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ABSTRACT Background Objectives Methods Results Conclusions Calibration of thromboplastins is required for accurate calculation of the international normalised ratio (INR). Accurate INR results are required for optimal dosing of vitamin K antagonists. Decreases in vitamin K antagonist usage have made the recruitment of sample sets for international sensitivity index (ISI) calibrations more difficult. A possible solution to this would be to allow the use of frozen–thawed samples in place of fresh plasmas in the calibration of secondary standards.We investigated the effect of freezing and thawing samples before usage in ISI calibrations of secondary standards.Multiple reagent/instruments were tested to identify the degree of difference between a fresh sample ISI calibration and one performed on frozen–thawed samples. Where possible, the two ISI calibrations were performed on the same sample set. Alternatively, a separate set of samples from different patients was used.The difference in ISI values was <3% for those datasets where the same samples were used, and <6% for those datasets where two sample sets were used. Additionally, other parameters required for a valid ISI calibration showed only minor differences—some calibrations showed fewer outliers in the frozen–thawed datasets. Mean normal prothrombin time for the international reference thromboplastins was <3.5% different across four different calibrations (two for rabbit thromboplastin and two for recombinant human thromboplastin).This modification to the WHO guidelines would facilitate the recruitment of test plasmas in advance of calibration solving the problem of requiring availability of fresh patient samples with a range of INRs in a 5‐h window.Trial Registration: Not a part of any clinical trial. [ABSTRACT FROM AUTHOR]

Hereditary factor VII (FVII) deficiency is an uncommon autosomal recessive disorder associated with mutations in the F7 gene, and laboratory investigations usually reveal isolated prolongation in prothrombin time (PT)/international normalized ratio (INR). Venom-induced consumptive coagulopathy (VICC) is distinguished by the activation of the coagulation pathway, which is triggered by procoagulant toxins in snake venom. Diagnosing snakebites in patients with hereditary FVII deficiency presents a challenge because prolonged time PT/INR is considered the most valuable diagnostic method for VICC. Therefore, it is possible that certain patients may not promptly receive an accurate diagnosis of hereditary FVII deficiency. We present a pedigree featuring hereditary FVII deficiency, which was diagnosed through Sanger sequencing, following a bamboo leaf green snake bite. [ABSTRACT FROM AUTHOR]

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

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 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]

Introduction: Acute hepatic failure due to yellow phosphorus rodenticide ingestion is often lethal. This study aimed to analyze demographic characteristics and prognostic indicators, focusing on hyperlactataemia as a potential early indicator of mortality in patients poisoned with yellow phosphorus rodenticide. Materials and methods: This was a retrospective study of 96 patients poisoned with a yellow phosphorus-containing rodenticide (Ratol paste, which contains 3% yellow phosphorus). We examined demographic details, clinical symptoms, and biochemical markers to identify prognostic indicators. Results: Demographics were similar among survivors and non-survivors. Mortality (36.5%) correlated with a higher ingested dose and treatment delays, with a mean (±SD) of 5.26 ± 2.2 survival days among those who died. Symptoms, including gastrointestinal and neurological features, typically appeared 48 h after ingestion. Non-survivors developed increased aminotransferase activities (74.3%), prolonged prothrombin time (65.7%), and hyperbilirubinaemia (65.7%) during hospitalization, significantly more commonly compared to survivors (P < 0.0001). Hyperlactataemia (lactate concentration >2 mmol/L) was present in 97.1% of non-survivors, with increased serial lactate concentrations observed in 88.6%. The median (interquartile range) admission lactate concentration among non-survivors was 4.6 mmol/L (3.36–7.53 mmol/L), and their peak median (interquartile range) lactate concentration was 6.1 mmol/L (8.74–10.6 mmol/L). In non-survivors, an increased lactate concentration preceded increased aminotransferase activities and prolonged prothrombin time. Logistic regression and receiver operating characteristic curve analysis confirmed that a 24 h lactate concentration ≥2.67 mmol/L predicted death with 94.3% sensitivity and 91.8% specificity. Discussion: The majority of patients who ingest yellow phosphorus remain asymptomatic initially and typically present to hospital following the onset of gastrointestinal symptoms, usually a day later. As progression to death occurs within a week of yellow phosphorus ingestion in most cases, determining prognosis as early as possible enables swift referral to a liver transplant centre. Based on our study, a 24 h lactate concentration ≥2.67 mmol/L appears to be an early prognostic indicator of death. In another study, a lactate concentration >5.8 mmol/L was found to be a poor prognostic indicator. Conclusions: Hyperlactataemia on admission and increased serial lactate concentrations appear to be early poor prognostic signs in patients with yellow phosphorus-induced liver failure. [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: 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]

This guidance document has been prepared on behalf of the International Council for Standardization in Haematology (ICSH). The aim of the document is to provide guidance and recommendations for the performance and interpretation of activated partial thromboplastin time (APTT) and prothrombin time (PT) plasma mixing tests in clinical laboratories in all regions of the world. The following areas are included in this document: preanalytical, analytical, postanalytical, and quality assurance considerations as they relate to the proper performance and interpretation of plasma mixing tests. The recommendations are based on good laboratory practice, published data in peer‐reviewed literature, and expert opinion. [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: Hypertrophic cardiomyopathy (HCM) is a crucial heart disease in cats. The clinical manifestations of HCM comprise pulmonary edema, dyspnea, syncope, arterial thromboembolism (ATE), and sudden cardiac death. D-dimer and prothrombin time (PT) are powerful biomarkers used to assess coagulation function. Dysregulation in these two biomarkers may be associated with HCM in cats. This study aims to assess D-dimer levels, PT, and proteomic profiling in healthy cats in comparison to cats with symptomatic HCM. Results: Twenty-nine client-owned cats with HCM were enrolled, including 15 healthy control and 14 symptomatic HCM cats. The D-dimer concentration and PT were examined. Proteomic analysis was conducted by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry and liquid chromatography-tandem mass spectrometry (LC-MS/MS). In symptomatic cats, D-dimer levels were statistically significantly higher (mean ± SEM: 372.19 ng/ml ± 58.28) than in healthy cats (mean ± SEM: 208.54 ng/ml ± 10.92) with P-value of less than 0.01, while PT was statistically significantly lower in symptomatic cats (mean ± SEM: 9.8 s ± 0.15) compared to healthy cats (mean ± SEM: 11.08 s ± 0.23) with P-value of less than 0.0001. The proteomics analysis revealed upregulation of integrin subunit alpha M (ITGAM), elongin B (ELOB), and fibrillin 2 (FBN2) and downregulation of zinc finger protein 316 (ZNF316) and ectonucleoside triphosphate diphosphohydrolase 8 (ENTPD8) in symptomatic HCM cats. In addition, protein-drug interaction analysis identified the Ras signaling pathway and PI3K-Akt signaling pathway. Conclusions: Cats with symptomatic HCM have higher D-dimer and lower PT than healthy cats. Proteomic profiles may be used as potential biomarkers for the detection and management of HCM in cats. The use of D-dimer as a biomarker for HCM detection and the use of proteomic profiling for a better understanding of disease mechanisms remain to be further studied in cats. [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]

Administration of high-dose vitamin K1 (VK1) overcomes coagulopathy and bleeding elicited by acute poisoning with long-acting anticoagulant rodenticides (LAARs). However, long-term (months) treatment is required due to long LAAR biological half-lives that may lead to poor compliance and recurrent coagulopathy. The half-lives of LAARs are extended by slow metabolism, and similar to warfarin, are thought to undergo enterohepatic recirculation. We now show that treatment with the bile acid sequestrant cholestyramine (CSA) administered concomitantly with VK1 decreases plasma LAAR levels and increases LAAR fecal excretion. Daily CSA treatment for 14 days did not reduce plasma VK1 levels, or increase prothrombin time. Collectively, these data show that CSA accelerates LAAR clearance from rabbits without adverse effects on VK1 anticoagulation, and could provide an additional therapeutic option for treatment of LAAR poisoning. [ABSTRACT FROM AUTHOR]

Fenfluramine (Fintepla®) is approved for the treatment of seizures associated with the rare epileptic encephalopathies Dravet syndrome and Lennox–Gastaut syndrome. Fenfluramine is extensively metabolized; thus, patients with hepatic impairment (HI) might experience changes in exposure to fenfluramine or its metabolites. In this phase 1 study, we investigated the pharmacokinetics (PK) and safety of a single oral dose of 0.35 mg/kg fenfluramine in subjects with mild (n = 8), moderate (n = 8), or severe (n = 7) HI (Child–Pugh A/B/C, respectively) and healthy control subjects (n = 22) matched for sex, age, and BMI. All subjects underwent serial sampling to determine total plasma concentrations of fenfluramine and its active metabolite, norfenfluramine. Hepatic impairment was associated with increases in fenfluramine exposures, mainly area‐under‐the‐curve (AUC). Geometric least squares mean ratios (90% confidence intervals) for fenfluramine AUC0‐∞ in mild, moderate, and severe HI versus healthy controls were 1.98 (1.36–2.90), 2.13 (1.43–3.17), and 2.77 (1.82–4.24), respectively. Changes in exposure to norfenfluramine in mild, moderate, and severe HI were minimal compared with normal hepatic function. Exposures to fenfluramine and norfenfluramine in all HI groups were within the ranges that have been characterized in the overall development program, including ranges examined in exposure–response relationships for efficacy and safety in patients, and determined to have an acceptable safety profile. Mild and moderate HI had a modest effect on fenfluramine exposure that was not clinically meaningful, whereas the higher fenfluramine exposure in severe HI may require dose reduction based on general caution in this population. The modest decrease in norfenfluramine exposure is not considered clinically relevant. [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]

Intravenous lipid emulsion is used in the rescue treatment of certain poisonings. A complication is interference with laboratory analyses. The aim of this study was to determine the impact of intravenous lipid emulsion on routine laboratory analysis of coagulation parameters ex vivo and determine if any of the analytical techniques remain reliable. Samples were obtained from 19 healthy volunteers and divided in triplicate. One sample served as a control, and the other two were diluted to simulate the treatment of an average adult with Intralipid® 20 per cent Fresenius Kabi 100 mL (dilution-1) or 500 mL (dilution-2). Coagulation tests performed were prothrombin time, activated prothrombin time, D-dimer concentration and fibrinogen. Coagulation testing was performed by three techniques. Test-1 was performed on a Sysmex CN6000 analyzer. Test-2 was performed with a manual mechanical endpoint method using the semi-automated Stago KC4 Delta. Test-3 involved high-speed centrifugation before repeat testing on the Sysmex CN6000 analyzer. For test-1, only nine (47 per cent) samples in dilution-1 could be analyzed for coagulation tests, and no coagulation tests could be analyzed for dilution-2 because of lipaemia. For test-2 and test-3, all samples could be analyzed, and all results of both testing methods fell within the limits of the laboratory reference range. Difficulties in laboratory analysis of patients having received intravenous lipid emulsion are due to multiple factors. Most automated coagulation analyzers use optical measurements, which can be unreliable in the presence of a high intravenous lipid concentration. By altering the lipaemia in the testing solution using high-speed centrifugation or by using manual mechanical endpoint detection, we were able to obtain reliable results. These findings are limited by the use of an ex vivo method and healthy volunteers. This ex vivo model confirms that Intralipid® interferes with routine coagulation studies. It is important that clinicians are aware and inform their laboratories of its administration. [ABSTRACT FROM AUTHOR]

Objective: To describe and compare prothrombin time (PT), activated partial thromboplastin time (aPTT), thromboelastography (TEG), HCT, and platelet count measurements in a hemorrhage/over‐resuscitation model. Design: Randomized crossover study. Setting: University teaching hospital. Animals: Six cats. Interventions: Anesthetized cats underwent 3 treatments at 2‐month intervals. The treatments were as follows: NHR—no controlled hemorrhage and sham resuscitation; LRS—controlled hemorrhage and lactated Ringer's solution (LRS) for resuscitation; and Voluven—controlled hemorrhage and 6% tetrastarch 130/0.4 for resuscitation. The LRS and Voluven were administered at 60 and 20 mL/kg/h, respectively, for 120 minutes. Blood samples were drawn for PT, aPTT, TEG, HCT, and platelet count measurements at a healthy check (T − 7d), after controlled hemorrhage (T0), at 60 and 120 minutes of resuscitation (T60 and T120), and at 24 hours after completion of resuscitation (T24h). Data were analyzed using a general linear mixed model approach (significance was P < 0.05). Measurements and Main Results: Total median blood loss (controlled hemorrhage and blood sampling from T0 to T120) at T120 was 11.4, 31.0, and 30.8 mL/kg for NHR, LRS, and Voluven, respectively. PT and aPTT during LRS and Voluven were prolonged at T60 and T120 compared to NHR (P < 0.001). On TEG, the reaction time, kinetic time, and alpha‐angle were within reference intervals for cats at all time points in all treatments, while maximum amplitude was less than the reference interval (40 mm) at T0, T60, and T120 during Voluven and at T60 and T120 during LRS compared to NHR (both P < 0.001). The HCT and platelet count were significantly lower at T60 and T120 during LRS and Voluven compared to NHR (P < 0.001). Conclusions: Hypocoagulopathy was observed during hemorrhage and liberal fluid resuscitation. Prolongation of PT and aPPT and decreased clot strength may have been caused by hemodilution and platelet loss. [ABSTRACT FROM AUTHOR]

Abstract Background Hypertrophic cardiomyopathy (HCM) is a crucial heart disease in cats. The clinical manifestations of HCM comprise pulmonary edema, dyspnea, syncope, arterial thromboembolism (ATE), and sudden cardiac death. D-dimer and prothrombin time (PT) are powerful biomarkers used to assess coagulation function. Dysregulation in these two biomarkers may be associated with HCM in cats. This study aims to assess D-dimer levels, PT, and proteomic profiling in healthy cats in comparison to cats with symptomatic HCM. Results Twenty-nine client-owned cats with HCM were enrolled, including 15 healthy control and 14 symptomatic HCM cats. The D-dimer concentration and PT were examined. Proteomic analysis was conducted by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry and liquid chromatography-tandem mass spectrometry (LC-MS/MS). In symptomatic cats, D-dimer levels were statistically significantly higher (mean ± SEM: 372.19 ng/ml ± 58.28) than in healthy cats (mean ± SEM: 208.54 ng/ml ± 10.92) with P-value of less than 0.01, while PT was statistically significantly lower in symptomatic cats (mean ± SEM: 9.8 s ± 0.15) compared to healthy cats (mean ± SEM: 11.08 s ± 0.23) with P-value of less than 0.0001. The proteomics analysis revealed upregulation of integrin subunit alpha M (ITGAM), elongin B (ELOB), and fibrillin 2 (FBN2) and downregulation of zinc finger protein 316 (ZNF316) and ectonucleoside triphosphate diphosphohydrolase 8 (ENTPD8) in symptomatic HCM cats. In addition, protein-drug interaction analysis identified the Ras signaling pathway and PI3K-Akt signaling pathway. Conclusions Cats with symptomatic HCM have higher D-dimer and lower PT than healthy cats. Proteomic profiles may be used as potential biomarkers for the detection and management of HCM in cats. The use of D-dimer as a biomarker for HCM detection and the use of proteomic profiling for a better understanding of disease mechanisms remain to be further studied in cats.

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

Background/Aims The SAMe-TT2R2 score is used for assessing anticoagulation control (AC) quality with warfarin. However, it is hard to apply SAMe-TT2R2 score in Asian patients with atrial fibrillation (AF), because it has not been proven in those populations. This study aimed to validate the SAMe-TT2R2 score in Asian patients with AF and suggest a modified SAMe-TT2R2 score for this population. Methods We analyzed 710 Korean patients with AF who were using warfarin. The AC quality was assessed as the mean time in therapeutic range (TTR). Each component of SAMe-TT2R2 score was evaluated for the relationship with AC. Further clinical factors that predict AC were analyzed. Identified factors were re-assorted and constructed as SA2Me-TTR scoring system. Results Of the components of the SAMe-TT2R2 score, female, age, and rhythm control were associated with AC. Heart failure and renal insufficiency were newly identified factors associated with AC. The modified SA2Me-TTR score was reconstructed with the relevant risk factors (S, female gender, 1 point; A, age < 60 yr, 2 points; Me, medical history of heart failure, 1 point; T, treatment for rhythm control, 1 point; T, history of stroke or transient ischemic attack, 1 point; R, renal insufficiency, 1 point). The modified SA2Me-TTR score demonstrated an excellent relationship with the grading of AC. The modified SA2Me-TTR score ≤ 1 identified patients with good AC (hazard ratio 2.46, 95% CI 1.75–3.47). Conclusions The modified SA2Me-TTR score was useful for guiding oral anticoagulants selection in Asian patients with AF.

Abstract Malaria infection leads to hematological abnormalities, including deranged prothrombin time (PT). Given the inconsistent findings regarding PT in malaria across different severities and between Plasmodium falciparum and P. vivax, this study aimed to synthesize available evidence on PT variations in clinical malaria. A systematic literature search was performed in PubMed, Embase, Scopus, Ovid, and Medline from 27 November 2021 to 2 March 2023 to obtain studies documenting PT in malaria. Study quality was evaluated using the Joanna Briggs Institute checklist, with data synthesized through both qualitative and quantitative methods, including meta-regression and subgroup analyses, to explore heterogeneity and publication bias. From 2767 articles, 21 studies were included. Most studies reported prolonged or increased PT in malaria patients compared to controls, a finding substantiated by the meta-analysis (P

Background and Aim: Cardiogenic embolism (CE) is a common complication of feline hypertrophic cardiomyopathy (HCM), leading to severe clinical symptoms. This study compared the effects of rivaroxaban and enoxaparin combined with clopidogrel on cats. Materials and Methods: This was a single-center, prospective, randomized controlled trial. In this study, rivaroxaban or enoxaparin plus clopidogrel was prescribed to 23 cats for at least one of the following events: Abnormal movement of the anterior mitral leaflet during systole, enlargement of the left atrium, spontaneous echocardiographic contrast, or presence of arterial thromboembolism. Oral rivaroxaban (2.5 mg, q24 h) was prescribed to six cats. Subcutaneous injections of enoxaparin (1 mg/kg, q24 h) plus oral clopidogrel (3 mg/kg, PO q24 h) for 60 days were administered to 17 cats. Renal insufficiency and bleeding complications were observed. Plasma concentrations of D-dimer, prothrombin time (PT), partial thromboplastin time, and international normalized ratio (INR) were evaluated. We analyzed the relationship between echocardiography parameters and the effects of coagulation. Blood samples were collected from all cats at baseline and at 1 and 2 months post-treatment. Results: Rivaroxaban alone and in combination with enoxaparin and clopidogrel significantly affected PT and INR. In cats treated with 2.5 mg/kg rivaroxaban for 60 days, no bleeding or recurrence of thrombus formation was observed. These data support the use of rivaroxaban for the treatment of HCM-associated thromboembolism in cats. Conclusion: Treatment of HCM-associated thromboembolism with rivaroxaban alone demonstrated clinical effectiveness with no clinical complications in cats.

Background Activation of coagulation is a common phenomenon in patients with high-grade glioma, a primary malignant brain tumor. Objective Identify if there is an alteration in the coagulation profile in patients with high-grade glioma compared to other patients with benign brain tumors. Methods Sociodemographic and clinical characteristics, ECOG at admission, prothrombin time, activated partial thromboplastin time, international normalized ratio, platelet count, and blood panel results of 21 high-grade glioma patients (cases) and 42 meningioma patients (controls) from northern Peru were reviewed. Bivariate and multivariate analysis with logistic regression were performed to determine which factors are associated with glioma. Results Both groups had high proportions of high blood pressure (29%) and diabetes mellitus (14%). According to multivariate analysis, altered values for prothrombin time, platelet count, and ECOG score were associated with glioma (p=0.01). Furthermore, alterations in the blood panel were observed in both cases and controls but failed to reach statistical significance. Conclusion Patients with high-grade glioma seem to suffer more from hypercoagulable states than other patients with benign brain tumors, suggesting careful vigilance and anticoagulant treatment for these patients.

Introduction: Dilute Russell's viper venom time (dRVVT) and activated partial thromboplastin time (APTT) are the mainstay assays in lupus anticoagulant (LA) detection yet they have limitations, particularly in relation to interferences and specificity. The recently validated Taipan snake venom time (TSVT) screening with ecarin time (ET) confirmatory assays overcome many of those limitations due to the innate specificity engendered from direct prothrombin activation, and insensitivity to the effects of vitamin K antagonists (VKA). The present study aimed to further evidence diagnostic utility of TSVT/ET by performing them in samples from 116 nonanticoagulated patients with established triple‐positive antiphospholipid syndrome (APS). Methods: Samples were identified in three expert centres who performed dRVVT, APTT and solid phase antiphospholipid antibody assays with reagents from a variety of manufacturers. All samples additionally received TSVT/ET analysis using standardised reagents. Results: Ninety seven of 116 (83.6%) were dRVVT‐ and APTT‐positive, 85/97 (87.6%) of which were TSVT/ET‐positive, 9/116 (7.8%) were dRVVT‐positive only, 6 of which were TSVT/ET‐positive, and 10/116 (8.6%) were APTT‐positive only, 5 of which were TSVT/ET‐positive. 96/116 TSVT/ET‐positivity returned a high sensitivity for LA of 82.8%. Low coefficients of determination revealed weak relationships between LA potency and anticardiolipin and anti‐β2‐glycoprotein I antibody titres for all three LA assays. Conclusions: TSVT/ET has high sensitivity for the clinically significant LA found in triple positive APS patients. TSVT/ET can establish multiple LA assay positivity in nonanticoagulated patients negative for one of dRVVT or APTT, and is the only assay pairing insensitive to VKAs, the recommended anticoagulation for APS. [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]

Background and purpose: The need for dose adjustment of caspofungin in patients with hepatic impairment is controversial, especially for those with Child–Pugh B or C cirrhosis. The purpose of this study was to investigate the safety and efficacy of standard-dose caspofungin administration in Child–Pugh B and C cirrhotic patients in a real-world clinical setting. Patients and methods: The electronic medical records of 258 cirrhotic patients, including 67 Child–Pugh B patients and 191 Child–Pugh C patients, who were treated with standard-dose of caspofungin at the Second Affiliated Hospital of Chongqing Medical University, China, from March 2018 to June 2023 were reviewed retrospectively. The white blood cells (WBC), hepatic, renal and coagulation function results before administration and post administration on days 7, 14 and 21 were collected, and the efficacy was assessed in all patients at the end of caspofungin therapy. Results: Favorable responses were achieved in 137 (53.1%) patients while 34 (13.2%) patients died. We observed that some patients experienced an increase of prothrombin time (PT) or international normalized ratio (INR), or a decrease of WBC, but no exacerbation of hepatic or renal dysfunction were identified and no patient required dose interruption or adjustment because of an adverse drug reaction during treatment with caspofungin. Conclusions: Standard-dose of caspofungin can be safely and effectively used in patients with Child–Pugh B or C cirrhosis, and we appealed to re-assess the most suitable dosing regimen in this population to avoid a potential subtherapeutic exposure. [ABSTRACT FROM AUTHOR]

Background: Macrotrabecular‐massive hepatocellular carcinoma (MTM‐HCC) is highly aggressive. Comparing the diagnosis ability of CT and gadoxetate disodium (Gd‐EOB‐DTPA) MRI for MTM‐HCC are lacking. Purpose: To compare the performance of Gd‐EOB‐DTPA MRI and CT for differentiating MTM‐HCC from non‐MTM‐HCC, and determine the prognostic indicator. Study Type: Retrospective. Subjects: Post‐surgery HCC patients, divided into the training (N = 272) and external validation (N = 44) cohorts. Field Strength/Sequence: 3.0 T, T1‐weighted imaging, in‐opp phase, and T1‐weighted volumetric interpolated breath‐hold examination/liver acquisition with volume acceleration; enhanced CT. Assessment: Three radiologists evaluated clinical characteristics (sex, age, liver disease, liver function, blood routine, alpha‐fetoprotein [AFP] and prothrombin time international normalization ratio [PT‐INR]) and imaging features (tumor length, intratumor fat, hemorrhage, arterial phase peritumoral enhancement, intratumor necrosis or ischemia, capsule, and peritumoral hepatobiliary phase [HBP] hypointensity). Compared the performance of CT and MRI for diagnosing MTM‐HCC. Follow‐up occurred every 3–6 months, and nomogram demonstrated the probability of MTM‐HCC. Statistical Tests: Fisher test, t‐test or Wilcoxon rank‐sum test, area under the curve (AUC), 95% confidence interval (CI), multivariable logistic regression, Kaplan–Meier curve, and Cox proportional hazards. Significance level: P < 0.05. Results: Gd‐EOB‐DTPA MRI (AUC: 0.793; 95% CI, 0.740–0.839) outperformed CT (AUC: 0.747; 95% CI, 0.691–0.797) in the training cohort. The nomogram, incorporating AFP, PT‐INR, and MRI features (non‐intratumor fat, incomplete capsule, intratumor necrosis or ischemia, and peritumoral HBP hypointensity) demonstrated powerful performance for diagnosing MTM‐HCC with an AUC of 0.826 (95% CI, 0.631–1.000) in the external validation cohort. Median follow‐up was 347 days (interquartile range [IQR], 606 days) for the training cohort and 222 days (IQR, 441 days) for external validation cohort. Intratumor necrosis or ischemia was an independent indicator for poor prognosis. Data Conclusion: Gd‐EOB‐DTPA MRI might assist in preoperative diagnosis of MTM‐HCC, and intratumor necrosis or ischemia was associated with poor prognosis. Evidence Level: 4 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Background and Aim: The effects of different doses of garlic supplementation on coagulation times after an acute endurance exercise are likely to be varied. The aim of this study was to investigate the effects of different doses of garlic supplementation on partial thromboplastin time (aPTT) and prothrombin time (PT) after an acute endurance exercise in young athletic men. Materials and Methods: Fifteen healthy young active men in the competition stage (age 27.0±7.9 years; weight 73.9±6.4 kg; and VO2max 49.59±0.35 ml/kg/min) with at least three years of experience of regular exercise in 5000 m endurance running voluntarily participated in this study. The subjects took different doses of garlic (500,750 and 1000 mg) and starch (placebo) in four separate sessions. In each session, four hours after taking the supplement or placebo, the subjects performed 30 min of running on treadmill at the intensity of 65-85% of target heart rate. Three blood samples were taken before supplementation, before exercise and immediately after exercise. The repeated measures ANOVA and Bonferroni tests were used to analyze the difference between different doses of garlic after acute endurance exercise and the difference between each doses of garlic and placebo at p<0.05. Results: Three dosage of 500, 750 and 1000 mg garlic were significantly increased aPTT. However, after acute endurance exercise, the three dosages of garlic significantly decreased aPTT. Additionally, the aPTT was significantly more decreased with 500 mg compared to 1000 mg of garlic after acute endurance exercise. There were no significant difference in PT after acute endurance exercise between three different dosage of garlic. Conclusion: It seems that after an acute endurance exercise in active men, 500 mg of garlic is more effective dose for reducing aPTT. [ABSTRACT FROM AUTHOR]

Coronary artery lesions (CALs) are a major complication of Kawasaki disease (KD); however, data on CAL incidence and risk factors in recurrent KD are limited. Ninety-seven children with recurrent KD were retrospectively enrolled from 2013 to 2022, and CAL incidence was tracked during admission, discharge, and during follow-up. Initially, 27.8% had CAL at admission and discharge, declining to 7.2% at 12 months post-discharge. Most patients (66 of 97, 68.0%) did not exhibit CAL at any of the time points, 7 cases presented CAL at all time points, indicating a persistent CAL. The remaining 20 cases presented CAL at admission but recovered at discharge or during follow-up. Notably, transient CALs had presented at discharge, or during the follow-up, but finally resolved at 12 months after discharge. Notably, prior IVIG resistance and increased prothrombin time seemed associated with CAL in recurrent KD, suggesting they could help identify patients needing close monitoring. The study highlights decreasing CAL incidence over time in recurrent KD but with diverse patterns, emphasizing the importance of monitoring and further investigations to confirm these findings. [ABSTRACT FROM AUTHOR]

An imbalance in coagulation is associated with cardiovascular events. For prevention and treatment, anticoagulants, currently mainly xabans and gatrans, are used. The purpose of the present study was to provide a head-to-head comparison since there are no studies directly evaluating these novel anticoagulants. An additional aim was to find whether selected anthropological and biochemical factors can affect their anticoagulant properties as they are used in fixed doses. In this cross-sectional study, blood from 50 generally healthy donors was collected, and coagulation responses to dabigatran, argatroban, rivaroxaban, and apixaban, at a concentration of 1 μM, were analyzed. Heparin was used as a positive control. Prothrombin time (PT) expressed as international normalized ratio (INR) and activated partial thromboplastin time (aPTT) were measured and compared. Rivaroxaban was the most active according to PT/INR while argatroban according to aPTT. The ex vivo anticoagulant effect measured by INR correlated inversely with body mass index (BMI) in all four anticoagulants tested. Shortening of aPTT was associated with higher cholesterol and triglyceride levels. No sex-related differences were observed in response to the anticoagulant treatments. As this was an ex vivo study and pharmacokinetic factors were not included, the influence of BMI is of high therapeutic importance. [ABSTRACT FROM AUTHOR]

Background: Severe coagulation abnormalities are common in patients with COVID-19 infection. We aimed to investigate the relationship between pro-inflammatory cytokines and coagulation parameters concerning socio-demographic, clinical, and laboratory characteristics. Methods: Our study included patients hospitalized during the second wave of COVID-19 in the Republic of Serbia. We collected socio-demographic, clinical, and blood-sample data for all patients. Cytokine levels were measured using flow cytometry. Results: We analyzed data from 113 COVID-19 patients with an average age of 58.15 years, of whom 79 (69.9%) were male. Longer duration of COVID-19 symptoms before hospitalization (B = 69.672; p = 0.002) and use of meropenem (B = 1237.220; p = 0.014) were predictive of higher D-dimer values. Among cytokines, higher IL-5 values significantly predicted higher INR values (B = 0.152; p = 0.040) and longer prothrombin times (B = 0.412; p = 0.043), and higher IL-6 (B = 0.137; p = 0.003) predicted longer prothrombin times. Lower IL-17F concentrations at admission (B = 0.024; p = 0.050) were predictive of higher INR values, and lower IFN-γ values (B = −0.306; p = 0.017) were predictive of higher aPTT values. Conclusions: Our findings indicate a significant correlation between pro-inflammatory cytokines and coagulation-related parameters. Factors such as the patient's level of education, gender, oxygen-therapy use, symptom duration before hospitalization, meropenem use, and serum concentrations of IL-5, IL-6, IL-17F, and IFN-γ were associated with worse coagulation-related parameters. [ABSTRACT FROM AUTHOR]

This article presents the biochemical properties of poly(lactide)-zinc (PLA-Zn) composites obtained by DC magnetron sputtering of zinc onto melt-blown nonwoven fabrics. The biochemical properties were determined by the evaluation of the activated partial thromboplastin time (aPTT) and prothrombin time (PT). The antimicrobial activity of the PLA-Zn samples was additionally tested against representative Gram-positive and Gram-negative bacteria strains. A structural study of the PLA-Zn has been carried out using specific surface area and total pore volume (BET) analysis, as well as atomic absorption spectrometry with flame excitation (FAAS). PLA-Zn composites exhibited an antibacterial effect against the analyzed strains and produced inhibition zones against E. coli and S. aureus. Biochemical investigations revealed that the untreated PLA fibers caused the acceleration of the clotting of human blood plasma in the intrinsic pathway. However, the PLA-Zn composites demonstrated significantly different properties in this regard, the aPTT was prolonged while the PT was not altered. [ABSTRACT FROM AUTHOR]

Background: Home INR testing (patient self-testing) is feasible and effective for warfarin patients but little is known about real-world differences in outcomes for patients using PST versus laboratory-based INR monitoring. Objective: To compare the safety/efficacy of patient self-testing of real-world warfarin therapy versus office/lab-based monitoring of therapy. Design/Setting/Participants/Exposure: A retrospective claims-based analysis of warfarin patients enrolled in the MarketScan® Commercial Claims and Encounters and Medicare databases between January 1, 2013, and March 30, 2020. Stratification was based on INR testing method: patient self-testing versus testing at physicians' offices/local laboratory. The probability of adverse events in each cohort was determined after adjusting for demographic and baseline clinical characteristics using a repeated measures analysis. Main Measures: Rates of all adverse events: deep venous thrombosis, pulmonary embolism, bleeding, and stroke. A secondary outcome of interest was emergency department visits. Key Results: A total of 37,837 patients were included in the analysis: 1592 patients in the patient self-testing group and 36,245 in the office-based therapy group. After adjusting for demographic and baseline clinical characteristics, patients in the office-based group had statistically significantly higher rates of all adverse events (incidence rate ratio [IRR]=2.07, 95% CI [1.82, 2.36]), and specific adverse events including thromboembolism (IRR=4.38, 95% CI [3.29, 5.84]), major bleed (IRR=1.45, 95% CI [1.28, 1.64]), and stroke (IRR=1.30, 95% CI [1.05, 1.61]) than patients in the patient self-testing group. Office-based patients also had a statistically significant higher rate of emergency department visits than patient self-testing patients (IRR = 1.65, 95% CI [1.47, 1.84]). Conclusions/Relevance: This analysis of real-world claims data shows lower rates of stroke, thromboembolism, and major bleeding, as well as fewer emergency department visits, with patient self-testing compared to office-based/lab INR monitoring. Our finding that PST is safe and effective among current users suggests that more patients may benefit from its use. [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]

Background: Isolated prolongation of activated partial thromboplastin time (APTT) has various causes including inheritable bleeding disorders, and has medical significance as it can lead to the cancelation of surgery. However, even an emergency surgery can be conducted in a patient presenting with severe APTT prolongation, provided careful evaluation and appropriate measures are taken. Hence, the identification of the underlying etiology of the prolonged APTT is crucial. To date, little evidence exists regarding the prevalence of isolated APTT prolongation in Japanese patients undergoing surgery. Herein, we aimed to clarify the prevalence of isolated prolongation of APTT in the preoperative setting and to identify the reasons underlying isolated, severely prolonged APTT. Methods: Preoperative coagulation data of all elective and emergent patients who presented to the anesthetic department between January 1, 2020, and June 30, 2023, were retrospectively collected. Isolated prolongation of APTT was defined as an APTT ≥ 37 s with an international normalized ratio of prothrombin time < 1.2. The underlying etiology of the patient with isolated, severely prolonged APTT (≥ 46 s) was investigated, and canceled surgical procedures in relation to the isolated APTT prolongation were searched. Results: Overall, 10,684 measurements from 9413 patients were included, of which 725 (6.8%) were identified as having isolated APTT prolongation. The reasons for the severely prolonged APTT (n = 60) were miscellaneous, with the most frequently detected etiology being antiphospholipid antibody positivity. Preoperative isolated APTT prolongation contributed to the cancellation of surgery in elective five cases. Conclusions: We clarified the prevalence of preoperative isolated prolongation of APTT. The presence of antiphospholipid antibody was the most frequently detected etiology of the patient with isolated, severely prolonged APTT. The present study provides an important dataset regarding the isolated prolongation of APTT in East Asian patients undergoing surgery. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the risk factors influencing the development of cefoperazone-induced coagulopathy in critically ill patients and determine the threshold of serum trough concentration. Methods: A retrospective case-control study was conducted in the intensive care unit patients treated with cefoperazone, and it was approved by the Ethical Committee of Drum Tower Hospital affiliated with the Medical School of Nanjing University (NO.2023-158-01). Patients were divided into the normal group and coagulopathy group based on prothrombin time. The clinical characteristics of the two groups were compared using univariate analysis. The serum concentration threshold and influencing factors of cefoperazone-induced coagulopathy in critically ill patients were analyzed using the receiver operating characteristic curve and multivariate logistic regression analysis. Results: A total of 113 patients were included, and cefoperazone-induced coagulopathy occurred in 39 patients, with an incidence of 34.5%. These patients experienced significant prothrombin time prolongation around day 6 (median) after cefoperazone application. The serum trough concentration threshold of cefoperazone-induced coagulopathy in critically ill patients was 87.765 mg/l. Multivariate logistic regression analysis revealed that the APACHE II score (p = 0.034), prophylactic use of vitamin K1 (p < 0.001), hepatic impairment (p = 0.014), and Cmin ≥ 87.765 mg/l (p = 0.005) were associated with cefoperazone-induced coagulopathy. Conclusion: Cefoperazone-induced coagulopathy usually occurs on the 6th day of cefoperazone use in critically ill patients. The risk will increase in patients with an APACHE II score > 25, hepatic impairment, and cefoperazone Cmin ≥ 87.765 mg/l. Vitamin K1 is effective in preventing this adverse reaction. [ABSTRACT FROM AUTHOR]

Malaria infection leads to hematological abnormalities, including deranged prothrombin time (PT). Given the inconsistent findings regarding PT in malaria across different severities and between Plasmodium falciparum and P. vivax, this study aimed to synthesize available evidence on PT variations in clinical malaria. A systematic literature search was performed in PubMed, Embase, Scopus, Ovid, and Medline from 27 November 2021 to 2 March 2023 to obtain studies documenting PT in malaria. Study quality was evaluated using the Joanna Briggs Institute checklist, with data synthesized through both qualitative and quantitative methods, including meta-regression and subgroup analyses, to explore heterogeneity and publication bias. From 2767 articles, 21 studies were included. Most studies reported prolonged or increased PT in malaria patients compared to controls, a finding substantiated by the meta-analysis (P < 0.01, Mean difference: 8.86 s, 95% CI 5.32–12.40 s, I2: 87.88%, 4 studies). Severe malaria cases also showed significantly higher PT than non-severe ones (P = 0.03, Hedges’s g: 1.65, 95% CI 0.20–3.10, I2: 97.91%, 7 studies). No significant PT difference was observed between P. falciparum and P. vivax infections (P = 0.88, Mean difference: 0.06, 95% CI − 0.691–0.8, I2: 65.09%, 2 studies). The relationship between PT and malaria-related mortality remains unclear, underscoring the need for further studies. PT is typically prolonged or increased in malaria, particularly in severe cases, with no notable difference between P. falciparum and P. vivax infections. The inconsistency in PT findings between fatal and non-fatal cases highlights a gap in current understanding, emphasizing the need for future studies to inform therapeutic strategies. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to ascertain pediatric age-specific reference ranges for prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (aPTT). Retrospective data were obtained from healthy children who had undergone preoperative tests and compared with those obtained from a group of adult patients. Methods: Reference individuals were determined by the indirect method. A total of 15,179 patients who presented to our hospital in 2022 and 2023 were retrospectively reviewed. Pediatric patients were divided into three age groups: 1-5 years (n=1949), 6--10 years (n=1563), and 11-17 years (n=508). The adult age group consisted of healthy individuals aged 18--50 years (n=11165). The tests were run in a coagulation autoanalyzer with the mechanical coagulometric measurement method. Reference ranges were analyzed using the non-parametric method statistically. Results: The mean PT, INR, and aPTT values were found to be 14.34±1.99 s, 1.07±0.16, and 31.43±3.47 s, respectively, in children aged 1-5 years; 14.48±1.40 s, 1.08±0.11, and 31.30±2.66 s, respectively, in those aged 6-10 years; and 14.73±1.12 s, 1.10±0.09, and 31.21±2.91 s, respectively, in those aged 11-17 years. Among the adults aged 18-50 years, the mean PT, INR, and aPTT values were 13.95±1.40 s, 1.04±0.11, and 30.21±2.86 s, respectively. The mean PT, INR, and aPTT values of children aged 1-5 years, 6-10 years, and 11-17 years were statistically significantly higher than those of adults aged 18-50 years (for each group p<0.01). Conclusion: It is important for laboratories to employ age-specific reference ranges for coagulation tests performed on children to ensure accurate diagnosis and avoid unnecessary further investigations. In this study, the reference ranges of the PT, INR, and aPTT parameters were determined for pediatric patients and found to be significantly higher than those of adults, which will be useful for clinical evaluation and diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to investigate the effects of lipemia on clinical chemistry and coagulation parameters in native ultralipemic (NULM) and intravenous lipid emulsion (IVLE) spiked samples. Materials and methods: The evaluation of biochemistry (photometric, ion-selective electrode, immunoturbidimetric method), cardiac (electrochemiluminescence immunoassay method) and coagulation (the viscosity-based mechanical method for prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen and the immunoturbidimetric method for D-dimer) parameters were conducted. In addition to the main pools, five pools were prepared for both types of lipemia, each with triglyceride (TG) concentrations of approximately 2.8, 5.7, 11.3, 17.0 and 22.6 mmol/L. All parameters' mean differences (MD%) were presented as interferographs and compared with the desirable specification for the inaccuracy (bias%). Data were also evaluated by repeated measures of ANOVA. Results: Prothrombin time and APTT showed no clinically relevant interference in IVLE-added pools but were negatively affected in NULM pools (P < 0.001 in both parameters). For biochemistry, the most striking difference was seen for CRP; it is up to 134 MD% value with NULM (P < 0.001) at the highest TG concentration, whereas it was up to - 2.49 MD% value with IVLE (P = 0.009). Albumin was affected negatively upward of 5.7 mmol/L TG with IVLE, while there was no effect for NULM. Creatinine displayed significant positive interferences with NULM starting at the lowest TG concentration (P = 0.028). There was no clinically relevant interference in cardiac markers for both lipemia types. Conclusions: Significant differences were scrutinized in interference patterns of lipemia types, emphasizing the need for careful consideration of lipemia interferences in clinical laboratories. It is crucial to note that lipid emulsions inadequately replicate lipemic samples. [ABSTRACT FROM AUTHOR]

Objective: Pharmacogenomics plays an important role in drug metabolism. A stable anticoagulation is important for primary and secondary prevention of cardioembolic stroke and cerebral venous sinus thrombosis (CVST). We report the role of cytochrome P450 (CYP2C9*2/*3) and vitamin K epoxide reductase subunit 1 (VKORC1) genotypes and acquired causes in maintaining stability of anticoagulation following acenocoumarin in cardioembolic stroke and CVST. Methods: The study comprised 157 individuals with cardioembolic stroke and CVST who were on acenocoumarin. Their comorbidities, comedication, and dietary habits were noted. Prothrombin time and international normalized ratio (INR) were measured during follow-up, and the coagulation status was categorized as stable (>50% occasions in therapeutic range) and unstable (>50% below and above therapeutic range). Genotyping of VKORC1, CYP2C9*2, and CYP2C9*3 was done by polymerase chain reaction-restriction fragment length polymorphism. Bleeding and embolic complications were noted. The predictors of unstable INR were evaluated using multivariate analysis. Results: INR was stable in 47.8% and unstable in 52.2% of patients. Patients with mutant genotypes required low dose of acenocoumarin. The predictors of unstable INR were metallic valve (odds ratio [OR] 4.07, 95% confidence interval [CI] 1.23-13.49, P = 0.02), use of digoxin (OR 0.031, 95% CI 0.13-0.74, P = 0.09), proton pump inhibitor (OR 0.23, 95% CI 0.06-0.91, P = 0.037), sodium valproate (OR 0.22, 95% CI 0.05-0.85, P = 0.029), and CYP2C9*2 genotype (OR 5.57, 95% CI 1.19-26.06, P = 0.02). Conclusions: Variant genotypes of VKORC1, CYP2C9*2, and CYP2C9*3 required lower dose of acenocoumarin, and CYP2C9*2 was associated with unstable INR. Comedication is a modifiable risk factor that needs attention. [ABSTRACT FROM AUTHOR]

Objective The aim of this research was to determine the frequency of antiphospholipid antibodies (aPL) in patients with COVID-19. Methods The frequency and titers of anticardiolipin antibodies (aCL) and anti-β2 glycoprotein I antibodies (aβ2GPI) were determined in sera of adult patients hospitalized with COVID-19. Immunoglobulin (Ig)G, IgA, IgM aCL, and aβ2GPI were measured using enzyme-linked immunosorbent assay. Results Eighty-three patients were included in the study. The mean age of patients was 62 ± 13.9 years, ranging from 23 to 86 years. Stratification according to severity of infection divided patients in 2 groups: 45 patients with moderate infection and 38 patients with critical or severe infection. Out of the 83 patients suffering from COVID-19, aPL (aCL or aβ2GPI) were detected in 24 patients (28.9%). IgG, IgA and IgM aβ2GPI were positive in 2.4%, 16.9% and 8.4%, respectively. IgG, IgA and IgM aCL showed positivity in 7.2%, 0%, and 4.8%, respectively. The frequency of aPL was 36.8% in patients with critical/severe infection and 22.2% in patients with moderate infection. In critical/severe patients, the frequency of aβ2GPI was significantly higher than aCL (34.2% vs 13.2%, P =.03) and aβ2GPI-IgA were significantly more frequent than aβ2GPI-IgG (21.1% vs 2.6%, P =.028). Conclusion In this cross-sectional study, aPL and particularly aβ2GPI-IgA were common in patients with COVID-19. [ABSTRACT FROM AUTHOR]

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Background & Objective: Uncertainties exist about the diagnostic and prognostic role of hemocytometry values in patients with COVID-19 especially in pregnancy. This study aims to investigate hemostatic changes in pregnant woman with coronavirus disease (COVID-19) and their relationship to disease severity. Materials & Methods: This research is an analytic observational study with case control design. Subject was gathered from Hasan Sadikin General Hospital Bandung, Indonesia patients' medical records from June 2021 - March 2022. Inclusion criteria for this study are all pregnant COVID-19 patients with prothrombin time (PT), activated partial thromboplastin time (aPTT), and D-dimer examination. The exclusion of this study, all pregnant COVID-19 patients without required examination. PT, aPTT, and D-dimer were measured by Stago kits on a Stago automated coagulation analyzer (STA Compact Max®). Data was then analyzed by Kruskal Wallis with IBM SPSS Statistic 26th with α=0.05. Results: Statistical analysis shows there's correlation between different severity levels with D-Dimer. This study shows the mean of D-Dimer of each severity levels; asymptomatic 4.85 mg/L, mild 2.86 mg/L, moderate 5.47 mg/L and severe 14.51 mg/L (p <0.000). Changes seen after mild group which increase to 5.47 mg/dL in moderate COVID-19 and furthermore increase in severe become 14.51 mg/L. No changes in PT and aPTT were found. Conclusion: In conclusion, our findings demonstrate that coagulopathy is associated with the severity of COVID-19 illness. D-dimer is an important parameter for evaluating the COVID-19 severity in pregnancy. This further could serve as a diagnostic category to differ the severity of COVID-19 in pregnancy. [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]

Background: To analyze the relationship between lipid metabolism, coagulation function, and bone metabolism and the contributing factor and staging of non-traumatic femoral head necrosis, and to further investigate the factors influencing the blood indicators related to the staging of non-traumatic femoral head necrosis. Methods: The medical records of patients with femoral head necrosis were retrieved from the inpatient medical record management system, and the lipid metabolism, bone metabolism, and coagulation indices of non-traumatic femoral head necrosis (including alcoholic, hormonal, and idiopathic group) were obtained according to the inclusion and exclusion criteria, including Low-Density Lipoprotein Cholesterol, Triglycerides, Non-High-Density Lipoprotein Cholesterol, Apolipoprotein A1, Apolipoprotein (B), Apolipoprotein (E), Uric Acid, Alkaline Phosphatase, Bone-specific Alkaline Phosphatase, Activated Partial Thromboplastin Time, Prothrombin Time, D-dimer, Platelet count. The relationship between these blood indices and the different stages under different causative factors was compared, and the factors influencing the stages of non-traumatic femoral head necrosis were analyzed using multivariate logistic regression. Results: (i) Gender, Age and BMI stratification, Low-density Lipoprotein Cholesterol, Triglycerides, Non-High-density Lipoprotein Cholesterol, Apolipoprotein (B), Apolipoprotein (E), Uric Acid, Bone-specific Alkaline Phosphatase, Activated Partial Thromboplastin Time, Plasminogen Time, D-dimer, and Platelet count of the alcohol group were statistically different when compared among the different ARCO staging groups; (ii) The differences in Age and BMI stratification, Triglycerides, Non-High-density Lipoprotein Cholesterol, Apolipoprotein A1, Apolipoprotein B, Apolipoprotein E, Uric Acid, Bone-specific Alkaline Phosphatase, Activated Partial Thromboplastin Time, Plasminogen Time, D-dimer, and Platelet count were statistically significant when compared among the different phases in the hormone group (P < 0.05); (iii) The differences in Age and BMI stratification, Non-High-Density Lipoprotein Cholesterol, Apolipoprotein A1, Apolipoprotein (B), Apolipoprotein (E), Uric Acid, Activated Partial Thromboplastin Time, D-dimer, and Platelet count were statistically significant when compared among the different stages in the idiopathic group (P < 0.05); (v) Statistically significant indicators were included in the multivariate logistic regression analysis, excluding the highly correlated bone-specific alkaline phosphatase, and the results showed that Low-density lipoprotein was negatively correlated with changes in the course of ARCO, and Non-High-Density Lipoprotein cholesterol, Apo B, Activated Partial Thromboplastin Time, and Platelet count were significantly and positively correlated with disease progression. Conclusion: An abnormal hypercoagulable state as well as an abnormal hyperlipidemic state are risk factors for the progression of non-traumatic femoral head necrosis under various exposure factors, as indicated by Non-High-Density Lipoprotein Cholesterol, Apolipoprotein B, Activated Fractional Thromboplastin Time, and Platelet Counts. [ABSTRACT FROM AUTHOR]

Background. The lack of preceding research in Sudan emphasizes the importance of this study, which contributes critical data to the global understanding of sleep-related health effects. This study investigates the complex relationship between sleep deprivation and blood-related factors, particularly focusing on full blood count and coagulation parameters. Methods. From January to March 2022, a case-control study was conducted in Kosti, Sudan. A control group of 11 healthy 23–33-year-olds (6 men and 5 women) had regular sleep patterns. Six men and five women ages 23–33 were chosen for this sleep-deprived case study. The case group was deprived of sleep from 7:00 p.m. to 7:00 a.m. for three days and allowed to sleep normally during the day. Daily at 7:00 a.m., antecubital vein blood was drawn. The ACL 7000 coagulation analyzer and Sysmex fully automated hematology analyzers were used for coagulation and whole blood count analysis. Data analysis included descriptive and inferential approaches like the Mann–Whitney U test for group comparisons. Results. The study found no significant differences in total white blood cell counts reported between case and control groups (p = 0.898). The case group had a substantial drop in lymphocyte counts on day 3 (p = 0.016). The third day showed significant differences in neutrophil and eosinophil levels (p = 0.003 and 0.000, respectively). The difference in hemoglobin and hematocrit on day 3 was statistically significant (p = 0.023). Platelet counts were stable. Both groups' prothrombin times were unaffected. On all three days, groups had significant differences in activated partial thromboplastin time (APTT) (p = 0.004). Therefore, the intrinsic coagulation system may have changed. Conclusion. This study demonstrates the complex link between sleep deprivation, coagulation indicators, and complete blood count. Monitoring blood indicators in poor sleep helps explain fundamental mechanisms and medicinal implications. [ABSTRACT FROM AUTHOR]

Background and Aim: Cardiogenic embolism (CE) is a common complication of feline hypertrophic cardiomyopathy (HCM), leading to severe clinical symptoms. This study compared the effects of rivaroxaban and enoxaparin combined with clopidogrel on cats. Materials and Methods: This was a single-center, prospective, randomized controlled trial. In this study, rivaroxaban or enoxaparin plus clopidogrel was prescribed to 23 cats for at least one of the following events: Abnormal movement of the anterior mitral leaflet during systole, enlargement of the left atrium, spontaneous echocardiographic contrast, or presence of arterial thromboembolism. Oral rivaroxaban (2.5 mg, q24 h) was prescribed to six cats. Subcutaneous injections of enoxaparin (1 mg/kg, q24 h) plus oral clopidogrel (3 mg/kg, PO q24 h) for 60 days were administered to 17 cats. Renal insufficiency and bleeding complications were observed. Plasma concentrations of D-dimer, prothrombin time (PT), partial thromboplastin time, and international normalized ratio (INR) were evaluated. We analyzed the relationship between echocardiography parameters and the effects of coagulation. Blood samples were collected from all cats at baseline and at 1 and 2 months post-treatment. Results: Rivaroxaban alone and in combination with enoxaparin and clopidogrel significantly affected PT and INR. In cats treated with 2.5 mg/kg rivaroxaban for 60 days, no bleeding or recurrence of thrombus formation was observed. These data support the use of rivaroxaban for the treatment of HCM-associated thromboembolism in cats. Conclusion: Treatment of HCM-associated thromboembolism with rivaroxaban alone demonstrated clinical effectiveness with no clinical complications in cats. [ABSTRACT FROM AUTHOR]