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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.

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Abstract 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) 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.

Background: Early antimicrobial therapy is crucial regarding the prognosis of vertebral osteomyelitis, but early pathogen diagnosis remains challenging. Objective: In this study, we aimed to differentiate the types of pathogens in iatrogenic vertebral osteomyelitis (IVO) and native vertebral osteomyelitis (NVO) to guide early antibiotic treatment. Methods: A total of 145 patients, who had confirmed spinal infection and underwent metagenomic next-generation sequencing (mNGS) testing, were included, with 114 in the NVO group and 31 in the IVO group. Using mNGS, we detected and classified 53 pathogens in the 31 patients in the IVO group and 169 pathogens in the 114 patients in the NVO group. To further distinguish IVO from NVO, we employed machine learning algorithms to select serum biomarkers and developed a nomogram model. Results: The results revealed that the proportion of the Actinobacteria phylum in the NVO group was approximately 28.40%, which was significantly higher than the 15.09% in the IVO group. Conversely, the proportion of the Firmicutes phylum (39.62%) in the IVO group was markedly increased compared to the 21.30% in the NVO group. Further genus-level classification demonstrated that Staphylococcus was the most common pathogen in the IVO group, whereas Mycobacterium was predominant in the NVO group. Through LASSO regression and random forest algorithms, we identified 5 serum biomarkers including percentage of basophils (BASO%), percentage of monocytes (Mono%), platelet volume (PCT), globulin (G), activated partial thromboplastin time (APTT) for distinguishing IVO from NVO. Based on these biomarkers, we established a nomogram model capable of accurately discriminating between the two conditions. Conclusion: The results of this study hold promise in providing valuable guidance to clinical practitioners for the differential diagnosis and early antimicrobial treatment of vertebral osteomyelitis. [ABSTRACT FROM AUTHOR]

A 1-year-old mixed breed dog initially presented with marked ascites due to a low-protein transudate resulting from portal hypertension. Laboratory evaluation revealed non-regenerative anemia, lymphopenia, thrombocytopenia, evidence of hepatic insufficiency [hypoalbuminemia, decreased urea, increased post-prandial bile acids, prolonged activated partial thromboplastin time (aPTT)] and Ehrlichia canis infection. Approximately a week later, the dog was declining and was euthanized. On autopsy, multifocal hepatic granulomas and acquired portosystemic shunts (APSS) were seen. Imprint cytology revealed fungal hyphae and pyogranulomatous inflammation in the liver and brain. Disseminated Cladophialophora bantiana phaeohyphomycosis was diagnosed by histologic examination, culture and PCR. Immunosuppression due to ehrlichiosis is suspected to have predisposed this animal to fungal infection. To the authors' knowledge, this is the first report of C. bantiana in the West Indies. [ABSTRACT FROM AUTHOR]

Acquired hemophilia A (AHA) is an acquired bleeding disorder caused by neutralizing antibodies (inhibitors) against Coagulation Factor VIII (FVIII:C), causing sudden hemorrhagic symptoms (i.e., subcutaneous bleeding, intramuscular bleeding, and hematuria). Herein, this study is aimed at presenting a case of AHA diagnosed based on hematuria and reviewing patients who were diagnosed with AHA due to hematuria. A 67‐year‐old woman was referred to Atsugi City Hospital with painless gross hematuria that began 4 weeks before presentation. Contrast‐enhanced computed tomography (eCT) revealed an approximately 2 cm mass in the right renal pelvis, and the patient's activated partial thromboplastin time (APTT) was elevated (61.4 s). The day after the endoscopic biopsy, the patient was in shock due to a large retroperitoneal hematoma. Although her condition stabilized after intravenous radioembolization, she underwent emergency surgeries several times because of rebleeding within the next 3 weeks. At that time, APTT was more prolonged at 106.4 s, and the FVIII:C level was 2%. Mixing tests showed an upwardly convex curve after 2‐h incubation, indicating the presence of an inhibitor. Factor VIII inhibitor titer was ≥5.1 Bethesda unit (BU)/mL. A combined product of Plasma‐Derived Factors VIIa and X (pd‐FVIIa/FX), as second‐line hemostatic therapy, as well as cyclophosphamide (CYP), were administered after Recombinant Activated Factor VIIa (rFVIIa) had been ineffective. Following this, the Factor VIII inhibitor titer was undetectable, FVIII:C levels were restored, and APTT decreased to within the normal range. Gross hematuria was significantly alleviated. However, the patient died of cytomegalovirus and fungal infections due to prolonged immunosuppressive therapy. Although AHA diagnosed based on hematuria may have a better prognosis than others, there have been occasional cases with severe outcomes. APTT, detected upon initial hematological testing in patients with hematuria, may be a potential indicator of an existing AHA. [ABSTRACT FROM AUTHOR]

Background: In critically ill cases, CRRT is a renal replacement intervention. The most common reason why CRRT terminates prematurely (non-electively) is clotting in the extracorporeal circuit, more especially in the filter. Aim of work: To determine the frequency of thrombotic and hemorrhage complications throughout CRRT, the role of antithrombin III level monitoring, the type of anticoagulation, and the dose and laboratory tests utilized to monitor it. Method: The study was carried out on 58 children who were undergoing CRRT. The children underwent a comprehensive history-taking, assessment, CRRT prescription parameters and alterations, vascular access data, anticoagulation type, dose, and adjustment, as well as monitoring of antithrombin III levels. Furthermore, any extracorporeal circuit clotting or bleeding was documented. Results: Of the 58 sessions that were examined, 25 (43.1%) resulted in filter clotting. The indication was cured in 16 cases (27.6%), 8 cases (13.8%) resulted in the patient's mortality, and 9 cases (15.5%) had life-threatening bleeding. The remaining 33 cases (56.9%) were not terminated with filter clotting. Forty-one (70.7%) of studied sessions used unfractionated heparin as anticoagulation, 22.4% used heparin-protamine, 5.2% was not anticoagulated, and one circuit (1.7%) was anticoagulated using regional citrate. Filter clotting incidence was significantly related to activated partial thromboplastin time (a PTT) value at the end of sessions (P value = 0.000), and platelets count after 4 h of session initiation (P value = 0.048). Antithrombin III levels pre-heparin infusion less than 80 were found in patients who received higher doses of a heparin bolus dose, median dose 35 (IQR 20–35), this relation is statistically significant (P value = 0.042). Conclusion: In the 58 cases that were examined, the incidence of bleeding was 32.8%; however, 19% of the cases were not severe. The incidence of filter clotting was 43.1% in the study group. a PTT value at the end of sessions, and platelets count after 4 h could be predictors of thrombotic complications during CRRT, antithrombin III deficiency before sessions is a predictor of filter clotting. [ABSTRACT FROM AUTHOR]

Introduction: Sepsis and septic shock are one of the leading causes of death worldwide. Rapid and precise diagnosis and appropriate antibiotic therapy is necessary to reduce mortality and morbidity in patients with sepsis. Though several biomarkers and scoring systems have been evaluated, prognostic markers to quickly and precisely establish the diagnosis or prognosis of patients with sepsis and septic shock are yet to be evaluated. Red cell distribution width (RDW) is measure of erythrocyte size variability and heterogenicity RDW is a newly identified risk marker that has been reported in various studies to be a predictor for morbidity and mortality in sepsis and septic shock. The aim of the study is to determine the values red cell distribution width in patient with sepsis and septic shock. Methodology: This study was a descriptive study including 100 patients who satisfy the Inclusion and exclusion criteria at various medical college tertiary hospital centres, Karnataka. Result: In our study majority were in the age group 61-70yr (38.0%). 27% patients were in age group of 51-60yr, 19% were in age group of 41-50 yr., 13% were in age group of 30-40yr. and 3% were in age group 26-30yr. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the impact of the drug–drug interaction between rivaroxaban and amiodarone on the clinical outcomes in patients with non-valvular atrial fibrillation (NVAF), focusing on pharmacokinetic and pharmacodynamic (PK/PD) aspects. A prospective study enrolling 174 patients with NVAF who were treated with rivaroxaban was conducted. The patients were divided into two groups based on postoperative antiarrhythmic and anticoagulation strategies: the rivaroxaban group (Control group) and the rivaroxaban plus amiodarone group (Riv/Amio group). The trough plasma concentrations (Ctrough) of rivaroxaban, activated partial thromboplastin time (APTT), prothrombin time (PT), and the clinical outcomes between the two groups were compared. Patients receiving 20 mg of rivaroxaban in the Riv/Amio group had a higher concentration of rivaroxaban Ctrough than those in the Control group (p = 0.009). Furthermore, in patients with moderate to severe renal impairment, rivaroxaban Ctrough was significantly increased in the Riv/Amio group. There was no significant difference in PT and APTT between the two groups. Regarding the clinical outcomes, the combination of rivaroxaban and amiodarone medication was associated with a higher incidence of bleeding events (p = 0.041; HR = 2.83, 95% CI 1.05–7.66) and clinically relevant non-major bleeding (p = 0.021; HR = 3.65, 95% CI 1.21–10.94). Finally, independent risk factors for bleeding in NAVF patients treated with rivaroxaban were identified as its combination with amiodarone (p = 0.044; OR = 2.871, 95% CI 1.028–8.023). The combination of rivaroxaban and amiodarone led to changes in rivaroxaban pharmacokinetics and an elevated risk of bleeding events. Therefore, physicians prescribing rivaroxaban medications should assess the potential bleeding risk associated with the concurrent use of amiodarone, particularly in patients with renal impairment. [ABSTRACT FROM AUTHOR]

Context.--: The prothrombin time (PT) and activated partial thromboplastin time (APTT) are screening tests used to detect congenital or acquired bleeding disorders. An unexpected PT and/or APTT prolongation is often evaluated using a mixing test with normal plasma. Failure to correct ("noncorrection") prolongation upon mixing is attributed to an inhibitor, whereas "correction" points to factor deficiency(ies). Objective.--: To define an optimal method for determining correction or noncorrection of plasma mixing tests through an international, multisite study that used multiple PT and APTT reagents and well-characterized plasma samples. Design.--: Each testing site was provided 22 abnormal and 25 normal donor plasma samples, and mixing studies were performed using local PT and APTT reagents. Mixing study results were evaluated using 11 different calculation methods to assess the optimal method based on the expected interpretation for factor deficiencies (correction) and noncorrection (inhibitor effect). Misprediction, which represents the failure of a mixing study interpretation method, was assessed. Results.--: Percentage correction was the most suitable calculation method for interpreting PT mixing test results for nearly all reagents evaluated. Incubated PT mixing tests should not be performed. For APTT mixing tests, percentage correction should be performed, and if the result indicates a factor deficiency, this should be confirmed with the subtraction III calculation where the normal pooled plasma result (run concurrently) is subtracted from the mixing test result with correction indicated by a result of 0 or less. In general, other calculation methods evaluated that performed well in the identification of factor deficiency tended to have high misprediction rates for inhibitors and vice versa. Conclusions.--: No single method of mixing test result calculation was consistently successful in accurately distinguishing factor deficiencies from inhibitors, with between-reagent and between-site variability also identified. [ABSTRACT FROM AUTHOR]

There is an unmet clinical need for effective anticoagulant therapies for the management of thromboembolic diseases that are not associated with a relevant risk of bleeding. Asundexian (BAY 2433334) is an oral, direct, small‐molecule inhibitor of activated factor XI (FXIa). Phase I data from healthy Caucasian male participants indicated predictable pharmacokinetic (PK) and pharmacodynamic (PD) profiles and no clinically relevant bleeding‐related adverse events (AEs). Reported here are data from two phase I, randomized, placebo‐controlled, single‐ and multiple‐dose escalation studies of asundexian conducted in 60 healthy men: 24 Japanese and 36 Chinese. Baseline characteristics were comparable between the treatment groups. All treatment‐emergent AEs were mild, with no serious AEs or AEs of special interest reported. Systemic exposure to asundexian increased dose proportionally after single or multiple dosing, with relatively low accumulation following multiple once‐daily dosing in both Chinese and Japanese volunteers. Asundexian induced dose‐dependent prolongation of activated partial thromboplastin time and inhibition of FXIa activity, with no effects on prothrombin time or FXI concentration in Japanese participants. There were no clinically relevant interethnic differences in PK profile across the Japanese, Chinese, and Caucasian (data from the previous phase I study) participants and no clinically relevant difference in PD response between Japanese and Caucasian participants. [ABSTRACT FROM AUTHOR]

Background: According to the International Standard (ISO10993-4), a test model using human blood must be used for blood compatibility evaluation of medical devices. However, various safety investigations have reported outcomes from animal models simulating clinical conditions. Additionally, the validation of animal blood in blood compatibility assessment models is limited. In this study, the differences in the reactivity of different species to coagulation and complement, as well as the main mechanisms governing blood clot formation upon contact with medical devices, were examined. Moreover, it aimed to acquire information required to design a hemocompatibility evaluation model and interpret the results. Results: Rabbits, porcine, rhesus monkeys, and cynomolgus monkeys were exposed to one negative and two positive control substances, and variations in the partial thromboplastin time (PTT) were observed. The activity of the complement system was observed in accordance with the test method in ISO 10993-4. Although the PTT absolute values varied across animal species, the normalized PTT values—61% for rabbits, 66% for pigs, 63% for rhesus monkeys, and 65% for cynomolgus monkeys—exhibited no statistically significant differences. After reacting human and porcine sera with the material, the test model using human serum distinguished the positive and negative control candidates, whereas the test model using porcine serum could not discriminate them. Conclusions: These results suggest similar reactivity in blood coagulation across species after substance contact. However, complement system activity indicated a significant difference in reactivity between human and porcine blood. This finding will be useful in the design of a blood compatibility evaluation model for medical devices and interpretation of the results. [ABSTRACT FROM AUTHOR]

Background: Subacute thyroiditis (SAT) is characterized by profound inflammation and fluctuations in thyroid hormones which may affect the hemostasis balance. This study investigates sex-specific associations between thyroid status, inflammation and hemostasis biomarkers in SAT. Methods: We included 52 patients (40 women and 12 men) treated with non-steroidal anti-inflammatory drugs (NSAID) or methylprednisolone (MPS). Free thyroxine (fT4), thyroid stimulating hormone, C-reactive protein, complete blood count and routine hemostasis parameters were assessed. Results: Both men and women were in hyperthyroid state and had comparable levels of inflammatory biomarkers. A shortened activated partial thromboplastin time (aPTT) was observed in 16.7% of the men and 10% of the women (p = 0.562), and a shortened prothrombin time (PT) was observed in 33% of the men and 12.5% of the women (p = 0.094). In men, aPTT positively correlated with fT4 (r = 0.627; p < 0.05), while PT positively correlated with leukocyte-based inflammatory indices in women (p < 0.05). NSAID-treated patients had lower aPTTs and platelet counts than those treated with MPS (p < 0.05). Principal component analysis extracted "proinflammatory", "prothrombotic" and "antithrombotic" factors, but the "proinflammatory" factor was the independent predictor of elevated fT4 in women (OR = 2.705; p = 0.036). Conclusions: Our data demonstrated sex-specific associations of thyroid status and inflammatory biomarkers with hemostasis parameters in SAT. Routine hemostasis screening tests may help in monitoring the changes in the hemostasis system over the course of SAT. [ABSTRACT FROM AUTHOR]

The study investigated the biological properties of a composite material composed of poly(lactide) (PLA) and iron (Fe) produced by sputtering iron onto melt-blown poly(lactide) nonwoven fabrics. The research aimed to thoroughly understand the structure and properties of these materials and their potential applications in biomedicine. We conducted comprehensive chemical and structural analyses using techniques such as microscopic analysis, flame atomic absorption spectrometry (FAAS), and Brunauer–Emmett–Teller (BET) surface area analysis to precisely determine the properties of PLA-Fe materials. Additionally, we evaluated their impact on blood coagulation processes by measuring activated partial thromboplastin time (aPTT) and prothrombin time (PT). We also performed biological analyses on human peripheral blood mononuclear cells (PBM cells) including cell viability and DNA damage. Our results clearly demonstrate that PLA-Fe materials do not significantly influence blood coagulation mechanisms, as they only slightly prolong aPTT time and have no effect on PT. This suggests their potential in biomedical applications. Our results indicate the absence of cyto- and genotoxic properties of PLA-Fe materials against normal blood cells. In conclusion, the research findings suggest that the novel poly(lactide) and iron-sputtered nonwoven fabrics are promising tools in the field of biomedicine, offering potentially innovative therapeutic solutions for the treatment of wounds and injuries. [ABSTRACT FROM AUTHOR]

Introduction: Screening and postoperative intervention of breast tumors are critical for the effective diagnosis and treatment of disease development, and reliable diagnostic/screening methods become a key link. Objective: Thromboelastogram (TEG), routine platelet (PLT) count, and the coagulation function indicators in patients with different breast diseases were determined and analyzed to explore their predictive value in secondary bleeding disorders. Methods: A total of 131 patients with breast diseases, admitted to Jiangsu University Affiliated Hospital from January 2019 to December 2022, were selected as the research subjects. The detection items were analyzed using the receiver operating curve (ROC) after grouping for secondary bleeding disorders of patients with breast cancer. Results: The reaction (R) and the coagulation (K) times were lower in the malignant breast disease group, while the coagulation angle (a), maximum amplitude (MA), coagulation index (CI), fibrinogen (FIB), and D-dimer (D-D) were higher than those in the benign breast disease group. The t-tests proved that the MA and FIB values were statistically significant (p < 0.05) in the benign and malignant breast disease groups. The R and K in patients with breast diseases were positively correlated with the activated partial thromboplastin time (aPTT) and D-D, but were negatively correlated with PLT. The a angle was negatively correlated with aPTT and D-D, but was positively correlated with PLT. The MA for PLT function was positively correlated with FIB and PLT. CI was negatively correlated with aPTT, thrombin time (TT), and D-D, but was positively correlated with PLT. ROC curve analysis showed that the CI and a angle had a significant predictive value, whereas the correlation of the other indicators was relatively low. Conclusion: Coagulation tests showed significant differences in patients with breast cancer, differing from those with benign breast diseases. TEG combined with conventional coagulation indicators is potentially valuable for the prediction of secondary bleeding disorders in patients with breast cancer. [ABSTRACT FROM AUTHOR]

Milvexian, an oral activated Factor XI (FXIa) inhibitor, is in clinical studies where it may be combined with antiplatelet agents, including aspirin and/or clopidogrel, to prevent thromboembolic diseases. This phase I trial assessed safety, pharmacokinetics, and pharmacodynamics of milvexian coadministration with aspirin and/or clopidogrel in healthy participants through 3 drug-drug interaction studies using a 3-period, 3-treatment, crossover design. A total of 113 participants were randomized to receive milvexian (200 mg; twice daily for 5 days) or matched placebo coadministered with once-daily aspirin (325 mg for 5 days) and/or clopidogrel (Day 1: 300 mg; Days 2–5: 75 mg). Milvexian was safe and well tolerated, with and without aspirin and/or clopidogrel. Eight mild bleeding adverse events (AEs) were reported in 5 of 113 participants across various treatment arms. Peak and total exposures of milvexian were similar with or without clopidogrel and/or aspirin. Exposure-dependent prolongation of activated partial thromboplastin time and reduction of FXI clotting activity by milvexian were similar with coadministration of aspirin and/or clopidogrel. Milvexian, with or without coadministration of aspirin and/or clopidogrel, did not affect bleeding time or platelet aggregation. Administration of milvexian alone or with aspirin and/or clopidogrel was safe and well tolerated without increased incidence of AEs, including bleeding. Pharmacokinetic and pharmacodynamic effects of milvexian, including bleeding time, were similar with or without aspirin and/or clopidogrel. ClinicalTrials.gov Identifier: NCT03698513. [ABSTRACT FROM AUTHOR]

A hemostatic sponge prototype was successfully synthesized from fish gelatin as an alternative to mammalian gelatin; it was mixed with alginate in certain combinations, double cross-linked with calcium ions, and gamma irradiated at a dose of 20 kGy to improve the characteristics and effectiveness of its function as a local hemostatic agent. There were improvements in the physicochemical and mechanical properties, porosity index, absorption capacity, biodegradation properties, biocompatibility, and hemocompatibility of the fish gelatin–alginate sponge (FGAS) prototypes compared with the pure fish gelatin sponge. Hemostatic activity tests showed that the means for clotting time, prothrombin time, and activated partial thromboplastin time were shorter in the FGAS prototype than in the negative control, and there was no significant difference compared with the commercial gelatin sponge. The hemostatic mechanism of the FGAS prototype combined a passive mechanism as a concentrator factor and an active mechanism through the release of calcium ions as a coagulation factor in the coagulation cascade process. [ABSTRACT FROM AUTHOR]

Background Hemophagocytic lymphohistiocytosis (HLH) is considered a rare disease with high morbidity and mortality risks. Most research on this disease is conducted in pediatric settings. Therefore, this study aimed to describe the clinical characteristics, laboratory findings, and outcomes related to HLH in people living with human immunodeficiency virus (HIV)/AIDS) and disseminated histoplasmosis. Methods A retrospective and descriptive study was conducted in a tertiary hospital in México City from January 2018 to December 2022, including people living with HIV who had disseminated histoplasmosis confirmed through direct microbiological or immunological methods with an HScore ≥169 or who met 5 of the 8 HLH-2004 criteria. Results HLH occurred in 36.1% (n = 26) of patients with HIV and disseminated histoplasmosis; the majority were men (84.9%), and their mean age (standard deviation) was 30.19 (5.6) years. The most frequent clinical manifestations were hepatomegaly (100%), fever (96.2%), and dyspnea (84.6%). The most common biochemical changes were hyperferritinemia (100%), elevated lactate dehydrogenase (100%), and bicytopenia (61.5%). Partial thromboplastin time (P =.012) and prothrombin time (P =.004) were associated with the 30-day mortality rate, and the 30-day survival rate was 65.4%. Conclusions We detected a high frequency of HLH; therefore, we encourage physicians to use diagnostic prediction tools (HLH-2004 and HScore criteria) in each reassessment for timely detection. [ABSTRACT FROM AUTHOR]

Introduction. Continuous renal replacement therapy (CRRT) is effective in treating acute kidney injury (AKI), but it requires anticoagulants. The study was conducted to compare the anticoagulant effect of low-molecular-weight heparin (LMWH) sodium and sodium citrate on AKI patients treated by CRRT. Methods. The medical records of 150 severe AKI patients treated by CRRT in the Second Affiliated Hospital of Hainan Medical College (China, Hainan) from January 2020 to January 2023 were analyzed retrospectively. LMWH sodium was administered as an anticoagulant for 72 patients in the control group, and the remaining 78 receiving sodium citrate were enrolled into the observation group. Outcomes compared between groups included coagulation indices, inflammatory factors and renal function indices prior and post therapy, filter lifespan and adverse reactions. Results. Post therapy, in contrast to the control group, the observation group showed notably lower prothrombin time (PT) and activated partial thromboplastin time (APTT) levels and a notably higher platelet (PLT) level (P < .05) and presented notably lower C-reactive protein (CRP) and interleukin-6 (IL-6) levels (P < .05). In contrast to the control group, the observation group experienced a notably longer filter service life and a notably lower total incidence of adverse reactions (P < .05). Conclusion. Sodium citrate had a better anticoagulant effect than LMWH for severe AKI patients treated by CRRT, improving renal function and filter longevity with fewer adverse effects. [ABSTRACT FROM AUTHOR]

Objective: Patients with ovarian cancer have a high risk of developing thrombosis. We aimed to investigate laboratory parameters associated with deep vein thrombosis (DVT) in patients treated for ovarian cancer. Methods: We retrospectively analyzed pre-operation laboratory data of patients with ovarian cancer for DVT at the National Cancer Center, Korea, between January 2000 and February 2021. The test items were white blood cell count, absolute neutrophil count (ANC), hemoglobin, platelets, monocytes, serum glucose, CA125, D-dimer, fibrinogen, prothrombin time (PT), activated partial thromboplastin time (aPTT), and body mass index (BMI). Differences between patients with and without DVT were compared with Wilcoxon rank-sum test. We analyzed the variables using logistic regression. Items with significant odds ratios were included in multivariate logistic regression. Significant variables were selected using backward elimination. Items were further categorized based on reference ranges. Univariate and multivariate analyses were performed to identify items with abnormal values associated with DVT. Results: From 3,147 patient samples analyzed, 286 (9.1%) patients with DVT were selected. Differences between patients with vs without DVT were statistically significant for hemoglobin, monocyte, serum glucose, CA125, PT, aPTT, fibrinogen, D-dimer, and BMI. After univariate and multivariate analysis, monocyte, glucose, and PT remained significant. Among the categorical variables, low hemoglobin, high monocyte, high CA125, prolonged PT, and high BMI remained significant after univariate and multivariate analysis. Conclusion: Pre-operation laboratory data of low hemoglobin, high monocyte percentage, high serum glucose, high CA125, prolonged PT, and high BMI were associated with DVT. [ABSTRACT FROM AUTHOR]

This study aimed to assess the correlation between neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and systemic immunoinflammatory index (SII) levels, and short-term prognosis in patients with acute ischemic stroke (AIS) undergoing intravenous thrombolysis with alteplase (rt-PA), and to develop a nomogram model for short-term prognosis prediction. The study collected data from cases of first-episode ischemic stroke treated with intravenous thrombolysis at Wuxi People's Hospital. Patients were categorized into either a poor prognosis group (n = 78) or a good prognosis group (n = 119) based on the modified Rankin Rating Scale score 30 days post-treatment. The results showed that peripheral blood levels of NLR, PLR and SII were significantly elevated in the poor prognosis group compared to the good prognosis group (p < 0.05). Receiver operating characteristic (ROC) curve analysis revealed that the area under the curves (AUC) of NLR, PLR and SII for predicting poor prognosis of intravenous thrombolytic therapy in AIS patients were 0.674, 0.770 and 0.779, respectively. Multivariate regression analysis identified blood glucose concentration, pre-thrombolysis National Institutes of Health Stroke Scale (NIHSS) score, prothrombin time (PT), activated partial thromboplastin time (APTT), and SII as independent influencing factors for poor prognosis of intravenous thrombolytic therapy in AIS patients (p < 0.05). A nomogram model based on these seven independent influencing factors yielded an AUC of 0.929, with calibration curve and Hosmer- Lemeshow test (χ² = 2.654, p = 0.954) confirming the model's good fit. Decision analysis curves demonstrated the clinical benefit of utilizing predictive models in aiding clinical decision-making. In conclusion, peripheral blood systemic inflammatory marker SII was identified as a risk factor for poor short-term prognosis in patients treated with intravenous thrombolysis. The constructed nomogram incorporating inflammatory clinical features exhibited efficient and promising clinical utility in predicting early prognosis of AIS patients treated with rt-PA thrombolysis. [ABSTRACT FROM AUTHOR]

The coagulation profile report is crucial for assessing blood clots and diagnosing various bleeding disorders. Key metrics in these reports include the international normalized ratio (INR), activated partial thromboplastin time (APTT), platelet count, and fibrinogen levels. Traditionally, these reports have been delivered through paper-based methods, which often face significant challenges such as human errors, delays in distribution, and limited accessibility. To address these issues, this preliminary investigation explores integrating technology into the reporting process for coagulation profiles. By leveraging a design-thinking approach, the study aims to understand the needs and preferences of stakeholders and users. This approach includes creating personas to represent different user types, mapping their experiences through empathy and journey maps, and generating and testing ideas through ideation and prototyping. The core objective of the study is to develop a mobile application that simplifies and enhances the reporting process of coagulation profiles. This application is designed to integrate seamlessly with Electronic Medical Record (EMR) systems, providing real-time notifications to healthcare providers when laboratory results are available. The proposed solution aims to improve the timeliness and accuracy of reporting, facilitating better patient care and more efficient workflows. The paper details the components of this solution, including the prototype design and the validation procedures used to ensure its effectiveness. The study seeks to revolutionize how coagulation profiles are documented and communicated in healthcare by adopting a digital reporting system. [ABSTRACT FROM AUTHOR]

Purpose: We previously proposed a new concept, the "critical unit", which covers the structural integrity and function of mitochondria and endothelium. Injury of the critical unit plays a key role in the development of critical illnesses. High levels of inflammation may lead to abnormalities of the critical unit, which is an important mechanism for critical illnesses, and both inflammation and critical unit dysfunction may affect patient prognosis. Here we evaluated the correlation between interleukin-6 (IL6) and the critical unit biomarkers in critically ill patients and the impact of both on prognosis. Patients and Methods: This study included adult patients admitted to the intensive care unit for various reasons from January 1st to May 31st, 2023. Baseline characteristics, intensive care unit parameters, and laboratory test and outcome data were obtained from the electronic medical records system. Critical unit parameters were measured using polymerase chain reaction and enzyme-linked immunosorbent assay methods. Correlations were examined between IL6, critical unit parameters, and various outcomes. Results: In critically ill patients, IL6 was closely associated with all the critical unit biomarkers (activated partial thromboplastin time, sphingosine 1-phosphate, mitochondrial DNA, mitochondrial fission 1, and Parkin) and the prognoses of patients. A nomogram was constructed using the critical unit biomarkers to predict the in-hospital mortality of critically ill patients. The area under the curve for the mortality prediction model was 0.708. In sensitivity analyses, the predictive effect was better in the non-surgery and tumor groups compared with the surgery and non-tumor groups, with area under the curve values of 0.885 and 0.891, respectively. Conclusion: Our study innovatively integrated mitochondrial and endothelial markers in the critical unit to comprehensively evaluate patient prognosis, which may be a trend in the future assessment of critically ill patients. There are few such studies, and ours may promote the progress of related research. [ABSTRACT FROM AUTHOR]

Background Clot waveform analysis can be used to evaluate clot formation profiles. This waveform can be obtained from activated partial thromboplastin time (APTT) assays without additional reagents and shows different patterns in hemophilia patients with coagulation factor VIII (F VIII) deficiency or abnormality. Objective To determine the clot wave pattern and its process in clot formation phases (pre-coagulation, coagulation, and post-coagulation) in normal and hemophilia A subjects, analyze for possible correlations between clot wave parameters and F VIII activity, and obtain the pattern of coagulation curves in hemophilia subjects as a step to assess clot waveform analysis as a possible screening tool for hemophilia. Methods In this cross-sectional study, we performed clot wave analysis in 145 adult and pediatric subjects with hemophilia to obtain the clot wave pattern in this condition. Clot wave analysis was also done in 160 subjects with normal hemostasis to obtain reference clot wave parameters. Results In this study, the starting point of coagulation phase in normal subjects was between 30-40 seconds, with a shorter precoagulation phase and steeper slope. Hemophilia patients had a longer pre-coagulation phase and flatter slope, especially in severe hemophilia A patients, who had longer and more variable coagulation starting points (P<0.001). The absolute values of maximum coagulation velocity (Min1), maximum coagulation acceleration (Min2), and maximum coagulation deceleration (Max2) of hemophilia A patients were also lower than those of normal hemostasis patients, with lower absolute value seen in severe than in mild-moderate hemophilia A patients. A moderate correlation was found between Min1, Min2, and Max2 with F VIII activity (P<0.001). Conclusion Clot wave analysis may be considered as a method for screening hemophilia patients to distinguish mild-moderate and severe hemophilia A patients in health facilities that lack the ability to perform F VIII assays. [ABSTRACT FROM AUTHOR]

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This study investigated the biochemical and microbiological properties of Cotton–Copper composite materials obtained using magnetron sputtering technology. Copper particles were precisely distributed on the fabric surface, ensuring free airflow without the need to create additional layers. The Cotton–Copper composite materials were subjected to physiochemical and biological investigations. The physiochemical analysis included the elemental analysis of composites (C, N, O, S, Cu) and analyses of their microscopic and surface properties (specific surface area and total pore volume). The biological investigations consisted of microbiological and biochemical–hematological tests, including evaluation of the activated partial thromboplastin time and prothrombin time. Experiments showed significant effectiveness of the antibacterial material against representative strains of fungi and bacterial species. We also demonstrated the ability of the cotton–copper material to interact directly with the plasmid DNA. [ABSTRACT FROM AUTHOR]

The research aimed to enhance the aqua-jet/spunlace cellulose nonwoven fabric by deposition of copper coating by magnetron sputtering technology. Plasma technology facilitated the efficient distribution of copper particles on the surface of the cellulose nonwoven fabric, while maintaining free airflow and eliminating the need for additional layers. New cellulose-copper composites exhibit potential in biomedical applications, while minimizing their impact on biological processes such as blood plasma coagulation. Consequently, they can be utilized in the production of dressings, bandages, and other medical products requiring effective protection against bacterial infections. The cellulose-copper composite material was subjected to the physiochemical and biological investigations. The physiochemical analysis included the elemental analysis of composites, their microscopic analysis and the surface properties analysis (specific surface area and total pore volume). The biological investigations consisted of biochemical-hematological tests including the evaluation of the activated partial thromboplastin time and pro-thrombin time. Biodegradable materials based on cellulose nonwoven fabrics with the addition of copper offer a promising alternative to conventional materials. Their innovative properties, coupled with environmental friendliness and minimal impact on biological processes, offer vast application possibilities in healthcare and the production of hygiene products. [ABSTRACT FROM AUTHOR]

Data on the pathophysiological mechanisms of hemostatic alterations in the thrombotic events that occur during Ramadan intermittent fasting (RIF), particularly in the natural coagulation inhibitors, are very limited. Thus, our objective was to evaluate the effect of RIF on the natural anticoagulants level, antithrombin, protein C, and total and free protein S (PS) in healthy participants. Participants were divided into two groups. Group I consisted of 29 healthy fasting participants whose blood samples were taken after 20 days of fasting. Group II included 40 healthy non-fasting participants whose blood samples were taken 2–4 weeks before the month of Ramadan. Coagulation screening tests including prothrombin time (PT), activated partial thromboplastin time (APTT) and plasma fibrinogen level, natural anticoagulants; antithrombin, protein C, free and total PS and C4 binding protein (C4BP) levels were evaluated in the two groups. High levels of total and free PS without change in antithrombin, protein C, and C4BP levels were noted in the fasting group as compared with non-fasting ones (p < 0.05). PT and APTT showed no difference between the two groups. However, the fibrinogen level was higher in the fasting group. In conclusion, RIF was found to be associated with improved anticoagulant activity in healthy participants, which may provide temporal physiological protection against the development of thrombosis in healthy fasting people. [ABSTRACT FROM AUTHOR]

The paper presents the study concerning the preparation and physio-chemical and biological properties of wool–copper (WO-Cu) materials obtained by the sputter deposition of copper onto the wool fibers. The WO-Cu material was subjected to physio-chemical and biological investigations. The physio-chemical investigations included the elemental analysis of materials (C, N, O, S, and Cu), their microscopic analysis, and surface properties analysis (specific surface area and total pore volume). The biological investigations consisted of the antimicrobial activity tests of the WO-Cu materials against colonies of Gram-positive (Staphylococcus aureus) bacteria, Gram-negative (Escherichia coli) bacteria, and fungal mold species (Chaetomium globosum). Biochemical–hematological tests included the evaluation of the activated partial thromboplastin time and pro-thrombin time. The tested wool–copper demonstrated the ability to interact with the DNA in a time-dependent manner. These interactions led to the DNA's breaking and degradation. The antimicrobial and antifungal activities of the WO-Cu materials suggest a potential application as an antibacterial/antifungal material. Wool–copper materials may be also used as customized materials where the blood coagulation process could be well controlled through the appropriate copper content. [ABSTRACT FROM AUTHOR]

The blood coagulation test is an indispensable test for monitoring the blood coagulation and fibrinolysis functions. Currently, activated partial thromboplastin time (APTT) is the most widely used approach to coagulation testing. However, APTT reagents need to be optimized due to the fact that they are unstable, highly variable, and cannot be easily controlled. In this study, we created apoptotic cell-inspired methacryloyloxyethyl phosphorylserine (MPS) particles for blood coagulation as an alternative to conventional APTT reagents. Particle size could be controlled by changing the concentration of the polymer. The blood coagulation ability of particles was stable at different environmental temperatures. Moreover, the procoagulant activity could be enhanced by increasing the concentration to 0.06 mg/mL and reducing the size of the particles to around 900 nm. Fibrin clotted by particles showed no significant difference from that formed by APTT regent Actin FSL. We propose that MPS particles are a potential alternative to Actin FS for the application of blood coagulation tests. [ABSTRACT FROM AUTHOR]

The study focused on analyzing the antioxidant properties of extracts from red palm weevil larvae Rhynchophorus ferrugineus, obtained using hexane, n-butanol, dichloromethane, and diethyl ether. Additionally, the anticoagulant effects of these extracts were evaluated through activated partial thromboplastin time (APTT) and prothrombin time (PT) assays. Results showed that the hexane, n-butanol, dichloromethane, and diethyl ether extracts from Rh. ferrugineus larvae exhibited antioxidant activity comparable to ascorbic acid, with IC50 values of 142.67, 122.24, 231.77 and 74.95 µg/ml, respectively, compared to 3.16 µg/ml for ascorbic acid. Also, the anticoagulant activity of Rh. ferrugineus (larvae) tested extracts using APTT assay showed 33.8, 44.3 and 50.9 sec. At 25, 50 and 75 µg/ml of hexane extract, respectively. Meanwhile, Rh. ferrugineus n-butanol extract recorded 46.9, 57.2 and 65.5 sec. At the same concentrations. Also, dichloromethane and diethyl ether recorded anticoagulant activity reached 31.2, 40.6, 48.7 and 44.3, 52.9, 62.1 sec. at 25, 50 and 75 µg/ml, respectively, vs. 59.8, 86.2 and 109.7 sec. For the Heparin sodium salt, use the same concentrations. Generally, all Rh. ferrugineus larval extracts tested proved to be antioxidant agents. The anticoagulant potential of Rh. ferrugineus tested extracts were weaker than those of heparin and needed more concentration to reach the commercial anticoagulant (Heparin sodium salt) in both assays (APTT and PT). [ABSTRACT FROM AUTHOR]