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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]

Thrombosis, a prevalent condition, can provoke severe health issues like acute coronary syndrome (ACS), deep vein thrombosis (DVT), and pulmonary embolism (PE). The rising incidence of these diseases annually significantly impacts patient wellbeing and poses a substantial burden on healthcare systems. Recombinant neorudin is a developing anticoagulant drug for thrombotic diseases whose phase I clinical trials has been completed. The distribution pattern of it and its active metabolite, hirudin, in thrombi, blood surrounding the thrombus and peripheral blood remains uncertain. This study explored their distribution using a rat arteriovenous bypass thrombosis model, revealing higher neorudin levels in blood surrounding the thrombus and elevated hirudin concentrations in thrombus. Recombinant neorudin significantly increased Thrombin Time (TT) in both plasma surrounding the thrombus and peripheral blood, and reduced the wet weight of the thrombus. The results above demonstrated the anticoagulant and antithrombotic efficacy of recombinant neorudin in vivo. Give the distribution pattern of neorudin and hirudin, we hypothesized that neorudin was cleaved at the site of thrombus formation to produce hirudin, leading to the rapid accumulation of hirudin within local thrombi and resulting in a higher concentration inside the thrombus. This insight was crucial for understanding the action mechanisms of anticoagulants in thrombosis management and provided a valuable guidance for therapeutic strategies in treating thrombotic diseases. [ABSTRACT FROM AUTHOR]

Background: Hemophagocytic Lymphohistiocytosis (HLH) carries a high mortality rate. Current existing risk-evaluation methodologies fall short and improved predictive methods are needed. This study aimed to forecast 30-day mortality in adult HLH patients using 11 distinct machine learning (ML) algorithms. Methods: A retrospective analysis on 431 adult HLH patients from January 2015 to September 2021 was conducted. Feature selection was executed using the least absolute shrinkage and selection operator. We employed 11 ML algorithms to create prediction models. The area under the curve (AUC), sensitivity, specificity, positive predictive value, negative predictive value, F1 score, calibration curve and decision curve analysis were used to evaluate these models. We assessed feature importance using the SHapley Additive exPlanation (SHAP) approach. Results: Seven independent predictors emerged as the most valuable features. An AUC between 0.65 and 1.00 was noted among the eleven ML algorithms. The gradient boosting decision tree (GBDT) algorithms demonstrated the most optimal performance (1.00 in the training cohort and 0.80 in the validation cohort). By employing the SHAP method, we identified the variables that contributed to the model and their correlation with 30-day mortality. The AUC of the GBDT algorithms was the highest when using the top 4 (ferritin, UREA, age and thrombin time (TT)) features, reaching 0.99 in the training cohort and 0.83 in the validation cohort. Additionally, we developed a web-based calculator to estimate the risk of 30-day mortality. Conclusions: With GBDT algorithms applied to laboratory data, accurate prediction of 30-day mortality is achievable. Integrating these algorithms into clinical practice could potentially improve 30-day outcomes. [ABSTRACT FROM AUTHOR]

Background: Cardiopulmonary bypass (CPB) causes coagulation disorders after surgery. This study aimed to compare the coagulation parameters after congenital cardiac surgery with miniaturised CPB (MCPB) versus conventional CPB (CCPB). Methods: We gathered information about children who underwent cardiac surgery between 1/1/2016 and 12/31/2019. Using propensity score–matched data, we compared the coagulation parameters and postoperative outcomes of the MCPB and CCPB groups. Results: A total of 496 patients (327 with MCPB, 169 withCCPB) underwent congenital cardiac surgery, and 160 matched pairs in each group were enrolled in the analysis. Compared with CCPB children, MCPB children had a lowermean prothrombin time (14.9 ± 2.0 vs 16.4 ± 4.1; p < 0.001)and international normalised ratio (1.3 ± 0.2 vs. 1.4 ± 0.3; p < 0.001), but higher thrombin time (23.4 ± 20.4 vs 18.2 ± 4.4; p = 0.002). The CCPB group had greaterperioperative changes inprothrombin time, international normalised ratio, fibrinogen, and antithrombin III activity (all p < 0.01) but lower perioperative changesin thrombin time (p = 0.001) thanthe MCPB group. Ultra-fasttrack extubation and blood transfusionrates, postoperative blood loss, and intensive care unitlength of stay were considerably decreased in the MCPB group. There were no considerable intergroup differences in the activated partial thromboplastin time or platelet count. Conclusions: Compared with CCPB, MCPB was associated with lower coagulation changes and better early outcomes, including shorter intensive care unit stay and less postoperative blood loss. [ABSTRACT FROM AUTHOR]

Pilot tends to have a high prevalence of dyslipidemia. The present study aimed to identify key factors of pilot hyperlipidemia through thorough analysis of physical examination data, and to provide pilot-targeted health guidance to manage hyperlipidemia risks. The physical examination data of 1,253 pilot inpatients from January 2019 to June 2022, were evaluated and divided into two groups based on whether or not the pilot had hyperlipidemia. A total of three multivariate analysis models including logistic model, multilevel model and boosting propensity score were applied to find the risk factors of pilot hyperlipidemia. In the group of pilots with hyperlipidemia, four risk factors, including thrombin time, carbohydrate antigen 199, lymphocyte count and rheumatoid factor, were significantly different from pilots without hyperlipidemia, which might be positively associated with the incidence of hyperlipidemia. In future studies regarding pilots, whether hyperlipidemia is connected to abnormalities in thrombin time, carbohydrate antigen 199 and rheumatoid factor should be further explored. Based on the findings of the present study, pilot health management should be more refined and personalized, and attention should be paid to the risk factors of hyperlipidemia including diet and lifestyle. [ABSTRACT FROM AUTHOR]

Wounds that influence the liver are shockingly normal in more youthful individuals. This condition might introduce itself clinically as subclinical hepatitis, intense hepatitis, persistent hepatitis, remunerated liver constant infection, decompensated liver cirrhosis, intense liver disappointment, or intense on persistent liver disappointment. These indications are possible. A liver capability test would frequently take a gander at various different biochemical markers, including complete bilirubin, direct bilirubin, Serum glutamic oxaloacetic transaminase, Serum glutamate pyruvate transaminase, egg whites, supportive of thrombin time, and gamma-glutamyl transferase. Novel biomarkers are presently effectively accessible as an immediate outcome of current specialized leap forwards and applications. The utilization of creature models is the beginning stage for the examination of these biomarkers, with the concentrate then, at that point, moving to human subjects. They can offer data that is demonstrative as well as data about the visualization. They give some enlightening data on the histological condition of the liver. Notwithstanding, they are restricted by the circumstances that they think of themselves as in. By directing an examination of marks of liver harm in youngsters, this exploration shows new conceivable outcomes and philosophies for the determination of liver sickness in kids. Concentrates on that focus on individual biomarkers as a restorative place of section are something that might be plausible to investigate not long from now. Hepatology is a subspecialty that is still during the time spent developing, and one of its subspecialties is the investigation of biomarkers. The developing weight of worldwide liver sickness, the shortfall of side effects until late in the regular history of an illness that might require a very long time to show, the presence of an obtrusive reference test (liver biopsy) to evaluate infection seriousness, and the absence of powerful instruments to survey the viability of restorative mediations are a portion of the critical drivers for this exploration. Furthermore, the shortfall of side effects until late in the regular history of a sickness that might require a very long time to show is one more key driver for this examination. Moreover, one of the essential motivations behind why this study is being directed is because of the deficiency of dependable instruments with which to assess the viability of restorative methodologies. [ABSTRACT FROM AUTHOR]

This study aimed to explore the effect of standardized nutrition nursing combined with low molecular weight heparin calcium in treating patients with hyperlipidemic pancreatitis. A total of 100 patients from Yancheng Third People's Hospital were randomly divided into the control group and treatment group using a random number table. The control group received basic treatment that included fasting, isotonic saline, Ibuprofen, gastrointestinal decompression, Fentanyl, Pantoprazole, octreotide, electrolyte balance maintenance, glucose control, and lipid-lowering drug + routine enteral nutrition nursing. On this basis, the treatment group received low molecular weight heparin calcium injection + standardized enteral nutrition nursing. The total effective rate of the treatment group was higher than that of the control group (94.00% versus 76.00%; P < 0.05). After intervention, compared with the control group, serum levels of prealbumin, albumin, and transferrin were significantly higher (P < 0.05), while serum levels of triglyceride, total cholesterol, and amylase were significantly lower (P < 0.05) in the treatment group. Furthermore, improvements in prothrombin time, thrombin time, fibrinogen level, and activated partial thrombokinase time in the treatment group were more obvious (P < 0.05), while serum levels of C-reactive protein, tumor necrosis factor-α, and interleukin-6 were significantly lower (P < 0.05) than those in the control group. No difference was found in the incidence of adverse reactions between the two groups (P > 0.05). Overall, standardized nutrition nursing combined with low molecular weight heparin calcium can reduce blood lipid levels and inflammatory responses, improve coagulation function, and promote the nutritional status of patients with hyperlipidemic pancreatitis. [ABSTRACT FROM AUTHOR]

This study evaluates the antiproliferative potential of flavanones, chromanones and their spiro-1-pyrazoline derivatives as well as their inclusion complexes. The main goal was to determine the biological basis of molecular pro-apoptotic activities and the participation of reactive oxygen species (ROS) in shaping the cytotoxic properties of the tested conjugates. For this purpose, changes in mitochondrial potential and the necrotic/apoptotic cell fraction were analyzed. Testing with specific fluorescent probes found that ROS generation had a significant contribution to the biological anticancer activity of complexes of flavanone analogues. TT (thrombin time), PT (prothrombin time) and APTT (activated partial tromboplastin time) were used to evaluate the influence of the compounds on the extrinsic and intrinsic coagulation pathway. Hemolysis assays and microscopy studies were conducted to determine the effect of the compounds on RBCs. [ABSTRACT FROM AUTHOR]

Monoclonal gammopathies frequently associate with hemostatic alterations. Thrombotic events occur with high incidence particularly upon treatment, while in rarer cases hemorrhagic diathesis can be observed. The pathology of these tendencies could be caused by thrombocytopenia or hyperviscosity burden of circulating monoclonal antibodies. Studies also suggest interference of monoclonal antibodies with primary hemostasis. We isolated monoclonal whole IgG paraproteins from two myeloma patients to observe their effect on thrombin formation and fibrin polymerization. Monoclonal whole IgG was prepared from sera of two newly diagnosed untreated multiple myeloma patients and control normal plasma samples. Fibrin formation was measured using thrombin time and dilute prothrombin time tests and thrombin formation was detected with a fluorimetric thrombin generation assay. In addition, molecular interactions were investigated by surface plasmon resonance (SPR). Thrombin time was prolonged upon addition of monoclonal IgG even at 30 g/L by 12 %, increasing up to 36 % at 60 g/L concentration. Dilute prothrombin time was prolonged by 20 % even at 30 g/L. Thrombin generation assay indicated an impairment in thrombin formation at the presence of monoclonal IgG compared to polyclonal at equivalent concentration. By an SPR assay we determined that both clonality IgG preparations interacted with fibrinogen, however interaction with human thrombin was only detected with monoclonal immunoglobulins (KD=1.03 × 10-7 M). Here we provide evidence that isolated monoclonal whole IgG from myeloma patients can impair both fibrin and thrombin formation and we demonstrate by SPR assay that it interacts with components of the final phase of the coagulation system. [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]

Aim: to assess adaptive hemostasis changes in multiple dichorionic pregnancy after in vitro fertilization (IVF). Materials and Methods. A prospective observational randomized controlled trial was conducted by examining 58 and 46 pregnant women with multiple dichorionic diamniotic twins resulting from applying assisted reproductive technologies (ART) and spontaneous delivery (comparison group), respectively. Hemostasis parameters were studied as follows: activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen, antithrombin, protein C, protein S, functions of protein С (РrоС Global test), D-dimer, platelet aggregation with adenosine-5-diphosphate (ADP), ristocetin, and collagen. Results. A high coagulation potential was revealed, more prominent after using ART (p < 0.05). Fibrinogen level gradually increased while gestation age increased, whereas APTT, PT and TT level decreased. In the group with natural conception, fibrinogen increased by 22 % in the second trimester, reaching 4.5 g/L (95 % CI = 4,2–4,8) and by 6 % in the third trimester, reaching 4.8 g/L (95 % CI = 4,3–5,4), whereas in the IVF group – by 26 %, reaching 5.3 g/L (95 % CI = 4,7–5,6) and by 21 %, reaching (6.5 g/L; 95 % CI = 5,2–6,8) in relevant trimester of pregnancy, respectively. Antithrombin level was lower in IVF patients – 76.8 % (95 % CI = 72.6 – 81.0) in the second trimester, reaching 70.6 % (95 % CI = 64.8–76.4) in the third trimester (p < 0.001). Protein C level did not differ significantly between groups and was low within the reference range. The aggregatogram demonstrated a high platelet hemostatic potential in IVF patients (p < 0.05) as early as in the first trimester: ADP-induced aggregation – 68.3 % (95 % CI = 62.9–73.7), ristocetin-induced aggregation – 53.1 % (95 % = CI 48.7–58.5), collagen-induced aggregation – 58.4 % (95 % CI = 52.1–64.7). In the third trimester, both platelet aggregation and functional activity (ADP-induced aggregation – 64.5 % [95 % CI = 59.3–69.7], ristocetin-induced aggregation – 68.4 % [95 % CI = 63.2–73.6], collagen-induced aggregation – 50.7 % [95 % CI = 44.3–57.1]; p < 0.05) and D-dimer level persistently increased, also more prominently in the IVF group (1.60 ± 0.46 ng/ml; p < 0.05). Conclusion. Gestational adaptation in induced multiple pregnancies is at high risk of breach in compensatory mechanisms and requires monitoring for timely detection of decompensation signs and their correction to prolong pregnancy till optimal delivery time frame.

Abstract Background Preeclampsia (PE), an obstetric disorder, remains one of the leading causes of maternal and infant mortality worldwide. In individuals with PE, the coagulation-fibrinolytic system is believed to be among the most significantly impacted systems due to maternal inflammatory responses and immune dysfunction. Therefore, this systematic review and meta-analysis aimed to assess the association of prothrombin time (PT), thrombin time (TT) and activated partial thromboplastin time (APTT) levels with preeclampsia. Methods This systematic review and meta-analysis was conducted in accordance with the PRISMA guidelines. Articles relevant to the study, published from July 26, 2013, to July 26, 2023, were systematically searched across various databases including PubMed, Scopus, Embase, and Hinari. The methodological quality of the articles was evaluated using the Joanna Briggs Institute critical appraisal checklist. Utilizing Stata version 14.0, a random-effects model was employed to estimate the pooled standardized mean difference (SMD) along with the respective 95% CIs. The I2 statistics and Cochrane Q test were utilized to assess heterogeneity, while subgroup analyses were performed to explore its sources. Furthermore, Egger’s regression test and funnel plot were employed to assess publication bias among the included studies. Results A total of 30 articles, involving 5,964 individuals (2,883 with PE and 3,081 as normotensive pregnant mothers), were included in this study. The overall pooled SMD for PT, APTT, and TT between PE and normotensive pregnant mothers were 0.97 (95% CI: 0.65–1.29, p

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]

Background: Preeclampsia (PE), an obstetric disorder, remains one of the leading causes of maternal and infant mortality worldwide. In individuals with PE, the coagulation-fibrinolytic system is believed to be among the most significantly impacted systems due to maternal inflammatory responses and immune dysfunction. Therefore, this systematic review and meta-analysis aimed to assess the association of prothrombin time (PT), thrombin time (TT) and activated partial thromboplastin time (APTT) levels with preeclampsia. Methods: This systematic review and meta-analysis was conducted in accordance with the PRISMA guidelines. Articles relevant to the study, published from July 26, 2013, to July 26, 2023, were systematically searched across various databases including PubMed, Scopus, Embase, and Hinari. The methodological quality of the articles was evaluated using the Joanna Briggs Institute critical appraisal checklist. Utilizing Stata version 14.0, a random-effects model was employed to estimate the pooled standardized mean difference (SMD) along with the respective 95% CIs. The I2 statistics and Cochrane Q test were utilized to assess heterogeneity, while subgroup analyses were performed to explore its sources. Furthermore, Egger's regression test and funnel plot were employed to assess publication bias among the included studies. Results: A total of 30 articles, involving 5,964 individuals (2,883 with PE and 3,081 as normotensive pregnant mothers), were included in this study. The overall pooled SMD for PT, APTT, and TT between PE and normotensive pregnant mothers were 0.97 (95% CI: 0.65–1.29, p < 0.001), 1.05 (95% CI: 0.74–1.36, p < 0.001), and 0.30 (95% CI: -0.08-0.69, p = 0.11), respectively. The pooled SMD indicates a significant increase in PT and APTT levels among PE patients compared to normotensive pregnant mothers, while the increase in TT levels among PE patients was not statistically significant. Conclusions: The meta-analysis underscores the association between PE and prolonged PT and APTT. This suggests that evaluating coagulation parameters like PT, APTT, and TT in pregnant women could offer easily accessible and cost-effective clinical indicators for assessing PE. However, multicenter longitudinal studies are needed to evaluate their effectiveness across various gestational weeks of pregnancy. [ABSTRACT FROM AUTHOR]

Given the growing number of patients receiving direct oral anticoagulant (DOAC), patients requiring rapid neutralization is also increasing in case of major bleedings or urgent surgery/procedures. Idarucizumab is commercialized as a specific antidote to dabigatran while andexanet alfa has gained the Food and Drug Administration and the European Medicines Agency approval as an oral anti-factor Xa inhibitors antidote. Other antidotes or hemostatic agents are still under preclinical or clinical development, the most advanced being ciraparantag. DOAC plasma levels measurement allows to appropriately select patient for antidote administration and may prevent unnecessary prescription of expensive molecules in some acute clinical settings. However, these tests might be inconclusive after some antidote administration, namely andexanet alfa and ciraparantag. The benefit of laboratory monitoring following DOAC reversal remains unclear. Here, we sought to provide an overview of the key studies evaluating the safety and efficacy of DOAC reversal using the most developed/commercialized specific antidotes, to discuss the potential role of the laboratory monitoring in the management of patients receiving DOAC specific antidotes and to highlight the areas that deserve further investigations in order to establish the exact role of laboratory monitoring in the appropriate management of DOAC specific antidotes. Anticoagulation monitoring and specific reversal agent targets DOAC: direct oral anticoagulant; dTT: diluted thrombin time; ECA: ecarin chromogenic assay; ECT: ecarin cloting time. [Display omitted] • Antidotes for direct oral anticoagulant (DOAC) reversal have been developed. • The role of laboratory monitoring in DOAC reversal using antidotes is unclear. • Dabigatran level prior to idarucizumab could predict reversal outcome. • Oral FXa inhibitor levels cannot be easily measured following andexanet alfa. • DOAC measurement using commercialized assays is not possible after ciraparantag. [ABSTRACT FROM AUTHOR]

Background: Dabigatran etexilate is a pro-drug hydrolyzed into dabigatran by carboxylesterases (CES) and is a substrate of the P-Glycoprotein encoded by the adenosine-triphosphate-binding cassette sub-family B member (ABCB)1 genes. We evaluated the functional response to dabigatran according to different CES1 and ABCB1 single-nucleotide polymorphisms (SNPs) in patients with atrial fibrillation (AF). Methods: A total of 100 consecutive patients with AF taking dabigatran were enrolled by two Italian centers. A venous blood sample was drawn for genetic determinations, as well as a measurement of the diluted thrombin time (dTT) and drug plasma concentrations, at the trough and peak. The main objective was the relationship between the dTT values and CES1 rs2244613, CES1 rs8192935 and ABCB1 rs4148738 SNP while on two different dabigatran doses (110 and 150 mg BID). Results: A total of 43 patients were on a 110 mg dabigatran dose and 57 on 150 mg. The DTT values at the trough and at peak were not different among patients with different CES1 rs2244613 and CES1 rs8192935 genotypes, regardless of the dabigatran dose. In patients on 150 mg dabigatran, the dTT values at the trough were 77 (44–111) ng/mL in patients with the ABCB1 rs4148738 heterozygous CT genotype vs. 127 (85–147) ng/mL in the wild-type CC genotype vs. 110 (47–159) ng/mL in the mutant trait TT genotype (p = 0.048). In patients with the ABCB1 rs4148738 CT genotype, OR for having dTT values at a trough below the median was 3.21, 95% CI 1.04–9.88 (p = 0.042). Conclusions: ABCB1 rs4148738 CT heterozygous is associated with the reduced anticoagulant activity of dabigatran at the trough in patients receiving the higher dose regimen. [ABSTRACT FROM AUTHOR]

Objective: This work measures the intra‐operative bleeding in end‐stage renal disease patients and assesses whether laboratory coagulation tests and nitrogenous compounds are related to a higher bleeding risk. Methods: Laboratory tests were performed on the day of surgery and some patients with thrombocytopenia and values above the normal levels of international normalised ratio (INR), thrombin time (TT) and activated partial thromboplastin time (aPTT) were identified. Results: Haemostatic time ranged from 2 to 35 min (mean of 8.51 min) after suture. Bleeding volume ranged from 0.02 to 67.06 mL (mean of 4.38 mL) and the bleeding volume per minute ranged from 0.05 to 2.10 mL/min (median of 0.6 mL/min). Only seven patients (16.27%) had abnormal bleeding (more than 0.6 mL/min). Spearman's coefficient showed weak correlations between bleeding volume (mL/min) and serum urea (r = 0.226), TT (r = 0.227), plasma urea (r = 0.148) and creatinine (r = 146), as well as very weak correlations with all other variables (r < 0.140) such as age, haemodialysis time, glycaemia, glycated haemoglobin, platelets, INR, aPTT and fibrinogen. Conclusion: It was not possible to associate any laboratory test or nitrogenous compounds present in the blood and saliva with an increased bleeding. [ABSTRACT FROM AUTHOR]

Background: Chamomile administration may have desirable effects in the perioperative setting. Current practice, however, discourages perioperative chamomile use due to a theoretical increase in bleeding. Therefore, we evaluated if chamomile acutely (within 4 h of ingestion) prolongs coagulation assays. Methods: Eight healthy volunteers were randomized to receive 2 interventions in a crossover design: (a) single dose of chamomile extract capsule (500 mg) and (b) single dose of chamomile tea (3 g in 150 mL water). Interventions were separated at least 3 days apart from each other. Blood was sampled pre-ingestion, 2 h post-ingestion, and 4 h post-ingestion for each intervention. The primary outcome was the maximal change in prothrombin time (PT) before vs after each intervention. Secondary outcomes included changes in international normalized ratio, activated partial thromboplastin time, thrombin time, reptilase time, and fibrinogen levels. Results: All 8 subjects completed the study. The average pre-ingestion PT values for tea and capsules were 11.9 (1.1) s and 12.0 (0.9) s, respectively. Tea significantly increased the average maximum PT by 0.7 (0.2) s (P = 0.0078). Extract capsules increased the maximum PT by 0.3 (0.2) s (P = 0.06). Neither PT prolongation met the predefined 10% threshold for clinical significance. No significant changes in secondary outcomes were observed. Conclusions: Chamomile tea ingestion prolongs PT. However, the clinical significance of this is unclear at this time and warrants further investigation. ClinicalTrials.gov Registration Number: NCT05272475. [ABSTRACT FROM AUTHOR]

Abstract This study investigates the expression and significance of urinary protein and coagulation‐fibrinolysis indicators in preeclampsia, categorized into mild preeclampsia (109 cases) and severe preeclampsia (97 cases) based on disease severity. Additionally, 110 patients with gestational hypertension (gestational hypertension group) were included for comparative analysis. General information, laboratory indicators, urinary protein, and coagulation‐fibrinolysis indicator levels were collected for each group. Significant differences were observed in blood pressure among groups (P .05). Total cholesterol, triglycerides, and low‐density Lipoprotein levels in severe preeclampsia were higher than those in mild preeclampsia and gestational hypertension groups, whereas high‐density lipoprotein, albumin, and platelet levels were lower in severe preeclampsia. No significant differences were observed in prothrombin time or D‐dimer levels among groups (P > .05). Urinary protein, urinary protein quantification, activated partial thromboplastin time, thrombin time, and fibrinogen were identified as influencing factors for adverse maternal and infant outcomes in severe preeclampsia patients. The study concludes that urinary protein and coagulation‐fibrinolysis indicators are elevated in preeclampsia, particularly in severe preeclampsia cases, suggesting their potential use as diagnostic influencing factors for severe preeclampsia.

This study investigates the expression and significance of urinary protein and coagulation‐fibrinolysis indicators in preeclampsia, categorized into mild preeclampsia (109 cases) and severe preeclampsia (97 cases) based on disease severity. Additionally, 110 patients with gestational hypertension (gestational hypertension group) were included for comparative analysis. General information, laboratory indicators, urinary protein, and coagulation‐fibrinolysis indicator levels were collected for each group. Significant differences were observed in blood pressure among groups (P <.05), while uric acid, serum creatinine, aspartate transaminase, alanine transaminase, and triglycerides showed no significant differences (P >.05). Total cholesterol, triglycerides, and low‐density Lipoprotein levels in severe preeclampsia were higher than those in mild preeclampsia and gestational hypertension groups, whereas high‐density lipoprotein, albumin, and platelet levels were lower in severe preeclampsia. No significant differences were observed in prothrombin time or D‐dimer levels among groups (P >.05). Urinary protein, urinary protein quantification, activated partial thromboplastin time, thrombin time, and fibrinogen were identified as influencing factors for adverse maternal and infant outcomes in severe preeclampsia patients. The study concludes that urinary protein and coagulation‐fibrinolysis indicators are elevated in preeclampsia, particularly in severe preeclampsia cases, suggesting their potential use as diagnostic influencing factors for severe preeclampsia. [ABSTRACT FROM AUTHOR]

Background: Minor ischemic stroke (MIS) is associated with early neurological deterioration (END) and poor prognosis. Here, we investigated whether argatroban administration can mitigate MIS-associated END and improve functional outcomes by monitoring activated partial thrombin time (APTT). Methods: Data were collected for patients with MIS admitted to our hospital from January 2019 to December 2022. Patients were divided into a dual antiplatelet therapy (DAPT) group (aspirin + clopidogrel) and an argatroban group (aspirin + argatroban). Those in the latter group who achieved a target APTT of 1.5-3-fold that of baseline and <100 s at 2 h after argatroban infusion were included in the argatroban subgroup. The primary outcome was the END rate of the DAPT group versus that of the argatroban group or the argatroban subgroup. Secondary outcomes included the proportion of patients with modified Rankin Scale (mRS) 0-2 at 7 and 90 days. In addition, baseline date were compared between patients with and without END in the argatroban group. Results: 363 patients were included in the DAPT group and 270 in the argatroban group. There were no significant differences in any above outcome between them. 207 pairs were included in the DAPT group and the argatroban subgroup after 1:1 propensity score matching (PSM). Significant differences were observed in the proportion of END (OR, 2.337; 95% CI, 1.200-4.550, p = 0.011) and mRS 0-2 at 7 days (OR, 0.624; 95% CI, 0.415-0.939, p = 0.023), but not in mRS 0-2 at 90 days or the hemorrhagic events between the two groups. In the argatroban group, univariate analysis showed that the rate of diabetes (OR, 2.316; 95% CI, 1.107-4.482, p = 0.023), initial random blood glucose (OR, 1.235; 95% CI, 1.070-1.425, p = 0.004), drinking history (OR, 0.445; 95% CI, 0.210-0.940, p = 0.031) or those reaching the target APTT (OR, 0.418; 95% CI, 0.184-0.949, p = 0.033) was significantly different among patients with and without END. However, there were no statistical differences in these parameters between them following multivariate analysis. Conclusion: In patients with MIS, argatroban administration and reaching the target APTT can reduce the incidence of END and improve short-term functional prognosis. [ABSTRACT FROM AUTHOR]

Objective: To investigate the value of the combined test of seven blood coagulation indexes, lipids and platelet agglutination on the evaluation of the hypercoagulable state of blood in parturient women. Methods: This is a retrospective study. Total 50 high risk parturient women who underwent an antenatal examination in Baoding Maternal and Child Health Hospital from June 2021 to January 2023 were selected as the observation group, while 50 normal parturient women who underwent antenatal examination without comorbidities and complications were randomly collected in a ratio of 1:1 as the control group. All subjects had venous blood drawn for testing of seven blood coagulation indexes, lipids and platelet agglutination before delivery, and their general data were recorded. Results: The activated partial thromboplastin time(APTT) in the observation group was lower than that in the control group, while thrombin time(TT) and D-dimer(DD) were both higher than those in the control group, with statistically significant differences(p<0.05); total cholesterol (TC) and triglyceride (TG) in the observation group were both higher than those in the control group, with statistically significant differences (p<0.05); adenosine diphosphate (ADP) and arachidonic acid (AA) in the observation group were both higher than those in the control group, with statistically significant differences (p<0.05). Moreover, the overall incidence of adverse pregnancy was higher in the observation group than in the control group, with a statistically significant difference (p<0.05). Conclusions: The combined test of seven blood coagulation indexes, lipids and platelet agglutination results in excellent performance in predicting and judging the presence or absence of the hypercoagulable state of blood in parturient women, with the combination of APTT+TT+DD+TG+ADP+AA being the preferred test. [ABSTRACT FROM AUTHOR]

Background: Congenital dysfibrinogenemia (CD) is a rare hereditary coagulation disorder resulting from mutations in fibrinogen genes. CD primarily presents with bleeding symptoms, but it can also lead to thrombotic events, including ischemic stroke. Case presentation: This report describes the case of a 52-year-old Chinese man who was admitted to the hospital twice due to recurrent cerebral infarction, characterized by sudden speech impairment and weakness in the right upper extremity. Brain MRI revealed multiple ischemic changes, predominantly in the left frontal and parietal lobes. Coagulation tests demonstrated reduced plasma fibrinogen (Clauss method), prolonged prothrombin time and thrombin time, and an elevated international normalized ratio. However, the ELISA assay indicated elevated levels of fibrinogen γ-chain protein. Despite a 2-month-old treatment regimen with aspirin, clopidogrel, and atorvastatin after the first hospitalization, the patient experienced a second ischemic stroke. Genetic analysis using whole-exome sequencing (WES) and Sanger sequencing identified a rare heterozygous missense variation, FGG c.952G>A (rs267606810), in both the stroke patient and his asymptomatic sister. Both individuals exhibited the same alterations in fibrinogen, characterized by reduced functional levels but increased antigenic protein. Subsequently, the patient was diagnosed with ischemic stroke associated with congenital dysfibrinogenemia. Conclusion: This case report expands the clinical phenotype spectrum associated with FGG c.952G>A (rs267606810) and underscores the significance of considering CD as a potential etiology for unexplained ischemic stroke, particularly in patients with a family history of coagulation disorders. [ABSTRACT FROM AUTHOR]

This guidance was prepared on behalf of the International Council for Standardisation in Haematology (ICSH) by an international working group of clinicians and scientists. The document focuses on tests and assays used for the assessment of fibrinogen function, particularly in the scenario of bleeding disorders. Thrombin clotting time (TT) is used as a screening test in some laboratories and also has some utility when direct anticoagulants are in use. The Clauss fibrinogen assay remains the method of choice for the assessment of fibrinogen function, but there are some situations where the results may be misleading. Prothrombin time derived fibrinogen assays are frequently used, but should be interpreted with caution; the results are not interchangeable between different methods and fibrinogen can be overestimated in certain clinical scenarios. Viscoelastic point of care methods may be helpful in emergency situations, while Reptilase time (and similar tests) are useful combined with TT in distinguishing heparin contamination of samples (i.e., if an incorrect blood draw is suspected) and the presence of direct thrombin inhibitors. Fibrinogen antigen assays should be used in the investigation of functional fibrinogen abnormalities; fibrinogen antigen and genetic testing are recommended in the confirmation of congenital fibrinogen disorders. The following recommendations for fibrinogen function assessment are based on published literature and expert opinion and should supplement local regulations and standards. [ABSTRACT FROM AUTHOR]

Introduction: The knowledge of dabigatran levels is helpful for decision‐making in specific situations such as urgent surgery or when the question of reversal arises (uncontrolled bleeding, eligibility for thrombolysis). However, a limited number of observational studies are available regarding comparisons between quantification methods. The objective of the study was to compare dabigatran plasma levels using three assays including the reference method (high‐performance liquid chromatography coupled with mass spectrometry), focusing on the agreement around the 30–50 ng/mL clinically relevant thresholds. Methods: Sixty healthy volunteers from DRIVING trial (NCT01627665) were given a single 300‐mg dabigatran etexilate dose. Serial blood samplings were performed at pre‐defined time points (0 to 24 h). We analyzed plasma samples using ultra‐performance‐liquid chromatography coupled with tandem mass spectrometry (UPLC‐MS) (dabigatran reference method); ii/diluted thrombin time (dTT) (Hemoclot‐DTI‐Hyphen‐Biomed); iii/ecarin‐based chromogenic assay (ECA‐II‐Stago). Results: Nine hundred sixty samples were analyzed using the three assays (2759 values). dTT and ECA‐II values were highly correlated with those of UPLC‐MS (Deming regression). Most values >50 ng/mL were higher using dTT and ECA‐II compared to UPLC‐MS: biases were constant, +14% and +16% with dTT and ECA‐II, respectively (Bland–Altman plots), suggesting that active metabolites accounted for ~15% of thrombin inhibition. Regarding values <30 ng/mL, 30–50 ng/mL, or ≥50 ng/mL, the agreement probability between dTT and ECA‐II was of 90.6% [88.4–92.5] (Cohen's kappa coefficient 0.84). Conclusion: dTT and ECA‐II assays rapidly provide accurate dabigatran‐level results for clinical practice, both assays being suitable in emergency, taking into account the thrombin inhibitory effect of dabigatran metabolites. [ABSTRACT FROM AUTHOR]

Background: The objective of this study is to determine the standard reference intervals for coagulation function and coagulation factors in children across various age groups. Methods: A statistical analysis was conducted on prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib), thrombin time (TT), and coagulation factors (II, V, VII, X, VIII, IX, XI, and XII) in 389 healthy children who underwent health checkups and pre-surgical examinations at the Children's Hospital of Zhejiang University School of Medicine. The children were categorized into four age groups. Results: The established normal reference ranges are as follows: PT (seconds): 10.00 - 12.26 for 1 month - 3 years, 10.24 - 12.66 for 3 - 18 years; APTT (seconds): 24.82 - 35.65 for 1 month - 1 year, 25.20 - 32.30 for 1 - 18 years; Fib (g/L): 1.21 - 2.44 for 1 month - 1 year, 1.48 - 2.70 for 1 - 3 years, 1.69 - 3.60 for 3 - 18 years; TT (seconds): 18.48 - 23.06 for 1 month - 1 year, 17.80 - 21.26 for 1 - 18 years; coagulation factor II (%): 68.77 - 105.07 for 1 month - 1 year, 78.20 - 119.40 for 1 - 18 years; V (%): 74.24 - 140.96 for 1 month - 3 years, 70.64 - 132.01 for 3 - 18 years; VII (%): 56.34 - 113.00 for 1 month - 18 years; X (%): 49.17 - 105.57 for 1 month - 1 year, 64.34 - 115.24 for 1 - 18 years; VIII (%): 43.53 - 130.07 for 1 month - 1 year, 45.92 - 144.90 for 1 - 18 years; IX (%): 28.55 - 69.17 for 1 month - 1 year, 46.29 - 97.48 for 1 - 18 years; XI (%): 44.64 - 139.00 for 1 month - 1 year, 57.50 - 139.98 for 1 - 18 years; XII (%): 30.16 - 94.48 for 1 month - 1 year, 36.88 - 115.50 for 1 - 18 years. Conclusions: This study successfully established standard reference intervals for coagulation function and coagulation factors in children of various age groups in Hangzhou, China. [ABSTRACT FROM AUTHOR]

Adenomyosis patients are in a hypercoagulable state, and studies have shown that carbohydrate antigen125 (CA125) may relate to the hypercoagulability and thrombosis of patients with adenomyosis, but there is still a lack of clarity regarding the changes in CA125-related coagulation indicators. This study was to explore the changes and influencing factors of CA125-related coagulation parameters in patients with adenomyosis.Methods: Retrospective observational study conducted on 200 patients with adenomyosis (AM group), 240 patients with uterine leiomyoma (LM group) and 81 patients with cervical intraepithelial neoplasia (CIN)-III (control group), of which the coagulation parameters were detected by clinical blood sample collection and statistical method analysis and informed consent was obtained.Results: The level of CA125 in the AM group was significantly higher than that in the LM group and control group. However, thrombin time (TT) shortened in the AM group when compared with the LM and control group. Activated partial thromboplastin time (APTT) in the AM group was shorter than in the control group. Multivariate logistic regression analysis found that adenomyosis was associated with CA125 level (OR=323.860, 95% CI 90.424– 1159.924, P< 0.001), APTT (OR=1.295, 95% CI 1.050– 1.598, P=0.016), TT (OR=0.642, 95% CI 0.439– 0.938, P=0.022), menorrhagia (OR=7.363, 95% CI 2.544– 21.315, P< 0.001), dysmenorrhea (OR=22.590, 95% CI 8.185– 62.347, P< 0.001). Correlation analysis revealed that APTT (r= − 0.207) and TT (r = − 0.174) were negatively correlated with the level of CA125.Conclusion: The shortening of CA125-related APTT and TT indicates that it is meaningful to detect coagulation parameters of patients with elevated CA125 levels early, dysmenorrhea and menorrhagia, and maybe further discover the hypercoagulability and prevent the occurrence of thrombus in adenomyosis. [ABSTRACT FROM AUTHOR]

Burr hole drainage (BHD) is the primary surgical intervention for managing chronic subdural hematoma (CSDH). However, it can lead to postoperative complications such as acute bleeding within the hematoma cavity and hematoma recurrence. The objective of this study is to identify the risk factors for these complications and develop a predictive model for acute hematoma cavity bleeding after BHD in patients with CSDH. This study presents a retrospective cohort investigation conducted at a single center. The clinical dataset of 308 CSDH patients who underwent BHD at a hospital from 2016 to 2022 was analyzed to develop and assess a prognostic model. The nonbleeding group exhibited a significant correlation between fibrinogen (FIB) and thrombin time (TT), whereas no correlation was observed in the bleeding group. Notably, both FIB and TT were identified as risk factors for postoperative acute bleeding within the hematoma cavity. We developed a prognostic model to predict the occurrence of postoperative acute bleeding within the hematoma cavity after BHD in patients with CSDH. The model incorporated FIB, TT, coronary artery disease, and Glasgow Coma Scale scores. The model exhibited good discrimination (area under the curve: 0.725) and calibration (Hosmer-Leeshawn goodness of fit test: P > 0.1). Furthermore, decision curve analysis demonstrated the potential clinical benefit of implementing this prediction model. The predictive model developed in this study can forecast the risk of postoperative acute bleeding within the hematoma cavity, thus aiding clinicians in selecting the optimal treatment approach for patients with CSDH. [ABSTRACT FROM AUTHOR]

Alginate-based materials have gained significant attention in the medical industry due to their biochemical properties. In this article, we aimed to synthesize Cotton–Alginate–Copper Composite Materials (COT-Alg(−)Cu(2+)). The main purpose of this study was to assess the biochemical properties of new composites in the area of blood plasma coagulation processes, including activated partial thromboplastin time (aPTT), prothrombin time (PT), and thrombin time (TT). This study also involved in vitro antimicrobial activity evaluation of materials against representative colonies of Gram-positive and Gram-negative bacteria and antifungal susceptibility tests. The materials were prepared by immersing cotton fibers in an aqueous solution of sodium alginate, followed by ionic cross-linking of alginate chains within the fibers with Cu(II) ions to yield antimicrobial activity. The results showed that the obtained cotton–alginate–copper composites were promising materials to be used in biomedical applications, e.g., wound dressing. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES Early-stage lung adenocarcinoma (ADC) has a great heterogeneity in prognosis that is difficult to evaluate effectively. Thus, we developed and validated an effective nomogram prognostic model based on the clinical and laboratory characteristics of stage I–IIA ADC. METHODS We included 1585 patients with pathologically diagnosed stage I–IIA ADC who underwent surgery at Shanghai Pulmonary Hospital. The nomogram was constructed based on the peripheral blood test and coagulation test indicators and evaluated using Calibration plots, concordance index, decision curve analysis and the X-tile software. Recurrence-free survival (RFS) and overall survival (OS) were estimated by the Kaplan–Meier method and the Cox proportional hazard regression model. The primary end point of this study was RFS. RESULTS Thrombin time and 4 clinical indicators for RFS were integrated into nomograms. A favourable agreement between the nomogram prediction and validation was observed in the calibration curves for RFS probabilities. The concordance index of the nomogram to predict RFS was 0.736 (95% confidence interval, 0.717–0.755). Moreover, significant differences were shown between the high-risk and low-risk groups in RFS and OS (P  <   0.001) after effective cut-off values of risk points were found based on the nomogram. CONCLUSIONS We established and validated a prognostic nomogram including thrombin time to predict RFS and OS of stage I–IIA ADC patients. This nomogram provided an effective prediction ability for the prognosis of stage I–IIA ADC patients. [ABSTRACT FROM AUTHOR]

Introduction and aims: Mim8 is a next generation bispecific antibody developed for the treatment of haemophilia A (HA). Mim8 has an increased potency compared to first generation molecules. The impact on Mim8 on non‐FVIII measuring haemostasis assays was assessed in plasma containing Mim8. Methods: Congenital severe HA plasma was spiked with increasing concentrations of Mim8 (0–20 μg/mL). 28 routine and specialist haemostasis assays were used to measure activities. These included tests for prothrombin time (PT), fibrinogen, thrombin, D‐dimer, anti‐Xa, heparin induced thrombocytopenia (HIT), clotting factors II–XII, factor XIII, von Willebrand factor (VWF), thrombophilia and DRVVT. Results and conclusions: Less than 10 % difference was calculated between plasma without Mim8 and plasma spiked to 15 μg/mL Mim8 in all assays except thrombin time (−10.5%), APTT‐based factor IX, XI and XII, Werfen VWF:RCo (10.6%) and Siemens LA1 (−26.4%) and LA2 (−16.9%). At the expected therapeutic steady state levels of Mim8 (5–8 μg/mL), less than 10% difference was calculated for thrombin time and Werfen VWF:RCo. APTT‐based assays of FIX, XI and XII are significantly elevated in the presence of Mim8 and should not be performed. A chromogenic FIX assay could be used to accurately measure FIX activity in the presence of Mim8. There was some interference in the DRVVT method we used so local assessment of other DRVVT methods is advised. Differences in all other tests would not be predicted to affect patient management. [ABSTRACT FROM AUTHOR]

Glycosaminoglycans (GAGs) play a crucial role due to their significant biomedical functions. Chondroitin sulfate (CS) and dermatan sulfate (DS), the main representative family of GAGs, were extracted and purified from garfish (Belone belone) by-products, i.e., skin (GSB), bones (GCB), and heads (GHB), and their composition and anticoagulant activity were investigated. CS/DS were purified by ion-exchange chromatography with yields of 8.1% for heads, 3.7% for skin, and 1.4% for bones. Cellulose acetate electrophoresis was also explored for analyzing the extracted CS/DS. Interestingly, GHB, GSB, and GCB possessed sulfate contents of 21 ± 2%, 20 ± 1%, and 20 ± 1.5%, respectively. Physico-chemical analysis showed that there were no significant differences (p > 0.05) between the variances for sulfate, uronic acid, and total sugars in the GAGs extracted from the different parts of fish. Disaccharide analysis by SAX-HPLC showed that the GSB and GCB were predominately composed of ΔDi-4S [ΔUA-GalNAc 6S] (74.78% and 69.22%, respectively) and ΔDi-2,4S [ΔUA2S-GalNAc 4S] (10.92% and 6.55%, respectively). However, the GHB consisted of 25.55% ΔDi-6S [ΔUA-GalNAc 6S] and 6.28% ΔDi-2,6S [ΔUA2S-GalNAc 4S]. Moreover, classical anticoagulation tests were also used to measure their anticoagulant properties in vitro, which included the activated partial thromboplastin time, prothrombin time, and thrombin time. The CS/DS isolated from garfish by-products exhibited potent anticoagulant effects. The purified CS/DS showed exceptional anticoagulant properties according to this research and can be considered as a new agent with anticoagulant properties. [ABSTRACT FROM AUTHOR]

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Clot waveform analysis (CWA) observes changes in transparency in a plasma sample based on clotting tests such as activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). Evidence indicates that not only an abnormal waveform but also peak times and heights in derivative curves of CWA are useful for the evaluation of hemostatic abnormalities. Modified CWA, including the PT with APTT reagent, dilute PT (small amount of tissue factor [TF]-induced clotting factor IX [FIX] activation; sTF/FIXa), and dilute TT, has been proposed to evaluate physiological or pathological hemostasis. We review routine and modified CWA and their clinical applications. In CWA-sTF/FIXa, elevated peak heights indicate hypercoagulability in patients with cancer or thrombosis, whereas prolonged peak times indicate hypocoagulability in several conditions, including clotting factor deficiency and thrombocytopenia. CWA-dilute TT reflects the thrombin burst, whereas clot-fibrinolysis waveform analysis reflects both hemostasis and fibrinolysis. The relevance and usefulness of CWA-APTT and modified CWA should be further investigated in various diseases. [ABSTRACT FROM AUTHOR]

Background: Direct thrombin inhibitors (DTIs) are usually monitored with the activated partial thromboplastin time (aPTT) or activated clotting time (ACT). Both are complex assays with multiple enzymatic steps, and performance may be influenced by physiologic and pathologic factors unrelated to the DTI. Simpler systems, such as clot-based dilute thrombin time (dTT) and chromogenic anti-factor IIa assays, have been developed for monitoring DTIs, but there is limited data on their performance in clinical settings. Methods: Medical records of patients who received bivalirudin between March 2020 and April 2022 at a single institution were reviewed for demographic data and adverse outcomes. Plasma samples drawn for aPTT testing were analyzed with chromogenic anti-IIa and dTT bivalirudin assays. Results were compared to bivalirudin dosing. Results: Results of aPTT assays from 32 patients were compared with the chromogenic (n = 136) and dTT (n = 120) bivalirudin assays. Correlations between the aPTT and the chromogenic and dTT assays were poor (Spearman coefficients 0.55 and 0.62, respectively). There was a stronger correlation when results of the chromogenic and dTT assays were compared to each other (Spearman coefficient 0.92). When assay results were compared to bivalirudin dose, there were stronger correlations with the chromogenic and dTT assays than with the aPTT (Spearman coefficients 0.51, 0.63 and 0.22, respectively). Conclusions: There was considerable variation between results of specific bivalirudin assays and the aPTT. While bivalirudin assay results correlated better with administered drug dose, suggesting improving reliability, more studies are needed to determine if there is correlation between testing and clinical outcomes. [ABSTRACT FROM AUTHOR]

The number of patients with indications for direct oral anticoagulants (DOACs) to prevent thrombotic events is steadily growing. However, in 1,1-2,2% of cases, ischemic strokes occur within DOAC therapy. In this case, DOAC use is a limitation for systemic thrombolysis, except for available reversal of anticoagulation. In order to immediately inactivate the anticoagulant effect of dabigatran etexilate (DE), reversal agent idarucizumab is used.Aim. To evaluate the effectiveness and safety of idarucizumab in clinical practice.Material and methods. The study included 9 patients taking DE who developed urgent conditions that required emergency reversal of anticoagulation with idarucizumab.Results. Normalization of thrombin time (TT) was achieved in 7 (77,8%) patients immediately after idarucizumab administration. In two patients, 10 minutes after the administration of a specific DE reversal agent, TT decreased, but did not reach reference values (case 1: TT decreased from 181 to 23,3 seconds; case 2: TT decreased from 181 to 18,3 seconds); 30 minutes after the idarucizumab administration, TT normalization was achieved.Conclusion. Nobody developed clinically significant arterial and/or venous thrombotic events during the entire period of hospitalization. Rapid reversal of anticoagulation with idarucizumab allows immediate systemic thrombolytic therapy or surgery in patients taking DE without the increase of bleeding or thrombosis risk and the need for control coagulation analysis.

Aims. The aim of this study is to assess the relationship between rivaroxaban plasma concentration quantified by the gold standard and anticoagulant activities measured by routine coagulation assays in Chinese atrial fibrillation (AF) patients. Whether the normal results of these tests were reliable to rule out clinically relevant rivaroxaban levels at various thresholds was also explored. The effect of clinical drug-drug interactions (DDIs) on the exposure and anticoagulant effect of rivaroxaban were further evaluated. Methods. 116 patients receiving rivaroxaban for the management of nonvalvular AF were recruited. Rivaroxaban concentrations and coagulation tests were measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and a blood coagulation analyzer, respectively. Results. The correlation of trough concentration (Ctrough) and prothrombin time (PT) or international normalized ratio (INR) was moderate with Spearman's correlation coefficient of 0.495 and 0.506, respectively. A normal PT/INR was unable to rule out Ctrough levels of >30 ng/mL and >50 ng/mL, but the negative predictive value reached 100% to exclude Ctrough of >100 ng/mL. Ctrough showed a small correlation with activated partial thromboplastin time (aPTT) (Spearman's correlation coefficient: 0.241) and no correlation with thrombin time (TT) (Spearman's correlation coefficient: 0.074). Neither aPTT nor TT accurately predicted Ctrough at any concentration. Peak concentration (Cpeak) did not correlate with any coagulation parameters. The presence of digoxin and febuxostat significantly increased rivaroxaban Ctrough by 2.18 fold and prolonged PT and INR by 44.16% and 43.60%, respectively. Conclusions. Normal routine coagulation assays were insufficient to monitor therapy with rivaroxaban. Poor correlations between rivaroxaban concentration and routine coagulation assays were observed in Chinese AF patients. The use of digoxin/febuxostat alone had no effect on rivaroxaban concentrations; however, combined strong breast cancer resistance protein inhibitor (febuxostat) and P-glycoprotein probe (digoxin) in patients with renal impairment is likely to cause clinically significant DDI with rivaroxaban. More studies are needed to establish routine therapeutic drug monitoring of rivaroxaban in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Regular prophylactic therapy has become an increasingly common treatment for severe hemophilia. Therefore, hypercoagulability—a potential risk factor of thrombosis—is a cause for concern in hemophilic patients treated with a high dose of FVIII concentrate. In clot waveform analysis (CWA)-thrombin time (TT), a small amount of thrombin activates clotting factor VIII (FVIII) instead of fibrinogen, resulting in FVIII measurements using CWA-TT with a small amount of thrombin. Methods: The coagulation ability of patients treated with FVIII concentrate or emicizumab was evaluated using activated partial thromboplastin time (APTT), TT and a small amount of tissue factor-induced FIX activation assay (sTF/FIXa) using CWA. Results: The FVIII activity based on CWA-TT was significantly greater than that based on the CWA-APTT or chromogenic assay. FVIII or FVIII-like activities based on the three assays in plasma without emicizumab were closely correlated; those in plasma with emicizumab based on CWA-TT and chromogenic assays were also closely correlated. CWA-APTT and CWA-TT showed different patterns in patients treated with FVIII concentrates compared to those treated with emicizumab. In particular, CWA-TT in patients treated with FVIII concentrate showed markedly higher peaks in platelet-rich plasma than in platelet-poor plasma. CWA-APTT showed lower coagulability in hemophilic patients treated with FVIII concentrate than in healthy volunteers, whereas CWA-sTF/FIXa did not. In contrast, CWA-TT showed hypercoagulability in hemophilic patients treated with FVIII concentrate. Conclusions: CWA-TT can be used to evaluate the thrombin bursts that cause hypercoagulability in patients treated with emicizumab. Although routine APTT evaluations demonstrated low coagulation ability in patients treated with FVIII concentrate, CWA-TT showed hypercoagulability in these patients, suggesting that the evaluation of coagulation ability may be useful when using multiple assays. [ABSTRACT FROM AUTHOR]

Anticoagulants are helpful as treatment for coagulation disorders. Medicinal plants have been demonstrated to be part of history as a traditional treatment for this disorder, and these plants have anticoagulant properties. Hence, the goal of this study is to review the available publications on anticoagulant activity in medicinal plants from the year 2011 until 2021 using Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines and bibliometric analysis. This review was performed based on the PRISMA guidelines and VOSviewer as a bibliometric analysis tool, using three search databases which were PubMed, MyMedR, and ScienceDirect. The findings of this study revealed that 27 articles met the inclusion criteria and focused on anticoagulant activity in medicinal plants. In each study, anticoagulant properties in medicinal plants were addressed. Meanwhile, the results of the bibliometric analysis demonstrated that China has the most publications for anticoagulant activity in medicinal plants and had the most collaboration among institutes in their country. For the most used keywords used by the author, the word "anticoagulant activity" came on top of the results. To conclude, this study can contribute to the field of study as it helps combine the data related to anticoagulant activities in medicinal plants. [ABSTRACT FROM AUTHOR]

Objective to investigate the efficacy of the 96% ethanol extract of Ziziphus mauritiana leaves on hemostasis activity in animal model study (Sprague-Dawley rats). A laboratory experimental in vitro and in vivo study were conducted with Sprague-Dawley (SD) rats with randomized controlled design with a posttest-only control group design. Fifteen animals were used as research material, divided into 5 groups, negative control group (NCG), positive control group with golden standard hemostatic agent tranexamic acid 5% (TXA), 25% concentration of Z. mauritiana leaves extract (ZM25), 50% concentration (ZM50), and 100% concentration (ZM100). The bleeding time and the amount of bleeding were calculated by cutting the tip of the tails of the SD rats. PT, aPTT and TT were measured by taking blood samples from the SD rats. The data analysed using the Shapiro Wilk normality test, normally distributed data followed by a one-way ANOVA test with a significance level (p<0.05), continued with the Post-Hoc test. The ZM100 group shows a significant difference with NCG, TXA and ZM25 groups in bleeding time. The NCG group shows a significant differences with all samples in the amount of bleeding. The ZM100 group shows a significant difference with all test groups in PT, aPTT and TT test. The ethanol extract of Z. mauritiana leaves can accelerate bleeding time and the amount of bleeding, the extract can also stimulate the acceleration of PT, aPTT and TT factor in the bleeding cascade at high concentrations (100%). [ABSTRACT FROM AUTHOR]

Background: Chamomile is consumed worldwide for enjoyment and its potentially desirable properties. Widespread patient resource websites, however, discourage preoperative chamomile intake, lest bleeding could worsen. This precaution, though, stems largely from indirect evidence in one case report. To evaluate if chamomile ingestion impacts coagulation assays via coumarin-like substances, we designed a randomized, placebo-controlled, crossover study. Materials and methods: Healthy volunteers were randomized to three interventions in a cross-over-design spanning 5 weeks per subject. Interventions included 7-day consumption of chamomile tea (3 tea bags × 3 times daily = 9 tea bags daily), a chamomile extract capsule (3 times daily), or a placebo capsule (3 times daily). A 7-day washout period elapsed between intervention periods. The primary outcome was the change in prothrombin time (PT) before vs. after each intervention. Secondary outcomes included changes in the international normalized ratio (INR), activated partial thromboplastin time (aPTT), thrombin time (TT), reptilase time (RT), and fibrinogen (FG) surrounding each intervention. Results: All 12 enrolled subjects were randomized and completed the study. The primary outcome of PT change (mean ± SD) was similar across interventions (chamomile tea = − 0.2 ± 0.4 s, extract capsule = − 0.2 ± 0.4 s, and placebo capsule = 0.1 ± 0.5 s; p = 0.34). INR change was 0 s (p = 0.07) for each intervention. The aPTT, TT, RT, and FG, did not change significantly across interventions (p = 0.8, p = 0.08, p = 0.8, and p = 0.2 respectively). Conclusions: Chamomile intake by tea or capsule does not prolong PT. These findings challenge the notion to avoid perioperative chamomile intake in patients not taking warfarin. Trial registration: ClinicalTrials.gov, NCT05006378; Principal Investigator: Jonathon Schwartz, M.D.; Registered August 16, 2021. [ABSTRACT FROM AUTHOR]

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Background: The aim of the study was to conduct a comprehensive performance evaluation of the Mindray CX-9000 fully automated coagulation analyzer for the detection of the seven coagulation items. Methods: The performance of activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (FIB), thrombin time (TT), D-dimer (D-D), fibrinogen degradation product (FDP), and antithrombin? (AT) was validated for precision, linear range, carryover contamination rate, reference interval validation, inter-method agreement, and anti-interference ability. Results: The intra-and inter-precision (coefficient of variation, CV%) of all seven items was less than the target CV%; the carryover contamination rates for different concentrations and between items were < 10%. The slope of the linear regression equation for the theoretical and measured values of the linear range was within 1 ± 0.05 and R = 0.975. The reference interval quoted from the manufacturer's reference interval passed = 95%. The CX- 9000 was compared with the results of the reference instrument STAGO R MAX (STA-R MAX) and the p-values for all items ranged from 0.822 to 0.987. Within the concentration range claimed by the manufacturer, the interference errors produced by all items met the manufacturer's claimed criteria, except for triglycerides which produced interference errors > 10% for the FIB, D-D, FDP, and bilirubin which produced interference errors for the FIB and D-D assays. Conclusions: The CX-9000 automatic coagulation analyzer has good stability and repeatability, a wide linear range of detection, low carryover contamination rate, and high resistance to interference, making it suitable for the testing of clinical specimens. [ABSTRACT FROM AUTHOR]

Background: The Clinical and Laboratory Standards Institute recommends rejecting hemolyzed samples for coagulation tests. Sysmex CS5100 analyzer using an optical method is commonly used in laboratories. The influence of hemolysis on coagulation test has rarely been studied when tested on Sysmex CS5100. Determining this influence is necessary. Methods: Freshly collected samples were artificially hemolyzed to simulate the hemolysis processes. Coagulation tests were conducted on a Sysmex CS5100 coagulation analyzer. Detection values before and after hemolysis were compared. Results: The results showed that after hemolysis detection, the prothrombin time (PT) statistically decreased, while the partial thromboplastin time (APTT) statistically increased. There were no significant differences in fibrinogen (Fg), thrombin time (TT), D-dimer (DD) or fibrinogen degradation products (FDPs). Antithrombin activity was elevated in hemolyzed samples. Conclusions: Although differences in PT and APTT were statistically significant, there was no need for rejection of hemolyzed samples due to insufficient clinical effects when tested on Sysmex CS5100 analyzer. Falsely elevated AT result may lead to misdiagnosis in patients with severe diseases, which should be carefully considered. [ABSTRACT FROM AUTHOR]

Congestive heart failure (CHF) is associated with significant morbidity and mortality. There has been renewed interest in using thrombo-inflammatory markers as prognostic tools in patients with CHF. To determine if thrombo-inflammatory markers are independent risk factors for 28-day mortality in hospitalized CHF patients, we retrospectively analyzed admission data extracted from 2008 consecutive patients admitted with a diagnosis of CHF to Zigong Fourth People’s Hospital. Multivariate Cox proportional hazards analysis demonstrated that the thrombo-inflammatory markers thrombin time, platelet/lymphocyte ratio (PLR), and D-dimer level were independent predictors of mortality. In addition, variables reflecting the severity of CHF (New York Heart Association class > 2), impaired renal function (elevated serum creatinine [SCr]), impaired organ perfusion (elevated BUN), and chronic liver disease were also independent predictors of mortality. Thrombo-inflammatory biomarkers were only weakly associated with SCr and the burden of co-morbidity, suggesting that thrombo-inflammation may in large part be attributable to CHF itself and that, moreover, its presence may confer an increased risk of mortality. Further large-scale prospective studies are needed to determine the existence and the consequences of a thrombo-inflammatory phenotype among patients with CHF.

Objective: To investigate the effects of autotransfusion and allogeneic transfusion on coagulation function, cellular immune function and nerve injury markers in patients with traumatic brain injury(TBI) undergoing craniotomy. Methods: The clinical data of 120 patients with TBI who underwent craniotomy in our hospital from April 2019 to May 2022 were retrospectively analyzed. Patients were divided into allogeneic transfusion group(n=58, allogeneic transfusion) and autotransfusion group(n=62, autotransfusion) according to different blood transfusion methods. Clinical indexes, cellular immune function, coagulation function, nerve injury markers and incidence of adverse reactions in the two groups were observed. Results: There were no significant differences in operation bleeding volume, blood transfusion and proportion of blood products containing coagulation components in the two groups(P＞0.05). CD3+, CD4+,CD4+/CD8+in the autotransfusion group were higher than those in the allogeneic transfusion group at discharge, and CD8+was lower than that in the allogeneic transfusion group(P＜0.05). There were no significant differences in prothrombin time(PT), thrombin time(TT) and fibrinogen(FIB), activated partial thrombin time(APTT) in the two groups at discharge(P＞0.05). The levels of S100 calc-binding protein B(S100B), glial fibrillary acid protein(GFAP) and neuron-specific enolase(NSE) in the autotransfusion group were lower than those in the allogeneic transfusion group at discharge(P＜0.05). There was no difference in the incidence of adverse reactions between the two groups(P＞0.05). Conclusion: Autotransfusion is used in patients with TBI undergoing craniotomy has little impact on the coagulation function of patients, and can also improve the cellular immune function of the body, and reduce the level of nerve injury markers. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of magnesium sulfate combined with labetalol on coagulation function, oxidative stress and vascular endothelial function in patients with severe preeclampsia. Methods: 94 patients with severe preeclampsia who came to Chaohu Hospital affiliated to Anhui Medical University from January 2020 to September 2022 were selected. The patients were randomly divided into control group (magnesium sulfate treatment, 47 cases) and study group (magnesium sulfate combined with labetalol treatment, 47 cases) by random number table method. Before and after treatment, the changes of systolic blood pressure (SBP), diastolic blood pressure (DBP), 24 h urine protein volume (24hUP), coagulation function, oxidative stress and vascular endothelial function indexes were observed in two groups, and the drug safety in the two groups was observed. Results: After treatment, SBP, DBP and 24hUP in the study group were lower than those in the control group (P<0.05). After treatment, endothelin-1 (ET-1) in the study group was lower than that in the control group, while nitric oxide (NO) was higher than that in the control group (P<0.05). After treatment, malondialdehyde (MDA) in the study group was lower than that in the control group, and superoxide dismutase(SOD) in the study group was higher than that in the control group (P<0.05). After treatment, the fibrinogen (Fg) and D-dimer (D-D) in the study group were lower than those in the control group, and the prothrombin time (PT) and thrombin time (APTT) in the study group were higher than those in the control group (P<0.05). There was no significant difference in the incidence of adverse reactions in the two groups (P>0.05). Conclusion: Labelolol combined with magnesium sulfate in the treatment of patients with severe preeclampsia can reduce 24hUP, effectively reduce blood pressure, improve coagulation function and vascular endothelial function, and alleviate oxidative stress damage. [ABSTRACT FROM AUTHOR]

Background: Microvascular invasion (MVI) plays an important role in tumor progression. The aim of this study is to establish and validate an effective hematological nomogram for MVI prediction in hepatocellular carcinoma (HCC). Methods: A retrospective study was performed in a primary cohort that includes 1306 patients clinicopathologically diagnosed with HCC, and a validation cohort contained 563 continuous patients. Univariate logistic regression was used to assess the association between variables included both clinicopathologic factors and coagulation parameters (prothrombin time, activated partial thromboplastin time, fibrinogen, and thrombin time [TT]) and MVI. Multiple logistic regression was used to construct a prediction nomogram. We tested the accuracy of the nomogram by discrimination and calibration, and then plotted decision curves to assess the benefits of the nomogram-assisted decisions in a clinical context. Results: In the two cohorts, patients without MVI had the longest overall survival (OS), compared the OS with MVI. The multivariate analysis indicated that age, sex, tumor node metastasis (TNM) stage, aspartate aminotransferase, alpha fetoprotein, C-reactive protein, and TT were identified as significant independent predictors of MVI of HCC patients. The Hosmer–Lemeshow test showed good point estimate associated P value between predicted risk and observed risk across the deciles. Moreover, the calibration performance of the nomogram risk scores in each decile of the primary cohort was within 5 percentage points of the mean predicted risk score, and in the validation cohort, the observed risk in 90% decile was within 5 percentage points of the mean predicted risk score. Conclusions: A noninvasive and easy-to-use nomogram was established and may be used to predict preoperative MVI in HCC. [ABSTRACT FROM AUTHOR]

Objective. Patients with cirrhosis and splenomegaly often have coagulation dysfunction which affects treatment and prognosis. This study explores the status, grading, and treatment strategies of coagulation dysfunction in patients with liver cirrhosis and splenomegaly. Methods. A retrospective cohort study was conducted on the clinical data on consecutive patients with cirrhosis and splenomegaly treated at Hainan General Hospital, China, from January 2000 to December 2020. Starting research in January 2022. Results. Among 1522 patients included into this study, 297 (19.5%) patients had normal results in all five coagulation tests (prothrombin time, prothrombin activity, activated partial thromboplastin time, thrombin time, and fibrinogen), and 1225 (80.5%) had coagulation dysfunction in at least one of these tests. There were significant differences (P < 0.05) in treatment efficacy on these patients for three of these five coagulation tests, with the exception of prothrombin activity and thrombin time. When coagulation dysfunction was classified into grades I, II, and III based on scores from the three significant coagulation tests, prothrombin time, activated partial thromboplastin time, and fibrinogen, significant differences in surgical outcomes were found among the three grades of coagulation dysfunction and between grades I and III (P < 0.05). The operative mortality rate in patients with grade III in treating liver cancer, portal hypersplenism, and/or splenomegaly was 6.5%. There was no significant difference between patients with grades I and II (P > 0.05). Conclusions. Approximately, 80% of patients with liver cirrhosis and splenomegaly had coagulation dysfunction. Surgery is feasible for grade I and II patients. For grade III patients, nonsurgical treatment should be given first, and surgery should only be considered when the coagulation function returns to normal or near-normal levels after treatment. This trial is registered with MR-46-22-009299. [ABSTRACT FROM AUTHOR]

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