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BACKGROUND: Endometriosis is considered as a systemic disease with the presence of proinflammatory cytokines in the circulation, which drives hypercoagulable state of endometriosis. Currently, endometriosis is classified into four stages: I (minimal), II (mild), III (moderate) and IV (severe). The aim of this study is to investigate the correlations between inflammatory markers and coagulation factors in patients diagnosed of endometriosis with stage IV. METHODS: This retrospective case-control study included 171 endometriosis patients with stage IV and 184 controls. Continuous data were expressed by mean ± standard deviation. Mann-Whitney U and χ2 tests were used to compare the medians and frequencies among the groups. Spearman analysis was conducted to determine the correlation among the measured parameters. The diagnostic values of the parameters differentiating endometriomas were tested by receiver operating characteristic (ROC) curve. RESULTS: The time of activated partial thromboplastin time (APTT) was decreased and the concentration of fibrinogen (FIB) and neutrophil-to-lymphocyte ratio (NLR) were increased in women of endometriosis with stage IV. The APTT were negatively correlated with NLR while the concentrations of FIB were positively correlated with NLR. The ROC analysis showed that the Area under the curve (AUC) of FIB was 0.766 (95% confidence interval:0.717-0.814) with sensitivity and specificity reaching 86.5 and 60.9%, respectively. The AUC of CA125 and CA199 was 0.638 (95% confidence interval: 0.578-0.697), 0.71 (95% confidence interval: 0.656-0.763) with sensitivity and specificity reaching 40.9 and 91.8%, 80.7 and 56.5% respectively. The combination of these factors showed the highest AUC of 0.895 (0.862-0.927) with sensitivity of 88.9% and specificity of 77.7%. CONCLUSION: In the present study, we found that inflammatory factors showed significant correlation with APTT or FIB in endometriosis with stage IV. Moreover, the coagulation factors combined with CA125 and CA199 were more reliable for identifying the endometriosis with stage IV.

L'hémophilie acquise A est une maladie auto-immune rare secondaire au développement d'anticorps (inhibiteur) dirigés contre le FVIII, avec un pronostic vital encore engagé. Le diagnostic est en règle évoqué devant des ecchymoses sous-cutanées plus ou moins diffuses associées à un allongement du TCA. Le plus souvent idiopathique, elle peut être associée à une maladie auto-immune, un cancer, la grossesse ou le post-partum ou à la prise de médicaments. La prise en charge thérapeutique passe par la correction éventuelle du syndrome hémorragique par des agents hémostatiques (facteur VII recombinant activé, concentré de complexe prothrombique ou facteur VIII humain porcin recombinant). L'éradication de l'inhibiteur fait appel à un traitement immunosuppresseur par corticoïdes seuls souvent associés à un agent cytotoxique ou du rituximab, dont l'indication doit tenir compte du taux de FVIII résiduel et du titre d'inhibiteur. Le but de cette revue est de faire le point sur les données épidémiologiques, cliniques, physiopathologiques, diagnostiques et de discuter les recommandations thérapeutiques actuelles. Acquired hemophilia A (AHA) is a rare autoimmune disorder due to autoantibodies against factor VIII, with a high mortality risk. It should be suspected in subjects with abnormal bleedings, especially subcutaneous bleed associated with prolonged activated partial thromboplastin time (aPTT). AHA is often idiopathic but is associated with autoimmune diseases, malignancies, pregnancy and postpartum period or drugs. Treatment is based on haemostatic agents as by-passants agents such as factor VIIa and activated prothrombine concentrate complex or recombinant porcine factor VIII for severe bleeding. Eradication of inhibitor should be established as soon as the diagnosis is confirmed with steroid alone often associated with cytotoxic agents or rituximab, depending on FVIII activity and inhibitor titer. The purpose of this review is to summarize the epidemiology, etiopathogenesis, diagnosis, treatment of AHA and discuss current recommendations. [ABSTRACT FROM AUTHOR]

It has been recognized that shortened activated partial thromboplastin time (aPTT) may be caused by various preanalytical conditions. As coagulation Factor VIII is included in the in vitro intrinsic coagulation cascade measured by aPTT, we hypothesized that the shortened aPTT could be a result of elevated FVIII activity. We aimed to inspect the connection of elevated FVIII with shortened aPTT, and the possible effect inflammation has on routine laboratory parameters. 40 patients from various hospital departments with aPTT measurement below the lower limit of the reference interval (<23.0 s) were included in the study. To compare the obtained results with aPTT measurements in the non-inflammatory state, samples from 25 volunteers (laboratory personnel) were collected. White blood cell count, C-reactive protein, aPTT, and FVIII values were measured in the control group. Only two samples among 40 patients with shortened aPTT (5 %) were clotted. Out of the remaining 38, 26 had FVIII activity above 150 % (upper limit of a reference interval), median value of 194 % (IQR: 143–243 %). Seven samples in the control group had shortened aPTT results (36 %). However, all coagulation samples were clot and hemolysis-free. Multiple regression identified only FVIII activity as an independent variable in predicting aPTT values (p=0.001). Our results support the thesis that shortened aPTT is rarely a consequence of preanalytical problems. Elevated FVIII activity causes shortened aPTT, not only in the inflammatory state but also in individuals with concentration of inflammatory markers within reference intervals. [ABSTRACT FROM AUTHOR]

This study evaluated the safety, tolerability, pharmacodynamics, and pharmacokinetics of recombinant neorudin (EPR‐hirudin [EH]) in patients with acute coronary syndrome (ACS), providing a basis for further therapeutic research. This open‐label, single‐center, nonrandomized, nonblinded, and noncontrolled trial categorized 24 patients with nonprogressive ACS who met the screening criteria into 3 groups. They received an intravenous injection of neorudin (0.4 mg/kg), followed by an intravenous drip at doses of 0.15, 0.30, and 0.45 mg/kg/h for 3 days in the low‐, medium‐, and high‐dose groups, respectively. The safety, tolerability, pharmacodynamics, and pharmacokinetics of EH were assessed after treatment, indicating that neorudin was safe and well tolerated in nonprogressive ACS. No serious adverse events or clinical composite end points were observed. The activated partial thromboplastin time and thrombin time increased significantly and dose dependently following EH administration across all groups compared to pretreatment values. Conversely, thrombin activity significantly decreased after drug administration but returned to baseline levels shortly after drug withdrawal. Within the administered dose range, neorudin exposure increased with the dose, and its half‐life was approximately 2 hours. Neorudin was found to be safe and tolerable for treating patients with nonprogressive ACS, demonstrating therapeutic efficacy at doses up to 0.45 mg/kg/h over a 3‐day period. [ABSTRACT FROM AUTHOR]

Chitosan, a derivative of chitin derived from the gladius of the marine cephalopod Doryteuthis sibogae , has drawn interest in biomedical research because of its possible antibacterial effects on human infections and inhibition of blood clotting. Chitosan was extracted from chitin isolated from the gladius of D. sibogae via demineralization and deproteination. Chitosan was structurally characterized using FT-IR, XRD, and FESEM. Additionally, the disc diffusion method was used to investigate the antibacterial efficacy of chitosan against three human pathogens. Effective antibacterial activity was demonstrated against both Gram-positive and Gram-negative microorganisms. Chitosan is a potent anticoagulant in anticoagulant assays employing activated partial thromboplastin time (APTT) and prothrombin time (PT). [Display omitted] • Chitosan, deacetylated derivative of chitin was isolated from marine cephalopod. • Chitosan was structurally characterized through FT-IR, XRD, and SEM analysis. • Antibacterial efficacy of chitosan was analyzed. • Anticoagulant property of chitosan was evaluated by calculating APTT and PT. [ABSTRACT FROM AUTHOR]

Background: The peripheral perfusion index (PI) reflects microcirculatory blood flow perfusion and indicates the severity and prognosis of sepsis. Method: The cohort comprised 208 patients admitted to the intensive care unit (ICU) with infection, among which 117 had sepsis. Demographics, medication history, ICU variables, and laboratory indexes were collected. Primary endpoints were in-hospital mortality and 28-day mortality. Secondary endpoints included organ function variables (coagulation function, liver function, renal function, and myocardial injury), lactate concentration, mechanical ventilation time, and length of ICU stay. Univariate and multivariate analyses were conducted to assess the associations between the PI and clinical outcomes. Sensitivity analyses were performed to explore the associations between the PI and organ functions in the sepsis and nonsepsis groups. Result: The PI was negatively associated with in-hospital mortality (odds ratio [OR] 0.29, 95% confidence interval [CI] 0.15 to 0.55), but was not associated with 28-day mortality. The PI was negatively associated with the coagulation markers prothrombin time (PT) (β −0.36, 95% CI −0.59 to 0.13) and activated partial thromboplastin time (APTT) (β −1.08, 95% CI −1.86 to 0.31), and the myocardial injury marker cardiac troponin I (cTnI) (β −2085.48, 95% CI −3892.35 to 278.61) in univariate analysis, and with the PT (β −0.36, 95% CI −0.60 to 0.13) in multivariate analysis. The PI was negatively associated with the lactate concentration (β −0.57, 95% CI −0.95 to 0.19), mechanical ventilation time (β −23.11, 95% CI −36.54 to 9.69), and length of ICU stay (β −1.28, 95% CI −2.01 to 0.55). Sensitivity analyses showed that the PI was significantly associated with coagulation markers (PT and APTT) and a myocardial injury marker (cTnI) in patients with sepsis, suggesting that the associations between the PI and organ function were stronger in the sepsis group than the nonsepsis group. Conclusion: The PI provides new insights for assessing the disease severity, short-term prognosis, and organ function damage in ICU patients with sepsis, laying a theoretical foundation for future research. [ABSTRACT FROM AUTHOR]

For several decades, therapeutic options for inherited deficiencies of factor VIII or IX (hemophilia A or B, respectively) have largely been the replacement of the missing clotting factor with plasma-derived or recombinant products. Hemostasis laboratories use standard activated partial thromboplastin time (aPTT)-based clotting or chromogenic assays to monitor plasma factor levels to guide therapy. The emergence in the past 10 years of extended half-life replacement products and other novel therapies for hemophilia has led to a reappraisal of assay suitability, with studies of product measurement showing some existing assay types or reagents to be unsuitable for some products. The hemostasis laboratory must adapt to the changing landscape by adding new assays or modifying existing assays to ensure accurate results for product measurement. These strategies include switching from a chromogenic assay to a clotting assay, or vice versa, changing an aPTT reagent brand, or introducing product specific calibrators. This article evaluates the effects of some of the newer treatment options on the laboratory testing of factor levels and related assays. [ABSTRACT FROM AUTHOR]

Unfractionated heparin (UFH) was uncovered in 1916, has been used as an anticoagulant since 1935, and has been listed in the World Health Organization's Model List of Essential Medicines. Despite the availability of many other anticoagulants, the use of heparin (either low molecular weight heparin [LMWH] or UFH) is still substantial. Heparin has pleotropic effects including anticoagulant and several nonanticoagulant properties such as antiproliferative, anti-inflammatory activity, and anticomplement effects. Although UFH has been widely replaced by LMWH, UFH is still the preferred anticoagulant of choice for patients undergoing cardiopulmonary bypass surgery, extracorporeal membrane oxygenation, and patients with high-risk mechanical cardiac valves requiring temporary bridging with a parenteral anticoagulant. UFH is a highly negatively charged molecule and binds many positively charged molecules, hence has unpredictable pharmacokinetics, and variable anticoagulant effect on an individual patient basis. Therefore, anticoagulant effects of UFH may not be proportional to the dose of UFH given to any individual patient. In this review, we discuss the anticoagulant and nonanticoagulant activities of UFH, differences between UFH and LMWH, when to use UFH, different methods of monitoring the anticoagulant effects of UFH (including activated partial thromboplastin time, heparin anti-Xa activity level, and activated clotting time), while discussing pros and cons related to each method and comparison of clinical outcomes in patients treated with UFH monitored with different methods based on available evidence. [ABSTRACT FROM AUTHOR]

Due to their widespread use, testing for direct oral anticoagulants (DOACs) has become urgent in certain clinical situations. Screening based on widely available, rapid, and simple hemostasis assays such as prothrombin time, activated partial thromboplastin time, or even diluted Russel Viper venom time may provide sufficient evidence of "over-coagulation" and could be used "in small/peripheral/spoke laboratories" as an emergency strategy, but is not thought to be reliable for driving clinical decision making. Given their good correlation with plasma concentration, urine dipsticks may be considered a valuable alternative for emergency screening, although their performance is dependent on renal function, may vary depending on the time since the last urination, and there may be problems of interfacing with the laboratory/hospital information system. Separation methods based on liquid chromatography and mass spectrometry may be clinically questionable, since they measure the concentration rather than the actual inhibitory effect of DOACs, are relatively expensive, cumbersome and time consuming, and therefore seem unsuitable for most conditions requiring urgent clinical decision making. A proposed approach therefore involves establishing a network of routine clinical laboratories, designating a reference center where DOAC tests could be available 24/7, establishing a clear diagnostic care pathway for ordering the tests from the laboratory and standard operating procedures for performing them, the use of the diluted thrombin time for dabigatran and anti-FXa assays (drug-calibrated) for rivaroxaban, apixaban, and edoxaban, as well as providing expert advice throughout the testing process, from ordering to interpretation of results. [ABSTRACT FROM AUTHOR]

Lupus anticoagulant (LA) is one of three tests identified as laboratory criteria for definite antiphospholipid syndrome (APS). The other two tests are anticardiolipin antibody (aCL) and anti-β2-glycoprotein I (aβ2GPI) antibody. The presence of LA is assessed using clot-based tests, while the presence of aCL and aβ2GPI is assessed by immunological assays. Since no test can be considered 100% sensitive or specific for LA, current guidelines recommend using two different clot-based assays reflecting different principles, with the dilute Russell viper venom time (dRVVT) and activated partial thromboplastin time (aPTT) recommended. Initially, LA-sensitive reagents are used to screen for LA, and then, in "screen-positive" samples, LA-"insensitive" reagents are used to confirm LA. Because LA assays are based on clot detection, anything that can interfere with fibrin clot development may affect test results. In particular, in addition to LA, the tests are also sensitive to the presence of a wide range of clinical anticoagulants, reflecting preanalytical issues for testing. We provide updated findings for LA testing in our geographic region, using recent data from the Royal College of Pathologists of Australasia Quality Assurance Programs, an international external quality assessment program with approximately 120 participants. Data show a wide variety of assays in use, especially for aPTT testing, and variable outcomes in reported numerical values with these assays when assessing proficiency samples. dRVVT testing mostly comprised reagents from three main manufacturing suppliers, which also showed differences in numerical values for the same homogeneous tested samples. Nevertheless, despite the use of different test reagents and processes, >98% of participants correctly identified LA-negative samples as LA-negative and LA-positive samples as LA positive. We hope our findings, reflecting on the heterogeneity of test processes and test data, help improve diagnostic testing for LA in the future. [ABSTRACT FROM AUTHOR]

Background: To investigate the clinical features, kidney pathology, treatment regimens, and clinical outcomes of IgA vasculitis nephritis (IgAVN) with nephrotic-range proteinuria in children. Methods: A retrospective review of children diagnosed with IgAVN between January 2019 and December 2022 was conducted. Participants were divided into two groups based on their urine protein/creatinine (UPCR) levels. Biodata, clinical characteristics, laboratory findings, pathologic features, treatment regimens, and outcomes were abstracted from case records and analyzed. Results: A total of 255 children were identified, 94 with nephrotic-range proteinuria (UPCR ≥ 200 mg/mmol) and 161 with non-nephrotic proteinuria (UPCR < 200 mg/mmol). Patients in the nephrotic-range proteinuria group were significantly younger and had worse grades of glomerular and acute tubulointerstitial injury compared to those in the non-nephrotic proteinuria group. Higher levels of blood urea nitrogen (BUN), D-dimer (DD), and fibrin degradation products (FDP), and lower levels of total protein (TP), albumin (ALB), urine creatinine (Cr), prothrombin time (PT), activated partial thromboplastin time (APTT), IgG, CD3 + cells, and CD4 + cells were found in patients in the nephrotic-range proteinuria group. Clinical outcome of patients with nephrotic-range proteinuria was significantly associated with ISKDC grading, proportion of glomerular crescents and severity of acute tubulointerstitial injury. Conclusions: Children with nephrotic-range proteinuria exhibit more severe disordered immunologic function, hypercoagulability, glomerular and tubulointerstitial pathological damage, and have worse outcomes than those with lower proteinuria levels. Clinicians should pay great attention to the kidney injury and more extensive studies are required to identify optimal treatment regimens to improve outcomes in patients. [ABSTRACT FROM AUTHOR]

Massive transfusion of blood products poses challenges in determining the need for transfusion and the appropriate volume of blood products. This review explores the use of machine learning (ML) models to predict transfusion risk during surgical procedure, focusing on the methodology, variables, and software employed to predict transfusion. This scoping review investigates the development and current state of machine learning models for predicting transfusion risk during surgical procedure, aiming to inform physicians about the field's progress and potential directions. The review was conducted using the databases Cochrane, Embase, and PubMed. The search included keywords related to blood transfusion, statistical models, and surgical procedures. Peer-reviewed articles were included, while literature reviews, case reports, and non-human studies were excluded. A total of 40 studies met the inclusion criteria. The most frequently studied biological variables included haemoglobin, platelet count, international normalized ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen, creatinine, white blood cells, and albumin. Clinical variables of importance included age, sex, surgery type, blood pressure, weight, surgery duration, american society of anesthesiology (ASA) status, blood loss, and body mass index (BMI). The software employed varied, with Python, R, SPSS, and SAS being the most commonly used. Logistic regression was the predominant methodology used in 20 studies. Our scoping review highlights the need for improved reporting and transparency in methodology, variables, and software used. Future research should focus on providing detailed descriptions and open access to codes of respective models, promoting reproducibility, and enhancing the clinical relevance of transfusion risk prediction models. [ABSTRACT FROM AUTHOR]

This study aimed to ascertain how the current two ART regimens used in Ghana affected HIV patients' coagulation profiles. A case-control study was conducted on 102 HIV positive patients at the Mampong Municipal Hospital. Coagulation parameters measured showed APTT was normal in majority of ART-experienced participants but prolonged in majority of ART-naïve participants. The mean platelet count was significantly higher in ART-experienced participants. No significant differences were found between the coagulation profiles of ART-experienced patients on two different drug regimens. In conclusion, current ART can enhance the coagulation profiles in HIV-infected patients, by improving platelet count and APTT. [ABSTRACT FROM AUTHOR]

Snow mountain garlic is traditionally eaten by Himalayan locals for its medicinal properties. Although different species of the genus Allium are known to have other biological effects, such as antiplatelet and antithrombotic activities, little is known about the anticoagulant effect of Snow mountain garlic, a member of the genus Allium. Therefore, the present study examined the in vitro anticoagulant effect of the aqueous extract, the lyophilized aqueous extract, and the isoflavone extract from the lyophilized aqueous extract of Snow mountain garlic in samples from 50 human blood donors. Compared to the control, concentrations of 25, 12.5, and 6.25 mg/100 µL lengthened the clotting times of prothrombin, and concentrations of 25 and 12.5 mg/100 µL lengthened the activated partial thromboplastin time (p ˂ 0.05). The isoflavone extract from the lyophilized aqueous extract containing isoflavones, organosulfur compounds, a polyphenol, and a steroid glycoside showed a significant effect (p ˂ 0.05) on the prothrombin time and the activated partial thromboplastin time at a dose of 20 µL (volume) compared to the control. The results regarding the use of Snow mountain garlic as a preventive measure and aid in treating thromboembolic disease are promising. [ABSTRACT FROM AUTHOR]

Liver transplantation is a complex surgical procedure in which various forms of coagulation dysfunction can occur, including perioperative hypercoagulability. The hemostasis balance in liver graft recipients with end-stage liver disease can shift to thrombosis or haemorrhage, depending on the associated risk factors and clinical conditions. Hypercoagulability can result in serious complications such as thromboembolism, which can affect the vessels of the newly transplanted liver graft. Standard coagulation tests (SCTs), such as prothrombin time and activated partial thromboplastin time (aPTT), have a poor ability to diagnose and monitor an early stage of hypercoagulability. Recent studies demonstrated that viscoelastic hemostatic elastic tests (VETs), such as rotational thromboelastometry (ROTEM) and thromboelastography (TEG), are promising alternative tools for diagnosing hypercoagulability disorders. VETs measure clotting and clot formation time, clot strength (maximum clot firmness), fibrin and platelet contribution to clot firmness, and fibrinolysis, which makes them more sensitive in identifying liver graft recipients at risk for thrombosis as compared with SCTs. However, developing evidence-based guidelines for the prophylaxis and treatment of hypercoagulability based on VET results is still needed. [ABSTRACT FROM AUTHOR]

The study published in the International Journal of Laboratory Hematology explores the impact of preanalytical conditions on fibrin monomers (FMs) and D-dimer biomarkers. The research involved 20 healthy volunteers and compared nine simulated conditions to a reference condition. The study found that certain preanalytical conditions significantly affected FMs levels, while D-dimer levels remained consistent across all conditions. The findings suggest that FMs assays are sensitive to preanalytical artifacts, highlighting the importance of stringent guidelines for accurate measurements. [Extracted from the article]

Objectives: Coronary artery bypass grafting (CABG) is essential for treating coronary artery disease, with postoperative aspirin crucial to prevent graft restenosis. However, its gastrointestinal side effects may limit tolerability in some patients. Indobufen presents a potential alternative, but its safety and efficacy need further validation. This study aimed to compare the efficacy and safety of indobufen versus aspirin in patients’ post-CABG. Methods: This retrospective observational study included 39 patients who underwent CABG at two centers from January to December 2023. Patients were retrospectively assigned to two groups based on the antiplatelet therapy they received: the indobufen group (n = 19) and the aspirin group (n = 20). The primary endpoint was a composite of non-fatal myocardial infarction, stroke, and revascularization due to acute coronary syndrome in the intention-to-treat population. Postoperative data on platelet count, hemoglobin, D-dimer, activated partial thromboplastin time (APTT), and hospital stay length were collected. Transfusion rate, bleeding, thrombotic events, and gastrointestinal adverse reactions were compared between the two groups. Results: Over the 8-to-18-month follow-up period, 5 patients (25%) in the aspirin group reached the primary endpoint, while none in the indobufen group did, a difference that was statistically significant (p = 0.02). Although the rates of nonfatal myocardial infarction, revascularization, stroke, and thrombotic events were higher in the aspirin group, these differences did not reach statistical significance. Importantly, the total bleeding events were markedly lower in the indobufen group (15.79% vs. 55%, p = 0.011), with major bleeding events also significantly reduced in the indobufen group (0% vs. 20%, p = 0.04). Both groups showed no significant differences were observed in postoperative hospital stay, hemoglobin, and D-dimer levels between the groups. However, the indobufen group demonstrated significantly lower platelet count and APTT. The average daily cost of indobufen was 27.8 times higher than that of aspirin. Conclusion: Indobufen demonstrates a comparable antiplatelet effect to aspirin and offers significant advantages in reducing gastrointestinal adverse reactions and bleeding risk. It can be considered a preferable alternative for patients who cannot tolerate or have contraindications to aspirin. Further large-scale clinical trials are needed to confirm its potential as the first-choice antiplatelet therapy post-CABG. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions No clear guidelines exist for perioperative anticoagulation management after durable left ventricular assist device insertion. In this study, we sought to compare outcomes between anti‐factor Xa (FXa) and activated partial thromboplastin time (aPTT) in monitoring unfractionated heparin (UFH) dosing after HeartMate 3 (HM3) insertion.This is a single‐center retrospective review of patients who received UFH after HM3 insertion between 01/2020–12/2022. Post‐operative UFH dose was titrated by aPTT goal 45–60 sec (n = 53) or FXa goal 0.1–0.2 U/mL (n = 59). Baseline differences between cohorts were balanced by inverse probability treatment weighting.At baseline, unadjusted FXa patients were more likely to be white (47.5% vs. 35.8%, p < 0.001), INTERMACS 1–2 (69.5% vs. 47.2%, p = 0.013), have history of coronary artery disease (66.1% vs. 43.4%, p = 0.026), and lower eGFR (54.1 vs. 63.7 mL/min/1.73 m2, p = 0.029) compared to the aPTT group. After adjusting for several bleeding/thrombosis risk factors, 97.5% of FXa and 91.0% of aPTT patients reached therapeutic levels with comparable UFH duration and maximum dose. Moreover, in‐hospital mortality (2.5% vs. 3.1%, p = 0.842), major bleeding events (4.2% vs. 9.2%, p = 0.360), and thromboembolic events (21.8% vs. 10.1%, p = 0.151) remained without significant differences between FXa and aPTT cohorts. There was a high degree of variability in FXa (r2 = 0.20) and aPTT (r2 = 0.22) values for any given UFH dose.No differences in frequency of bleeding or thromboembolic events were observed in this study between FXa versus aPTT cohorts after HM3 implantation. More longitudinal studies are warranted to determine whether or not one assay is superior to the other. [ABSTRACT FROM AUTHOR]

Background Study Design and Methods Results Discussion Anticoagulation during extracorporeal membrane oxygenation (ECMO) might still lead to severe bleeding complications. Heparin is the most frequently used anticoagulant, but novel drugs could be promising. Argatroban is a new alternative to heparin. To date, no robust studies have confirmed the clear superiority of argatroban (AG) over heparin, although it has some advantages and may be safer.An observational study was conducted in all adult veno‐venous ECMO patients with COVID‐19‐associated acute respiratory distress syndrome admitted to the University Hospital Ostrava (n = 63). They were anticoagulated with heparin in the first period and with AG in the second period, targeting the same activated partial thromboplastin time (aPTT; 45–60 s). Bleeding complications requiring transfusion and life‐threatening bleeding events were evaluated. The primary objective was to compare heparin and AG in terms of bleeding, transfusion requirements and mortality‐related bleeding.The total time on ECMO per patient was 16 days with an in‐hospital mortality of 55.6%. The red blood cell consumption in the AG group (median 2.7 transfusions/week) was significantly lower than in the heparin group (median 4.2 transfusions/week, p = 0.011). Life‐threatening bleeding complications were higher in the heparin group compared to the AG group (35.7% vs. 10.2%, p = 0.035), and mortality‐related bleeding complications were also higher in the heparin group (21.4% vs. 2.0%, p = 0.032).Argatroban is an interesting alternative to heparin with less bleeding, less need for red blood cell transfusions and improved safety of ECMO with less mortality‐related bleeding. [ABSTRACT FROM AUTHOR]

Background Methods Results Discussion Despite prophylactic platelet transfusions, hypoproliferative thrombocytopenia is associated with bleeding; historical risk factors include hematocrit (HCT) ≤$$ \le $$25%, activated partial thromboplastin time ≥$$ \ge $$30 s, international normalized ratio ≥$$ \ge $$1.2, and platelets≤$$ \le $$5000/μL.We performed a post hoc analysis of bleeding outcomes and risk factors in participants with hematologic malignancy and hypoproliferative thrombocytopenia enrolled in the American Trial to Evaluate Tranexamic Acid Therapy in Thrombocytopenia (A‐TREAT) and randomized to receive either tranexamic acid (TXA) or placebo.World Health Organization (WHO) grade 2+ bleeding occurred in 46% of 330 participants, with no difference between the TXA (44%) and placebo (47%) groups (p = 0.66). Overall, the most common sites of bleeding were oronasal (18%), skin (17%), gastrointestinal (11%), and genitourinary (11%). Among participants of childbearing potential, 28% experienced vaginal bleeding. Platelets ≤5000/μL and HCT < 21% (after adjusting for severe thrombocytopenia) were independently associated with increased bleeding risk (HR 3.78, 95% CI 2.16–6.61; HR 2.67, 95% CI 1.35–5.27, respectively). Allogeneic stem cell transplant was associated with nonsignificant increased risk of bleeding versus chemotherapy alone (HR 1.34, 95% CI 0.94–1.91).The overall rate of WHO grade 2+ bleeding was similar to previous reports, albeit with lower rates of gastrointestinal bleeding. Vaginal bleeding was common in participants of childbearing potential. Platelets ≤5000/μL remained a risk factor for bleeding. Regardless of platelet count, bleeding risk increased with HCT < 21%, suggesting a red blood cell transfusion threshold above 21% should be considered to mitigate bleeding. More investigation is needed on strategies to reduce bleeding in this population. [ABSTRACT FROM AUTHOR]

It is common practice in laboratories to store biological samples in ultra-low temperature (ULT) freezers. There is growing interest in raising the temperature of ULT freezers in order to save energy and reduce expenses, as energy conservation becomes increasingly important and sustainable laboratory practices gain popularity. In our laboratory, plasma samples are stored for three months for diagnostic purposes. We therefore took the opportunity to investigate the effect of two different storage temperatures (−70 °C vs −80 °C), on activated partial thromboplastin time (APTT), factor VIII (FVIII), international normalized ratio (INR) and factor VII (FVII) measurements on paired plasma samples collected from 26 individuals after three months of storage. Automated coagulation analysers CS-5100 and ACL TOP were used to perform the tests. We found no consistent difference between the two storage temperatures for any of the four coagulation parameters (all p-values > 0.05). We conclude that the temperature of ULT freezers used to store plasma samples for APTT, FVIII, INR, and FVII measurements can be safely increased from −80 to −70 °C without affecting the stability of the samples. [ABSTRACT FROM AUTHOR]

The pharmacokinetics, pharmacodynamics, immunogenicity, and safety of osocimab single doses in healthy Chinese and Japanese volunteers over 149 days were evaluated. Two phase 1 single‐blinded, placebo‐controlled studies with 27 Japanese and 50 Chinese participants were conducted. Osocimab was investigated with IV doses of 0.3, 1.25, and 2.5 mg/kg (Chinese study) and 0.3, 1.25, and 5.0 mg/kg (Japanese study), as well as SC doses of 3.0 and 6.0 mg/kg (Chinese study) and 6.0 mg/kg (Japanese study). The maximum plasma concentration was reached 1–3 h and 4–6 days after IV and SC administration, respectively. Osocimab exhibited a deviation from dose‐proportional pharmacokinetics for AUC but not Cmax; higher doses had higher apparent clearance and disproportionately lower total exposure. A slightly lower exposure was observed in Japanese compared with Chinese volunteers after IV administration; conversely, relatively higher exposure in Japanese volunteers with SC dosing was identified. Osocimab was associated with a dose‐dependent increase in activated partial thromboplastin time (aPTT). Maximal aPTT prolongations were observed 1–4 h and 2–6 days after IV and SC administration, respectively. Anti‐drug antibodies of low titer were detected in 1/9 (11.1%) Japanese volunteers administered placebo and 26/40 (65.0%) Chinese volunteers administered osocimab. Adverse events were reported in 8/18 (44.4%) Japanese and 28/40 (70.0%) Chinese volunteers who received osocimab, as well as in 1/9 (11.1%) Japanese and 6/10 (60.0%) Chinese volunteers who received placebo. In conclusion, data did not suggest a clear dose‐proportionality for osocimab within the investigated dose range. The effect of osocimab on aPTT was expected per its mechanism of action. Osocimab was generally well tolerated. [ABSTRACT FROM AUTHOR]

Background: The venom of Bothrops lanceolatus, a viperid species endemic to the Lesser Antillean Island of Martinique, induces thrombosis in a number of patients. Previous clinical observations indicate that thrombotic events are more common in patients bitten by juvenile specimens. There is a need to develop an experimental model of this effect in order to study the mechanisms involved. Methodology/Principal findings: The venoms of juvenile and adult specimens of B. lanceolatus were compared by (a) describing their proteome, (b) assessing their ability to induce thrombosis in a mouse model, and (c) evaluating their in vitro procoagulant activity and in vivo hemostasis alterations. Venom proteomes of juvenile and adult specimens were highly similar, albeit showing some differences. When injected by the intraperitoneal (i.p.) route, the venom of juvenile specimens induced the formation of abundant thrombi in the pulmonary vasculature, whereas this effect was less frequent in the case of adult venom. Thrombosis was not abrogated by the metalloproteinase inhibitor Batimastat. Both venoms showed a weak in vitro procoagulant effect on citrated mouse plasma and bovine fibrinogen. When administered intravenously (i.v.) venoms did not affect classical clotting tests (prothrombin time and activated partial thromboplastin time) but caused a partial drop in fibrinogen concentration. The venom of juvenile specimens induced partial alterations in some rotational thromboelastometry parameters after i.v. injection. When venoms were administered i.p., only minor alterations in classical clotting tests were observed with juvenile venom, and no changes occurred for either venom in rotational thromboelastometry parameters. Both juvenile and adult venoms induced a marked thrombocytopenia after i.p. injection. Conclusions/Significance: An experimental model of the thrombotic effect induced by B. lanceolatus venom was developed. This effect is more pronounced in the case of venom of juvenile specimens, despite the observation that juvenile and adult venom proteomes are similar. Adult and juvenile venoms do not induce a consumption coagulopathy characteristic of other Bothrops sp venoms. Both venoms induce a conspicuous thrombocytopenia. This experimental model reproduces the main clinical findings described in these envenomings and should be useful to understand the mechanisms of the thrombotic effect. Author summary: Envenomings by the viperid species Bothrops lanceolatus, endemic of the Caribbean Island of Martinique, are characterized by a thrombotic effect responsible for infarcts in various organs. Until now, no experimental in vivo models of this effect have been described. In this study, we developed a mouse model of thrombosis by using the intraperitoneal route of venom injection. The venom of juvenile specimens of B. lanceolatus induced the formation of abundant thrombi in the lungs, whereas the effect was much less pronounced with the venom of adult specimens. This difference in the ability of juvenile and adult venoms occurs despite both venoms having highly similar proteomic profiles. Both adult and juvenile venoms showed a weak in vitro procoagulant effect on plasma and fibrinogen, underscoring a thrombin-like (pseudo-procoagulant) activity. In vivo, the venoms did not affect the classical clotting tests (prothrombin time and activated partial thromboplastin time) but induced a partial drop in fibrinogen concentration and limited alterations in rotational thromboelastometry parameters when injected by the i.v. route. In contrast, few alterations of these parameters were observed after i.p. injection of venoms, in conditions in which thrombosis occurred, hence evidencing the lack of a consumption coagulopathy. After i.p. injection both venoms induced a pronounced thrombocytopenia. This experimental model reproduces some of the main clinical manifestations of envenoming by this species. This model can be used to identify the toxins responsible for the thrombotic effect, to study the mechanism(s) of thrombosis and to assess the preclinical efficacy of antivenoms and novel therapies. [ABSTRACT FROM AUTHOR]

Objective: This paper was aimed at unveiling the effect of low-molecular-weight heparin calcium (LMWH) combined with magnesium sulfate and labetalol on coagulation, vascular endothelial function, and pregnancy outcome in early-onset severe preeclampsia (EOSP). Methods: Pregnant women with EOSP were divided into the control group and the study group, each with 62 cases. Patients in the control group were treated with labetalol and magnesium sulfate, and those in the study group were treated with LMWH in combination with the control grou Blood pressure (systolic blood pressure [SBP] and diastolic blood pressure [DBP]), 24-h urine protein, coagulation indices [D-dimer (D-D), plasma fibrinogen (Fg), prothrombin time (PT), activated partial thromboplastin time (APTT), and prothrombin time (TT)], endothelial function [endothelin (ET-1) and nitric oxide (NO)], oxidative stress indices [oxidized low-density lipoproteins (ox-LDL), lipid peroxidation (LPO), superoxide dismutase (SOD), and malondialdehyde (MDA)], pregnancy outcome, and adverse effects occurred in the two groups were compared. Results: After treatment, lower SBP, DBP, and 24-h urine protein levels; lower Fg and D-D levels; higher PT, APPT, and TT levels; higher NO levels; lower ET-1 levels; lower ox-LDL, MDA, and LPO levels; higher SOD levels; and lower incidence of adverse pregnancy and adverse reactions were noted in the study group in contrast to the control group. Conclusion: EOSP patients given with LMWH combined with magnesium sulfate and labetalol can effectively reduce the patient's blood pressure and urinary protein level; improve coagulation function, oxidative stress, and vascular endothelial function indices; reduce the adverse pregnancy outcomes; and improve the safety of treatment. [ABSTRACT FROM AUTHOR]

Fucosylated chondroitin sulfate (FCS) was prepared from Bohadschia ocellata using protease hydrolysis. The structural characteristics of FCS were confirmed through chemical composition analysis using FTIR spectroscopy, 1H NMR, and 13C NMR. FCS from B. ocellata (FCS-Bo) exhibited an average molecular weight of approximately 122 kDa. The biological activities of FCS-Bo, including anticoagulant, anti-cancer, and Protein Tyrosine Phosphatase 1B (PTP1B) inhibition, were evaluated. FCS-Bo displayed potent anticoagulant properties, markedly extending activated partial thromboplastin time, prothrombin time, and thrombin time when compared to the heparin control. In anti-cancer bioactivity research, FCS-Bo efficiently inhibited colony formation in the colon cancer cell lines HCT-116, HT-29, and DLD-1, achieving inhibition rates of up to 65%. Additionally, FCS-Bo exhibited significant inhibition of PTP1B, with an IC50 as low as 0.0326 µg/mL, suggesting its potential for improving insulin sensitivity and managing conditions such as type 2 diabetes and obesity. [ABSTRACT FROM AUTHOR]

Background Septic melioidosis is associated with high mortality in resource-limited settings. The current study aims to find 28-d all-cause mortality predictors within 24 h of admission in melioidosis patients presenting to an emergency department. Methods This retrospective cohort study (2018–2022) included melioidosis patients divided into two groups based on their primary outcomes (28-d mortality). All the clinically relevant factors significant in univariate analysis were selected for binary logistic regression analysis. Those factors significant in logistic regression analysis were considered independent predictors of mortality. Results Of the 53 patients with melioidosis, the 28-d mortality of melioidosis patients admitted to the emergency department was 51% (n=27). Respiratory involvement, renal dysfunction, haemodynamic instability, elevated aspartate transaminase, elevated activated partial thromboplastin time, elevated CRP, elevated procalcitonin, decreased albumin, decreased absolute neutrophil count, decreased absolute lymphocyte count and use of piperacillin-tazobactam or azithromycin were significant predictors of mortality on univariate analysis. Vasopressor requirement (p=0.03) and low serum albumin level (0.041) at presentation were independent predictors of mortality. Conclusion Vasopressor requirement and low albumin levels at presentation in the emergency department are independent predictors of mortality. There is a need to create awareness among primary care physicians to enable early diagnosis and prompt initiation of treatment. [ABSTRACT FROM AUTHOR]

Aims: It is unclear whether activated partial thromboplastin time (aPTT) or anti‐Xa is more accurate for monitoring heparin anticoagulation in mechanical circulatory support (MCS) patients. This study investigates the relationship between aPTT and anti‐Xa in MCS patients and identifies predictors of discordance. Methods and results: aPTT and anti‐Xa were simultaneously measured in a prospective cohort of MCS patients receiving unfractionated heparin at a tertiary academic medical centre. Therapeutic aPTT and anti‐Xa levels were 60–100 s and 0.3–0.7 IU/mL, respectively, and concordance was defined as both levels being subtherapeutic, therapeutic, or supratherapeutic. To identify predictors of discordance, both a machine learning random forest model and a multivariate regression model were applied to patient demographics, device type, and 14 laboratory variables; 23 001 pairs of simultaneously measured aPTT/anti‐Xa were collected from 699 MCS patients. aPTT and anti‐Xa were concordant in 35.5% of paired observations and discordant in 64.5% (aPTT > antiXa 61.5%; aPTT < antiXa 3.0%). Discordance with a high aPTT relative to anti‐Xa (aPTT > antiXa) was associated with high INR, eGFR, and total bilirubin, as well as low platelets, haemoglobin, pre‐albumin, white blood cell count, and haptoglobin. Total artificial heart and durable ventricular assist devices were more likely to be associated with aPTT > anti‐Xa than temporary MCS devices. Conclusions: aPTT and anti‐Xa were frequently discordant in MCS patients receiving heparin anticoagulation. Clinical conditions common in MCS patients such as concurrent warfarin use, malnutrition, haemolysis, and thrombocytopenia, as well as durable type of MCS devices were associated with a high aPTT relative to anti‐Xa. [ABSTRACT FROM AUTHOR]

Background: Malaria is an intravascular parasitic-related blood disease that causes bleeding, coagulopathy, and thrombocytopenia. However, limited data shows the effect of Plasmodium species infection on basic coagulation parameters and platelet count. Thus, this study aimed to assess basic coagulation parameters and platelet count among malaria patients. Method: A cross-sectional study was conducted among 240 study participants (120 cases and 120 controls) from June 1, 2021, to February 30, 2022. A convenient sampling technique was employed to select study participants. The blood sample was collected by a trained laboratory technologist for platelet counts, prothrombin time (PT), partial thromboplastin time (PTT), international normalization ratio (INR), blood film, and serological testing. The collected data were analyzed in SPSS version 23. Data were analyzed by the Mann-Whitney U test, Kruskal Wallis H, and Spearman's rank-order correlation tests. Descriptive findings were presented through median, tables, and chart. In all cases, a P-value < 0.05 was considered statistically significant. Results: The percentage of mild, moderate, and high malaria parasitemia levels per microliter of blood was 21.7%, 20%, and 58.3%, respectively. The overall median malaria parasitemia was 10,304 per microliter of blood. Among malaria patients, 77.5%, 61.7%, and 51.7% had prolonged PT, INR, and APTT, respectively as compared to control. Moreover, 26.7% of Plasmodium-infected participants had mild thrombocytopenia as compared to the control group (P < 0.001). Conclusion: The value of PT, APTT, and INR were significantly elevated, whereas the level of platelet count was inversely reduced when the malaria parasitemia level increased as compared to controls (p < 0.001). [ABSTRACT FROM AUTHOR]

This article discusses the use of the ProtekDuo cannula for drainage in central venopulmonary-aortic ECMO during bilateral orthotopic lung transplantation. It presents a case report of a patient who successfully used the ProtekDuo cannula for an extended period of time. The article emphasizes the importance of organ donation and the challenges in meeting the demand for organs. It also addresses ethical considerations and the need for further research in organ transplantation. This resource provides valuable information for those interested in understanding the complexities and advancements in this field. [Extracted from the article]

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

Activated partial thromboplastin time (aPTT)-based clot waveform analysis (CWA) is a plasma-based global haemostatic assay. Elevated CWA parameters have been associated with hypercoagulability in venous thromboembolism, but its role in arterial thrombotic disease is uncertain. This study aims to explore the relationship between aPTT-based CWA and acute myocardial infarction (AMI) and its complications. In a retrospective cohort study of patients with AMI who underwent emergency cardiac catheterisation, pre-procedural aPTT and CWA parameters—min1, min2 and max2 were measured. These were compared against a control group of patients, consisting of patients who underwent elective orthopaedic and urological procedures. Within the AMI cohort, we also compared aPTT and CWA parameters of those with and without clinical complications of AMI. Results: Compared to controls (N = 109), patients with AMI (N = 214) had shorter aPTT (26.7 ± 3.3 s vs 27.9 ± 1.7 s, P < 0.001) and higher CWA parameters (min1: 6.11 ± 1.40%/s vs 5.58 ± 1.14%/s; min2: 0.98 ± 0.23%/s2 vs 0.90 ± 0.19%/s2; max2: 0.81 ± 0.20%/s2 vs 0.74 ± 0.16%/s2, all P ≤ 0.001). There was an increased incidence of elevated CWA parameters, in the AMI group, with odds ratio (OR) of 2.06 [95% CI 1.10–3.86], 2.23 (95% CI 1.18–4.24) and 2.01 (95% CI 1.07–3.77) for min1, min2 and max2, respectively. Similarly, elevated min1 and min2 were both individually associated with the presence of adverse outcomes of AMI, both with ORs of 2.63 (95% CI 1.24–5.59). Elevated aPTT-based CWA parameters are significantly associated with the occurrence of AMI and its complications. These findings identify the potential utility of CWA as risk and prognostic markers for AMI and warrants future works. [ABSTRACT FROM AUTHOR]

Introduction: Coronavirus disease 2019 (COVID-19) patients are predisposed to thrombotic events. COVID-19 coagulopathy can be associated with ADAMTS-13 (a disintegrin-like and metalloprotease with thrombospondin type I repeats 13) levels. ADAMTS-13, the cleaving protease of highly thrombogenic ultra-large von Willebrand Factor (vWF) multimers, was rarely investigated in COVID-19 patients and inconsistent results were obtained. We measured ADAMTS-13 levels of patients admitted to emergency department. Methodology: A prospective study was carried out with 180 individuals at the Emergency Department of Uşak Training and Research Hospital. The patients were divided into three groups: mild COVID-19 (group 2), severe COVID-19 with oxygen saturation below 94% (group 3), and control group (group 1). ADAMTS-13 levels were analyzed with an enzyme linked immunosorbent assay (ELISA) kit (SunRed, Shanghai, China). Demographic data, clinical findings, and routine laboratory test results (alanine aminotransferase (ALT), aspartate aminotransferase (AST), white blood cell, lymphocyte, platelet, C-reactive protein (CRP), lactate dehydrogenase (LDH), prothrombin time, international normalized ratio (INR), partial thromboplastin time, D-dimer, creatinine, urea) were evaluated. Results: ADAMTS-13 serum levels were slightly lower in groups 2 and 3 compared to the control group, with no significant difference between the ADAMTS-13 median values (p > 0.05). Groups 1 and 2 exhibited comparable outcomes. Group 3 demonstrated notably elevated levels of CRP, LDH, D-dimer, AST, ALT, creatinine; and decreased platelet counts and INR levels (p < 0.05). Conclusions: COVID-19-associated coagulopathy is still unclear. Based on our data, ADAMTS-13 levels cannot be used as a biomarker to help stratify patients' risks at the time of admission. [ABSTRACT FROM AUTHOR]

Objective: A large proportion of neonatal deaths not related to congenital anomalies are attributed to preterm births. The aim of this study was to compare the coagulation parameters in pregnant women with premature uterine contractions (PUC) who have preterm births with those who have term births and to determine the role of these coagulation parameters in predicting preterm delivery. Methods: Seventy-two pregnant women with PUC who applied to the Department of Obstetrics and Gynecology at the Okmeydanı Training and Research Hospital, University of Health Sciences, were included in the study. The coagulation parameters of 36 women who had preterm births were compared with those of 36 women who had term births. In analysing the findings of the study, statistical analyses were performed using IBM SPSS Statistics 22 (IBM SPSS, Turkey). The data were analyzed using Shapiro-Wilks, one-way, ANOVA, Tamhane's T2 test, and Student's t-test etc. Results: The activated partial thromboplastin time (aPTT) was significantly shorter in the preterm birth group (25.64±3.24 seconds) compared to the term birth group (26.153±2.49 seconds). International normalized ratio (INR) and prothrombin time (PT) levels were similar in both groups and subgroups. Fibrinogen levels were lower in the preterm birth group (397.56±54.67 mg/dL) compared to those who delivered at term (409.78±65.06 mg/dL). Fibrinogen levels were significantly lower in the preterm labor subgroup (388±50.72 mg/dL) compared to the preterm premature rupture of membranes (PPROM) subgroup (431±58.09 mg/dL). Conclusion: In this study, it was observed that the aPTT values in the preterm birth group were significantly shorter compared to the term birth group. Fibrinogen levels were found to be lower in the preterm birth group compared to those who delivered at term. Within the preterm labour subgroup, fibrinogen levels were significantly lower than those in the PPROM subgroup. INR and PT levels were similar across both groups and subgroups. The aPTT values were also similar between the preterm labour and PPROM subgroups. [ABSTRACT FROM AUTHOR]

Summary: Idiopathic hypereosinophilic syndrome (iHES) is a condition wherein persistent hypereosinophilia associated with end‐organ damage occurs without any known causes. Due to the rarity of the disease, insufficient knowledge has been accumulated. We therefore conducted a retrospective, multicentre, nationwide survey on iHES in Japan. A total of 57 patients were identified. For 43 patients who received any treatment, all cases were first treated with corticosteroids. An eosinophil percentage of less than 30% in the bone marrow and the absence of oedema were identified as factors associated with steroid dependency. The 5‐year overall survival was 88.2%, and five patients died during follow‐up; factors associated with worse overall survival were age >50, haemoglobin <12 g/dL, activated partial thromboplastin time >34 s, the presence of dyspnoea, the presence of thrombotic tendency and the presence of renal failure. Given the rarity of fatalities in our cohort, time‐to‐next‐treatment (TTNT) was further analysed; the presence of renal failure, splenomegaly and lung abnormalities were associated with worse TTNT. Our nationwide study not only demonstrated clinical characteristics and the outcome of patients with iHES but also for the first time revealed clinical factors associated with steroid dependency and duration of first‐line corticosteroid efficacy. [ABSTRACT FROM AUTHOR]

Objective: To compare the accuracy of a point‐of‐care coagulation analyzer (POCCA) with a reference laboratory coagulation analyzer (LabCA) and to evaluate for confounding factors that could alter the performance of the POCCA. Design: Prospective, observational study. Setting: Two university veterinary teaching hospitals. Animals: Forty‐three client‐owned dogs undergoing coagulation testing between April 2020 and June 2021. Methods: Samples were obtained from dogs undergoing coagulation testing as part of a diagnostic workup. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were measured on the POCCA and on the LabCA. PCV, platelet count, total plasma protein, hyperbilirubinemia, hemolysis, lipemia, and autoagglutination were recorded. Results: Moderate correlation was seen for PT and strong correlation was seen for aPTT between the POCCA and the LabCA (PT: 0.59, P < 0.0001; aPTT: 0.71, P < 0.0001). The POCCA results were consistent with normal or hypocoagulable samples for 30 of 38 PT and 33 of 37 aPTT results, as identified by the LabCA. Samples with PCV of 30%–55% were moderately correlated (PT: 0.63, P = 0.0004; aPTT: 0.63, P = 0.0003), but those outside that range were more likely to register an error message on the POCCA or provide disparate results. When hemolysis was present, there was a weak correlation between the POCCA and the LabCA for PT (rho: 0.38 [95% confidence interval: 0.19–0.76], P = 0.18) and a strong correlation for aPTT (rho: 0.86 [95% confidence interval: 0.62–0.95], P < 0.0001). Samples with hyperbilirubinemia were strongly correlated for PT (0.97, P = 0.002) but not for aPTT. Lipemia and autoagglutination were not observed. Conclusion: There was an acceptable correlation in patients with PCV within the manufacturer's recommended reference range; however, measurements on samples with PCV outside the reference range were inconsistent with the LabCA. Caution should be used when using the POCCA in patients with coagulopathy and anemia or other potential confounders. [ABSTRACT FROM AUTHOR]

Purpose: Anticoagulation therapy aims to improve the outcome of critically ill patients with severe COVID-19-associated pneumonia. Activated partial thromboplastin time (aPTT) is commonly used to maintain the target therapeutic range of continuous infusion of unfractionated heparin (UFH). The UFH infusion efficacy can be evaluated by determining the time in therapeutic range (TTR) using a modified Rosendaal method. The present study's primary aim was to evaluate TTR based on the aPTT in critically ill patients with severe forms of COVID-19 pneumonia and its influence on survival. The secondary aim was to evaluate the time spent above (TATR) and below the therapeutic range (TBTR). Patients and Methods: We performed a retrospective analysis of critically ill patients with COVID-19-associated pneumonia. All patients received a continuous infusion of UFH from the 2nd to 8th day since admission to the ICU. TTR, TATR, and TBTR were calculated using the modified Rosendaal method, and survival days were analyzed by regression (censored after 60 days). Results: Of 103 patients, the median TTR was 49% (IQR 38– 63%), TATR 11% (IQR 5– 20%), and TBTR 33% (IQR 22– 51%). The regression analysis indicated a positive impact of higher TTR and TATR on the number of survival days [β=0.598 (p=0.0367) and β=1.032 (p=0.0208), respectively] and a negative impact of higher TBTR [β=− 0.681 (p=0.0033)] on the number of survival days. Conclusion: Higher TTR and TATR were associated with better survival of critically ill patients with a severe course of COVID-19-associated pneumonia. Higher TBTR was associated with worse survival in these patients. [ABSTRACT FROM AUTHOR]

Objective: To analyse the demographic, clinical and laboratory data of Beninese patients with haemophilia. Method: A prospective survey was conducted in three different hospitals of Benin from April 2021 to March 2022, to analyse clinical and biological features of patients with haemophilia previously diagnosed or identified based on personal/family history. Results: A total of 101 patients were studied, 97 with haemophilia A and 4 with haemophilia B, including 26 new cases identified after family investigation. Their median age was 11 years, and the most frequent initial manifestations were cutaneous‐mucosal haemorrhages (29.70%) and post‐circumcision haemorrhages (25.74%). Previous joint bleedings were present in 77% of them, with an arthropathy in 65 cases, which particularly affected the knees (75%), elbows (41%) and ankles (29%). Factor VIII (FVIII) levels combined with activated partial thromboplastin time (APTT) values did not always enable, as would be expected, the distinction between severe and moderate haemophilia, since they were >1 IU/dl in 31 of 74 patients with APTT > 80 s, and between 1 and 2 IU/dl in 26 other cases with previous joint haemorrhages, including 18 with chronic arthropathy. Therefore, for these patients, severe haemophilia could not be excluded, and this uncertainty probably reflects technical difficulties affecting the pre‐analytical and analytical stages of the APTT and FVIII/IX assays. Conclusion: Our study proved that haemophilia is a significant reality in Benin, but also remains under‐diagnosed in some districts of the country. In addition, more reliable biological tests are needed in the future to better define the severity of the disease and improve treatment of patients. [ABSTRACT FROM AUTHOR]

It is known that, as a reason for the change in the blood hemostasis system in Alzheimer's disease (AD), it has been established that beta-amyloid (Aβ) protofibrils, affecting the composition of the blood and blood vessels, often accumulate in the vessels and cause structural changes in the composition of the blood. This article studied the effect of polyphenols eforbin and PC-6 on the system of coagulation and platelet hemostasis in healthy and modele AD blood of rats. To simulate AD, laboratory white outbred male rats, weighing 200 - 300 g, were used. Acute aluminum neurotoxicosis was caused by three subcutaneous injections of 0.2 mL of 10 % aluminum chloride solution into rats. Isolated platelets by centrifugation at 1,150 rpm for five minutes to sediment the red blood cells. Blood plasma coagulation in healthy rats and with AD in vitro was assessed using generally accepted tests: Activated partial thromboplastin time, prothrombin time, thrombin time. Platelet aggregation was recorded using the Born method. Experiments to study calcium-dependent processes in platelets used the fluorescent probe Fluo 3-AM to measure the amount of Ca2+ in the cytosol. Using the Grinkevich equation, the amount of cytosolic Ca2+ was calculated. In experiments, we studied the effect of polyphenols eforbin and PC-6 on the coagulation factors of the blood plasma of rats in a healthy and AD state using various APTT, TT and PT tests. The results showed that blood clotting time is prolonged under the influence of polyphenols. Acceleration of blood clotting time has been observed in AD. Also, when studying the effect of polyphenols on platelet aggregation, inhibition of aggregation induced by ADP and collagen was observed. Under AD conditions, spontaneous aggregation was observed. When studying the effect of polyphenols on calcium-dependent platelet processes, it was found that by inhibiting calcium channels, they reduce the amount of intracellular calcium in the cell. It has been established that the polyphenols used significantly inhibit the activation of the hemostatic system that occurs in AD under the influence of Aβ protofibrils.lt was observed that polyphenols can have an inhibitory effect on the activation of plasma factors, which leads to increased plasma coagulation and inflammation under the influence of Aβ protofibrils, internal and external blood coagulation mechanisms, and normalization of the plasma communication system. Polyphenols Eforbin and PC-6, under normal conditions and in AD, inhibit platelet aggregation induced by ADP. The inhibition of platelet aggregation by polyphenols suggests that it may be related to its ability to prevent the entry of Ca2+ into platelets by blocking Ca2+ channels located in the plasma membrane. [ABSTRACT FROM AUTHOR]

A 74-year-old male patient presented with anaemia, thrombocytopenia, and extensive haemorrhages over both thighs and back. A coagulation work-up revealed markedly elevated Prothrombin Time (PT) and activated Partial Thromboplastin Time (aPTT). Reduced functional values of fibrinogen as determined by clot-based assay (126.4 mg/dL), as well as factor V (17.5%) and factor X (27.8%), were noted. These abnormalities were corrected by mixing studies with normal plasma. Neoplastic plasma cells were seen in the bone marrow biopsy, while abdominal fat biopsies showed no amyloid deposition. Serum electrophoresis and immunofixation were positive for monoclonal gammopathy. The patient was diagnosed with multiple myeloma complicated by multiple acquired factor deficiencies. The patient showed a complete response within six months of treatment, which included bortezomib and cyclophosphamide. Multiple myeloma is a monoclonal proliferation of plasma cells that results in increased production of free immunoglobulin light chains, resulting in increased paraproteins. These paraproteins bind with and inhibit various clotting factors, resulting in their inactivation and depletion. Factor X deficiency in these cases is usually attributed to concomitant amyloidosis, whose fibrils bind to Factor X. However, these deficiencies can occur in the absence of amyloidosis as well. While various reports of this entity have highlighted isolated factor deficiencies including factors V, VII, IX, and X, multiple factor deficiency is a rare occurrence, with no other cases being reported from southern India. [ABSTRACT FROM AUTHOR]

Background: Nearly half of patients with diabetes experience diabetic peripheral neuropathy (DPN), resulting in a mere 53% survival rate within 3 years. Aberrations in coagulation function have been implicated in the pathogenesis of microvascular complications, prompting the need for a thorough investigation into its role as a contributing factor in the development and progression of DPN. Methods: Data were gathered from 1211 type 2 diabetes patients admitted to five centers from September 2018 to October 2022 in China. DPN was evaluated by symptoms and electromyography. Motor and sensory nerve conduction velocity (NCV) was appraised and the NCV sum score was calculated for the median, ulnar, and peroneal motor or sensory nerves. Results: Patients with DPN exhibited alterations in coagulation function. (i) Specifically, they exhibited prolonged thrombin time (p = 0.012), elevated fibrinogen (p < 0.001), and shortened activated partial thromboplastin time (APTT; p = 0.026) when compared to the control group. (ii) After accounting for potential confounders in linear regression, fibrinogen, and D‐dimer were negatively related to the motor NCV, motor amplitude values, and mean velocity and amplitude. Also, fibrinogen was associated with higher Michigan neuropathy screening instrument (MNSI) scores (β 0.140; p = 0.001). This result of fibrinogen can be validated in the validation cohort with 317 diabetic patients. (iii) Fibrinogen was independently associated with the risk of DPN (OR 1.172; p = 0.035). In the total age group, DPN occurred at a slower rate until the predicted fibrinogen level reached around 3.75 g/L, after which the risk sharply escalated. Conclusions: Coagulation function is warranted to be concerned in patients with type 2 diabetes to predict and prevent the occurrence of DPN in clinical practice. [ABSTRACT FROM AUTHOR]

Objective: To verify the administration of a new nano delivery system coated with Tirofiban on preventing early thrombosis in vein graft. Methods: Forty New Zealand white rabbits were randomly divided into five groups with eight rabbits in each group. The rabbits of all groups underwent jugular vein transplantation, except group I with only neck opening and closing operation. Vein grafts of group II were preprocessed by intravenous injection of normal saline; group III were preprocessed by tirofiban alone; group IV were preprocessed by unloaded nanoparticles of PLGA-PEG; group V were preprocessed by PLGA-PEG coated with tirofiban. Coagulation and platelet function of peripheral and vein graft blood were detected at 1, 2, 4, 12 h and 1, 3, 7, 10, 14 days after operation. Patency rate of vein graft and blood flow index were measured by vascular ultrasound at third, seventh, 10th, and 14th days after operation; two rabbits in each group were randomly sacrificed at the corresponding time of detection. Pathological differences of vein grafts were observed by HE stainin. Results: The patency rate of vein grafts in group V was significantly higher than that in group II to IV. The platelet and platelet aggregation rate in group V were inhibited in vein graft blood significantly. The post-operative PT and APTT in vein graft blood in group V were increased obviously while the FBG, D-dimer and FDP were significantly inhibited. Except group I, the lumen loss rate of vein grafts in group V was significantly lower than that in other groups, and vein graft blood in group V had a significant lower expression of platelet P-selectin and GP IIb/IIIa receptor than that in other groups. Conclusion: This study proves that PEG-PLGA coated with tirofiban can effectively prevent early vein graft stenosis from thrombosis by inhibition of platelet function, coagulation function. [ABSTRACT FROM AUTHOR]

Direct oral anticoagulants (DOACs) are increasingly used for the treatment of thrombosis. While inhibitors of factor IIa and factor Xa have shown effectiveness, the risk of bleeding remains a significant concern. Recently, direct factor XIa inhibitors—including asundexian and milvexian—have emerged as potential anticoagulation therapies, based on clinical observations that patients with factor XIa deficiencies seldom present with spontaneous bleeding tendencies. The interferences associated with DOACs in routine and specialised coagulation assays are well-described; however, the interferences associated with emerging FXIa inhibitors are largely uncharacterised. Here, we briefly report the impact of asundexian and milvexian in routine coagulation assays using in vitro plasma-based systems. Asundexian and milvexian induce concentration-dependent prolongations in APTT-based assays with curvilinear regressions, which may be suitable for the measurement of pharmacodynamic effects at peak levels ex vivo. We also report differential sensitivities of APTT-based assays—particularly at higher FXIa inhibitor concentrations—highlighting the clinical need for an extensive evaluation of interferences associated with FXIa inhibitors in coagulation assays. [ABSTRACT FROM AUTHOR]

Background/Aims: Ulcerative colitis (UC) is an incurable, relapsing-remitting inflammatory disease that increases steadily. Mucosal healing has become the primary therapeutic objective for UC. Nevertheless, endoscopic assessments are invasive, expensive, time-consuming, and inconvenient. Therefore, it is crucial to develop a noninvasive predictive model to monitor endoscopic activity in patients with UC. Methods: Clinical data of 198 adult patients with UC were collected from January 2016 to August 2022 at Huadong Hospital, China. Results: Patients with UC were randomly divided into the training cohort (70%, n=138) and the validation cohort (30%, n=60). The receiver operating characteristic curve value for the training group was 0.858 (95% confidence interval [CI], 0.781 to 0.936), whereas it was 0.845 (95% CI, 0.731 to 0.960) for the validation group. The calibration curve employed the Hosmer-Lemeshow test (p>0.05) to demonstrate the consistency between the predicted and the actual probabilities in the nomogram of these two groups. The decision curve analysis validated that the nomogram had clinical usefulness. Conclusions: The nomogram, which incorporated activated partial thromboplastin time, fecal occult blood test, β2-globulin level, and fibrinogen degradation products, served as a prospective tool for evaluating UC activity in clinical practices. [ABSTRACT FROM AUTHOR]

To assess the role of intraprostatic injection of tranexamic acid (TXA) in reducing blood loss during transurethral resection of the prostate (TURP). We conducted a randomized, controlled, double-blind trial involving 60 patients with benign prostatic hyperplasia aged 50-85 years, undergoing monopolar TURP. Patients' prostatic weights ranged from 50 to 80 g. They were divided equally into two groups: group I received an intraprostatic injection of 1 g of TXA (Cyklokapron) dissolved in 50 mL of 0.9 % saline at multiple sites, while group II (control) received a 60 mL saline injection. Comprehensive clinical assessments and standard laboratory tests, including screenings for TXA hypersensitivity, were performed for all patients. Group I exhibited significantly lower intraoperative blood loss and hemoglobin concentration in irrigation fluid immediately postsurgery and at the 6-hour postoperative mark compared to group II (P <.05). Coagulation parameters—activated partial thromboplastin time, prothrombin time, fibrinogen level, and thrombin clotting time—showed no significant differences between the groups preoperatively or at 6 and 24 hours postoperatively. No thromboembolic events or other complications were reported in either group. The intraprostatic injection of TXA during monopolar TURP is safe, with minimal adverse effects, and effectively reduces blood loss. The study was registered on ClinicalTrials.gov No (ID: NCT05913466). [ABSTRACT FROM AUTHOR]

Glioblastomas are among the most malignant tumors which, despite aggressive treatment, currently have an abysmal prognosis. These lesions are known to cause local and systemic perturbations in the coagulation system, leading to neoangiogenesis and a high risk of venous thromboembolism. Indeed, there have been multiple proposals of the coagulation system being a possible target for future treatment of these patients. However, nonselective anticoagulant therapy has proven suboptimal and leads to a significant increase of intracranial hemorrhage. Thus, recognizing factors that lead to hypercoagulation is considered paramount. Hyperglycemia is a well-known prothrombotic factor, a fact that has received little attention in neuro-oncology. We previously hypothesized that patients with brain tumors could be highly susceptible to iatrogenic glycemia dysregulation. Here, we analyzed the connection between glycated hemoglobin (HbA1c) and the routine coagulation markers (D-dimers, prothrombin time and activated partial thromboplastin time [aPTT]) in patients with de novo intracranial glioblastomas. Included in this study were 74 patients who were operated on in 2 hospitals: Clinical Hospital Dubrava, Zagreb, Croatia; University Hospital Center Split, Split, Croatia; and University Hospital de la Princesa, Madrid, Spain. We found a significant inverse correlation between HbA1c and aPTT (ρ = –0.379; P = 0.0009). We also found a significant inverse correlation between Ki67 immunoreactivity and aPTT (ρ = –0.211; P = 0.0082). No connection was found between HbA1c and D-dimers or prothrombin time. Our results suggest that patients with hyperglycemia, with a more proliferative glioblastoma, could in fact have their coagulation profile significantly disrupted, primarily through the intrinsic coagulation pathway. Such findings could have great clinical importance. Further research in this area could help to elucidate the vicious connection between glioblastomas and coagulation and to combat this deadly disease. [ABSTRACT FROM AUTHOR]

This document discusses the stability of coagulation assays in plasma samples. The study found that the stability of coagulation assays varied depending on the specific assay and storage conditions. For example, prothrombin time (PT) and fibrinogen (Fbg) were stable for 24 hours at room temperature (RT) only in plasma aliquots, while activated partial thromboplastin time (aPTT) showed a clinically significant increase after 4 hours at RT. The study also found that storage at 4-8 °C should be avoided for PT and aPTT testing. Overall, the results suggest that coagulation samples have longer stability than current guidelines indicate, with the exception of aPTT. [Extracted from the article]

Objective This study aimed to evaluate the usefulness and safety of gelatin–thrombin matrix sealants (GTMSs) in minimally invasive microscopic discectomy, a surgical procedure commonly used to treat lumbar disc herniation. Materials and Methods Out of 484 patients who underwent minimally invasive microscopic discectomy between April 2018 and December 2022, 35 patients with a history of surgery at the same level were excluded, resulting in a total of 449 patients included in the study. Among them, 316 patients were treated using GTMS, whereas 133 were treated using collagen-based absorbable local hemostatic agents. Patient characteristics, surgical duration, intraoperative blood loss, postoperative drainage volume, intraoperative dural injury, and incidence of postoperative epidural hematoma were analyzed and compared between the two groups. Results No significant differences in patient demographics were observed between the two groups, except for activated partial thromboplastin time and prothrombin time. Although there were no significant differences in the mean surgical time and intraoperative blood loss between the two groups, they tended to be shorter and less in the GTMS group (56.3 ± 20.2 vs. 58.2 ± 20.4 minutes [ p = 0.36] and 10.0 ± 15.4 vs. 11.8 ± 8.3 g [ p = 0.20]). The volume of postoperative drainage was significantly lower in the GTMS group than that in the comparison group (35.3 ± 21.8 vs. 49.5 ± 34.1 g [ p < 0.01]). There was a trend indicating a difference in the number of intraoperative dural injuries and the need for reoperation due to postoperative epidural hematoma (2 vs. 3 ± 20.4 minutes [ p = 0.21] and 1 vs. 2 [ p = 0.16]). Conclusion The use of a GTMS in minimally invasive microscopic discectomy appears to be beneficial in reducing postoperative drainage volume. It has also been shown that it may improve clinical outcomes such as intraoperative dural injury and postoperative epidural hematoma. Furthermore, further consideration of the medical economic impact is required. [ABSTRACT FROM AUTHOR]

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This was an open‐label, single‐dose, phase I study to characterize the pharmacokinetics (PKs), pharmacodynamics (PDs), and safety of edoxaban in pediatric subjects from birth to 18 years at risk for venous thromboembolism (VTE). Children requiring anticoagulant therapy were enrolled into 5 age cohorts (0 to < 6 months (N = 12), 0.5 to < 2 years (N = 13), 2 to < 6 years (N = 13), 6 to < 12 years (N = 13), and 12 to < 18 years (N = 15)) receiving tablet or oral suspension of edoxaban at doses expected to be equivalent to 30 or 60 mg once daily (q.d.) in adult subjects with VTE. Sixty‐six pediatric subjects were enrolled and completed the study. Edoxaban plasma concentration peaked between 1 and 3 hours and declined rapidly until 4–8 hours. The range of mean total apparent clearance across 5 age cohorts at low and high doses was 0.47 to 1.11 L/h/kg. The ranges of mean volume of central compartment and apparent peripheral volume were 2.31 to 3.59 L/kg and 1.92 to 4.14 L/kg, respectively. Across all age groups, the estimated median exposures were within the 0.5‐ to 1.5‐fold of the median area under the plasma drug concentration‐time curve (AUC) in adult subjects receiving corresponding doses (30 mg q.d. for low dose and 60 mg q.d. for high dose). In all age groups, PD parameters (prothrombin time, activated partial thromboplastin time, and anti‐Factor Xa activity) showed a linear PK‐PD relationship and were in line with previous adult data. The results support further evaluation of the pediatric doses in larger pivotal trials. [ABSTRACT FROM AUTHOR]

Thrombosis and inflammation are primary contributors to the onset and progression of ischemic stroke. The contactkinin pathway, initiated by plasma kallikrein (PK) and activated factor XII (FXIIa), functions bidirectionally with the coagulation and inflammation cascades, providing a novel target for therapeutic drug development in ischemic stroke. In this study, we identified a bat-derived oligopeptide from Myotis myotis (Borkhausen, 1797), designated LE6 (Leu-Ser-Glu-Glu-Pro-Glu, 702 Da), with considerable potential in stroke therapy due to its effects on the contact kinin pathway. Notably, LE6 demonstrated significant inhibitory effects on PK and FXIIa, with inhibition constants of 43.97 μmol/L and 6.37 μmol/L, respectively. In vitro analyses revealed that LE6 prolonged plasma recalcification time and activated partial thromboplastin time. In murine models, LE6 effectively inhibited carrageenan-induced mouse tail thrombosis, FeCl3-induced carotid artery thrombosis, and photochemically induced intracerebral thrombosis. Furthermore, LE6 significantly decreased inflammation and stroke injury in transient middle cerebral artery occlusion models. Notably, the low toxicity, hemolytic activity, and bleeding risk of LE6, along with its synthetic simplicity, underscore its clinical applicability. In conclusion, as an inhibitor of FXIIa and PK, LE6 offers potential therapeutic benefits in stroke treatment by mitigating inflammation and preventing thrombus formation. [ABSTRACT FROM AUTHOR]