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Search Results (621)

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Keywords = prothrombin

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12 pages, 785 KB  
Article
Method Comparison of PT, INR, and aPTT Results Obtained Using Two Coagulation Analyzers in Routine Laboratory Practice
by Betül Özbek Kurtul, Bağnu Dündar, Gül İpek Gündoğan, Sevgi Kocyigit Sevinc, Tuğba Elgün and Asiye Gök Yurttaş
Diagnostics 2026, 16(18), 2989; https://doi.org/10.3390/diagnostics16182989 - 15 Sep 2026
Abstract
Background/Objectives: Prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (aPTT) are routinely used coagulation assays, and analyzer–reagent differences may affect result comparability. This study evaluated analytical comparability between the Sysmex CS-2500 System using Siemens reagents and the Tokra Medical [...] Read more.
Background/Objectives: Prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (aPTT) are routinely used coagulation assays, and analyzer–reagent differences may affect result comparability. This study evaluated analytical comparability between the Sysmex CS-2500 System using Siemens reagents and the Tokra Medical NOVAE II for PT, INR, and aPTT. Methods: Residual routine citrated plasma specimens were measured on both systems. The CS-2500 was designated as the comparator system. Passing–Bablok regression and Bland–Altman analysis were used as the primary method-comparison approaches; Pearson and Spearman correlations and exploratory categorical agreement were secondary analyses. Results: Fifty paired measurements were analyzed for PT and INR and 54 for aPTT. For all three parameters, the 95% confidence interval (CI) for the Passing–Bablok intercept included 0 and the 95% CI for the slope included 1, providing no statistically supported evidence of constant or proportional bias by regression. Mean paired differences (NOVAE II minus CS-2500) were +1.27 s for PT, +0.023 for INR, and +2.32 s for aPTT. The 95% limits of agreement were −0.15 to +2.69 s for PT, −0.112 to +0.159 for INR, and −1.70 to +6.33 s for aPTT. Categorical agreement was influenced by analyzer-specific reference intervals and by the low prevalence of abnormal results. Conclusions: The two analyzer–reagent systems showed positive analytical associations, but the magnitude and dispersion of paired differences varied by assay. Because no clinical equivalence margins were prespecified and markedly pathological or therapeutic-range samples were sparsely represented, these findings support analytical comparison and local verification but do not establish clinical interchangeability. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
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16 pages, 3672 KB  
Article
Akhirin Preserves Hemostatic Wound Repair Through Non-Hematopoietic Regulation of the Vascular Injury Microenvironment
by Mohammad Badrul Anam, Mikiko Kudo, Terumasa Umemoto, Keisuke Yamashita, Rie Kawano and Kunimasa Ohta
J. Dev. Biol. 2026, 14(3), 41; https://doi.org/10.3390/jdb14030041 - 7 Sep 2026
Viewed by 241
Abstract
Hemostasis and wound healing are highly coordinated processes that involve rapid clot formation followed by controlled remodeling of the injured tissue microenvironment. Prior work on Akhirin (AKH), a secreted extracellular matrix protein containing two von Willebrand factor A domains and an LCCL domain, [...] Read more.
Hemostasis and wound healing are highly coordinated processes that involve rapid clot formation followed by controlled remodeling of the injured tissue microenvironment. Prior work on Akhirin (AKH), a secreted extracellular matrix protein containing two von Willebrand factor A domains and an LCCL domain, has established it as a regulator of the neural stem niche in the developing brain and spinal cord injury microenvironment. However, its role as a non-hematopoietic molecule in the vascular injury response remains unknown. Here, we present evidence that AKH contributes to hemostasis and wound repair outside the neural niche. Our immunohistochemical and biochemical analyses demonstrated AKH around arterial tissues, suggesting a potential role at the blood-vessel interface. AKH-deficient mice exhibited a striking phenotype characterized by prolonged tail bleeding and delayed wound closure, indicating impaired vascular injury repair in vivo. Furthermore, bone marrow transplantation failed to rescue the prolonged bleeding phenotype, supporting a predominant non-hematopoietic contribution. Intriguingly, analysis of classical coagulation revealed an apparent paradox: activated partial thromboplastin time was shortened, whereas prothrombin time was not significantly altered. In contrast, increased expression of tissue plasminogen activator, urokinase-type plasminogen activator, and urokinase-type plasminogen activator receptor in AKH-deficient samples suggested dysregulated local fibrinolytic remodeling. Together, these findings identify AKH as a previously unrecognized extracellular regulator of hemostatic wound repair. Rather than indicating a defect in classical coagulation cascade activation, the findings associate AKH deficiency with impaired hemostatic control and altered expression of plasminogen activator system components, suggesting a role for AKH in the local vascular injury response. Full article
(This article belongs to the Special Issue Mechanisms of Morphogenesis, Degeneration, and Regeneration)
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11 pages, 469 KB  
Article
Transfusion Burden in Neonates with Hypoxic–Ischemic Encephalopathy Undergoing Therapeutic Hypothermia
by Domenico Umberto De Rose, Chiara Maddaloni, Sara Ronci, Francesca Campi, Stefano Caoci, Ludovica Martini, Iliana Bersani, Immacolata Savarese, Irma Capolupo, Daniela Longo, Pierpaolo Berti, Ottavia Porzio, Matteo Luciani and Andrea Dotta
Children 2026, 13(9), 1185; https://doi.org/10.3390/children13091185 - 2 Sep 2026
Viewed by 190
Abstract
Background/Objectives: Neonates with hypoxic–ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH) frequently develop coagulation abnormalities and bleeding complications, yet data on transfusion burden and its clinical correlates in this population remain limited. Materials and Methods: We performed a secondary analysis of a [...] Read more.
Background/Objectives: Neonates with hypoxic–ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH) frequently develop coagulation abnormalities and bleeding complications, yet data on transfusion burden and its clinical correlates in this population remain limited. Materials and Methods: We performed a secondary analysis of a retrospective single-center cohort of neonates with HIE treated with TH between 2014 and 2022. Transfusion burden was defined as receipt of at least one blood component and coagulation/plasma products during hospitalization and the total number of transfusion episodes. Demographic, perinatal, biochemical, and clinical severity variables were collected. Univariable and multivariable logistic regression analyses were used to identify factors independently associated with transfusion exposure. Brain magnetic resonance imaging (MRI) findings were compared between transfused and non-transfused infants. Results: Among 142 included neonates, 74 (52.1%) received at least one blood product. The median number of transfusion episodes among transfused infants was 2 (IQR 1–3). Fresh frozen plasma and prothrombin complex concentrate were the most frequently administered products. Transfused infants showed higher markers of illness severity. In multivariable analysis, clinically visible bleeding (adjusted odds ratio [aOR] 12.95, 95% CI 1.34–124.97) and need for respiratory support (aOR 2.98, 95% CI 1.19–7.45) remained independently associated with transfusion exposure. Pathological brain MRI findings, including intracranial bleeding and hypoxic–ischemic injury, were more frequent among transfused infants. Conclusions: blood components and coagulation/plasma-derived products transfusions are common in neonates with HIE undergoing TH and appear to primarily reflect underlying disease severity. These findings highlight the need for optimized, evidence-based transfusion strategies in this vulnerable population. Full article
(This article belongs to the Special Issue Advances in Neonatal Transfusion: Risk Factors and Outcome)
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9 pages, 768 KB  
Article
Circulating Metabolites Associated with Prothrombin Time in Children with Congenital Heart Disease: An Untargeted Metabolomics Study
by Shengxu Li, Dave Watson, Alissa Jorgenson, Zainab Adelekan, Kathleen Garland, Benjamin Deonovic, Leah Burns, Weihong Tang, David M. Overman and Marnie T. Huntley
Metabolites 2026, 16(9), 640; https://doi.org/10.3390/metabo16090640 - 1 Sep 2026
Viewed by 173
Abstract
Background: Coagulation markers are used to guide clinical anticoagulation decisions. We aimed to identify circulating metabolites that are associated with coagulation markers in children with congenital heart disease (CHD). Methods: Plasma samples were separated from whole blood under consistent conditions. Untargeted metabolomic data [...] Read more.
Background: Coagulation markers are used to guide clinical anticoagulation decisions. We aimed to identify circulating metabolites that are associated with coagulation markers in children with congenital heart disease (CHD). Methods: Plasma samples were separated from whole blood under consistent conditions. Untargeted metabolomic data were measured in plasma from up to 203 young patients (age range: 0 days–24 years) with CHD before cardiac surgery. Coagulation markers included activated partial thromboplastin time (aPTT), prothrombin time (PT), and activated clotting time (ACT). Weighted Gene Co-expression Network Analysis (WGCNA) was performed to explore metabolite modules (clusters). Associations of metabolites with the coagulation markers were assessed cross-sectionally with regression models, with false discovery rate (FDR) correction for multiple comparison. Associations between coagulation markers and “eigenmetabolites” from WGCNA modules were assessed by correlation analysis. Results: A total of 776 metabolites were included in the final analysis. Among these, 20 metabolites were associated with PT and one (valine) with ACT (FDR q value < 0.05). Among the metabolites associated with PT, the top three were retinol, 1-palmitoyl-GPI (16:0), and X-25371 (identity unknown). One module from WGCNA with metabolites from the lipid super pathway was correlated with PT (p = 0.004). Conclusions: In this first attempt to identify novel metabolites for coagulation markers, we report 21 metabolites associated with PT or ACT in children with CHD. Future studies are needed to replicate these findings in independent cohorts and to elucidate the biological mechanisms linking these metabolites to hemostatic regulation. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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20 pages, 1704 KB  
Article
Impact of Associated Infections on the Clinical Course and Risk-Stratification Profile of Pulmonary Embolism: Comparative Analysis Using PESI, Wells, Padua, and IMPROVE Scores
by Daniela Nicoleta Crisan, Raluca Dumache, Talida Georgiana Cut, Alexandra Herlo, Marius Florentin Popa, Lucian-Flavius Herlo, Nina Ivanovic, Andreea Nelson Twakor, Gabriela-Florentina Țapoș and Adelina Raluca Marinescu
Diagnostics 2026, 16(17), 2779; https://doi.org/10.3390/diagnostics16172779 - 29 Aug 2026
Viewed by 214
Abstract
Background: Pulmonary embolism (PE) remains a major cause of cardiovascular morbidity and mortality, and associated infections may modify its clinical course. This study evaluated the impact of viral infections on pulmonary embolism severity, mortality, and the performance of established risk scores. Methods: This [...] Read more.
Background: Pulmonary embolism (PE) remains a major cause of cardiovascular morbidity and mortality, and associated infections may modify its clinical course. This study evaluated the impact of viral infections on pulmonary embolism severity, mortality, and the performance of established risk scores. Methods: This retrospective observational study included 729 patients with confirmed PE admitted between January 2020 and December 2025. Patients were grouped according to the presence of associated infections. We analysed clinical data, comorbidities, thrombus localization, laboratory parameters, infection type, treatment, mortality, and Pulmonary Embolism Severity Index (PESI), Wells, Padua, and International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) scores. We performed between-group comparisons, logistic regression, and ROC curve analyses. Results: Patients with associated infections had higher crude mortality than those without infections (27.7% vs. 18.4%, p = 0.006). They also showed higher PESI and IMPROVE scores for venous thromboembolism (VTE), increased white blood cell (WBC) count, markedly elevated D-dimers, longer prothrombin time, and different thrombus localization. Viral infection category was independently associated with mortality, with the IMPROVE score showing the highest ROC discrimination among evaluated scores. Conclusions: Associated infections define a higher-risk PE phenotype. Risk stratification should integrate infection status, laboratory markers, and conventional PE/VTE scores. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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16 pages, 1813 KB  
Article
Real-World Assessment of Direct Oral Factor Xa Inhibitors: Dosing Appropriateness, Drug Exposure, and Inter-Platform Comparability of Chromogenic Anti-Xa Assays
by Yoonjung Kim, Sojin Lee, Yongjung Park and Kyung-A Lee
Diagnostics 2026, 16(17), 2725; https://doi.org/10.3390/diagnostics16172725 - 26 Aug 2026
Viewed by 215
Abstract
Background/Objectives: Direct oral factor Xa inhibitors (DOACs) show substantial interindividual exposure variability in real-world practice, yet interpretation of plasma drug concentrations remains challenging because routine monitoring is not standardized. This study evaluated dosing appropriateness, plasma drug exposure measured by chromogenic anti-factor Xa assays, [...] Read more.
Background/Objectives: Direct oral factor Xa inhibitors (DOACs) show substantial interindividual exposure variability in real-world practice, yet interpretation of plasma drug concentrations remains challenging because routine monitoring is not standardized. This study evaluated dosing appropriateness, plasma drug exposure measured by chromogenic anti-factor Xa assays, inter-platform comparability, and associations with routine coagulation tests. Methods: This single-center retrospective study included 392 plasma samples from 292 patients with atrial fibrillation treated with apixaban (n = 207), edoxaban (n = 147), or rivaroxaban (n = 38). Post-dose outpatient spot samples were analyzed using Sysmex CS-5100 and CN-6000 analyzers with two chromogenic anti-factor Xa assay systems (BIOPHEN™ DiXaI and BIOPHEN™ Heparin LRT) and drug-specific calibrators. Correlations between routine assays (prothrombin time [PT]/international normalized ratio [INR], activated partial thromboplastin time [aPTT]) and DOAC concentrations, as well as inter-platform agreement, were assessed using Spearman’s rank correlation and Passing-Bablok regression. Dosing appropriateness was determined according to Food and Drug Administration-approved labeling. Results: Overall dosing appropriateness was 69.2% (edoxaban 73.3%, apixaban 70.5%, rivaroxaban 45.5%), whereas inappropriate underdosing was the predominant prescribing pattern (26.9%), particularly among patients without formal dose-reduction criteria. PT/INR demonstrated the strongest correlation with edoxaban concentrations (rs = 0.83, p < 0.001). Inter-analyzer correlation between the CS-5100 and CN-6000 was excellent (r = 0.885–0.996), with LRT reagents providing highly consistent results across platforms. Conclusions: Real-world outpatient DOAC concentrations demonstrated substantial variability and frequent off-label underdosing. Chromogenic anti-factor Xa assays showed strong inter-platform agreement, particularly with LRT reagents, supporting their analytical reliability for laboratory assessment of DOAC exposure. Because exact dosing times were unavailable, these concentrations should be interpreted as heterogeneous spot samples rather than standardized pharmacokinetic reference intervals; these findings may nonetheless support individualized interpretation of outpatient spot sample DOAC concentrations in selected clinical settings. Full article
(This article belongs to the Special Issue Laboratory Diagnosis of Cardiovascular Diseases)
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10 pages, 1627 KB  
Case Report
Severe Upper Gastrointestinal Bleeding in a 12-Year-Old Boy with Acute SARS-CoV-2 Infection Complicating Perforated Appendicitis: A Case Report and Differential Considerations
by Kristina Yotova, Nikolay Balgaranov, Venetsiya Bozhanova and Stanimira Elkina
Gastroenterol. Insights 2026, 17(3), 47; https://doi.org/10.3390/gastroent17030047 - 24 Aug 2026
Viewed by 237
Abstract
Background: Gastrointestinal (GI) involvement is increasingly recognised in paediatric SARS-CoV-2 infection and multisystem inflammatory syndrome in children (MIS-C), but severe GI bleeding remains rare. Its pathogenesis in this setting is multifactorial: direct viral injury, hyperinflammatory microvascular damage, treatment-related mucosal injury, and coagulopathy may [...] Read more.
Background: Gastrointestinal (GI) involvement is increasingly recognised in paediatric SARS-CoV-2 infection and multisystem inflammatory syndrome in children (MIS-C), but severe GI bleeding remains rare. Its pathogenesis in this setting is multifactorial: direct viral injury, hyperinflammatory microvascular damage, treatment-related mucosal injury, and coagulopathy may all contribute, and the relative role of each is often difficult to disentangle. Case Presentation: A previously healthy 12-year-old boy underwent appendectomy for perforated appendicitis with peritonitis. On postoperative Day 1, he developed high fever and was found to be SARS-CoV-2 PCR-positive; SARS-CoV-2 IgM and IgG were also positive. He met the positive clinical elements of the CDC 2023 case definition for MIS-C (persistent fever, multisystem involvement—gastrointestinal, hepatic, haematological, and markedly elevated inflammatory markers), although perforated appendicitis with peritonitis is a sufficient alternative explanation and the diagnosis cannot be regarded as secure (see Discussion). Treatment included broad-spectrum antibiotics (meropenem, amikacin, metronidazole), methylprednisolone 2 mg/kg/day, and intravenous immunoglobulin (IVIG) 2 g/kg. On Day 4 in the paediatric intensive care unit (PICU), the patient developed sudden haematemesis with fresh blood through the nasogastric tube and haemodynamic collapse. Coagulation studies revealed prolonged INR (1.6) and reduced prothrombin activity (42%). The patient was stabilised with packed red blood cells, fresh frozen plasma, and intravenous vitamin K. Fibrogastroscopy demonstrated diffuse mucosal bleeding without ulcers or anatomical defects; histology showed mucosal hyperaemia, mixed basal inflammation with intraepithelial lymphocytes, and small erosions. Melena persisted for several days. The child recovered fully and was discharged after 20 days with substantially improved but not fully normalised laboratory values (residual mild anaemia, Hb 110 g/L, and elevated CRP 32.7 mg/L and D-dimer 5.88 mg/L). Conclusions: Severe upper GI bleeding is a rare but life-threatening event in children with severe SARS-CoV-2 infection and MIS-C. In our case, several mechanisms may have acted in combination, although none could be confirmed individually: possible direct viral enterocyte injury via ACE-2 receptors, hyperinflammatory microangiopathy, high-dose corticosteroid-related mucosal injury, possible broad-spectrum antibiotic-associated vitamin K deficiency, and postoperative critical-illness stress. Their relative contributions cannot be determined from a single retrospective case. Bleeding occurred despite continuous PPI prophylaxis, suggesting that PPI cover alone is insufficient when multiple risk factors coexist; the clinical implication is that risk-factor-based (rather than universal) PPI prophylaxis, together with monitoring of vitamin K-dependent coagulation, should be considered in critically ill children receiving high-dose corticosteroids and prolonged broad-spectrum antibiotics. Full article
(This article belongs to the Section Alimentary Tract)
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22 pages, 1434 KB  
Article
Chemical Profiling and In Vitro Bioactivities of Extracts from the Red Alga Jania rubens Collected from the Lebanese Coast
by Rayan Kassir, Fatima El-Mched, Zeina Radwan, Zeina Dassouki and Hiba Mawlawi
Mar. Drugs 2026, 24(9), 295; https://doi.org/10.3390/md24090295 - 24 Aug 2026
Viewed by 394
Abstract
Jania rubens (J. rubens), a Mediterranean red seaweed, is rich in bioactive compounds with potential medicinal applications. This study investigates the therapeutic potential of Lebanese J. rubens through in vitro evaluation of its anti-diabetic, anti-coagulant, anti-inflammatory and anti-hemolytic activities. Various extracts [...] Read more.
Jania rubens (J. rubens), a Mediterranean red seaweed, is rich in bioactive compounds with potential medicinal applications. This study investigates the therapeutic potential of Lebanese J. rubens through in vitro evaluation of its anti-diabetic, anti-coagulant, anti-inflammatory and anti-hemolytic activities. Various extracts were prepared and characterized using GC-MS and HPLC. Biological activities were assessed through α-amylase inhibition assays, effects on prothrombin time and partial thromboplastin time, anti-inflammatory activity and anti-hemolytic activity. Significant α-amylase inhibition was observed with dichloromethane/methanol and lipid extracts, comparable to acarbose. All types of extracts prolonged PT and PTT, with the lipid extract showing the strongest effect at higher concentrations. Additionally, dichloromethane/methanol extracts exhibited potent anti-hemolytic activity. Moreover, all extracts showed strong anti-inflammatory activity, achieving levels of inhibition of heat-induced BSA denaturation comparable to diclofenac. Characterization revealed 11 amino acids in the protein extracts, and significant fatty acids in the lipid profile. The crude extracts contained diverse compounds, including flavonoids, aldehydes, diterpenoids, terpenoids, fatty acids, and sterol esters, which may contribute to the observed biological activities. These results highlight J. rubens as a potential reservoir of bioactive compounds with promising in vitro activities related to diabetes, thrombotic disorders, inflammation, and oxidative stress. Further research is needed to isolate the active compounds, validate their efficacy in vivo, assess safety, and elucidate the underlying mechanisms. Full article
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14 pages, 1178 KB  
Article
Beyond the Thrombophilia Panel: Real-World Overuse, Limited Interpretability, and Poor Guideline Concordance in a Hematology Referral Cohort
by Aysenur Ozturk Ari, Ibrahim Ethem Pinar, Vildan Ozkocaman and Fahir Ozkalemkas
Diagnostics 2026, 16(16), 2643; https://doi.org/10.3390/diagnostics16162643 - 19 Aug 2026
Viewed by 332
Abstract
Background: Hereditary thrombophilia testing is frequently performed outside guideline-supported indications, generating low-value results and diagnostic uncertainty. We evaluated the spectrum, laboratory validity, and appropriateness of thrombophilia testing in patients referred to hematology. Methods: This single-center retrospective cohort included 131 adults referred between September [...] Read more.
Background: Hereditary thrombophilia testing is frequently performed outside guideline-supported indications, generating low-value results and diagnostic uncertainty. We evaluated the spectrum, laboratory validity, and appropriateness of thrombophilia testing in patients referred to hematology. Methods: This single-center retrospective cohort included 131 adults referred between September 2021 and November 2022 with a completed six-variant hereditary thrombophilia panel. Demographic, clinical, thrombotic, and laboratory data were reviewed, and testing appropriateness was assessed against the 2011 Turkish Society of Hematology guideline. Results: Ischemic stroke (25.2%), pulmonary embolism (21.4%), and recurrent pregnancy loss (16.0%) were the leading indications. Of 120 evaluable requests, only seven (5.8%) met guideline-supported criteria, and 42 (32.0%) were ordered during acute thrombosis. Factor V Leiden was associated with pulmonary embolism (48.6% vs. 22.1%, p = 0.003) and deep vein thrombosis (28.6% vs. 9.5%, p = 0.003), whereas ischemic stroke was less frequent among carriers (11.4% vs. 33.7%, p = 0.017). PAI-1, MTHFR c.1298A>C, and prothrombin G20210A showed no consistent associations. Of six low protein C results, only two were confirmed; none of eight low protein S results remained valid after timing and confirmation criteria were applied. Lupus anticoagulant was positive in 18 patients, yet only six underwent appropriately timed repeat testing, establishing four new antiphospholipid syndrome diagnoses. Conclusions: Most thrombophilia panels were ordered inappropriately, and test timing frequently compromised interpretability. Clinically meaningful information arose mainly from factor V Leiden and properly confirmed acquired thrombophilia testing. Targeted, indication-driven testing with strict attention to timing and confirmation should replace indiscriminate panel use. Full article
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10 pages, 297 KB  
Article
A Novel Fixed-Dose Activated Prothrombin Complex Concentrate Regimen for Warfarin-Associated Hemorrhages: A Retrospective Cohort Comparison of Two Regimens
by Francisco Ibarra, Evan Cheng and Benjamin Falkenstein
Pharmacy 2026, 14(5), 121; https://doi.org/10.3390/pharmacy14050121 - 19 Aug 2026
Viewed by 248
Abstract
The optimal fixed-dose strategy for managing warfarin-associated hemorrhages remains unknown and few studies have evaluated the use of Factor VIII Inhibitor Bypass Activity (FEIBA). This retrospective cohort study’s primary efficacy outcome was the percentage of patients who achieved a post-FEIBA INR ≤ 1.5 [...] Read more.
The optimal fixed-dose strategy for managing warfarin-associated hemorrhages remains unknown and few studies have evaluated the use of Factor VIII Inhibitor Bypass Activity (FEIBA). This retrospective cohort study’s primary efficacy outcome was the percentage of patients who achieved a post-FEIBA INR ≤ 1.5 following receipt of the old and new dosing regimens. In the old group patients received 500 or 1000 units for an INR < 5 or ≥5, respectively. In the new group patients received 1000, 1500, or 2000 units for an INR < 5, 5–9.9, or ≥10, respectively. Eighteen patients were included in each group. The median (IQR) pre-FEIBA INR in the old and new groups was 6.1 (3.1–12.9) and 5.3 (3.4–13.0), respectively [difference: −0.8 (95 CI%, −7.2 to 6.5)]. The median (IQR) post-FEIBA INR in the old and new groups was 1.6 (1.4–2.1) and 1.4 (1.2–1.5), respectively [difference: −0.2 (95% CI: −0.6 to 0.0)]. A post-FEIBA INR ≤ 1.5 was achieved in 14 (78%) patients in the new group and 9 (50%) patients in the old group (relative risk: 1.56; 95% CI, 0.91 to 2.7; p = 0.16). The post-FEIBA INR values in the patients who did not achieve a post-FEIBA INR ≤ 1.5 in the new group were 1.6, 1.6, 1.8, and 2.4. Among patients with a baseline INR ≥ 10, significantly more patients in the new group achieved a post-FEIBA INR ≤ 1.5 compared to the old group (86% vs. 17%, respectively). These findings suggest that the new FEIBA dosing regimen may improve INR reversal compared with the previous regimen, particularly among patients with a baseline INR ≥ 10, but larger studies are needed to confirm this observation. Full article
(This article belongs to the Section Pharmacy Practice and Practice-Based Research)
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25 pages, 4767 KB  
Review
Biomarkers of Hypercoagulability and Thromboinflammation in Cervical Cancer-Associated Thrombosis: A Systematic Review with Translational Insights from Breast Cancer
by Dana Taizhanova, Nurgul Serikbay, Pedro Henrique Fernandes do Carmo Las Casas, Jovana Mijucic, Bodaubay Roza, Dmitry Zubkov, Diana Toleubekova, Veronica Bovt, Zoubida Tazi Mezalek, Patrick Vandreden, Mohammed A. Baghdadi, Nida Saleem, Alfonso Tafur, Eleftheria Elmina Lefkou, Fakiha Siddiqui, Prakasha Kempaiah, Jawed Fareed, Victoria Bitsadze and Grigoris T. Gerotziafas
Int. J. Mol. Sci. 2026, 27(16), 7302; https://doi.org/10.3390/ijms27167302 - 16 Aug 2026
Viewed by 420
Abstract
Cancer-associated thrombosis (CAT) is a major cause of morbidity and mortality in patients with malignancy. Biomarkers of hypercoagulability and thromboinflammation may improve risk stratification and support personalised thromboprophylaxis, but evidence remains heterogeneous, particularly in cervical cancer. A systematic review was conducted according to [...] Read more.
Cancer-associated thrombosis (CAT) is a major cause of morbidity and mortality in patients with malignancy. Biomarkers of hypercoagulability and thromboinflammation may improve risk stratification and support personalised thromboprophylaxis, but evidence remains heterogeneous, particularly in cervical cancer. A systematic review was conducted according to PRISMA 2020. PubMed/MEDLINE, Scopus, Embase, and Web of Science were searched for studies published between January 2009 and March 2025 evaluating biological, molecular, genetic, and imaging biomarkers associated with hypercoagulability and thromboinflammation in women withcervical cancer. Evidence from breast cancer and broader CAT studies was incorporated to provide translational context. Owing to substantial methodological heterogeneity, findings were synthesised qualitatively. Twenty-five cervical cancer studies met eligibility criteria. D-dimer was the most extensively investigated biomarker and was consistently associated with VTE risk, although specificity was limited. Biomarkers of thrombin generation and fibrinolytic activation, including thrombin–antithrombin complexes, prothrombin fragment 1+2, and plasmin–α2-antiplasmin complex, demonstrated greater mechanistic specificity. Multimarker panels integrating coagulation, fibrinolysis, endothelial injury, platelet activation, and inflammation showed superior predictive performance compared with single biomarkers. Emerging biomarkers, including circulating tumour DNA, extracellular vesicles, and microRNAs, further supported tumour-driven thromboinflammation. SERPINE1 and F2 gene variants were associated with thrombotic risk and adverse prognosis. Current evidence supports further evaluation of integrated multimodal biomarker strategies for CAT risk assessment, but prospective, standardised, tumour-specific studies are required before biomarker-guided approaches can be implemented in clinical practice. Full article
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18 pages, 2141 KB  
Case Report
Cerebral Venous Sinus Thrombosis Revealing ALK-Positive Anaplastic Large-Cell Lymphoma in a Patient with Inherited Thrombophilia and Concomitant Infection: Case Report and Narrative Review
by Traian Flavius Dan, Alexandra Timeea Pis, Ana-Maria-Smaranda Ulucean, Alexandra Copil, Razvan Bertici, Adelina Miron, Andreea Mihaela Borz, Georgiana Munteanu, Nicoleta Iacob, Ioana Ionita, Silviana Nina Jianu and Dragos Catalin Jianu
Life 2026, 16(8), 1329; https://doi.org/10.3390/life16081329 - 13 Aug 2026
Viewed by 353
Abstract
Cerebral venous sinus thrombosis (CVST) is an uncommon cerebrovascular disorder with heterogeneous manifestations and may occasionally precede the diagnosis of an underlying malignancy. We report the case of a 24-year-old man who presented with recurrent fever, headache, pharyngodynia, and systemic inflammation initially attributed [...] Read more.
Cerebral venous sinus thrombosis (CVST) is an uncommon cerebrovascular disorder with heterogeneous manifestations and may occasionally precede the diagnosis of an underlying malignancy. We report the case of a 24-year-old man who presented with recurrent fever, headache, pharyngodynia, and systemic inflammation initially attributed to a sinonasal or odontogenic infectious process. He subsequently developed binocular horizontal diplopia, left abducens nerve palsy, papilledema, severe headache, and nausea. Neuroimaging demonstrated extensive CVST involving the left internal jugular vein, bilateral transverse sinuses, and superior sagittal sinus, without ischemic, hemorrhagic, or tumoral brain parenchymal lesions. Thrombophilia testing identified heterozygous prothrombin G20210A as the only established inherited thrombophilic factor. Despite initial neurological stabilization, the patient developed a rapidly recurrent frontal calvarial, epicranial, and cranio-dural lesion extending toward the superior sagittal sinus, without brain parenchymal involvement or imaging evidence of leptomeningeal disease. Initial morphological assessment suggested Langerhans cell histiocytosis. However, comprehensive histopathological and immunohistochemical reassessment demonstrated diffuse strong CD30 expression, nuclear and cytoplasmic ALK positivity, CD43 expression, and focal epithelial membrane antigen and granzyme B positivity, while CD1a and S100 were negative. These findings established the diagnosis of systemic ALK-positive anaplastic large cell lymphoma with secondary extra-axial cranio-dural involvement. Systemic staging demonstrated disseminated nodal disease and a noncontiguous cranio-dural extranodal lesion, consistent with stage IV disease. Treatment with anticoagulation and six cycles of brentuximab vedotin combined with cyclophosphamide, doxorubicin, and prednisone resulted in a favorable neurological and oncological outcome, with no metabolically active or residual enhancing disease on follow-up imaging. This case emphasizes the importance of continued etiological investigation in young patients with extensive CVST and an atypical clinical course, even when plausible infectious and inherited thrombotic risk factors coexist. Full article
(This article belongs to the Section Medical Research)
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28 pages, 3415 KB  
Article
Natural Bioactive Compounds from Delonix regia Seeds Revealed Through Integrated Phytochemical, Biomedical and In Silico Evaluation
by Husam Qanash, Aisha M. H. Al-Rajhi, Abdulrahman S. Bazaid, Manar F. Alghassab, Fahad Almarshadi, Walid Alesefir, Waleed Hakami, Amro Duhduh and Abdu Aldarhami
Pharmaceuticals 2026, 19(8), 1272; https://doi.org/10.3390/ph19081272 - 12 Aug 2026
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Abstract
Background/Objectives: Delonix regia seeds contain phytochemicals with therapeutic potential, but their activity against Helicobacter pylori and biomedical properties remain incompletely characterized. This study aimed to characterize the phenolic and amino acid composition of D. regia seed extract (DRSE) and evaluate its anticancer, [...] Read more.
Background/Objectives: Delonix regia seeds contain phytochemicals with therapeutic potential, but their activity against Helicobacter pylori and biomedical properties remain incompletely characterized. This study aimed to characterize the phenolic and amino acid composition of D. regia seed extract (DRSE) and evaluate its anticancer, wound-healing, anti-inflammatory, anticoagulant, antibacterial, antibiofilm and urease-targeted docking activities. Methods: DRSE was analyzed by high-performance liquid chromatography (HPLC) and amino acid analysis. Biological effects were assessed using MTT cytotoxicity, scratch wound-healing, bovine serum albumin (BSA) denaturation, prothrombin time (PT) and partial thromboplastin time (PTT), antibacterial and crystal violet antibiofilm assays. Gallic acid and vanillin were docked against H. pylori urease (PDB ID: 1E9Y). Results: Gallic acid was the predominant phenolic compound (1417.90 µg/g), while aspartic and glutamic acids dominated the amino acid fraction. DRSE showed preferential cytotoxicity toward A431 carcinoma cells (IC50 = 108.97 ± 0.68 µg/mL) compared with HFB4 fibroblasts (IC50 = 318.56 ± 2.06 µg/mL), yielding a selectivity index of 2.92. Scratch closure was comparable to the control (81.71% versus 80.85%), although the migration rate increased to 16.12 µm. DRSE inhibited protein denaturation by 91.20% (IC50 = 6.39 ± 0.19 µg/mL) and prolonged PT and PTT to 27.37 and 90.50 s, respectively. It inhibited H. pylori with minimum inhibitory and bactericidal concentrations of 31.25 µg/mL and suppressed biofilm formation by 95.39%. Gallic acid and vanillin showed comparable urease docking scores of −4.72 and −4.71 kcal/mol. Conclusions: DRSE showed selective anticancer, anti-H. pylori, antibiofilm, anti-inflammatory, anticoagulant, and moderate pro-migratory activities. Mechanistic, safety and in vivo studies are warranted. Full article
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14 pages, 1205 KB  
Article
Numerical and Interpretive Comparability of Optical and Mechanical Coagulation Analyzers: A Zlog-Supported Method Comparison Study
by Xinjian Cai, Wei Yang, Qiuxia Lu and Yiteng Lin
Diagnostics 2026, 16(16), 2511; https://doi.org/10.3390/diagnostics16162511 - 9 Aug 2026
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Abstract
Background/Objectives: In laboratories using coagulation analyzers with different clot-detection principles and platform-specific reference intervals (RIs), numerical agreement does not necessarily ensure concordant clinical interpretation. We evaluated how analytical agreement and RI-based interpretation diverge between mechanical and optical coagulation analyzers. Methods: Paired duplicate measurements [...] Read more.
Background/Objectives: In laboratories using coagulation analyzers with different clot-detection principles and platform-specific reference intervals (RIs), numerical agreement does not necessarily ensure concordant clinical interpretation. We evaluated how analytical agreement and RI-based interpretation diverge between mechanical and optical coagulation analyzers. Methods: Paired duplicate measurements were performed on the STA R Max (Stago) and ACL TOP 750 LAS (Werfen) for prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), international normalized ratio (INR), and antithrombin (AT). Numerical agreement was assessed by Passing–Bablok regression and log-ratio Bland–Altman analysis against predefined total allowable error (TEa) limits. Each result was standardized using its platform-specific RI, and the between-platform zlog difference (Δzlog) described differences in RI-relative position. Results: Stago yielded higher values than Werfen for PT, APTT, TT, and FIB, with mean biases of +15.6% to +20.4%, whereas INR and AT showed close agreement (−1.1% and +1.6%). Interpretive concordance among the primary assays ranged from 61.9% for APTT to 89.2% for FIB. The analytical-by-interpretive matrix identified specimens that were within TEa but classified differently and specimens that were beyond TEa but retained the same RI classification. Median Δzlog values were −0.43 for PT, +0.09 for APTT, −0.66 for TT, and +0.77 for FIB. Conclusions: Numerical and interpretive comparability are distinct dimensions. Combining the analytical-by-interpretive matrix with Δzlog can reveal clinically relevant divergence not apparent from bias-versus-TEa assessment alone. In this purposively selected dataset, divergence arose mainly from RI offset for TT and analytical dispersion for APTT; the sample-specific discordance rates are not population prevalence estimates. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
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12 pages, 1299 KB  
Article
Factors Affecting Temporal Changes in Ablated Liver Volume After Radiofrequency Ablation for Hepatocellular Carcinoma Evaluated by Three-Dimensional Volumetric Computed Tomography
by Mayumi Higashi, Masahiro Tanabe, Yuna Fujii, Haruki Furutani, Jo Ishii, Yuto Takemura, Norikazu Tanabe, Issei Saeki, Taro Takami and Katsuyoshi Ito
Tomography 2026, 12(8), 112; https://doi.org/10.3390/tomography12080112 - 7 Aug 2026
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Abstract
Objectives: To evaluate associations between shrinkage of ablated liver area on computed tomography (CT) over time after radiofrequency ablation (RFA) and clinical parameters related to liver function and fibrosis. Methods: Patients with hepatocellular carcinoma who underwent RFA and follow-up CT were retrospectively reviewed. [...] Read more.
Objectives: To evaluate associations between shrinkage of ablated liver area on computed tomography (CT) over time after radiofrequency ablation (RFA) and clinical parameters related to liver function and fibrosis. Methods: Patients with hepatocellular carcinoma who underwent RFA and follow-up CT were retrospectively reviewed. The ablated area volume (AAV) on CT obtained within 1 week and around 6 months after RFA was measured, and reduction rate of AAV was calculated. The AAV reduction rate was compared among Child-Pugh classification, modified albumin-bilirubin (mALBI) grades, FIB-4 index categories, and lesion locations using generalized estimating equations (GEE). Univariable and multivariable GEE analyses were performed to evaluate associations between the AAV reduction rate and clinical parameters. Results: Fifty-three lesions in 41 patients (median age, 76 [range, 38–88] years, 24 men) were evaluated. The AAV reduction rate was significantly lower in Child-Pugh class B than class A (p < 0.001) and in mALBI grade 2b than grade 1 (p < 0.001) or grade 2a (p = 0.004). Significant differences were also observed among FIB-4 index groups (p < 0.001) and among lesion locations, with lower AAV reduction rates in medial and anterior segments than in lateral (p < 0.001) and posterior (p = 0.017) segments. Univariable GEE analyses showed significant associations between AAV reduction rate and cholinesterase, albumin, total bilirubin (T-Bil), prothrombin time, platelet count, and FIB-4 index (p < 0.05). Multivariable GEE analysis demonstrated that both albumin and T-Bil remained independently associated with AAV reduction rate (p < 0.001). Conclusions: The AAV reduction rate tended to be lower in patients with impaired liver function and advanced liver fibrosis. Full article
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