 68.8%), PTN (62.1%, 54.2%), and MK (82.8%, 35.4%). Conclusions: Decreased circulating HP and increased MK and PTN levels are characteristics of acute DVT that may indicate endogenous HP sequestration through binding to these growth factors. This imbalance could lead to less free HP being available, which would encourage the formation of thrombus. Therapeutic approaches that target MK- and PTN-mediated HP interactions may constitute a unique approach for the therapy of acute DVT, as evidenced by the partial normalization seen after exogenous heparin delivery. Full article

Platelet-rich plasma (PRP) is a cornerstone of regenerative medicine, offering therapeutic potential across numerous clinical disciplines. Its efficacy relies on concentrated platelets and plasma components that release growth factors, cytokines, and extracellular vesicles to orchestrate tissue repair, immunomodulation, and angiogenesis. Recent findings have uncovered novel mechanisms, such as mitochondrial transfer from platelets to target cells and the delivery of bioactive microRNAs that regulate inflammation and metabolic reprogramming. However, despite its potential, PRP therapy is often limited by inconsistent results. In this review, we examine how patient-specific factors—including age, comorbidities, and lifestyle—and technical variables in preparation and storage, influence the biological quality of the final product. Therefore, standardizing protocols and accounting for individual biological variability are essential for achieving reproducible outcomes. In conclusion, PRP is a complex therapeutic agent whose success depends on both intrinsic bioactive content and extrinsic processing factors. Integrating these molecular insights with personalized patient assessment is crucial to optimizing PRP treatment procedures. Future research should focus on refining standardization to fully establish PRP as a precision medicine tool in regenerative therapy. Full article