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12 pages, 260 KB  
Review
Role of Thromboelastometry in Sepsis-Induced Coagulopathy: A Narrative Review
by Andrzej Lubiewski and Mariusz Siemiński
Med. Sci. 2026, 14(3), 385; https://doi.org/10.3390/medsci14030385 - 9 Jul 2026
Viewed by 426
Abstract
Sepsis-induced coagulopathy (SIC) represents an early, predominantly prothrombotic disturbance that is difficult to detect using conventional coagulation tests. This review aims to evaluate whether rotational thromboelastometry (ROTEM) provides added value in the diagnosis and phenotyping of SIC compared with standard laboratory parameters. We [...] Read more.
Sepsis-induced coagulopathy (SIC) represents an early, predominantly prothrombotic disturbance that is difficult to detect using conventional coagulation tests. This review aims to evaluate whether rotational thromboelastometry (ROTEM) provides added value in the diagnosis and phenotyping of SIC compared with standard laboratory parameters. We summarize current evidence on SIC pathophysiology and its relationship to disseminated intravascular coagulation (DIC), with particular focus on mechanisms driving hypercoagulability and fibrinolytic shutdown. The limitations of routine tests, platelet count, PT/INR, fibrinogen, and fibrin-related markers are examined, especially their inability to capture early dynamic changes in coagulation. We then outline the principles of ROTEM and review clinical studies assessing its application in sepsis. Available data consistently demonstrate increased clot firmness, frequently driven by elevated fibrinogen, along with impaired fibrinolysis. These patterns often precede overt SIC or DIC and are associated with worse clinical outcomes, including organ dysfunction and mortality. Finally, we discuss the implications of these findings for clinical management. While routine anticoagulation in unselected septic patients remains unsupported, integrating SIC criteria with ROTEM profiles may improve risk stratification and help identify prothrombotic phenotypes that could benefit from targeted therapies. Overall, ROTEM appears to be a valuable adjunct to conventional testing, with potential to refine diagnostic accuracy and guide future interventional strategies in septic coagulopathy. Full article
18 pages, 1314 KB  
Review
Management of Hereditary Hypofibrinogenemia During Pregnancy: A Scoping Review Towards Personalized Obstetric Care
by Grigorios Karampas, Konstantinos Karkalemis, Anastasia Bagiasta, Dimitra Metallinou, Ermioni Tsarna, Marikaiti Lefaki, Chryssoula Staikou, Makarios Eleftheriades, Panagiotis Christopoulos and Marianna Politou
J. Clin. Med. 2026, 15(12), 4666; https://doi.org/10.3390/jcm15124666 - 16 Jun 2026
Viewed by 365
Abstract
Background: Hereditary fibrinogen disorders comprise a rare and heterogeneous group of conditions characterized by highly variable clinical phenotypes, ranging from entirely asymptomatic to severe hemorrhage or paradoxical thrombosis. Within this spectrum, hereditary hypofibrinogenemia (HH) poses a significant obstetrical challenge due to the [...] Read more.
Background: Hereditary fibrinogen disorders comprise a rare and heterogeneous group of conditions characterized by highly variable clinical phenotypes, ranging from entirely asymptomatic to severe hemorrhage or paradoxical thrombosis. Within this spectrum, hereditary hypofibrinogenemia (HH) poses a significant obstetrical challenge due to the lack of evidence-based management guidelines during pregnancy. Methods: A scoping review of the literature was conducted to identify reported cases of pregnancies with HH reaching the third trimester. PubMed, Scopus, and Cochrane Library were searched through April 2026 for eligible studies reporting maternal and neonatal outcomes, fibrinogen replacement therapy during pregnancy, and peri- and postpartum management. A complementary LeapSpace search was also performed. Data were extracted using a structured form and owing to the heterogeneity and descriptive nature of the available evidence, results were synthesized narratively. Results: Out of 202 unique records identified, a total of 13 studies, comprising 33 pregnancies, were included. All evidence arose from case reports and small case series, with substantial variability in patient characteristics and clinical management. Successful outcomes are associated with early diagnosis, careful assessment of medical and obstetrical history, and close multidisciplinary surveillance. Maintaining fibrinogen levels above 50–100 mg/dL during pregnancy and ≥150 mg/dL peripartum appeared beneficial. The use of global coagulation assessment tools such as rotational thromboelastometry (ROTEM®), particularly the FIBTEM® assay, may support individualized management beyond fibrinogen levels alone; however, up to date it has been incorporated in the management of a single pregnancy. Conclusions: Management of pregnancy in women with HH should be individualized and multidisciplinary, with tailored fibrinogen supplementation strategies to optimize maternal and neonatal outcomes. Small sample sizes and the heterogeneity of the reported results limit the certainty of these findings, requiring further research to establish subtype-specific recommendations and to define additional coagulation parameters that may improve perinatal care. Full article
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22 pages, 3989 KB  
Article
Precipitation-Based Encapsulation of Fibrinogen in Calcium Carbonate for Non-Compressible Hemorrhage Control
by Henry T. Peng, Tristan Bonnici, Catherine Tenn, Christian J. Kastrup and Andrew Beckett
Pharmaceuticals 2026, 19(6), 923; https://doi.org/10.3390/ph19060923 - 11 Jun 2026
Viewed by 436
Abstract
Background: Uncontrolled hemorrhage, especially at non-compressible sites, remains a major cause of preventable trauma deaths. This study reports the development of fibrinogen-loaded calcium carbonate (CaCO3) microparticles that combine hemostatic activity with self-propelling capability for targeted delivery against blood flow, with [...] Read more.
Background: Uncontrolled hemorrhage, especially at non-compressible sites, remains a major cause of preventable trauma deaths. This study reports the development of fibrinogen-loaded calcium carbonate (CaCO3) microparticles that combine hemostatic activity with self-propelling capability for targeted delivery against blood flow, with a focus on understanding formulation-dependent trade-offs among particle yield, protein loading, clotting performance, and transport behavior. Methods: Microparticles were synthesized via a precipitation method using different carbonate sources and characterized for yield, morphology, size, and fibrinogen encapsulation. Hemostatic function was assessed using rotational thromboelastometry (ROTEM) in fibrinogen-deficient plasma. Propulsion behavior was evaluated following exposure to protonated tranexamic acid (TXA+), which triggers CO2 generation. Particle size and encapsulation were examined by microscopy and fluorescence imaging. Results: The precipitation method produced spherical micrometer-sized particles, with fibrinogen inclusion reducing yield and particle size relative to unload controls. Fluorescence microscopy confirmed successful encapsulation. Encapsulation efficiency varied with formulation, with sodium carbonate-based particles showing higher relative fibrinogen loading. ROTEM analysis demonstrated that fibrinogen-loaded particles significantly improved clot formation, increasing maximum clot firmness compared to fibrinogen-free particles, although performance remained formulation-dependent. TXA+-triggered propulsion achieved maximum speeds up to 4.221 cm/s. Fibrinogen-loaded particles exhibited longer activation lag times than unloaded particles, indicating a trade-off between hemostatic functionality and propulsion kinetics. Conclusions: Fibrinogen-loaded CaCO3 microparticles exhibit both hemostatic activity and chemically triggered motion in vitro. The study identifies key formulation-dependent trade-offs between particle yield, fibrinogen loading, clotting performance, and propulsion behavior. While these findings support the feasibility of combining localization and clot stabilization mechanisms, further studies under physiologically relevant flow conditions and in vivo models are required to evaluate their potential for active delivery in non-compressible hemorrhage. Full article
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12 pages, 3561 KB  
Article
Perioperative Coagulation Dynamics Assessed by ROTEM and Conventional Assays: A Prospective Longitudinal Study with Focus on Fibrinogen in Major Non-Cardiac Surgery
by Michal Hosala, Denisa Osinova, Matej Sukenik, Janka Hosalova Matisova, Tomas Fecko, Jana Sendreyova, Kristina Maria Belakova, Miroslava Drotarova, Monika Brunclikova, Sohaib Mukhtar Agouba, Veronika Voskova Gemelova and Tomas Simurda
J. Clin. Med. 2026, 15(11), 4264; https://doi.org/10.3390/jcm15114264 - 31 May 2026
Viewed by 410
Abstract
Background: Perioperative assessment of hemostasis remains challenging, particularly in non-cardiac surgery, where the incidence of clinically significant bleeding is relatively low. Viscoelastic testing enables real-time evaluation of whole-blood coagulation, but its perioperative dynamics and agreement with conventional assays require further characterization. Methods: In [...] Read more.
Background: Perioperative assessment of hemostasis remains challenging, particularly in non-cardiac surgery, where the incidence of clinically significant bleeding is relatively low. Viscoelastic testing enables real-time evaluation of whole-blood coagulation, but its perioperative dynamics and agreement with conventional assays require further characterization. Methods: In this prospective single-center observational study, 53 patients undergoing major non-cardiac surgery were included in the final analysis. Hemostatic parameters were assessed preoperatively, intraoperatively at two-hour intervals, and 24 h postoperatively using ROTEM (EXTEM, INTEM, and FIBTEM) and conventional coagulation assays. Longitudinal changes and correlations between fibrinogen concentration according to Clauss and ROTEM-derived parameters were analyzed. Results: Fifty-three patients undergoing major hepatopancreatobiliary surgery completed longitudinal perioperative monitoring. Pancreaticoduodenectomy and liver resection accounted for 60.7% and 39.3% of procedures, respectively. Serial perioperative ROTEM and laboratory assessments demonstrated time-dependent changes in coagulation parameters, including decreased intraoperative fibrinogen and antithrombin III levels and shortening of INTEM clotting time. Clinically significant bleeding was infrequent, with severe intraoperative bleeding observed in 7.4% of patients. Strong correlations were confirmed between fibrinogen concentration according to Clauss and FIBTEM-derived parameters, particularly FIBTEM MCF (r = 0.811, p < 0.001), whereas the correlation with FIBTEM A10 was moderate (r = 0.574, p < 0.001). No significant association was observed between preoperative fibrinogen concentration and perioperative blood loss. Conclusions: This study provides a longitudinal characterization of perioperative coagulation dynamics and demonstrates strong agreement between fibrinogen concentration according to Clauss and ROTEM-derived parameters. The findings are primarily descriptive and highlight the methodological consistency between viscoelastic and conventional fibrinogen assessment. Further studies are required to determine their clinical relevance in perioperative management. These findings suggest that ROTEM-derived parameters may provide a rapid functional estimate of fibrinogen status in the perioperative setting, potentially supporting clinical assessment, although their role in guiding management requires further validation. Full article
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15 pages, 440 KB  
Article
The Role of Rotational Thromboelastometry in High-Risk-of-Bleeding Endoscopic Procedures in Patients with Decompensated Liver Cirrhosis
by Irina Girleanu, Laura Huiban, Cristina Muzica, Camelia Cojocariu, Cătălin Victor Sfarti, Stefan Chiriac, Sebastian Zenovia, Gheorghe G. Balan, Raluca Avram, Ana Maria Sîngeap, Iulian Buzincu, Ana Maria Trofin, Ioana-Miruna Balmuș, Carol Stanciu and Anca Trifan
Diagnostics 2026, 16(9), 1289; https://doi.org/10.3390/diagnostics16091289 - 25 Apr 2026
Viewed by 423
Abstract
Background/Objectives: This study aimed to evaluate the differences between two blood product transfusion protocols [a standard coagulation (SC) group and a rotational thromboelastometry (ROTEM) group] in patients with decompensated liver cirrhosis (LC) undergoing high-bleeding-risk endoscopic procedures. Methods: Between December 2024 and [...] Read more.
Background/Objectives: This study aimed to evaluate the differences between two blood product transfusion protocols [a standard coagulation (SC) group and a rotational thromboelastometry (ROTEM) group] in patients with decompensated liver cirrhosis (LC) undergoing high-bleeding-risk endoscopic procedures. Methods: Between December 2024 and March 2025, we conducted a prospective cohort study including adult decompensated cirrhotic patients who needed prophylactic blood product transfusion before high-bleeding-risk endoscopic procedures. The prophylactic blood product transfusion strategy in the SC group was based on conventional coagulation tests (INR, platelets, and fibrinogen), and in the ROTEM group on viscoelastic parameters. Results: A total of 72 patients were included in this study (36 patients in each group); most were male (63.9%), Child–Pugh B (54.2%), and had LC with a predominance of alcoholic etiology (51.4%). There were no clinically significant differences regarding the baseline characteristics between the study groups. The most frequent endoscopic procedure was polypectomy (76.4%). Postinterventional bleeding occurred after eight procedures in the SC group and after four procedures in the ROTEM group (p = 0.206). Endoscopic hemostasis was effective. Patients from the ROTEM group received fewer FFP transfusions than the SC group (5.6% vs. 69.4%; p < 0.0001). Blood product transfusion was needed less in patients evaluated using ROTEM compared with the SC group (41.2% vs. 100%; p < 0.0001). There were no differences in the length of hospital stay (p = 0.618) or 30-day mortality (p = 0.643) between the two study groups. Conclusions: ROTEM-guided transfusion management was associated with a significant reduction in blood product use compared with standard coagulation test-based management. However, this difference should be interpreted in the context of the distinct transfusion thresholds applied in the two groups, as the standard coagulation arm followed predefined laboratory-based criteria that may have increased the likelihood of prophylactic transfusion. No statistically significant differences were observed in bleeding complications, length of hospital stay, or 30-day mortality. Therefore, these findings reflect differences in transfusion strategies rather than demonstrating clinical superiority of ROTEM-based management and should be considered preliminary. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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10 pages, 234 KB  
Article
Platelet Function and Morphology in Patients with Sepsis and Septic Shock: A Retrospective Pilot Study
by Piotr F. Czempik
Hemato 2026, 7(2), 13; https://doi.org/10.3390/hemato7020013 - 21 Apr 2026
Viewed by 1217
Abstract
Background: Sepsis remains a leading cause of mortality in the intensive care unit (ICU). Platelets (PLTs) are central to coagulation, inflammation, and the maintenance of endothelial integrity. Although thrombocytopenia is an established prognostic marker in sepsis, alterations in PLT function and morphology may [...] Read more.
Background: Sepsis remains a leading cause of mortality in the intensive care unit (ICU). Platelets (PLTs) are central to coagulation, inflammation, and the maintenance of endothelial integrity. Although thrombocytopenia is an established prognostic marker in sepsis, alterations in PLT function and morphology may provide additional insight into disease progression. Methods: This retrospective pilot study examined adult ICU patients diagnosed with sepsis or septic shock. Extracted data included demographic characteristics, clinical variables, and laboratory parameters. Platelet function was evaluated using impedance aggregometry and rotational thromboelastometry (ROTEM), while PLT morphology metrics were obtained from complete blood counts. Statistical analyses comprised Spearman’s rank correlation and logistic regression. Results: Twenty patients were included. Platelet aggregation was impaired across ASPI, ADP, and TRAP-6 assays despite normal PLT counts and morphology. ROTEM-derived measure of PLT contribution to clot strength was within normal ranges. No correlations were observed between PLT function and PLT morphology parameters. An inverse correlation was identified between ROTEM-derived PLT contribution to clot strength and SOFA score (r = −0.60, p = 0.03). Neither PLT function nor PLT morphology was associated with ICU mortality. Conclusions: Functional PLT deficits may occur in sepsis in the absence of structural abnormalities. ROTEM-derived PLT contribution to clot strength may inversely reflect sepsis severity. Platelet function parameters appear unlikely to predict short-term mortality in septic patients. Full article
(This article belongs to the Section Plasma Cell Disorders)
16 pages, 965 KB  
Review
The Importance of the “Damage Control” Strategy in Multiple Organ Injuries, Pathophysiology and Principles of Hemorrhage Control
by Oliwia Klimek, Jakub Dudek, Anna Czesyk, Bartosz Sierant, Wiktoria Górecka, Grzegorz Gogolewski, Tomasz Jurek, Zuzanna Ochocka and Amelia Jankowska
J. Clin. Med. 2026, 15(7), 2549; https://doi.org/10.3390/jcm15072549 - 26 Mar 2026
Viewed by 1807
Abstract
Background/Objectives: Damage Control Resuscitation (DCR) is a critical strategy in the management of severe trauma, focusing on the optimisation of the patient’s physiological condition. This study reviews current DCR strategies, emphasizing the mitigation of the “diamond of death”—hypothermia, acidosis, coagulopathy, and hypocalcemia—while [...] Read more.
Background/Objectives: Damage Control Resuscitation (DCR) is a critical strategy in the management of severe trauma, focusing on the optimisation of the patient’s physiological condition. This study reviews current DCR strategies, emphasizing the mitigation of the “diamond of death”—hypothermia, acidosis, coagulopathy, and hypocalcemia—while addressing complex disturbances like respiratory distress syndrome (ARDS) and (acute kidney injury) AKI in high-ISS (Injury Severity Score) patients. Methods: A systematic review of 59 contemporary sources was conducted, encompassing clinical trials (e.g., CRASH-2), military-to-civilian protocol translations, and guidelines from the C and European Resuscitation Council. The analysis focused on pre-hospital interventions, in-hospital transfusion protocols, and the impact of transport logistics on survival. Results: Evidence highlights that aggressive crystalloid resuscitation (over 5 L) significantly increases mortality, favoring balanced blood component therapy (1:1:1 ratio) or Whole Blood guided by viscoelastic testing like rotational thromboelastometry (ROTEM) or thromboelastography (TEG). Pre-hospital success is driven by rapid hemorrhage control via tourniquets, early administration of Tranexamic Acid (TXA), no aggressive crystalloids, permissive hypotension, proactive calcium supplementation is recommended in early care. Furthermore, the integration of Helicopter Emergency Medical Services (HEMS) is independently associated with improved survival in multi-organ trauma by reducing time to definitive care and facilitating “en-route” damage control. Conclusions: The evolution of rescue strategies focused on mitigating the effects of the diamond of death, combined with the implementation of permissive hypotension and optimized HEMS logistics, constitutes the foundation of a modern model aimed at minimizing mortality in multi-organ trauma. Full article
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19 pages, 1344 KB  
Review
Alternate and Emerging Anticoagulation Strategies for Extracorporeal Membrane Oxygenation: A Scoping Review
by Akshay Kumar, Nicole Carlo, Rithish Nimmagadda, Juber Dastagir Shaikh, Sourabh Khatri and Vivek Varghese
J. Clin. Med. 2026, 15(6), 2337; https://doi.org/10.3390/jcm15062337 - 18 Mar 2026
Viewed by 814
Abstract
Background: Unfractionated heparin (UFH) remains the standard anticoagulant for extracorporeal membrane oxygenation (ECMO), despite complications, such as heparin resistance, heparin-induced thrombocytopenia, bleeding and variable pharmacokinetics. This has prompted the search for alternative and novel anticoagulation strategies, including pharmacologic agents, circuit modifications, and [...] Read more.
Background: Unfractionated heparin (UFH) remains the standard anticoagulant for extracorporeal membrane oxygenation (ECMO), despite complications, such as heparin resistance, heparin-induced thrombocytopenia, bleeding and variable pharmacokinetics. This has prompted the search for alternative and novel anticoagulation strategies, including pharmacologic agents, circuit modifications, and monitoring approaches. This scoping review aimed to map the breadth and characteristics of evidence on ECMO anticoagulation strategies beyond UFH. Methods: A comprehensive search of peer-reviewed and gray literature was conducted across PubMed, Cochrane, Clinical Trials, WHO Trials Registry, and conference abstracts through manual searches in key journals. Clinical, pre-clinical, and gray literature studies evaluating pharmacologic agents, anticoagulation-free or heparin-sparing, biocompatible circuits, and monitoring innovations were included. Data were charted and synthesized descriptively to identify trends, gaps, and emerging directions. Results: A total of 269 records were included. Evidence was highly heterogeneous among study designs, populations, ECMO modalities, and outcome definitions. Most clinical studies were retrospective cohorts and adult-centered, with limited multicenter randomized controlled trials and underrepresentation of neonatal and pediatric populations. Direct thrombin inhibitors were frequently studied and clinically implemented alternatives to UFH. Other agents, including nafamostat mesylate, prostaglandin E1, and factor pathway inhibitors remain early in clinical investigation. Anticoagulation-free strategies and biocompatible circuit technologies were mostly supported through pre-clinical and single-center studies. Monitoring and modeling innovations, like TEG, ROTEM, real-time imaging, and machine learning, are quickly emerging. Conclusions: ECMO anticoagulation is transitioning from UFH reliance toward diversified and personalized strategies. Future research should prioritize multicenter randomized controlled trials, standardize protocols, expand to neonatal and pediatric investigation, and integrate strategies. Full article
(This article belongs to the Special Issue New Advances in Extracorporeal Life Support (ECLS))
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20 pages, 2038 KB  
Article
Platelet Preservation and Functionality in Blood Treated for Autotransfusion: A Comparative In Vitro Study on Human Blood and In Vivo Study Using a Massive Hemorrhage Swine Model
by Marine Schott, Estelle Leroux, Chloé Libaud, Audrey Lafragette, Mallorie Depond, Ophélie Dauphouy, Benoît Decouture, Aurélia Leroux, Stéphanie Boutroy-Perrin, Patricia Forest-Villegas, Olivier Gauthier and Gwenola Touzot-Jourde
BioMed 2026, 6(1), 9; https://doi.org/10.3390/biomed6010009 - 12 Mar 2026
Viewed by 1668
Abstract
During hemorrhagic procedures, autotransfusion is one of the main strategies for patient blood management. While conventional cell savers only concentrate red blood cells due to the centrifugation method, the innovative same™ autotransfusion medical device (i-SEP, Nantes, France), based on a hollow-fiber filtration technology, [...] Read more.
During hemorrhagic procedures, autotransfusion is one of the main strategies for patient blood management. While conventional cell savers only concentrate red blood cells due to the centrifugation method, the innovative same™ autotransfusion medical device (i-SEP, Nantes, France), based on a hollow-fiber filtration technology, has the ability to preserve red blood cells along with the majority of platelets. Background/Objectives: The present study aimed at comparing the functionality of preserved platelets in the clot formation by using Quantra® and/or ROTEM® Point-Of-Care coagulation tests, after blood treatment for autotransfusion with either a standard centrifugation-based system (Xtra® device, LivaNova, London, UK), or the filtration-based same™ device. Methods: First, coagulation was assessed in an in vitro experiment, where human blood samples were used to obtain ten treated blood products by each autotransfusion device that were evaluated with or without supplementation of plasma poor or rich in platelets. Then, to confirm the potential clinical benefit of the platelet preservation in a surgical context, coagulation was studied in vivo using a massive surgical hemorrhagic model on eight minipigs per device. Samples were collected after reinfusion steps and during a 6 h post-operative follow-up. Results: Both in vitro and in vivo, the same™ device consistently retained more platelets compared to the Xtra® device. This enhanced preservation resulted in significantly stronger clot formation, likely due to higher platelet concentration and superior functional integrity. Conclusions: These findings highlight the potential clinical benefit of same™-recovered platelets for improving hemostasis during hemorrhagic surgery. Full article
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11 pages, 738 KB  
Article
Milk Thistle’s Secret Weapon: Thromboelastometry Reveals How Silybin Modulates Coagulation in Human Plasma In Vitro
by Justyna Małkowska, Joanna Boinska, Giulia Sperduti, Katarzyna Siemiątkowska-Grzybowska, Ewa Żekanowska, Daniel Załuski and Artur Słomka
Appl. Sci. 2026, 16(3), 1310; https://doi.org/10.3390/app16031310 - 28 Jan 2026
Viewed by 820
Abstract
Background: Silybin, the primary active constituent of the milk thistle extract silymarin, has been historically recognized for its hepatoprotective properties. More recently, its potential effects on blood coagulation have garnered attention, suggesting a broader pharmacological profile. Methods: This study aimed to investigate silybin’s [...] Read more.
Background: Silybin, the primary active constituent of the milk thistle extract silymarin, has been historically recognized for its hepatoprotective properties. More recently, its potential effects on blood coagulation have garnered attention, suggesting a broader pharmacological profile. Methods: This study aimed to investigate silybin’s impact on hemostasis using rotational thromboelastometry (ROTEM) in normal human plasma. ROTEM enables the dynamic assessment of clot formation, providing a detailed analysis of coagulation processes in real-time. We specifically focused on the effects of silybin concentrations of 10 µM, 50 µM, and 100 µM on the ROTEM parameters compared to controls using normal human plasma with 0.1% dimethyl sulfoxide (DMSO). The parameters derived from the tests included clotting time (CT), α-angle (α), and amplitude at 10 and 20 min (A10 and A20) for each of the three channels: intrinsic pathway thromboelastometry (INTEM), extrinsic pathway thromboelastometry (EXTEM), and fibrinogen thromboelastometry (FIBTEM). Each measurement was performed four times. Results: Analysis of the INTEM assay results demonstrated that silybin at concentrations of 10 µM and 50 µM significantly reduced clotting time (CT) compared to the control. Additionally, all tested silybin concentrations significantly decreased the α-angle in the INTEM test. In the EXTEM assay, no significant effect on CT was observed at any silybin concentration. However, consistent with the INTEM findings, all silybin concentrations resulted in a significant reduction in the α-angle. In the FIBTEM assay, silybin at 10 µM and 50 µM significantly shortened CT. Furthermore, all tested concentrations led to a significant decrease in the α-angle and A20, while a reduction in A10 was observed only at the 50 µM concentration compared to the control. Conclusions: This study demonstrates that silybin modulates ROTEM parameters in a manner that tends to vary with concentration, with the strongest effects observed at lower concentrations (10–50 µM), notably reducing CT, α-angle, and clot firmness (A10, A20). These findings suggest a potential role of silybin in influencing coagulation dynamics. Full article
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11 pages, 222 KB  
Article
Hemostatic Changes Following Red Blood Cell Transfusion in Critically Ill Patients: A Retrospective Cohort Study
by Piotr F. Czempik
J. Clin. Med. 2025, 14(22), 8048; https://doi.org/10.3390/jcm14228048 - 13 Nov 2025
Viewed by 819
Abstract
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 [...] Read more.
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 article belongs to the Section Intensive Care)
30 pages, 2059 KB  
Review
Thrombotic Risk and Coagulation Imbalance in Cirrhosis and Hepatocellular Carcinoma: Clinical Implications and Management
by Leonardo Stella, Matteo De Siati, Rosa Talerico, Maria Pallozzi, Lucia Cerrito, Silvia Sorrentino, Antonio Gasbarrini, Erica De Candia, Roberto Pola and Francesca Romana Ponziani
Cancers 2025, 17(21), 3413; https://doi.org/10.3390/cancers17213413 - 23 Oct 2025
Cited by 7 | Viewed by 2489
Abstract
Hepatocellular carcinoma (HCC) is characterized by a complex disruption of hemostatic balance, increasing the risk of both thrombotic and hemorrhagic events. Thrombotic complications, most notably portal vein thrombosis (PVT) and venous thromboembolism (VTE), have a significant impact on clinical outcomes and therapeutic strategies. [...] Read more.
Hepatocellular carcinoma (HCC) is characterized by a complex disruption of hemostatic balance, increasing the risk of both thrombotic and hemorrhagic events. Thrombotic complications, most notably portal vein thrombosis (PVT) and venous thromboembolism (VTE), have a significant impact on clinical outcomes and therapeutic strategies. Cirrhosis contributes to the precarious equilibrium between pro- and anticoagulant forces through impaired synthesis of coagulation factors, endothelial dysfunction, and systemic inflammation. In the presence of HCC tumor-driven mechanisms, such as tissue factor expression, extracellular vesicle release, platelet activation, and suppression of fibrinolysis exacerbate this prothrombotic state. In this scenario, advanced diagnostic tools such as thrombin generation assay (TGA) and rotational thromboelastometry (ROTEM) offer a more accurate assessment of coagulation dynamics than conventional tests, enabling better risk stratification especially for therapeutic purposes. Anticoagulant therapy has demonstrated clinical benefit in selected cases of non-malignant PVT and VTE, particularly when liver function is preserved. While prophylactic strategies are still under investigation, data suggest they may be safely implemented in selected surgical patients. In the setting of immunotherapy, especially regimens involving anti-VEGF agents, anticoagulation may be considered with careful management of bleeding risk due to portal hypertension. An individualized approach to anticoagulation, supported by functional coagulation testing, is gaining acceptance as a means to safely reduce thrombotic burden and potentially improve outcomes in patients with HCC. Full article
(This article belongs to the Special Issue Novel Insights into Mechanisms of Cancer-Associated Thrombosis)
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14 pages, 1357 KB  
Article
Innovations in Platelet Cryopreservation: Evaluation of DMSO-Free Controlled-Rate Freezing and the Role of a Deep Eutectic Solvent as an Additional Cryoprotective Agent
by Rahel Befekadu, Natasha Bosnjak, Michael Uhlin, Agneta Wikman and Per Sandgren
Int. J. Mol. Sci. 2025, 26(20), 10013; https://doi.org/10.3390/ijms262010013 - 15 Oct 2025
Cited by 1 | Viewed by 1966
Abstract
Cryopreservation is a well-established method for extending platelet shelf-life and addressing supply shortages. Traditionally, this involves dimethyl sulfoxide (DMSO) as a cryoprotective agent (CPA), but recent studies suggest that using controlled rate freezing (CRF) with only NaCl may offer a less toxic alternative. [...] Read more.
Cryopreservation is a well-established method for extending platelet shelf-life and addressing supply shortages. Traditionally, this involves dimethyl sulfoxide (DMSO) as a cryoprotective agent (CPA), but recent studies suggest that using controlled rate freezing (CRF) with only NaCl may offer a less toxic alternative. To explore further optimization, this study assessed whether adding 10% choline chloride–glycerol, a deep eutectic solvent (DES), could enhance platelet quality in CRF/NaCl cryopreservation. Ten double-dose buffy coat platelet units were divided into test (DES-treated) and control (NaCl-only) groups. After DES exposure (10% for 20 min), all units were prepared using the NaCl protocol and frozen at −80 °C with CRF equipment, then stored for over 90 days. Upon thawing and reconstitution in AB plasma, no significant differences were observed in platelet content post-thaw between control and test units (255 ± 43 vs. 257 ± 41 × 109/unit), post-thaw recovery (>85%): respectively, Δψ (JC-1% pos 63 ± 15 vs. 68 ± 17), LDH (% of total 10 ± 6 vs. 9 ± 6), (CD63% 77 ± 9 vs. 82 ± 7), (CD62P % 72 ± 15 vs. 76 ± 11), (CD42b % 78 ± 9 vs. 80 ± 9), (CD61% 79 ± 9 vs. 78 ± 9), (CD41% 81 ± 11 vs. 83 ± 7), (PAC-1% 33 ± 10 vs. 32 ± 8), (Pecam-1% 78 ± 11 vs. 80 ± 8), (GPIV % 72 ± 10 vs. 74 ± 11), (LAMP-1% 26 ± 14 vs. 11 ± 9), (MPCD61+ % 41 ± 11 vs. 46 ± 10), (ROTEM CT 56 ± 7 vs. 55 ± 6), (ROTEM CFT 110 ± 70 vs. 106 ± 67) and (ROTEM MCF 35 ± 6 vs. 36 ± 6). These findings support the feasibility of CPA-free CRF-based platelet cryopreservation while maintaining functional integrity. Full article
(This article belongs to the Special Issue New Advances in Thrombosis: 3rd Edition)
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21 pages, 412 KB  
Article
Unveiling the Hemostatic Signature of Prematurity: A Prospective Rotational Thromboelastometry-Based Analysis
by Martha Theodoraki, Alexia Eleftheria Palioura, Aikaterini-Pothiti Palioura, Abraham Pouliakis, Zoi Iliodromiti, Theodora Boutsikou, Nicoletta Iacovidou and Rozeta Sokou
Medicina 2025, 61(9), 1718; https://doi.org/10.3390/medicina61091718 - 21 Sep 2025
Cited by 3 | Viewed by 1590
Abstract
Background and Objectives: The evaluation of the haemostatic mechanism in premature neonates remains particularly challenging, due to their immature haemostatic system, the influence of inflammation and the variety of clinical factors. This prospective study aimed at (a) assessing the haemostatic profile of [...] Read more.
Background and Objectives: The evaluation of the haemostatic mechanism in premature neonates remains particularly challenging, due to their immature haemostatic system, the influence of inflammation and the variety of clinical factors. This prospective study aimed at (a) assessing the haemostatic profile of clinically stable preterm neonates by Rotational Thromboelastometry [ROTEM; (EXTEM, INTEM, FIBTEM assays)], (b) establishing reference ranges, and (c) investigating potential differences in comparison to healthy term neonates. We also evaluated the impact of clinical and perinatal factors on the haemostatic status of this vulnerable population. Materials and Methods: 69 premature neonates with no underlying morbidity and 226 healthy term neonates were the study subjects. In term neonates, blood was collected on the 2nd-3rd day of life, if sampling was required for any other reason (hyperbilirubinemia, ABO blood group incompatibility screening, maternal thyroid antibodies, or insufficient prenatal care), whereas in premature neonates, blood was collected between the 4nd-10th day after stabilisation. The parameters measured for each ROTEM assay included Clotting Time (CT), Clot Formation Time (CFT), Alpha angle (α, degrees), Clot Amplitude at 5 and 10 min (A5, A10), Maximal Clot Firmness (MCF), and Lysis Index at 30, 45 and 60 min (Li30, Li45, and Li60 respectively). Results: The data analysis demonstrated a prothrombotic profile in preterm neonates, characterized by increased values of A5, A10, (MCF), and α-angle, and shortened CT and CFT across all assays (EXTEM, INTEM, FIBTEM), when compared to term neonates. A statistically significant inverse correlation was observed between gestational age and clot lysis parameters (INTEM Li45, Li60). Additionally, hematocrit levels were negatively correlated with clot amplitude and kinetics of clot development, while platelet count was positively associated with clot firmness parameters (A5, A10, MCF) and α-angle. Mode of delivery and the presence of gestational diabetes did not significantly affect ROTEM assay values. Preterm neonates with a history of respiratory distress syndrome (RDS) exhibited a more pronounced hypercoagulable profile compared to those without RDS, as reflected by the enhanced clot strength and reduced CT, findings that may be attributed to postnatal pulmonary inflammation and its systemic effects on coagulation. Conclusions: This study introduces for the first time reference values for the parameters of ROTEM assays (EXTEM, INTEM, FIBTEM) in clinically stable preterm neonates—a highly vulnerable patient group with a distinct need for accurate and individualized monitoring of their haemostatic status. The combined assessment of these assays enhances diagnostic precision, and offers a more comprehensive evaluation of neonatal haemostasis. By defining reference ranges in whole blood, this work provides novel data that support the integration of ROTEM into clinical transfusion algorithms. Full article
(This article belongs to the Special Issue From Conception to Birth: Embryonic Development and Disease)
26 pages, 643 KB  
Review
The Fibrinolytic System in Bacterial Sepsis: A Comprehensive Review of Current Assessment Methods
by Florin Scarlatescu, Ecaterina Scarlatescu, Jecko Thachil, Dana R. Tomescu and Daniela Bartos
J. Clin. Med. 2025, 14(17), 6055; https://doi.org/10.3390/jcm14176055 - 27 Aug 2025
Cited by 7 | Viewed by 2562
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Sepsis: Current Updates and Perspectives)
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