Haemophilia testing of young girls in Canada: Describing the current recommendations for factor level and genetic testing and the experiences of Canadian parents.

INTRODUCTION: It is widely acknowledged that haemophilia affects women and girls, yet current testing recommendations for factor level and genetic testing vary and do not universally incorporate updated research. Canadian parents have expressed frustration at inconsistent recommendations and reported instances where delayed testing led to missed diagnosis and preventable bleeding. AIM: Study aim was to explore and describe the practice of haemophilia-related testing of young girls in Canada. METHODS: A mixed methods study was carried out with two populations: (1) Nurses working in haemophilia care completed a survey regarding the current testing recommendations of their Haemophilia Treatment Centre (HTC), (2) Parents of obligate or potential haemophilia carriers completed a structured interview with questions about their family experience of haemophilia and testing decisions for daughters. RESULTS: Twenty-six survey responses were received and showed wide variation in the usual recommendations of Canadian HTCs. Different factor level testing recommendations may be given to obligate and potential carriers despite no difference in bleeding risk. Only a minority of HTCs currently recommend an early baseline factor level (< 10 years) to obligate carriers (27%) or potential carriers (15%). For genetic testing of potential carriers, 70% of HTC would approve a family request for genetic testing of a minor with specific conditions. The majority of parents interviewed felt dissatisfied with their testing experience (58%) and highlighted many issues related to delayed testing recommendations. CONCLUSION: Updated, nationally affirmed testing recommendations are needed that align with research on bleeding in women and girls affected by haemophilia.

Bleeding outcomes in critically ill patients on heparin with discordant aPTT and anti-Xa activity.

Activated partial thromboplastin time (aPTT) and unfractionated heparin (UFH) level via the anti-factor Xa activity assay (anti-Xa) are commonly used assays for UFH monitoring. While discordance between the two assays is common, its impact on critically ill patient outcomes is unclear. This study aimed to compare the incidence of major bleeding events among critically ill patients with discordant aPTT and anti-Xa activity while on UFH, to patients with no discordance. This was a single-center, retrospective cohort study of critically ill adult patients who had simultaneous anti-Xa and aPTT levels while receiving continuous UFH infusion. The primary outcome was the incidence of a major bleeding event up to 24 h after UFH discontinuation. Secondary outcomes included incidence of 30-day thrombosis and hospital length of stay (LOS). Among 264 included patients, 156 patients (59%) had at least one discordant paired level. Patients with discordance had an increased risk of major bleeding events (14% versus 5%; unadjusted risk ratio, 3.0; 95% CI 1.2-7.8; p = 0.01), and increased risk of thrombotic events (4% versus 0%; p = 0.04). Hospital LOS was similar between the two groups (13.8 days versus 11.4 days; p = 0.08). In this cohort of critically ill patients receiving continuous UFH, discordance in aPTT and anti-Xa activity was frequently observed and was associated with an increased risk of major bleeding events. While both assays remain viable monitoring options, evaluating simultaneous levels may aid in the management of critically ill patients. In patients with discordance, an individualized approach balancing bleeding and thrombotic risks should be considered.

Adherence and Quality of Life in Adult Patients With Haemophilia A, Haemophilia B and Von Willebrand Disease: A National Cross-Sectional Survey.

BACKGROUND: New treatments for patients with bleeding disorders (PWB) have emerged, including products with extended half-life and subcutaneous administration. These less frequent treatments can potentially enhance quality of life (QoL), but adherence becomes critically important. AIM: To investigate adherence and QoL among PWB and explore the correlation between treatment adherence and QoL in adult patients with haemophilia A (HA), haemophilia B (HB) and Von Willebrand disease (vWD) in Denmark. METHOD: This survey used disease-specific patient-reported questionnaires: Veritas-PRO and Veritas-PRN to measure adherence, and Haemo-A-QoL and VWD-QoL to assess QoL. RESULTS: Responses were obtained from 149 patients with HA, 32 with HB and 118 with vWD. Adherence was reported by 87.1% of patients on prophylaxis and 71.2% of patients treated on demand, according to Veritas-PRO and Veritas-PRN cut-off scores. High QoL was generally reported, decreasing with age in HA and HB, but not in vWD. CONCLUSION: Danish patients with HA, HB and vWD reported high QoL and high adherence to prescribed treatments. There was no correlation between treatment adherence and QoL among the different patient groups. These findings highlight the need for further research to better understand adherence behaviours and identify opportunities to further improve QoL in PWB.

Predictors of diagnostic delays and loss to follow-up in women with von Willebrand disease: a single-center retrospective cohort study.

Background: Women with von Willebrand disease (VWD) often face diagnostic delays, leading to increased bleeds, stress, and healthcare use. The factors influencing these delays and their effects on gynecologic outcomes are not well understood. Objectives: This study aimed to 1) identify the prevalence and predictors of diagnostic delays and loss to follow-up in women with VWD and 2) determine how these delays affect severe gynecologic bleeding, emergency visits, transfusions, and hysterectomies. Methods: We conducted a single-center retrospective cohort study and included women aged ≥18 years diagnosed with VWD. Delayed diagnosis was defined as ≥3 bleeding events prior to VWD diagnosis, excluding easy bruising due to its subjectivity. Loss to follow-up was defined as ≥5 years since the last hematology visit. We used logistic regression for analysis. Results: Among 178 diagnosed women (median age, 27 years), 71 (40%) experienced ≥3 bleeding events before diagnosis. The median time from the first bleeding event to VWD diagnosis was 14.2 years. Severe bleeding events significantly predicted diagnostic delays (adjusted odds ratio, 3.1; 95% CI, 1.5-6.2). Fifty-four (30%) women were lost to follow-up, with remote era of initial bleed and VWD type identified as significant predictors. Delays were associated with increased risks of hysterectomies (odds ratio, 2.7; 95% CI, 1.2-6.3) and other gynecologic procedures. Conclusion: Delayed diagnosis and loss to follow-up in VWD are common even in a specialized Hemophilia Treatment Centre. Such delays lead to more severe bleeding and increased gynecologic interventions. Prompt diagnosis is paramount for better patient outcomes and reduced healthcare utilization.

Enhanced Venous Thrombosis and Hypercoagulability in Murine and Human Metabolic Dysfunction-Associated Steatohepatitis.

BACKGROUND: Patients with metabolic dysfunction-associated steatohepatitis (MASH) are at an increased risk of developing venous thromboembolic events (VTE), including deep vein thrombosis (DVT). To date, the study of DVT in MASH has been hampered by the lack of reliable models that mimic the pathological aspects of human disease. OBJECTIVES: To evaluate DVT severity and hypercoagulability in murine and human MASH. METHODS: Transcriptional changes in the liver, plasma markers of coagulation, and DVT severity were evaluated in mice fed a chow diet or a high-fructose, high-fat, and high-cholesterol, MASH diet for 24 weeks. Plasma analyses of coagulations markers and thrombin generation assay were performed in a well-characterized cohort of patients with or without MASH. RESULTS: Mice fed the MASH diet developed steatohepatitis and fibrosis, mimicking human MASH. Liver RNA-sequencing revealed a significant upregulation of pathways related to inflammation and coagulation concomitant with increased plasma coagulation markers including increased prothrombin fragment 1+2, thrombin-antithrombin complex, plasminogen activator inhibitor-1 levels, and endothelin 1. MASH exacerbated DVT severity in mice, as evidenced by increased thrombus weight and higher thrombosis incidence (15/15 vs. 11/15 in controls, p=0.0317). Higher endothelin 1 release and increased apoptosis were found in endothelial cells stimulated with supernatants of palmitate-stimulated HepG2 cells. Patients with MASH exhibited increased plasma coagulation markers and delayed thrombin generation. CONCLUSION: We report enhanced DVT severity and hypercoagulability, both in murine and human MASH. Our model of MASH-DVT can facilitate a better understanding of the fundamental mechanisms leading to increased VTE in patients with MASH.

The in vitro effects of acidemia and acidemia reversal on coagulation in dogs.

Background: The effect of acidemia on blood coagulation remains inadequately understood in veterinary medicine. Therefore, we assessed the effect of in vitro acidification of canine whole blood on coagulation and investigated whether acidemia-induced coagulopathy could be reversed by reversing acidemia. Methods: Citrated whole blood samples were taken from six healthy Beagle dogs and categorized, based on pH adjustment, into neutral, weak acidemia (WA), strong acidemia (SA), and reversal from SA. Then, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen concentration, conventional thromboelastography (TEG) parameters, and velocity curve (V-curve) variables of TEG were assessed. Results: The PT, aPTT, and most TEG parameters showed significant coagulopathy in the SA group compared to the neutral group, with additional significant changes in reaction time (R), clot kinetic (K), maximum amplitude (MA), split point (SP), elasticity (E), thrombodynamic potential index (TPI), and coagulation index (CI) between the SA and WA groups. Among V-curve variables, the maximum rate of thrombus generation (MRTG) and total thrombus generation were significantly inhibited in the SA group compared to the neutral group, with significant differences in the time to maximum rate of thrombus generation (TMRTG) between the WA and SA groups. In the reverse group, aPTT, R, K, α-angle, MRTG, TMRTG, SP, TPI, and CI exhibited significant recovery compared to the SA group. Conclusion: The in vitro induction of acidemia in canine whole blood leads to impairment of coagulation profiles, and pH correction can reverse most acidemia-induced coagulopathy.

A Serendipitous Finding of Coagulation Factor VII Deficiency in Two Asymptomatic Patients.

Congenital Factor VII (FVII) deficiency is a rare autosomal recessive disorder with a prevalence of approximately 1:500,000. It plays a crucial role in initiating coagulation by activating Factors IX and X. Diagnosis typically involves prolonged prothrombin time (PT) and varies widely in clinical presentation. Management includes fresh frozen plasma (FFP), prothrombin complex concentrates (PCC), and recombinant activated FVII (rFVIIa), with rFVIIa often preferred due to its safety and efficacy. We present two pediatric cases: a five-year-old boy with a prolonged PT at 55% and FVII levels at 25.1%, and a two-year-old boy with a PT at 24% and FVII levels at 4.6%. Both cases highlight the importance of thorough hemostatic evaluation and tailored management strategies in FVII deficiency.

Risk Factors for Mortality in Critically Ill Patients with Coagulation Abnormalities: A Retrospective Cohort Study.

OBJECTIVE: Coagulation abnormalities are common and prognostically significant in intensive care units (ICUs) and are associated with increased mortality. This study aimed to explore the association between the levels of coagulation markers and the risk of mortality among ICU patients with coagulation abnormalities. METHODS: This retrospective study investigated patients with coagulation abnormalities in the ICU between January 2021 and December 2022. The initial point for detecting hemostatic biomarkers due to clinical assessment of coagulation abnormalities was designated day 0. Patients were followed up for 28 days, and multivariate logistic regression analysis was utilized to identify risk factors for mortality. RESULTS: Of the 451 patients analyzed, 115 died, and 336 were alive at the end of the 28-day period. Multivariate analysis revealed that elevated thrombin-antithrombin complex (TAT), tissue plasminogen activator inhibitor complex (tPAIC), prolonged prothrombin time, and thrombocytopenia were independent risk factors for mortality. For nonovert disseminated intravascular coagulation (DIC) patients, older age and thrombocytopenia were associated with increased risks of mortality, whereas elevated levels of plasmin α2-plasmin inhibitor complex (PIC) were found to be independent predictors of survival. In patients with overt DIC, elevated levels of tPAIC were independently associated with increased risks of mortality. Nevertheless, thrombocytopenia was independently associated with increased risks of mortality in patients with pre-DIC. CONCLUSION: Coagulation markers such as the TAT, tPAIC, PIC, and platelet count were significantly associated with mortality, underscoring the importance of maintaining a balance between coagulation and fibrinolysis. These findings highlight the potential for targeted therapeutic interventions based on specific coagulation markers to improve patient outcomes.

The clinical effect of endoscopic and open surgery in the treatment of thyroid cancer and their effect on the blood coagulation state: a comparative study.

Purpose: This study was performed to compare the therapeutic efficacy of endoscopic surgery and open surgery and their effects on postoperative blood coagulation state in patients with thyroid cancer, and to provide evidence for the prevention measurement of thrombosis in the perioperative period. Methods: One hundred patients with thyroid cancer who received treatment in our hospital from January 2021 to December 2021, were randomly divided into an endoscopic group and an open surgery group, with 50 patients in each group. The patients in the open surgery group were treated by traditional open surgery, while patients in the endoscopic group accepted endoscopic surgery. The clinically therapeutic effect and blood coagulation of the 2 groups were compared. Results: Intraoperative blood loss and length of hospital stay were lower, and operative time was longer in the endoscopic group than in the open surgery group (P < 0.05). The 24-hour postoperative fibrinogen and D-dimer levels were higher in both groups than in the preoperative period, while PT was shorter (P < 0.05). There were no significant differences in postoperative complications and follow-up between the 2 groups (P > 0.05), but the incidence of complications, postoperative metastases, and thrombosis was relatively low in the endoscopic group. Conclusion: In the treatment of patients with thyroid cancer, endoscopic surgery has the advantages of less blood loss, fewer complications, and so on. Endoscopic and open surgery can lead to a hypercoagulable state, but the effect of endoscopic surgery is better than that of open surgery.

An Automated pre-Dilution Setup for Von Willebrand Factor Activity Assays.

Accurate quantification of von Willebrand factor ristocetin cofactor activity (VWF:RCo) is critical for the diagnosis and classification of von Willebrand disease, the most common hereditary and acquired bleeding disorder in humans. Moreover, it is important to accurately assess the function of von Willebrand factor (VWF) concentrates within the pharmaceutical industry to provide consistent and high-quality biopharmaceuticals. Although the performance of VWF:RCo assay has been improved by using coagulation analyzers, which are specialized devices for blood and blood plasma samples, scientists still report a high degree of intra- and inter-assay variation in clinical laboratories. Moreover, high, manual sample dilutions are required for VWF:RCo determination of VWF concentrates within the pharmaceutical industry, which are a major source for assay imprecision. For the first time, we present a precise and accurate method to determine VWF:RCo, where all critical pipetting and mixing steps are automated. A pre-dilution setup was established on CyBio FeliX (Analytik-Jena) liquid handling system, and an adapted VWF:RCo method on BCS-XP analyzer (Siemens) is used. The automated pre-dilution method was executed on three different, most frequently used coagulation analyzers and compared to manual pre-dilutions performed by an experienced operator. Comparative sample testing revealed a similar assay precision (coefficient of variation = 5.9% automated, 3.1% manual pre-dilution) and no significant differences between the automated approach and manual dilutions of an expert in this method. While no outliers were generated with the automated procedure, the manual pre-dilution resulted in an error rate of 8.3%. Overall, this operator-independent protocol enables standardization and offers an efficient way of fully automating VWF activity assays, while maintaining the precision and accuracy of an expert analyst. Key features • Automated pre-dilution setup for von Willebrand factor concentrates of various natures. • Combination of a liquid handling system (CyBio FeliX) with a coagulation analyzer (BCS-XP). • Simplifies method transfer to other laboratories. • Basic training for CyBio FeliX and BCS-XP is required. Graphical overview VWF:RCo assay principle and measurement setup. Platelets (yellow ellipsoids) with negative surface charge (- - -) are treated with formaldehyde, which partly denatures the cell surface and thus stabilizes platelets for use as assay reagents. Stabilized platelets (dark-yellow-framed yellow ellipsoids) are then brought in contact with ristocetin A (chemical structure shown; black dots), which binds to the platelet surface and facilitates binding of VWF (green circles). The graphs show an example of quantitative determination of platelet agglutination by measurement of light transmission, where increasing amounts of VWF increase light transmission over time. The photo in the left-bottom corner shows the CyBio FeliX setup for VWF sample dilution and the photo in the right-bottom corner displays the BCS-XP system, which is used for VWF:RCo measurements.

Coagulo-Net: Enhancing the mathematical modeling of blood coagulation using physics-informed neural networks.

Blood coagulation, which involves a group of complex biochemical reactions, is a crucial step in hemostasis to stop bleeding at the injury site of a blood vessel. Coagulation abnormalities, such as hypercoagulation and hypocoagulation, could either cause thrombosis or hemorrhage, resulting in severe clinical consequences. Mathematical models of blood coagulation have been widely used to improve the understanding of the pathophysiology of coagulation disorders, guide the design and testing of new anticoagulants or other therapeutic agents, and promote precision medicine. However, estimating the parameters in these coagulation models has been challenging as not all reaction rate constants and new parameters derived from model assumptions are measurable. Although various conventional methods have been employed for parameter estimation for coagulation models, the existing approaches have several shortcomings. Inspired by the physics-informed neural networks, we propose Coagulo-Net, which synergizes the strengths of deep neural networks with the mechanistic understanding of the blood coagulation processes to enhance the mathematical models of the blood coagulation cascade. We assess the performance of the Coagulo-Net using two existing coagulation models with different extents of complexity. Our simulation results illustrate that Coagulo-Net can efficiently infer the unknown model parameters and dynamics of species based on sparse measurement data and data contaminated with noise. In addition, we show that Coagulo-Net can process a mixture of synthetic and experimental data and refine the predictions of existing mathematical models of coagulation. These results demonstrate the promise of Coagulo-Net in enhancing current coagulation models and aiding the creation of novel models for physiological and pathological research. These results showcase the potential of Coagulo-Net to advance computational modeling in the study of blood coagulation, improving both research methodologies and the development of new therapies for treating patients with coagulation disorders.

A surface-functionalized whole blood-based dielectric microsensor for assessment of clot firmness in a fibrinolytic environment.

Accurate assessment of fibrin clot stability can predict bleeding risk in coagulopathic conditions such as thrombocytopenia and hypofibrinogenemia. Hyperfibrinolysis - a clinical phenotype characterized by an accelerated breakdown of the fibrin clot - makes such assessments challenging by obfuscating the effect of hemostatic components including platelets or fibrinogen on clot stability. In this work, we present a biofunctionalized, microfluidic, label-free, electronic biosensor to elicit unique, specific, and differential responses from the multifactorial processes of blood coagulation and fibrinolysis ex vivo. The microsensor tracks the temporal variation in the normalized real part of the dielectric permittivity of whole blood (<10 µL) at 1 MHz as the sample coagulates within a three-dimensional, parallel-plate, capacitive sensing area. Surface biofunctionalization of the microsensor's electrodes with physisorption of tissue factor (TF) and aprotinin permits real-time assessment of the coagulation and fibrinolytic outcomes. We show that surface coating with TF and manual addition of TF result in a similar degree of acceleration of coagulation kinetics in human whole blood samples. We also show that surface coating with aprotinin and manual addition of aprotinin yield similar results in inhibiting tissue plasminogen activator (tPA)-induced upregulated fibrinolysis in human whole blood samples. Validated through a clinically relevant, complementary assay - rotational thromboelastometry for clot viscoelasticity - we finally establish that a microsensor dual-coated with both TF and aprotinin detects the hemostatic rescue in the tPA-induced hyperfibrinolytic profile of whole blood and the hemostatic dysfunction due to concurrent platelet depletion in the blood sample, thus featuring enhanced ability in evaluating complex, combinatorial coagulopathies.

Endothelial colony-forming cells in the spotlight: insights into the pathophysiology of von Willebrand disease and rare bleeding disorders.

Endothelial cells deliver a vital contribution to the maintenance of hemostasis by constituting an anatomical as well as functional barrier between the blood and the rest of the body. Apart from the physical barrier function, endothelial cells maintain the hemostatic equilibrium by their pro- and anticoagulant functions. An important part of their procoagulant contribution is the production of von Willebrand factor (VWF), which is a carrier protein for coagulation factor VIII and facilitates the formation of a platelet plug. Thus, VWF is indispensable for both primary and secondary hemostasis, which is exemplified by the bleeding disorder von Willebrand disease that results from qualitative or quantitative deficiencies in VWF. A cellular model that was found to accurately reflect the endothelium and its secretory organelles are endothelial colony-forming cells, which can be readily isolated from peripheral blood and constitute a robust ex vivo model to investigate the donor's endothelial cell function. This review summarizes some of the valuable insights on biology of VWF and pathogenic mechanisms of von Willebrand disease that have been made possible using studies with endothelial colony-forming cells derived from patients with bleeding disorders.

Blood Coagulation Activities and Influence on DNA Condition of Alginate-Calcium Composites Prepared by Freeze-Drying Technique.

The aim of this research was to synthesize and characterize alginate-calcium composites using a freeze-drying method, with a focus on their potential applications in biomedicine. This study specifically explored the biochemical properties of these composites, emphasizing their role in blood coagulation and their capacity to interact with DNA. Additionally, the research aimed to assess how the cross-linking process influences the structural and chemical characteristics of the composites. Detailed analyses, including microscopic examination, surface area assessment, and atomic absorption spectrometry, yielded significant results. The objective of this study was to examine the impact of calcium chloride concentration on the calcium content in alginate composites. Specifically, the study assessed how varying concentrations of the cross-linking solution (ranging from 0.5% to 2%) influence the calcium ion saturation within the composites. This investigation is essential for understanding the physicochemical properties of the materials, including calcium content, porosity, and specific surface area. The results are intended to identify the optimal cross-linking conditions that maximize calcium enrichment efficiency while preserving the material's structural integrity. The study found that higher calcium chloride concentrations in alginate cross-linking improve the formation of a porous structure, enhanced by two-stage freeze-drying. Increased calcium levels led to a larger surface area and pore volume, and significantly higher calcium content. Furthermore, assays of activated partial thromboplastin time (aPTT) showed a reduction in clotting time for alginate composites containing calcium ions, indicating their potential as hemostatic agents. The aPTT test showed shorter clotting times with higher calcium ion concentrations, without enhanced activation of the extrinsic clotting pathway. The developed alginate material with calcium effectively supports hemostasis and reduces the risk of infection. The study also explored the capacity of these composites to interact with and modify the structure of plasmid DNA, underscoring their potential for future biomedical applications.

Circulating microRNAs targeting coagulation and fibrinolysis in patients with severe COVID-19.

BACKGROUND: Coronavirus-19 disease (COVID-19) frequently causes coagulation disturbances. Data remains limited on the effects of microRNAs (miRNAs) on coagulation during COVID-19 infection. We aimed to analyze the comprehensive miRNA profile as well as coagulation markers and blood count in hospitalized COVID-19 patients. METHODS: Citrated plasma samples from 40 patients (24 men and 16 women) hospitalized for COVID-19 were analyzed. Basic coagulation tests, von Willebrand factor (VWF), ADAMTS13, blood count, C-reactive protein, and 27 miRNAs known to associate with thrombosis or platelet activation were analyzed. MiRNAs were analyzed using quantitative reverse transcription polymerase chain reaction (RT qPCR), with 10 healthy controls serving as a comparator. RESULTS: Among the patients, 15/36 (41%) had platelet count of over 360 × 109/L and 10/36 (28%) had low hemoglobin of < 100 g/L, while 26/37 (72%) had high VWF of over 200 IU/dL. Patients had higher levels of the miRNAs miR-27b-3p, miR-320a-3p, miR-320b-3p, and miR-424-5p, whereas levels of miR-103a-3p and miR-145-5p were lower than those in healthy controls. In total, 11 miRNAs were associated with platelet count. Let-7b-3p was associated with low hemoglobin levels of < 100 g/L. miR-24-3p, miR-27b-3p, miR-126-3p, miR-145-5p and miR-338-5p associated with high VWF. CONCLUSION: COVID-19 patients differentially express miRNAs with target genes involved in fibrinolysis inhibition, coagulation activity, and increased inflammatory response. These findings support the notion that COVID-19 widely affects hemostasis, including platelets, coagulation and fibrinolysis.

When innovation meets patient blood management - a new way to see bleeding.

The first step in innovation is to identify a problem of real relevance and systematically address it to deliver a sophisticated and viable solution. Disruptive innovation is a process where technology, products, or services are transformed or replaced by a better innovative solution. This superiority must be perceived by users as being more accessible, simple, or convenient. Patient Blood Management (PBM) suggests the notion of the timely application of evidence-based medical and surgical concepts designed to maintain hemoglobin concentration, optimize hemostasis and minimize blood loss thus improving patient outcomes, that is, they are aimed at changing patient care, assisting healthcare professionals in disease treatment and cure as well as risk reduction. Thus, innovation in PBM is a new frontier to be pursued. The management of patient's blood and preparation for surgical procedures is an enormous challenge that helps minimize anemia and control blood loss during hospitalization, ensuring they are discharged in adequate clinical conditions. Until 2016, there was no standard definition or classification for the severity of intraoperative bleeding or hemostasis. The development of a PBM program when combined to the development of a bleeding scale such as the validated Intraoperative Bleeding (VIBe) Scale, represents a new solution that balances perioperative blood loss and more importantly, enables a critical cultural change which can be useful to help surgeons communicate anticipated hemostatic needs throughout a case and therefore enhance efficiency leading to better outcomes.

Enhanced stock market forecasting using dandelion optimization-driven 3D-CNN-GRU classification.

The global interest in market prediction has driven the adoption of advanced technologies beyond traditional statistical models. This paper explores the use of machine learning and deep learning techniques for stock market forecasting. We propose a comprehensive approach that includes efficient feature selection, data preprocessing, and classification methodologies. The wavelet transform method is employed for data cleaning and noise reduction. Feature selection is optimized using the Dandelion Optimization Algorithm (DOA), identifying the most relevant input features. A novel hybrid model, 3D-CNN-GRU, integrating a 3D convolutional neural network with a gated recurrent unit, is developed for stock market data analysis. Hyperparameter tuning is facilitated by the Blood Coagulation Algorithm (BCA), enhancing model performance. Our methodology achieves a remarkable prediction accuracy of 99.14%, demonstrating robustness and efficacy in stock market forecasting applications. While our model shows significant promise, it is limited by the scope of the dataset, which includes only the Nifty 50 index. Broader implications of this work suggest that incorporating additional datasets and exploring different market scenarios could further validate and enhance the model's applicability. Future research could focus on implementing this approach in varied financial contexts to ensure robustness and generalizability.

Thromboelastography as an early prediction method for hypofibrinogenemia in emergency department patients with primary postpartum hemorrhage.

BACKGROUND: Timely and accurate assessment of coagulopathy is crucial for the management of primary postpartum hemorrhage (PPH). Thromboelastography (TEG) provides a comprehensive assessment of coagulation status and is useful for guiding the treatment of hemorrhagic events in various diseases. This study aimed to evaluate the role of TEG in predicting hypofibrinogenemia in emergency department (ED) patients with primary PPH. METHODS: We conducted a retrospective observational study in the ED of a university-affiliated tertiary hospital between November 2015 and August 2023. TEG was performed upon admission. The cutoff value for hypofibrinogenemia was 200 mg/dL. The primary outcome was the presence of hypofibrinogenemia. RESULTS: Among the 174 patients, 73 (42.0%) had hypofibrinogenemia. The need for massive transfusion was higher in the hypofibrinogenemia group (37.0% vs. 5.0%, p < 0.001). Among the TEG parameters, all values were significantly different between the groups, except for lysis after 30 min, suggesting a tendency toward hypocoagulability. Multivariable analysis revealed that the alpha angle (odds ratio (OR) 0.924, 95% confidence interval (CI) 0.876-0.978) and maximum amplitude (MA) (OR 0.867, 95% CI 0.801-0.938) were independently associated with hypofibrinogenemia. The optimal cutoff values for the alpha angle and maximum amplitude (MA) for hypofibrinogenemia were 63.8 degrees and 56.1 mm, respectively. CONCLUSION: Point-of-care TEG could be a valuable tool for the early identification of hypofibrinogenemia in ED patients with primary PPH.

Direct reinfusion of pericardial blood complications: A case of acute respiratory distress syndrome and disseminated intravascular coagulation.

Background: Direct reinfusion of pericardial blood during cardiac surgery triggers a systemic inflammatory response. Although various inflammatory mediators have been identified as triggers, the role of damage-associated molecular patterns (DAMPs) remains poorly understood. Despite guidelines recommending against this practice owing to its harmful effects, it is sometimes used in emergencies. Case Presentation: A 72-year-old man with atrial fibrillation and cerebral infarction developed cardiac tamponade during catheter ablation. He underwent pericardial drainage and direct blood reinfusion. He was transferred to our ICU, where he developed acute respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC). Despite aggressive management, the patient died 41 days after admission. Conclusion: This case highlights severe adverse events following direct reinfusion of pericardial blood. These findings suggest a significant role for DAMPs in mediating these inflammatory responses. Direct reinfusion of pericardial drainage blood should be avoided during emergencies to prevent life-threatening complications.