Search Results (236)

Background: Total knee arthroplasty in patients with hemophilia remains the most effective surgical intervention for end-stage hemophilic arthropathy, yet it poses unique surgical and perioperative challenges that are rarely encountered in standard osteoarthritis cases. This article synthesizes technical, anatomical, and perioperative considerations specific to hemophilic patients and integrates prospective clinical data derived exclusively from the hemophilic cohort of our long-term study (twenty patients, twenty knees; 2015–2024). Emphasis is placed on deformity correction, bone loss management, implant selection, hemostatic strategies, transfusion patterns, and perioperative pitfalls. The objective is to provide a comprehensive narrative reference for surgeons managing complex hemophilic knees, consolidating both evidence-based recommendations and practical perioperative “tips and tricks” accumulated across more than a decade of clinical experience. Methods: This prospective observational study evaluated twenty consecutive male patients with hemophilia who underwent primary total knee arthroplasty for advanced hemophilic arthropathy between 2015 and 2024 at our institution. The following variables were collected: operative time measured from skin incision to skin closure, postoperative transfusion requirement, length of hospitalization measured in days, early postoperative complications, and functional recovery as assessed by the Knee Society Score. Early complications included postoperative bleeding or hematoma, superficial or deep infection, and stiffness requiring intensive physiotherapy or manipulation under anesthesia. Results: The mean age at the time of surgery was 44.8 years with a standard deviation of 7.2 years, ranging from 31 to 59 years. The mean operative time in the hemophilic cohort was 154.54 min with a standard deviation of 18.36 min. The range of operative time was from 120 to 180 min. Nine of the twenty patients, representing 45 percent, required postoperative blood transfusion. The mean length of hospital stay in the hemophilic cohort was 12.3 days with a standard deviation of 2.38 days, ranging from 9 to 17 days. The mean Knee Society Score improved from 38 points preoperatively to 82 points at final follow-up, representing a mean increase of 44 points. Conclusions: Total knee arthroplasty in hemophilic patients is safe and effective when specialized surgical techniques, comprehensive synovectomy, precise deformity correction, optimized hemostasis, and structured postoperative coagulation factor replacement are implemented. Functional outcomes and prosthetic survival are excellent in experienced centers. Full article

The recent rise in whole blood usage for traumatic hemorrhagic shock has renewed interest in the impact of leukocytes on hemostatic function during cold storage. This study investigated whether tissue factor (TF)-bearing extracellular vesicles (EVs) are released from human monocytic cells during cold storage or upon rewarming and whether this process is mechanistically linked to apoptosis. We further examined the contribution of superoxide anion generated by NADPH oxidase (NOX). Methods: THP-1 cells were incubated at 4 °C for up to 24 h with/without test reagents and subsequently rewarmed at 37 °C. Cells were washed by centrifugation before rewarming as required. TF activity in the cell supernatant was quantified, EVs were analyzed by flow cytometry with size-defined gating, and NOX activity normalized to p22^phox was measured by cytochrome c reduction. Results: TF levels and apoptotic cells increased during cold storage. TF release was enhanced 1–2 h after cell lavage following cold exposure, indicating active shedding of TF-bearing EVs rather than passive leakage from damaged membranes. Flow cytometry demonstrated that TF-bearing EVs were distinct from apoptotic vesicles, with a substantial proportion falling within the microvesicle size range. Cold exposure enhanced NOX activity. Both superoxide dismutase (SOD) and catalase inhibited TF release during cold storage; however, only SOD suppressed TF release after cell lavage. Conclusions: TF-bearing EVs are actively shed from human monocytic cells during and after cold storage via a NOX-dependent, superoxide-mediated mechanism. Extracellular SOD suppressed this procoagulant EV release, suggesting a potential strategy to modulate hemostatic alterations associated with cold-stored blood. Full article

Viscoelastic testing (VET) is widely used to guide hemostatic therapy in patients with coagulopathy. One important application is the detection of fibrinolysis, defined as a reduction in clot amplitude after maximum clot firmness (MCF), quantified as maximum lysis (ML). Low ML values have recently been associated with adverse outcomes in trauma and sepsis. However, the biological basis of low ML remains unclear. Objective: To determine whether low ML values reflect reduced plasmin-mediated fibrinolysis in tissue factor (TF) activated viscoelastic assays (EX-assay). Methods: A total of 120 healthy adults (52.5% female; mean age 38.2 ± 14.1 years) were studied. EX-assay without fibrinolysis inhibition were compared with assays containing the antifibrinolytic agent tranexamic acid (AP-assay). VET parameters obtained with and without fibrinolysis inhibition were compared using paired analyses, Pearson correlation, and Bland–Altman methods. Results: Clot firmness at 10 min (CA10) was similar with or without fibrinolysis inhibition; although MCF differed statistically, the difference was clinically negligible. ML ranged from 1% to 13% in both assays, with nearly identical mean values (5.9 ± 2.6% vs. 6.0 ± 2.6%). Correlation analysis demonstrated strong agreement for CA10, MCF, and ML between assays, and Bland–Altman analysis confirmed minimal bias for ML. Conclusions: Low ML values in TF-triggered viscoelastic assays were unaffected by tranexamic acid, suggesting that they are unlikely to reflect plasmin-mediated fibrinolysis. These findings support the contribution of alternative mechanisms, such as platelet-mediated clot retraction. Full article

Mesenchymal stromal cells are increasingly used for their immunomodulatory and regenerative properties, yet their interaction with the hemostatic system remains incompletely understood. This review examines the mechanisms through which these cells influence coagulation within the broader framework of immunothrombosis. Evidence from in vitro studies, animal models, and early clinical observations indicates that mesenchymal stromal cells can promote thrombin generation through tissue factor expression and phosphatidylserine exposure, while also engaging complement pathways, platelets, and innate immune responses. Counter-regulatory mechanisms, including adenosine-mediated platelet inhibition and immune reprogramming after cellular clearance, contribute to a context-dependent biological effect. Functional assays, rather than tissue factor expression alone, appear necessary to estimate the effective procoagulant potential of these products. Clinical data suggest that major thrombotic events remain uncommon, although subclinical activation of coagulation pathways may occur. The hemostatic impact of mesenchymal stromal cells depends on multiple variables, including cell source, dose, route of administration, and host inflammatory status. The available evidence supports a working model in which early coagulation and complement activation may be followed by immune modulation, supporting integrated strategies to optimise both safety and therapeutic efficacy. A central conclusion is that tissue factor, although mechanistically necessary for MSC-associated procoagulant activity, is not by itself an independent predictor of clinical thrombotic risk; the effective coagulation response also depends on phosphatidylserine exposure, membrane context, and host inflammatory conditions. Full article

Background: Pediatric liver disease is frequently associated with abnormal conventional coagulation tests; however, prothrombin time expressed as international normalized ratio (PT-INR) incompletely reflect global hemostatic balance. Thrombin generation assay (TGA) provide an integrated assessment of coagulation and may offer complementary information in children with acute liver failure (ALF) and chronic liver disease (CLD). Methods: We enrolled 61 pediatric patients with liver disease (50 CLD, 8 ALF, 3 extrahepatic portal vein obstruction EHPVO) and 51 healthy controls. Platelet-poor plasma was prepared according to international recommendations. Thrombin generation was measured using ST Genesia (STG) with normalization to reference plasma. Group comparisons were performed using non-parametric tests; correlations between PT-INR and thrombin generation parameters were assessed, and principal component analysis (PCA) was used to explore the variance structure of thrombin generation indices and conventional coagulation variables. Results: PT-INR was significantly higher in patients than controls, particularly in ALF. Bleeding events were uncommon. Compared with controls, patients showed reduced levels of fibrinogen and multiple procoagulant/anticoagulant factors (including antithrombin and protein C), with increased factor VIII. Among thrombin generation parameters, the endogenous thrombin potential (ETP) ratio differed significantly across groups (p = 0.001), while correlations between PT-INR and thrombin generation parameters were weak or absent, no significant associations were observed even at higher Pediatric/Model for End-Stage Liver Disease scores. PCA separated thrombin generation indices from PT-INR and conventional coagulation factors, suggesting complementary information. Conclusions: In pediatric liver disease, PT-INR does not reliably reflect global coagulation capacity. Thrombin generation testing provides additional, integrative information on hemostasis and may improve laboratory assessment beyond conventional tests. Full article

Gene therapy is reshaping the therapeutic paradigm in hemophilia by enabling sustained endogenous clotting factor production after a single administration. This approach moves disease management beyond lifelong replacement therapy. While clinical trials have demonstrated marked reductions in bleeding rates and treatment burden, real-world implementation has revealed emerging complexities. These include interindividual variability in transgene expression reflected by a progressive reduction in circulating FVIII or FIX activity over time, uncertainty regarding the long-term durability of expression, immune-mediated constraints, and episodes of transaminase elevation. This review addresses a critical transition point in the field: the shift from proof-of-concept efficacy toward integration of gene therapy into long-term hemophilia care. We examine determinants of therapeutic stability, host–vector immune interactions, and mechanisms underlying loss or fluctuation of expression, with emphasis on monitoring strategies and post-therapy management pathways. Immunogenic processes affecting vector transduction, hepatocellular responses, and transgene persistence are discussed alongside current approaches to immune modulation. This review uniquely focuses on post-gene therapy clinical integration rather than vector design or trial outcomes. Beyond direct factor correction, evolving therapeutic concepts targeting coagulation rebalancing and immune regulation are considered within a systems-based framework. Psychosocial adaptation and patient-reported outcomes are also explored, underscoring that therapeutic success extends beyond hemostatic control. In aggregate, these perspectives position gene therapy not as a singular curative event but as a component of an evolving, biologically integrated management strategy. Long-term follow-up translational research (LTFU) and coordinated global efforts will be essential to optimize durability, safety, and equitable access. Full article

Clonal hematopoiesis refers to the clonal expansion of hematopoietic stem and progenitor cells, driven by somatic mutations. Major mutated genes in clonal hematopoiesis include genes involved in epigenetic regulation including DNA methylation and/or chromatin modification (e.g., DNMT3A, TET2, and ASXL1), tumor suppressors (e.g., TP53), signal transduction (e.g., JAK2), and RNA splicing (e.g., SF3B1 and SRSF2). Clonal hematopoiesis includes clonal hematopoiesis of indeterminate potential (CHIP), clonal cytopenia of unknown significance (CCUS), and myelodysplastic syndromes/neoplasms (MDS). CHIP occurs when the frequency of the variant allele equals or exceeds 2% (4% for X-linked genes in males) in the absence of cytopenias. CHIP is common among older persons and is associated with an increased risk of hematologic cancer. CHIP is also associated with an increased risk of atherosclerotic disease including acute myocardial infarction, stroke, cardiac failure, and abdominal aneurysm. Increasing evidence suggests that CHIP is associated with venous thromboembolic disease. Somatic mutations lead to proliferation of hematopoietic progenitor cells and their progeny, resulting in excessive activation of granulocytes and monocytes. It could be postulated that chronic inflammation caused by clonal expansion of myeloid cells carrying mutations in DNMT3A, TET2, and ASXL1 (“DTA”) genes may constitute an independent risk factor in clot formation and endothelial-cell damage. DTA mutations correlate with elevated proinflammatory cytokines such as IL-1β and IL-6 and enhanced activation of inflammasomes. Moreover, JAK2 mutations may have a direct role in the activation of platelets and coagulation. In vivo murine studies have demonstrated that activation of the JAK-STAT signaling pathway promotes neutrophil extracellular trap (NET) formation, contributing to a prothrombotic state. Insights from related clonal disorders such as paroxysmal nocturnal hemoglobinuria and the VEXAS syndrome support the concept that mutation-driven innate immune activation can directly perturb hemostatic balance. This review aims to summarize the association between clonal expansion of hematopoietic cells and thrombotic disease, and highlight how somatic mutations in hematopoietic cells may contribute to vascular disease and thrombogenesis. Full article

Diabetes mellitus (DM) is a complex metabolic disorder associated with a heightened risk of cardiovascular events, largely driven by a hypercoagulable and hypofibrinolytic state. The pathophysiological interplay between chronic hyperglycemia, oxidative stress, insulin resistance, and systemic inflammation fosters profound alterations in the coagulation cascade, endothelial function, and platelet activity. This narrative review synthesizes evidence from studies published between 2008 and 2026, focusing on coagulation and platelet-related biomarkers selected based on their biological relevance to thrombosis, endothelial dysfunction, and inflammation, as well as the availability of clinical and interventional data across different forms of DM. Although there are numerous biomarkers involved in the pathogenesis of various forms of diabetes, this narrative review critically examines key coagulation biomarkers—including D-dimer, fibrinogen, prothrombin, tissue thromboplastin or tissue factor, P-selectin, soluble urokinase plasminogen activator receptor, thrombomodulin, plasminogen activator inhibitor-1, von Willebrand factor, and β-thromboglobulin—across distinct diabetes subtypes, including type 1, type 2, gestational, and secondary forms linked to endocrinopathies and pancreatic diseases. The literature reveals substantial subtype-specific heterogeneity in hemostatic alterations. For instance, Type 1 DM is characterized by early endothelial dysfunction and platelet activation, while Type 2 DM presents with elevated coagulation factors, impaired fibrinolysis, and a proinflammatory milieu. Gestational DM exhibits pregnancy-specific changes in coagulation, yet distinguishing them from obesity-related effects remains challenging. Secondary diabetes forms, such as those associated with Cushing’s syndrome or pancreatitis, further underscore the diversity in thrombotic risk profiles. Among the coagulation and platelet activation biomarkers reviewed, fibrinogen, P-selectin, and plasminogen activator inhibitor-1 demonstrate the most consistent associations with glycemic control, vascular dysfunction, and therapeutic modulation, particularly in type 2 diabetes, suggesting greater potential for clinical translation. In contrast, evidence for markers such as D-dimer, tissue factor or tissue thromboplastin, and soluble urokinase plasminogen activator receptor remains heterogeneous and insufficient for routine clinical application. By synthesizing mechanistic insights and clinical data, this review highlights the urgent need for subtype-tailored coagulation assessment in diabetes management. A better understanding of the dynamic alterations in coagulation pathways may facilitate earlier detection of vascular complications and inform personalized antithrombotic strategies. Full article

Hemostatic biomaterial agents are widely used during surgery and trauma care to control bleeding, yet their effects on wound healing remain incompletely understood. This study evaluated the impact of oxidized non-regenerated cellulose (ONRC), oxidized regenerated cellulose (ORC), and a gelatin-based hemostat (GELA) on wound healing at 14 and 30 days in a mouse model. Full-thickness wounds were created in C57BL/6J mice (n = 192) and compared to sham controls. Tissue samples were analyzed histologically, supported by immunohistochemistry for Ki-67 and α-SMA and qPCR for VEGF, TGF-β, and FGF-2. Histology demonstrated preserved tissue architecture across groups with progressive resorption of cellulose-based materials, whereas GELA showed localized fibrous structures and enhanced extracellular matrix formation. At day 14, no significant differences were observed in proliferation, contraction, VEGF, or FGF-2 expression; however, TGF-β was significantly reduced in the ORC group. By day 30, GELA significantly increased epidermal proliferation, while contraction markers were elevated in both GELA and ORC. VEGF expression was reduced in GELA and ORC, whereas ONRC showed increased TGF-β expression. FGF-2 remained unchanged across groups. All investigated hemostatic materials were well tolerated during the early postoperative phase (up to day 14), indicating short-term biocompatibility within the scope of this model. In contrast, material-specific differences in cellular activity and growth factor expression became apparent during the later remodeling phase (day 30). These findings suggest differential effects on cellular and molecular aspects of tissue remodeling; however, no conclusions can be drawn regarding overall healing quality or clinical safety, as no quantitative macroscopic or functional outcome measures were assessed. Full article

Objective: To compare perioperative outcomes between robotic and conventional total laparoscopic hysterectomy in terms of operative time, intraoperative blood loss, and postoperative recovery in surgically complex cases. Methods: This retrospective cohort study included patients that underwent total laparoscopic hysterectomy between 2020 and 2022. As robotic surgery was preferentially applied to more complex cases in an effort to minimize the risk of open conversion, propensity score matching based on uterine weight and history of abdominal surgery was performed. The normality of continuous variables was assessed using the Shapiro–Wilk test; non-normally distributed variables are reported as median [interquartile range] and compared using the Mann–Whitney U test. Multivariate linear regression with log-transformed estimated blood loss was conducted to evaluate the independent association of surgical approach with hemostatic outcomes. Results: After 1:1 matching, 93 patients were analyzed per group. Robotic surgery was associated with longer operative time but lower estimated blood loss when compared with conventional laparoscopy. Postoperative hemoglobin decline, length of hospital stay, and complication rates were comparable between groups. In multivariate analysis, uterine weight and operative time were the primary determinants of estimated blood loss; surgical approach showed a modest, independent association with lower log-transformed estimated blood loss after adjustment for these factors. Conclusions: Robotic and conventional total laparoscopic hysterectomy demonstrated comparable perioperative safety profiles with different operative trade-offs. Observed differences in estimated blood loss reflect complex interactions between surgical difficulty, operative time, and instrumentation rather than inherent platform superiority. These findings support an individualized approach to surgical modality selection based on case complexity, to minimize risk of intraoperative complication leading to open conversion. Full article

Background/Objectives: Patients with severe hemophilia A on prophylaxis with emicizumab exhibit a mild/moderate bleeding phenotype that requires the use of either recombinant FVIII (rFVIII) or bypassing agents (BPAs) in patients with inhibitors, in the case of breakthrough bleeding or surgery. Since factor IX (FIX) limits the formation of the FIXa–emicizumab–FX complex, exogenously added FIX might enhance complex formation and thrombin generation. This study aimed to compare the procoagulant effects of various FIX concentrates with recombinant activated FVII (rFVIIa), activated prothrombin complex concentrate (aPCC), and rFVIII in SHA patients with and without inhibitors under emicizumab prophylaxis. Methods: Hemostatic changes were monitored using two optimized global coagulation assays: rotational thromboelastometry and calibrated automated thrombin generation. Tubes containing corn trypsin inhibitor (CTI) were used during blood collection to prevent activation. Low concentrations of tissue factor (TF) were used to trigger coagulation in both assays. Results: Ex vivo addition of recombinant FIX concentrates significantly increased the procoagulant activity of emicizumab, achieving levels comparable to therapeutic doses of rFVIIa or rFVIII, and the proportion of active FIXa within the concentrates is a major contributor to their procoagulant function. We assessed the influence of FVIII inhibitors on the hemostatic efficacy of rFIX concentrates and BPAs, finding that rFIX-induced thrombin generation increased in the presence of inhibitors, and no significant differences were observed with BPAs. Conclusions: These findings suggest that FIX concentrates could be an effective alternative to BPAs for emicizumab-treated patients, particularly those with inhibitors. Further studies are needed to confirm their in vivo efficacy and to evaluate thrombotic risk. Full article

Background: Direct oral anticoagulants (DOACs) have transformed antithrombotic therapy but carry significant bleeding risks requiring prompt reversal. Recent regulatory changes have altered the reversal landscape, notably with the withdrawal of andexanet alfa from the U.S. market. Anticoagulation stewardship programs (ASPs) are essential for navigating this evolving environment and optimizing safe use of anticoagulants. Methods: This narrative review synthesizes evidence from landmark clinical trials (RE-VERSE AD, ANNEXA-4, ANNEXA-I), contemporary guidelines, emerging literature on reversal agents, and critical regulatory updates including the 2025 U.S Food and Drug Administration (FDA) withdrawal of andexanet alfa. Results: Idarucizumab remains the only FDA-approved specific antidote for dabigatran. Following the withdrawal of andexanet alfa, prothrombin complex concentrates (PCCs), both 4-factor and activated are now the primary reversal options for Factor Xa inhibitors, with recent evidence demonstrating comparable hemostatic efficacy. Ciraparantag, a universal reversal agent, is currently in Phase III development. Effective ASPs must now adapt protocols to the post-andexanet era while ensuring timely access to alternative reversal strategies. Conclusions: The reversal landscape has undergone a fundamental transformation with the loss of andexanet alfa. Success in DOAC-associated bleeding management now depends on optimizing PCC-based strategies, integrating systematic stewardship approaches, and preparing for emerging universal antidotes. Institutions must urgently update algorithms, ensure PCC availability, and monitor outcomes in this new therapeutic environment. Full article

Historically, stage T4 non-small cell lung cancer (NSCLC) with direct spinal invasion was considered a definitive surgical contraindication due to the perceived inability to achieve negative margins without catastrophic morbidity. This paradigm has shifted through the advancement of specialized surgical techniques, which facilitate radical en-bloc resection in highly selected candidates by adhering to the en-bloc concept. This concept mandates the retrieval of the tumor and invaded vertebral segments as a single, contiguous unit to prevent intralesional transgression and local recurrence. Achieving microscopic negative margins (R0) stands as the most critical prognostic factor, as radical resection offers a significantly improved potential for long-term survival. Technical success requires a meticulously planned multidisciplinary approach encompassing varied surgical corridors—ranging from combined anterior–posterior windows to single-stage posterior-only approaches—tailored to the tumor’s anatomical level. Furthermore, preoperative hemostatic optimization using dual-energy computed tomography (DECT) for vascular assessment and transarterial embolization (TAE) has become indispensable for managing the hypervascularity of the invaded vertebral bone. This review synthesizes these evolving strategies, illustrated by a case of a 74-year-old male with stage T4 NSCLC where an R0 resection was achieved through a two-stage approach integrating uniportal video-assisted thoracoscopic surgery (VATS). Ultimately, en-bloc management provides a feasible and potential surgical strategy toward long-term survival for localized, spine-invasive lung cancer within a multidisciplinary treatment framework. Full article

Background: Nasopharyngeal carcinoma diagnosis requires endoscopic biopsy, but intraoperative hemorrhage frequently impairs visualization and compromises tissue sampling quality. This prospective case series evaluated topical tranexamic acid (TXA) as a hemostatic adjunct to improve biopsy conditions in suspected nasopharyngeal malignancy. Methods: Adults (≥18 years) with clinically/radiologically suspected nasopharyngeal tumors underwent pre-biopsy laboratory screening and exclusion of thromboembolic risk factors. After topical lidocaine anesthesia, a TXA-soaked cotton pledget was applied to the lesion for 10 min prior to forceps biopsy using 0° 4 mm endoscopy. Bleeding severity was graded pragmatically (minimal: ≤3 gauze pledgets; moderate: >3 or cauterization). Comparative analyses excluded rare diagnoses (n = 1). Results: Of 40 enrolled patients, 34 underwent biopsy (mean age 58.4 ± 12.3 years). All 34 biopsies (100%) yielded conclusive histopathological diagnoses. Adequate hemostasis was achieved in 97.1% (33/34), with minimal bleeding in 76.5% and moderate/massive in 23.5%. Non-keratinizing squamous cell carcinoma (44.1%) showed higher moderate bleeding rates than other diagnoses (Fisher’s exact p = 0.00035). Mean hospitalization was 1.79 ± 1.92 days, uniform across categories. No TXA-related adverse events occurred. Conclusions: Topical TXA provided safe, effective hemostasis during nasopharyngeal biopsy across diverse pathologies, achieving 100% diagnostic adequacy and short hospital stays. Controlled trials comparing TXA versus standard hemostatic techniques are warranted. Full article

Advanced chronic kidney disease (CKD) presents a complex hemostatic paradox, characterized by a simultaneous increase in bleeding and thromboembolic risks. This study aimed to evaluate and compare the safety and efficacy of apixaban versus acenocoumarol in a real-world cohort of patients across advanced CKD stages (pre-dialysis and hemodialysis). We conducted a retrospective observational study including 84 adults with CKD stages 4 and 5 (40.5% in stage 4; 59.5% in stage 5, of whom 86.0% were on chronic hemodialysis) receiving oral anticoagulation for at least 3 months. Patients were stratified by CKD stage and anticoagulant type (apixaban vs. acenocoumarol). Clinical outcomes included major and clinically relevant bleeding, anticoagulant overdose, and thromboembolic events. Bleeding events were more frequent in CKD stage 5 than in stage 4 (66.0% vs. 44.1%, p = 0.06), highlighting a pronounced hemorrhagic burden that increases with disease progression. Apixaban was associated with significantly fewer total bleeding events (44.4% vs. 66.7%, p = 0.04) and a lower rate of anticoagulant overdoses (5.6% vs. 18.8%, p = 0.04) compared with acenocoumarol. Thromboembolic event rates did not differ significantly between the two anticoagulant groups (13.9% vs. 16.7%, p = 0.72). Conventional risk scores (CHA₂DS₂-VASc and HAS-BLED) showed limited discriminatory capacity for actual clinical events in this advanced CKD population. In patients with advanced CKD, oral anticoagulation is associated with a high hemorrhagic burden that intensifies as renal function declines. Apixaban demonstrated a more favorable safety profile than acenocoumarol without a loss of thromboembolic protection. These findings suggest that stage-specific biological factors, rather than conventional risk models alone, should guide anticoagulation strategies in this population. Full article