Search Results (123)

Background/Objectives: Intraoperative bleeding remains one of the major challenges in pediatric liver transplantation (PLT), contributing significantly to perioperative morbidity, transfusion-related complications, and prolonged recovery. Although viscoelastic testing has improved intraoperative hemostatic management, there are currently no validated preoperative tools capable of predicting bleeding risk in this vulnerable population. Methods: We conducted a prospective, single-center observational study including 43 consecutive pediatric patients who underwent orthotopic liver transplantation between May 2008 and August 2009. A comprehensive dataset encompassing demographic, clinical, biochemical, and surgical variables was collected. A multivariable linear regression model was developed to predict intraoperative blood loss (IBL). Variable selection was guided by Mallows’ Cp criterion to ensure optimal model fit and clinical interpretability. Model performance was assessed using adjusted R², diagnostic residual analysis, and internal validation to verify regression assumptions. Results: Six independent predictors of IBL were identified: presence of ascites, prior abdominal surgery, operative time, baseline fibrinogen concentration, platelet count, and recipient weight. The final model explained 35.2% of IBL variance (adjusted R² = 0.352; F = 7.68; p < 0.001). Model diagnostics confirmed linearity, normal distribution of residuals, and homoscedasticity, supporting its robustness and reliability. Conclusions: This multivariable model provides an interpretable, clinically applicable framework for individualized preoperative estimation of blood loss in PLT. It may assist in planning perioperative patient blood management strategies and serve as a foundation for future decision-support systems. Limitations include the single-center design and modest sample size; however, internal validation supported the stability and reliability of the model. Full article

Coronary artery disease (CAD) remains the leading cause of cardiovascular mortality worldwide. Accurate and non-invasive quantification of coronary hemodynamics, namely in the right coronary artery (RCA), is essential for clinical decision-making but remains challenging due to the complex interaction among vessel geometry, pulsatile flow, and blood rheology. This study presents and validates a transparent computational framework for non-invasive fractional flow reserve (FFR) estimation using patient-specific RCA geometries reconstructed from coronary computed tomography angiography (CCTA) using SimVascular 27-03-2023. The proposed workflow integrates realistic boundary conditions through a Womersley velocity profile and a three-element Windkessel outlet model, coupled with a viscoelastic blood rheology formulation (sPTT) implemented via user-defined functions (UDFs). This work integrates all clinically relevant conditions of invasive FFR assessment into a single patient-specific computational framework, while delivering results within a time frame compatible with clinical practice, representing a meaningful methodological advance. The methodology was applied to seven patient-specific cases, and the resulting non-invasive FFR values were compared with both invasive wire-based measurements and commercial HeartFlow^® outputs (Mountain View, CA, USA). Under hyperemic conditions, the computed FFR values showed strong agreement with invasive references, with a mean relative error of 8.4% ± 6.3%, showing diagnostic consistency similar to that of HeartFlow^® (8.3% ± 8.1%) for the selected dataset. These findings demonstrate the ability of the proposed CFD-based pipeline to accurately replicate physiological coronary behavior under hyperemia. This novel workflow provides a fully on-site, open-source, reproducible, and cost-effective framework. Ultimately, this study advances the clinical applicability of non-invasive CFD tools for the functional assessment of CAD, particularly in the RCA. Full article

Background/Objectives: The timely evaluation of blood clot formation and breakdown is essential in the care of patients with severe bleeding or critical illness. Resonant acoustic rheometry is a novel, non-contact ultrasound method that measures changes in the viscoelastic properties of blood in a standard microplate format. Here, we present the first clinical description of whole blood coagulation and fibrinolysis assessed with resonant acoustic rheometry, with paired thromboelastography measurements for comparison. Methods: In this retrospective analysis, whole blood samples from three critically ill patients were divided and tested under four different conditions that included a control mixture, kaolin activation, tissue factor activation, and a tissue factor mixture supplemented with tissue plasminogen activator. The resonant acoustic rheometry system obtained real time measurements of resonant surface waves and displacements from the samples. Heat maps and spectrograms of the resonant surface waves were analyzed to determine the onset of clotting, the rate of viscoelastic stiffening, the time to maximum rigidity, and the onset as well as magnitude of fibrinolysis. These measurements were compared with thromboelastography reaction time, clot strength, fibrinogen contribution, and lysis values. Results: Resonant acoustic rheometry detected reproducible transitions from liquid to clot and from clot to lysis in all samples. Activator-dependent changes in clot initiation and propagation matched the expected hierarchy observed in thromboelastography. Significantly, samples exposed to tissue plasminogen activator demonstrated a clear fall in resonant frequency and a corresponding rise in surface displacement that reflected fibrinolysis. The technique also reproduced clinically meaningful patterns of hemostasis that aligned with each patient’s underlying disease. Conclusions: Whole blood clotting can be measured with resonant acoustic rheometry in a manner that aligns with established clinical assays. These results suggest strong potential for future use of resonant acoustic rheometry as a cost-effective, complementary platform for rapid, scalable, and clinically informative hemostatic assessment. Full article

Introduction: Postpartum hemorrhage remains a leading cause of maternal morbidity and mortality worldwide. While antifibrinolytic agents such as tranexamic acid are effective in treating established postpartum hemorrhage, the benefit of prophylactic tranexamic acid remains debated. The presence and frequency of early postpartum hyperfibrinolysis during routine childbirth have not been thoroughly investigated. Material & Methods: This prospective observational study was registered on ClinicalTrials.gov (NCT05975112) and conducted at the Medical University Hospital Graz between June 2023 and June 2024. Blood samples were collected from 413 women immediately after umbilical cord clamping; 379 were included in the analysis—291 undergoing Caesarean section and 88 vaginal delivery. Hyperfibrinolysis was assessed using thromboelastography and defined as an LY30 value > 8%. Additional coagulation parameters—including fibrinogen, D-dimer, activated partial thromboplastin time, and prothrombin time—were measured. Correlation analyses between viscoelastic and conventional parameters were performed using Pearson’s correlation coefficients. Results: No cases of clinically significant hyperfibrinolysis (LY30 > 8%) were observed. However, 15.5% of women showed elevated LY30 values (>0%). LY30 values were significantly higher in vaginal deliveries compared to Caesarean sections (p = 0.003). A moderate correlation between maximum amplitude (MA) and fibrinogen was observed (r = 0.52), strongest in vaginal deliveries (r = 0.65). Other correlations were weak or negligible. Conclusions: Clinically relevant hyperfibrinolysis was not observed immediately postpartum in women without hemorrhage. These findings are consistent with current guidelines recommending tranexamic acid for therapeutic rather than routine prophylactic use. Viscoelastic testing may be useful for rapid assessment in early-stage bleeding. Further research should explore fibrinolytic activity later in the postpartum period. Full article

Immunothrombosis can substantially affect the course and outcomes of severe infections and immune-mediated diseases. While inflammatory thrombi are neutrophil-rich, impact of neutrophils on clot contraction, a key modulator of thrombus stability and obstructiveness, was unknown. This study investigated how neutrophils and neutrophil extracellular traps (NETs) affect the rate and extent of platelet-driven clot contraction. Isolated human neutrophils were stimulated with phorbol-12-myristate-13-acetate (PMA) to induce NETosis, confirmed by fluorescence microscopy and scanning electron microscopy. Thrombin-induced clots, formed from whole blood or platelet-rich plasma, were supplemented with non-activated or PMA-activated neutrophils. Clot contraction kinetics and viscoelasticity were analyzed. PMA-activated neutrophils significantly enhanced the rate and final extent of clot contraction compared to controls. This promoting effect was abolished by deoxyribonuclease (DNAse) I, confirming that it was mediated by NETs embedded in the fibrin network. The factor Xa inhibitor rivaroxaban also abrogated this effect, indicating a role for NET-induced endogenous thrombin generation and platelet hyperactivation. Thromboelastography revealed that NETs made clots softer and more deformable. We conclude that activated neutrophils promote clot contraction via NETs embedded in the fibrin network, which enhance platelet contractility via endogenous thrombin production and increase clot deformability, suggesting that inflammatory thrombosis may require treatments addressing this enhanced contractility. Full article

Background/Objectives: Red blood cells actively influence hemostasis by enhancing platelet activation, promoting thrombin generation, and contributing to clot structure. Their transfusion may alter coagulation dynamics, yet conventional tests often miss these effects, highlighting the need for viscoelastic monitoring. Methods: This retrospective single-center study carried out in the intensive care unit analyzed ROTEM, conventional coagulation tests, and CBC data pre–post-single-unit RBC transfusion. Platelet and fibrinogen contributions to clot strength were assessed. Statistical comparisons used the Wilcoxon signed-rank test, with significance set at p < 0.05. Ethical approval was waived. Results: Thirty-five patients were analyzed; ROTEM revealed reduced fibrinogen contribution to clot strength and decreased hyperfibrinolysis post-transfusion. Conventional tests showed minimal changes, except for a significant increase in D-dimer levels. Conclusions: Transfusion of a single RBC in non-bleeding critically ill patients with severe anemia may lead to diminished fibrinogen-based clot architecture or fibrin cross-linking, as well as a decrease in hyperfibrinolysis. Most of the hemostatic effects of RBC transfusion cannot be detected by conventional coagulation tests. The net effect of RBC transfusion remains undetermined and requires further mechanistic studies. Full article

This paper investigates the feasibility of diagnosing abdominal aortic aneurysm (AAA) via deep learning (DL)-enabled analysis of non-invasive arterial pulse waveform signals. We generated arterial blood pressure (BP) and pulse volume recording (PVR) waveform signals across a diverse synthetic patient cohort using a systemic arterial circulation model coupled with a viscoelastic model relating arterial BP to PVR while simulating a range of AAA severity levels. We confirmed the plausibility of the synthetic data by comparing the alterations in the simulated waveform signals due to AAA against previously reported in vivo findings. Then, we developed a convolutional neural network (CNN) with continuous property-adversarial regularization that can estimate AAA severity from brachial and tibial PVR signals. We evaluated the algorithm’s performance in comparison with an identical CNN trained on invasive arterial BP waveform signals. The DL-enabled PVR-based algorithm achieved robust AAA detection across different severity thresholds with area under the ROC curve values >0.89, and showed reasonable accuracy in severity estimation, though slightly lower than its invasive BP counterpart (MAE: 12.6% vs. 10.3%). These findings suggest that DL-enabled analysis of PVR waveform signals offers a non-invasive and cost-effective approach for AAA diagnosis, potentially enabling accessible screening through operator-agnostic and point-of-care technologies. Full article

Red blood cell (RBC), accounting for approximately 45% of total blood volume, are essential for oxygen delivery and carbon dioxide removal. Their unique biconcave morphology, high surface area-to-volume ratio, and remarkable deformability enable them to navigate microvessels narrower than their resting diameter, ensuring efficient microcirculation. RBC deformability is primarily determined by membrane viscoelasticity, cytoplasmic viscosity, and cell geometry, all of which can be altered under various physiological and pathological conditions. Reduced deformability is a hallmark of numerous diseases, including sickle cell disease, malaria, diabetes mellitus, sepsis, ischemia–reperfusion injury, and storage lesions in transfused blood. As these mechanical changes often precede overt clinical symptoms, RBC deformability is increasingly recognized as a sensitive biomarker for disease diagnosis, prognosis, and treatment monitoring. Over the past decades, diverse techniques have been developed to measure RBC deformability. These include single-cell methods such as micropipette aspiration, optical tweezers, atomic force microscopy, magnetic twisting cytometry, and quantitative phase imaging; bulk approaches like blood viscometry, ektacytometry, filtration assays, and erythrocyte sedimentation rate; and emerging microfluidic platforms capable of high-throughput, physiologically relevant measurements. Each method captures distinct aspects of RBC mechanics, offering unique advantages and limitations. This review synthesizes current knowledge on the pathophysiological significance of RBC deformability and the methods for its measurement. We discuss disease contexts in which deformability is altered, outline mechanical models describing RBC viscoelasticity, and provide a comparative analysis of measurement techniques. Our aim is to guide the selection of appropriate approaches for research and clinical applications, and to highlight opportunities for developing robust, clinically translatable diagnostic tools. Full article

Background: Fibrinolytic impairment is one of the key factors involved in the pathogenesis of hemostasis disturbances in sepsis, significantly contributing to microthrombosis, organ dysfunction, and mortality rates. While hemostatic assessment in sepsis typically focuses on coagulation activation, evaluating fibrinolytic activity remains challenging due to methodological limitations and a lack of standardization of the currently available methods. Objectives: This comprehensive review examines current methods for assessing fibrinolytic activity in bacterial sepsis, their clinical applications, strengths and limitations, and future perspectives for improved diagnostic approaches. Methods: We conducted a systematic literature search and identified 52 studies that investigated fibrinolysis assessment in adult patients with bacterial sepsis using biomarkers or global tests. Studies included mainly observational cohorts examining various fibrinolytic assessment methods. Results: Fibrinolytic shutdown, primarily mediated by the overproduction of plasminogen activator inhibitor-1 (PAI-1), occurs early in sepsis and correlates with disease severity and mortality. Current assessment methods include plasma biomarker measurements (PAI-1, plasmin-antiplasmin complexes, D-dimer), global plasma-based tests (clot lysis time, plasmin generation assays), and whole-blood viscoelastic testing (rotational thromboelastometry, ROTEM; thromboelastography, TEG). Modified viscoelastic tests incorporating tissue plasminogen activators demonstrate enhanced sensitivity for detecting fibrinolytic resistance. Despite efforts, standardization is still limited, and routine clinical implementation has not been achieved yet. Conclusions: Fibrinolytic assessment provides important prognostic information in sepsis, despite methodological challenges. The integration of point-of-care viscoelastic testing with modified protocols shows promise for real-time evaluation. Future research should focus on developing standardized, automated assays suitable for routine clinical practice, enabling personalized therapeutic interventions that target fibrinolytic dysfunction in sepsis. Full article

Patient blood management (PBM) is a multidisciplinary approach aimed at improving patient outcomes through targeted anemia treatment that minimizes allogeneic blood transfusions, employs blood conservation techniques, and avoids inappropriate use of blood product transfusions. Viscoelastic testing (VET) techniques, such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM), have led to significant advancements in PBM. These techniques offer real-time whole-blood assessment of hemostatic function. This provides the clinician with a more complete hemostasis perspective compared to that provided by conventional coagulation tests (CCTs), such as the prothrombin time (PT) and the activated partial thromboplastin time (aPTT), which only assess plasma-based coagulation. VET does this by mapping the complex processes of clot formation, stability, and breakdown (i.e., fibrinolysis). As a result of real-time whole-blood coagulation assessment during hemorrhage, hemostasis can be achieved through targeted transfusion therapy. This approach helps fulfill an objective of PBM by helping to reduce unnecessary transfusions. However, challenges remain that limit broader adoption of VET, particularly in hospital settings. Of these, standardization and the high cost of the devices are those that are faced the most. This discussion highlights the potential of VET application in PBM to guide blood-clotting therapies and improve outcomes in patients with coagulopathies from various causes that result in hemorrhage. Another aim of this discussion is to highlight the limitations of implementing these technologies so that appropriate measures can be taken toward their wider integration into clinical use. Full article

The mechanical stability and deformability of erythrocytes are vital for their function as they traverse capillaries, where shear stress can reach up to 10 Pa under physiological conditions. Human serum albumin (HSA) is known to help maintain erythrocyte stability by influencing cell shape, membrane integrity, and resistance to hemolysis. However, the precise mechanisms by which albumin exerts these effects remain debated, with some studies indicating a stabilizing role and others suggesting the opposite. This review highlights that under high shear rates, albumin molecules may undergo unfolding due to normal stress differences. Such structural changes can significantly alter albumin’s interactions with the erythrocyte membrane, thereby affecting cell mechanical stability. We discuss two potential scenarios explaining how albumin influences erythrocyte mechanics under shear stress, considering both the viscoelastic properties of blood and those of the erythrocyte membrane. Based on theoretical analyses and experimental evidence from the literature, we propose that albumin’s effect on erythrocyte mechanical stability depends on (i) the transition between unfolded and folded states of the protein and (ii) the impact of shear stress on the erythrocyte membrane’s ζ-potential. Understanding these factors is essential for elucidating the complex relationship between albumin and erythrocyte mechanics in physiological and pathological conditions. Full article

Background/Objectives: Liver transplantation (LT) is often complicated by severe bleeding and coagulopathy. Viscoelastic testing (VET) offers real-time, bedside assessment of coagulation and may improve transfusion management compared to standard tests. This study evaluates the clinical impact of VET implementation during liver transplantation on bleeding, transfusion requirements, complications, and mortality in a single Eastern European tertiary transplant center. Methods: We conducted a single-center before-and-after study comparing patients undergoing LT before and after the implementation of VET. All procedures were performed by the same surgical and anesthetic team using a standardized protocol. Data were collected retrospectively for the Before VET group and prospectively for the After VET group. We compared transfusion requirements, bleeding, complications, and mortality. Results: A total of 59 patients were included, 22 in the After VET group and 37 in the Before VET group. VET implementation was associated with lower intraoperative blood loss (median 4000 mL vs. 6000 mL, p = 0.017) and reduced red blood cell (RBC) transfusion volume (670 mL vs. 1000 mL, p = 0.008). FFP (0.23 vs. 1.59 units, p = 0.007) and platelet use (0.68 vs. 1.81 units, p = 0.035) were also significantly lower in the VET group, while fibrinogen use was higher (3.00 g vs. 2.00 g, p = 0.036). No differences were observed in complication rates or mortality at 30 days and 1 year in this small before-and-after study. Conclusions: VET improved transfusion precision and individualized coagulation management during LT, leading to reduced use of blood products. These findings support the adoption of VET as a standard of care in LT protocols, as it may enhance patient safety, even though no differences in postoperative complications or mortality were observed. Full article

The low effectiveness of various brain cancer treatment methods is due to a number of significant challenges. Most of them are unable to penetrate the blood–brain barrier (BBB) when drugs are administered systemically through the bloodstream. Nanoscale particles play a special role among materials capable of binding drug molecules and successfully crossing the BBB. Biopolymeric nanoparticles (NPs) demonstrate excellent biocompatibility and have the remarkable ability to modify the environment surrounding tumor cells, thereby potentially improving cellular uptake of delivery agents. In our research, nanoscale polyelectrolyte complexes (PECs) ranging in size from 56 to 209 nm were synthesized by ionic interaction of the oppositely charged polysaccharides pectin and chitosan. The structural characteristics of these complexes were carefully characterized by infrared (FTIR) and Raman spectroscopy. The immobilization efficiency of antitumor drugs was comprehensively evaluated using UV spectrophotometry. The cytotoxicity of the NPs was evaluated in the U87-MG cell line. The preliminary data indicate a significant decrease in the metabolic activity of these tumor cells. Important details on the interaction of the NPs with an endothelial layer structurally similar to the BBB were obtained by simulating the BBB using a model based on human blood vessels. Our studies allowed us to establish a significant correlation between the kinetic parameters of drug immobilization and the ratio of biopolymer concentrations in the initial compositions, which provides valuable information for future optimization of drug delivery system design. Full article

The manipulation of cells and bioparticles has garnered significant interest in the field of viscoelastic microfluidics, particularly regarding its capacity for single-stream focusing within a three-dimensional and simple microchannel structure. The inherent simplicity of this method enables the effective manipulation of particles, facilitating the separation and focusing of various cell types, including blood cells, circulating tumor cells (CTCs), and microalgae. However, the viscoelastic nature of the particles imposes limitations in the handling of submicron-sized particles, due to a significant decrease in the viscoelastic force acting on the particle. In this study, we propose a microfluidic device featuring a cruciform cross-sectional microchannel with 45 µm and 45 µm of its vertical and horizontal size, respectively. The cruciform microchannel, which has a 270° reflex angle on four corners, can increase the viscoelastic force on the particles, allowing the device to focus submicron-sized particles down to 180 nm in a single-stream manner. It is important to note that the single-stream formation was maintained, while the channel width at the outlet region was drastically increased, allowing for the enrichment of submicron-sized particles. For biological feasibility, the proposed device also demonstrates the single-stream focusing on biological particles such as bacteria. The presented microfluidic device would have great potential for the focusing and enrichment of nanoparticles including bacteria in a highly robust manner, expecting its use in the various fields such as diverse biological analysis and biomedical research. Full article

Perioperative blood management strategies include evidence-based guidelines to efficiently manage blood products and transfusions while minimizing blood loss and improving patient outcomes. Perioperative Medicine has made evident that anemia is often under-recognized and not appropriately addressed prior to surgery. Early recognition and correction of anemia is imperative for better surgical optimization, fewer transfusions perioperatively, and improved outcomes. Patient blood management utilize evidence-based guidelines for the establishment of a framework to promote treatment of the causes of anemia, reduce blood loss and coagulopathy as well as to improve patient safety and outcomes by efficiently managing blood products, decrease complications associated with blood transfusions and reduce overall costs. Both liberal and restrictive strategies for blood transfusions established thresholds for hemoglobin: restrictive transfusion threshold of hemoglobin 7–8 g/dL in stable patients, and a higher transfusion threshold of hemoglobin > 8 g/dL may be considered in patients with cardiac disease. Intraoperatively, tests such as viscoelastic testing, including rotational thromboelastometry and thrombelastography, offer real-time analysis of a patient’s clotting ability, allowing for targeted transfusions of fresh frozen plasma, platelets, cryoprecipitate or antifibrinolytic drugs. Complications associated with blood transfusions include allergic reactions, delayed hemolytic reactions, transfusion related acute lung injury, transfusion-associated circulatory overload, and the transmission of infectious diseases such as Hepatitis B, Hepatitis C, and Human-immunodeficiency virus. This review will discuss the management of blood products for surgical patients in the entire perioperative setting, with specific considerations for the peri-, intra- and post-operative stages. Full article