Conventional pneumatic tourniquets typically rely on fixed empirical pressures that do not account for patient-specific vascular characteristics or dynamic hemodynamic changes, potentially exposing tissues to unnecessary mechanical and ischemic stress. This single-center retrospective cohort study evaluated the clinical performance and safety of an automated systolic blood pressure (SBP)-responsive pneumatic tourniquet in 203 consecutive eligible patients who met the predefined inclusion and exclusion criteria and underwent upper-extremity surgery between January 2023 and September 2024. Continuous or high-frequency SBP measurements were synchronized with cuff-pressure waveforms to characterize real-time closed-loop pressure modulation. Primary outcomes included hemostatic effectiveness and breakthrough bleeding, while secondary outcomes included cuff-pressure behavior, the relationship between SBP and cuff pressure, perioperative hemodynamic stability, and postoperative neurologic or cutaneous complications. The mean tourniquet cuff pressure was 39.61 ± 2.41 kPa (approximately 297 ± 18 mmHg), with values ranging from 34 to 46 kPa. A significant positive correlation was observed between preoperative SBP and cuff pressure (r = 0.706, p < 0.001). Hemostasis was consistently effective, with no breakthrough bleeding observed (0%; 95% CI, 0%-1.8%). Perioperative blood pressure showed only modest fluctuations, and no postoperative neurologic deficits, paresthesia, skin injury, or distal perfusion abnormalities were identified. These findings suggest that a fully automated SBP-responsive tourniquet can provide reliable hemostasis, dynamically maintain physiologically appropriate occlusion pressures, and achieve a favorable short-term safety profile without Doppler-based calibration or manual pressure adjustment, supporting its potential as an individualized and workflow-efficient approach to surgical tourniquet management.

We report the case of a previously healthy 19-year-old woman with a large left coronary trunk-to-right atrium fistula, managed by percutaneous closure. Post-procedural antithrombotic therapy included apixaban and low-dose aspirin. One month later, the patient developed severe metrorrhagia with no identifiable organic cause, prompting unilateral modification of antithrombotic therapy without multidisciplinary discussion. Two months post-intervention, she presented with an acute ST-segment elevation myocardial infarction, likely resulting from thrombus formation at the prosthesis site. Coronary flow of the left anterior descending artery was restored by successful thromboaspiration without stenting.

The therapeutic landscape of hemophilia, a rare inherited bleeding disorder, has rapidly evolved, introducing several novel modalities: extended half-life (EHL) coagulation factor concentrates, non-factor therapies, hemostasis-rebalancing agents, and gene therapy. These advances have improved clinical outcomes by reducing bleeding and treatment burden. However, individualizing treatment in routine practice has become more complex. This narrative review aims to provide a practical summary of available treatment options for pharmacologists, policymakers, and other readers who are not hemophilia specialists. A practical decision framework integrates available data with the clinical indication (regular prophylaxis, management of breakthrough bleeding, and perioperative care), patient-specific modifiers (age, lifestyle, inhibitor status, venous access, joint phenotype, comorbidities, and thrombosis risk). Drug therapies are discussed according to clinical evidence, including pivotal phase 3 trials, long-term extension studies, real-world data, and late-stage development programs. Factor replacement remains critical for hemostatic control during acute bleeding, surgery, and other interventions where predictable and measurable exposure is needed, whereas non-factor and rebalancing therapies provide low-burden prophylactic alternatives with distinct safety profiles and monitoring challenges. Direct comparisons between treatment classes are limited, making treatment individualization essential. Gene therapy has demonstrated more durable outcomes in hemophilia B than in hemophilia A. This review supports shared decision-making and individualized treatment selection in modern hemophilia care. While clinical trial evidence is limited by the scarcity of head-to-head comparisons and incomplete integration of real-world determinants, registry data collection will be essential.

Despite advances in factor VIII (FVIII) replacement and emicizumab prophylaxis, people with hemophilia A may experience breakthrough bleeding, progressive joint disease, treatment burden, and inhibitor-related limitations. Denecimig (Mim8) is a fully human, next-generation FVIIIa-mimetic bispecific antibody engineered to provide subcutaneous prophylaxis irrespective of FVIII inhibitor status.

Hemophilia is an inherited bleeding disorder caused by deficiency of coagulation factor VIII or IX and results in impaired thrombin generation and recurrent bleeding. Prophylactic factor replacement remains the standard treatment; however, its limitations, including the burden of intravenous treatment, inhibitor development, and residual bleeding, necessitate alternative strategies. Non-factor therapies restore hemostatic balance independently of factor replacement. These agents include factor VIIIa-mimetic bispecific antibodies and rebalancing therapies that enhance thrombin generation by inhibiting anticoagulant pathways such as tissue factor pathway inhibitor or antithrombin. Regardless of inhibitor status, non-factor therapies reduce bleeding rates, provide sustained prophylactic efficacy, and improve quality of life in patients with hemophilia A or B. However, several significant challenges remain unresolved. Because these therapies modify physiological procoagulant and anticoagulant pathways, excessive rebalancing may increase thrombotic risk, particularly when additional factor concentrates or bypassing agents are used for breakthrough bleeding or surgery. Furthermore, standardized laboratory assays for assessing global hemostatic potential are lacking, and long-term safety, optimal patient selection, and perioperative management require further clarification. Therefore, this review summarizes current and emerging non-factor therapies for hemophilia, focusing on their mechanisms of action, clinical evidence, safety considerations, unmet needs, and future perspectives for safe implementation in clinical practice.

Uterine cancer, or endometrial cancer, is the most common gynecological cancer after breast cancer. It primarily affects postmenopausal women, and abnormal vaginal bleeding is its main warning sign. Risk factors include age, obesity, and non-insulin-dependent diabetes. The prognosis depends on the stage at diagnosis, the histological type, and molecular factors included in the 2023 International Federation of Gynecology and Obstetrics classification, which helps guide treatment decisions between surgery, radiation therapy, and chemotherapy.

The 2026 Lasker~DeBakey Clinical Medical Research Award has been awarded to Kunihiro Hattori, Takehisa Kitazawa, and Tomoyuki Igawa (Chugai Pharmaceuticals, Tokyo, Japan) for invention of a bispecific antibody that joins blood clotting Factors IXa (FIXa) and X (FX), restoring deficient Factor VIII (FVIII) activity in patients with hemophilia A and preventing severe bleeding in this hereditary disorder. Starting from the 1960s, types of FVIII-replacement therapy remarkably improved on-demand hemostatic treatment for ongoing bleeds and enabled prophylactic reduction of bleeding episodes. However, these agents required burdensome intravenous infusions multiple times per week, and ~30% of patients developed neutralizing anti-FVIII antibodies (FVIII inhibitors). To address these unmet medical needs, in 2000, Hattori-a molecular and hematology biologist, Kitazawa-a hematology biologist and translational researcher, and Igawa-a biochemist and protein engineer, conceived, designed, and created over the span of 10 y a novel FVIII-mimetic. Instead of a native protein construct, they engineered a bispecific IgG antibody against FIXa and FX, circumventing the need for FVIII and enabling subcutaneous administration up to once per month. Importantly, they identified the biophysical requirements for the bispecific to mimic FVIII function effectively and safely, and their breakthrough protein engineering design made possible favorable pharmacokinetics and physicochemical properties with efficient manufacturability. Their collective research efforts demonstrate how imagination, determination, and multidisciplinary scientific research come together to improve patients' lives.

Anticoagulants are essential for preventing and treating thromboembolism across a wide range of clinical settings. Yet, they share a narrow therapeutic index that demands a precise understanding of their pharmacodynamic behavior. Thrombin generation provides an integrated measure of anticoagulant effects by capturing the timing, velocity, and total amount of thrombin formed over time. We reviewed the literature to establish a unified theoretical framework, grounded in mechanistic rationale and supported by experimentation, to better define the pharmacodynamics of anticoagulation therapy using thrombin generation as a common language to compare anticoagulant effects across drug classes. Unfractionated and low-molecular-weight heparins and vitamin K antagonists exert broad, multitargeted inhibition that profoundly suppresses peak thrombin and the endogenous thrombin potential. Direct factor Xa inhibitors primarily blunt propagation, direct thrombin inhibitors delay initiation while preserving overall thrombin output, and factor XIa inhibitors act mainly under low tissue factor conditions. Agents that engage multiple components of the coagulation cascade (prothrombinase formation, thrombin feedback activation, or zymogen depletion) produce deeper, cumulative suppression of thrombin generation and maintain efficacy under highly prothrombotic conditions, as seen with mechanical heart valves, antiphospholipid antibody syndrome, and catheter-associated thrombosis. In contrast, selective inhibitors achieve pharmacodynamic predictability but may lose responsiveness in the face of extreme coagulation activation. From a pharmacodynamic perspective, not all anticoagulants are the same. Divergent mechanisms map to unique, reproducible, and informative pharmacodynamic signatures that are characterized using thrombin generation. These signatures help explain why some patients experience breakthrough thrombosis or bleeding despite "on-target" drug levels. Embedding thrombin generation within clinical research allows anticoagulant effects to be interpreted through a mechanistic lens that bridges molecular pharmacology with patient-level variability. This synthesis provides a common language for comparing anticoagulants and lays the foundation for an individualized, pharmacologically informed approach to anticoagulation therapy.