Partial Thromboplastin Time Research Articles

Protein disulfide isomerase uses thrombin-antithrombin complex as a template to bind its target protein and alter the blood coagulation rates.

During inflammation and situations of cellular stress protein disulfide isomerase (PDI) is released in the blood plasma from the platelet and endothelial cells to influence thrombosis. The addition of exogenous PDI makes the environment pro-thrombotic by inducing disulfide bond formation in specific plasma protein targets like vitronectin, factor V, and factor XI. However, the mechanistic details of PDI interaction with its target remain largely unknown. A decrease in the coagulation time was detected in activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) on addition of the purified recombinant PDI (175 nM). The coagulation time can be controlled using an activator (quercetin penta sulfate, QPS) or an inhibitor (quercetin 3-rutinoside, Q3R) of PDI activity. Likewise, the PDI variants that increase the PDI activity (H399R) decrease, and the variant with low activity (C53A) increases the blood coagulation time. An SDS-PAGE and Western blot analysis showed that the PDI does not form a stable complex with either thrombin or antithrombin (ATIII) but it uses the ATIII-thrombin complex as a template to bind and maintain its activity. A complete inhibition of thrombin activity on the formation of ATIII-thrombin-PDI complex, and the complex-bound PDI-catalyzed disulfide bond formation of the target proteins may control the pro- and anti-thrombotic role of PDI.

Machine learning algorithm predicts urethral stricture following transurethral prostate resection

PurposeTo predict the post transurethral prostate resection(TURP) urethral stricture probability by applying different machine learning algorithms using the data obtained from preoperative blood parameters.MethodsA retrospective analysis of data from patients who underwent bipolar-TURP encompassing patient characteristics, preoperative routine blood test outcomes, and post-surgery uroflowmetry were used to develop and educate machine learning models. Various metrics, such as F1 score, model accuracy, negative predictive value, positive predictive value, sensitivity, specificity, Youden Index, ROC AUC value, and confidence interval for each model, were used to assess the predictive performance of machine learning models for urethral stricture development.ResultsA total of 109 patients’ data (55 patients without urethral stricture and 54 patients with urethral stricture) were included in the study after implementing strict inclusion and exclusion criteria. The preoperative Platelet Distribution Width, Mean Platelet Volume, Plateletcrit, Activated Partial Thromboplastin Time, and Prothrombin Time values were statistically meaningful between the two cohorts. After applying the data to the machine learning systems, the accuracy prediction scores for the diverse algorithms were as follows: decision trees (0.82), logistic regression (0.82), random forests (0.91), support vector machines (0.86), K-nearest neighbors (0.82), and naïve Bayes (0.77).ConclusionOur machine learning models’ accuracy in predicting the post-TURP urethral stricture probability has demonstrated significant success. Exploring prospective studies that integrate supplementary variables has the potential to enhance the precision and accuracy of machine learning models, consequently progressing their ability to predict post-TURP urethral stricture risk.

D-Dimer, Activated Partial Thromboplastin Time, and Prothrombin Time Comparison in Different Severity Levels of COVID-19 in Pregnancy: A Single Center Study

D-Dimer, Activated Partial Thromboplastin Time, and Prothrombin Time Comparison in Different Severity Levels of COVID-19 in Pregnancy: A Single Center Study

Prophylactic Unfractionated Heparin in Antepartum Hospitalizations: A Randomized Controlled Trial.

To assess the effect of gestational age-based dosing of unfractionated heparin (UFH) compared with standard dosing of UFH for thromboprophylaxis on an elevated serum activated partial thromboplastin time (aPTT) during prolonged antepartum hospitalizations. This was a randomized trial of pregnant persons who were admitted in the antepartum period for at least 72 hours. Participants were randomly allocated to the standard dose of UFH (5,000 units subcutaneously every 12 hours) or the gestational age-based dose of UFH (first trimester [less than 14 weeks]: 5,000 units subcutaneously every 12 hours; second trimester [14-27 6/7 weeks]: 7,500 units subcutaneously every 12 hours; third trimester (28 weeks or more): 10,000 units subcutaneously every 12 hours). The primary outcome was the proportion of antepartum patients who had an elevated serum aPTT value above the normal range (more than 36.2 seconds) 6 hours after an UFH dose. Secondary outcomes included the development of venous thromboembolism (VTE) and reported side effects of heparin administration. Between December 15, 2020, and April 1, 2022, 97 patients with antepartum hospitalizations were screened and 46 were randomized: 22 allocated to standard dosing and 24 allocated to gestational age-based dosing of UFH. A significantly greater proportion of antepartum patients who received gestational age-based dosing had an abnormal elevation in aPTT compared with those who received standard dosing (33.3% vs 4.8%, P =.02). Gestational age-based dosing resulted in higher maximum [interquartile range] aPTT (30.4 [27.4, 37.5] vs 26.6 [23.0, 29.6], P =.01) and anti-Xa levels (0.09 [0.09, 0.11] vs 0.09 [0.09, 0.09], P =.04). There was no significant difference in VTE between groups ( P =.47). Gestational age-based dosing of UFH for thromboprophylaxis of antepartum hospitalizations was associated with significantly increased rates of elevated coagulation parameters compared with standard fixed dosing. This study suggests a need for close monitoring if higher doses of UFH during pregnancy are used later in gestation. The efficacy of gestational age-based dosing compared with standard dosing for UFH to prevent thromboembolic events remains an area for future investigation. ClinicalTrials.gov , NCT04635839.

Association of prothrombin time, thrombin time and activated partial thromboplastin time levels with preeclampsia: a systematic review and meta-analysis

BackgroundPreeclampsia (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.MethodsThis 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.ResultsA 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.ConclusionsThe 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.

Оценка системы гемостаза кроликов после прижизненного экспериментального моделирования забрюшинной гематомы

The purpose of research is to study the dynamics of the hemostasis system in rabbits after intravital experimental modeling of retroperitoneal hematoma. The object of the study was 50 male rabbits of the Gray Giant breed, from which experimental and control groups of 25 individuals each were formed. Animals of the experimental group under non-inhalation anesthesia underwent intravital modeling of a retroperitoneal hematoma using a method we developed, including taking blood from the ear artery with the addition of an anticoagulant and subsequent injection of autologous blood into the retroperitoneal space. Animals in the control group were subjected to non-inhalational anesthesia only. Intravital experimental modeling of retroperitoneal hematoma in rabbits led to a number of significant changes in the hemostatic system, which were most pronounced in the first 14 days after the experiment. The international norma-lized ratio (INR) in the experimental group of animals had significantly low values compared to the control group only on the 1st, 3rd and 7th days, and the activated partial thromboplastin time (aPTT) – on the 1st, 3rd days , 7th and 14th days after the experiment. There were no significant differences in the level of fibrinogen in blood plasma between the animals of the experimental and control groups. Thrombin time (TT) in animals of the experimental group was significantly higher only on the 1st, 3rd, 7th and 14th days, and the D-dimer content was significantly higher in all studied periods after the experiment in comparison with the control group animals. The highest level of D-dimer in the blood plasma of animals in the experimental group was recorded on the 7th day and probably indicated that in retroperitoneal hematomas the most active processes of fibrinolysis occur at this time. Low values of INR in the first 7 days and aPTT in the first 14 days, as well as prolongation of TT in the first 14 days after the experiment, give reason to believe that with retroperitoneal hematomas, the threshold for the likelihood of thrombus formation increases during these periods.

Biocompatible polyethersulfone membrane modified by hydrophilic polymer decorated magnetic nanoparticles gilded by facile external magnetic field

AbstractPolymer‐based membranes such as polyethersulfone are widely used for hemodialysis and bio‐related applications; however, this type of membrane still fails to satisfy optimum performance in terms of clearance, safety, and bio‐adaptability. Herein, a polymer brush of polyvinylpyrrolidone is decorated on the surface of magnetic nanoparticles by using reversible addition‐fragmentation chain transfer polymerization (RAFT), and under the guidance of an external magnetic field, the prepared magnetic nanoparticles with the polymer brush system are blended with a polyethersulfone membrane during a liquid‐liquid phase inversion process. The prepared membranes with different loads of the pure magnetic nanoparticle and polyvinylpyrrolidone@magnetic nanoparticle polymer brushes are prepared, compared with the pristine membrane, the modified membrane shows a high flux value at 349 L m−2 h−1 and 99.9% bovine serum albumin protein rejection. This membrane also demonstrated improved hydrophilicity and pore structure compared with the pristine membrane. Concerning the blood biocompatibility analysis, the modified membranes acquire prolonged time for clotting factors such as prothrombin time, activated partial thromboplastin time, and thrombin time while exhibiting less fibrinogen concertation at 0.4 g L−1. Furthermore, for the first time, an innovative method for fouling detection based on magnetic field attenuation due to protein accumulation on the membrane surface is reported; the method in this work could be a positive booster for the safe use of polymeric membranes in hemodialysis and bio‐based applications.

Long-term oral administration of Kelisha capsule does not cause hepatorenal toxicity in rats

Ethnopharmacological relevanceKelisha capsules (KLS) are often used to treat acute diarrhoea, bacillary dysentery, heat stroke, and other diseases. One of its components, Asarum, contains aristolochic acid I which is both nephrotoxic and carcinogenic. However, the aristolochic acid (AA) content in KLS and its toxicity remain unclear. Aim of the studyThe aims of this study were to quantitatively determine the contents of five aristolochic acid analogues (AAAs) in Asarum and KLS, and systematically evaluate the in vivo toxicity of KLS in rats. Materials and methodsUltra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to determine the content of the five AAAs in Asarum and KLS. Sprague–Dawley rats were administered KLS at 0, 0.75, 1.5, and 3.0 g/kg respectively, and then sacrificed after 4 weeks of administration or after an additional 2 weeks of recovery. The endpoints assessed included body weight measurements, serum biochemistry and haematology indices, and clinical and histopathological observations. ResultsThe AAAs content in Asarum sieboldii Miq. (HB-ESBJ) were much lower than those of the other Asarums. The contents of AA I, AA IVa, and aristolactam I in KLS were in the ranges of 0.03–0.06 μg/g, 1.89–2.16 μg/g, and 0.55–1.60 μg/g, respectively, whereas AA II and AA IIIa were not detected. None of the rats showed symptoms of toxic reactions and KLS was well tolerated throughout the study. Compared to the control group, the activated partial thromboplastin time values of rats in the 1.5 and 3.0 g/kg groups significantly reduced after administration (P < 0.05). In addition, the serum triglycerides of male rats in the 0.75 and 1.5 g/kg groups after administration, and the 0.75, 1.5, 3.0 g/kg groups after recovery were significantly decreased (P < 0.01 or P < 0.001). No significant drug-related toxicological changes were observed in other serum biochemical indices, haematology, or histopathology. ConclusionsThe AA I content in KLS met the limit requirements (<0.001%) of the Chinese Pharmacopoeia. Therefore, it is safe to use KLS in the short-term. However, for safety considerations, attention should be paid to the effects of long-term KLS administration on coagulation function and triglyceride metabolism.

Anti-Xa/APTT discrepancy in heparinized ImpellaTM-supported cardiogenic shock patients can predict mortality

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Fonds Wetenschappelijk Onderzoek Flanders. Background Meticulous management of unfractionated heparin (UFH) is important to avoid complications in patients receiving percutaneous mechanical circulatory support (pMCS) for cardiogenic shock (CS). Whereas the anti-Xa assay directly measures UFH activity, the activated partial thromboplastin time (APTT) remains the most frequently used test. The APTT covers the intrinsic and common coagulation pathway and can be influenced by various confounding (laboratory) factors during critical illness, unrelated to the patient’s (anti)coagulation state. Purpose We investigated a CS population supported with isolated left-sided Impella™ and UFH-anticoagulation. UFH-levels were guided by anti-Xa with APTT in parallel. Here, we focus on those samples with anti-Xa in-range and discrepantly prolonged parallel APTT-measurements. We differentiated the APTT-prolongation according to reduced fibrinogen levels and/or prolonged INR (factor XI/XII consumption vs. concomitant conditions) and correlated this with mortality during Impella™-support. Methods Between April-2017 and June-2022, all CS patients with isolated left-sided ImpellaTM-support (&amp;gt;24h) and UFH anticoagulation monitored by anti-Xa with APTT in parallel were assessed at two high-volume tertiary institutions. In-range anti-Xa samples (between 0.20-0.30IU/mL or 0.31-0.50IU/mL based on the patient’s profile) were selected. In-range APTT values were considered between 40-55s and 55-80s respectively. Samples with prolonged APTT as compared to the in-range anti-Xa were allocated in 4 groups based on fibrinogen (&amp;lt;1.5g/dL or ≥ 1.5g/dL) and INR (&amp;lt;1.5 or ≥1.5) on the same day as the sample with prolonged APTT. Mortality of patients with normal fibrinogen ànd INR was then compared to those with abnormal fibrinogen and/or INR via a Chi² test. Results Ninety-three ImpellaTM-runs (77 men, 83%) with a median age of 56 years (IQR 46-66) were analyzed. Median support was 6 days (IQR 4-12). Among the 1914 in-range anti-Xa samples, parallel APTT was prolonged in 468 samples (24%) across 59 patients. 80 Samples from 2 patients were excluded due to absence of fibrinogen and/or INR measurements on the same day. The mortality in patients with prolonged APTT but normal fibrinogen levels and normal INR (N=29; due to FXI/FXII-consumption) was significantly lower compared to the remaining 28 patients who showed samples with reduced fibrinogen levels and/or prolonged INR (10% vs. 32%; p=0.043). Conclusions Fibrinogen-levels and INR uncover the underlying etiology in discrepant APTT-prolongation as compared to an in-range anti-Xa value in a CS population during left-sided ImpellaTM support. In patients with prolonged APTT and reduced fibrinogen (&amp;lt;1.5 g/dL) and/or prolonged INR (≥1.5), the risk of mortality is significantly elevated. This is due to concomitant conditions with high mortality (liver failure, sepsis, DIC,…). We advocate to monitor such patients carefully and treat them in a patient/disease tailored approach.

Heparin monitoring in ImpellaTM-supported cardiogenic shock patients: the benefit of parallel dual testing

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Fonds Wetenschappelijk Onderzoek Flanders. Background Coagulopathic complications often jeopardize the outcome of critically ill patients in cardiogenic shock (CS) during percutaneous mechanical circulatory support (pMCS). Therefore, meticulous management of heparin therapy is mandatory to ensure appropriate anticoagulation management. In this context, the most convenient and most frequently used test is the activated partial thromboplastin time (APTT). However, the APTT-test can be prolonged or shortened independent of the patient's anticoagulation status due to various confounding factors during critical illness (e.g., sepsis, liver failure, factor XI/XII consumption). Alternatively, the anti-Xa assay directly measures heparin activity. Therefore, to optimize heparin anticoagulation during critical illness, an anti-Xa-guided protocol for heparin titration combined with parallel APTT measurements to assess both bleeding and thrombotic risk has recently been proposed. (1) Purpose We aimed to investigate the correlation between parallel anti-Xa and APTT-measurements in an anti-Xa-guided heparin anticoagulated CS population during left-sided ImpellaTM support. Methods Between April-2017 and June-2022, all CS patients with isolated left-sided ImpellaTM-support (&amp;gt;24h) and heparin anticoagulation monitored by anti-Xa with APTT in parallel were assessed at two high-volume tertiary institutions. Anti-Xa was considered in range between 0.20-0.30IU/mL or 0.31-0.50IU/mL based on the patient’s profile (per center protocol, underlying atrial fibrillation or venous thromboembolism). In range APTT values were considered 40-55s and 55-80s respectively. Correlation between parallel anti-Xa and APTT values was assessed by Pearson correlation. A Pearson correlation coefficient of 0.7 or lower was considered to confer a weak correlation. Results Ninety-three ImpellaTM-patient runs (77 men, 83%) with a median age of 56 years (IQR 46-66) were analyzed. Median support duration was 6 days (IQR 4-12). In total, 2447 parallel anti-Xa/APTT samples were analyzed, showing an overall Pearson correlation coefficient of 0.50 (p&amp;lt;0.001) (Fig. 1A). For samples with in-range anti-Xa (N=1914), matching APPT was shortened in 460 (24%), in-range in 986 (52%) and prolonged in 468 (24%) samples (Fig. 1B). Conclusions We highlight a weak correlation between anti-Xa and APTT in an anti-Xa guided heparin anticoagulated CS population during left-sided ImpellaTM support. Heparin titration based on APTT alone would result in over- (24%) or undertitration (24%) in 48% of our cases, due to confounding factors influencing the APTT-assay in critically ill, exposing these patients to coagulopathy associated problems. Therefore, we strongly advocate a combined (anti-Xa/APTT) testing anticoagulation monitoring strategy to adequately manage the coagulation state of this critically ill population. Future trials will investigate whether this approach will effectively reduce the high coagulopathy associated morbidity and mortality on pMCS.

European practices on antithrombotic management during percutaneous mechanical circulatory support in adults: an international survey of the ACVC Association of the ESC joint with EuroELSO

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Fonds Wetenschappelijk Onderzoek Flanders. Background/introduction Bleeding and thrombotic complications impair the outcomes of patients on percutaneous mechanical circulatory support (pMCS) with veno-arterial extracorporeal membrane oxygenation (V-A ECMO) and/or microaxial flow pumps such as the Impella™. Very recent MCS-trials still show a 23.9% moderate/major bleeding incidence during V-A ECMO. Antithrombotic practices are an important determinant of the meticulous coagulopathic risk management, but guidelines here are non-existing. Purpose Providing an overview of the current European practices in antithrombotic management in adults on pMCS is a first but crucial step to design trials, standardize practice and improve outcome. Methods This online cross-sectional survey was distributed via a digital newsletter and social media platforms through the Association of Acute Cardiovascular Care (ACVC) and the European Extracorporeal Life Support Organization (EuroELSO). The survey was accessible between 17.04 and 23.05.2023. The target population were European clinicians involved in adult critical care and pMCS-management. Results We included responses from 105 different units from 26 European countries. 72.4% Of the European responders have an institutional anticoagulation protocol installed. Unfractionated heparin is the predominantly used anticoagulant (Impella™: 97.0% and V-A ECMO: 96.1%). Argatroban is the preferred alternative in case of heparin-induced thrombocytopenia (Impella™: 52.3% and V-A ECMO: 50.7%). 10.8% And 14.5% of the anticoagulation protocols rely on anti-factor-Xa assay with activated partial thromboplastin time (APTT) in parallel for Impella™ and V-A ECMO, respectively. Up to 43.1% (Impella™) and 32.9% (V-A ECMO) of the European respondents rely on a monitoring strategy with APTT alone. Anticoagulant targets for heparin vary significantly between institutions. 54.0% And 42.7% of the European survey participants administer dual antiplatelet therapy (DAPT) during Impella™ and V-A ECMO support after acute coronary syndrome without percutaneous coronary intervention (PCI), increasing to 93.7% and 84.0% after recent PCI, respectively. Typical thresholds for transfusion or administration of blood products without acute bleeding also vary substantially and are frequently not predefined. Conclusion Large heterogeneity in antithrombotic practices is observed across Europe. Consequently, device-associated coagulopathic complications may largely vary due to non-standardized management and heterogeneity between institutions. This survey underpins the importance of urgent prospective trials investigating important basic questions concerning antithrombotic therapy during pMCS (anticoagulation targets, monitoring strategy, concomitant use of DAPT among others).

Complete blood count, coagulation biomarkers, and lung function 6 months after critical COVID-19.

Understanding the recovery of post-COVID-19 organ dysfunction is essential. We evaluated coagulation 6 months post-COVID-19, examining its recovery and association with lung function. Patients treated for COVID-19 at intensive care units between 3/2020 and 1/2021 were analyzed for complete blood count (CBC) and coagulation biomarkers (prothrombin time activity (%) (PT%), activated partial thromboplastin time (APTT), fibrinogen, coagulation factor VIII (FVIII), antithrombin (AT), and D-dimer) during the 6 months post-hospitalization. Results were compared with acute phase values and correlated with pulmonary function tests (PFT), including forced vital capacity (FVC) and hemoglobin-corrected diffusing capacity percentage of predicted (DLCOc%), recorded 6 months post-hospitalization. We examined the association between coagulation biomarkers and DLCOc% using linear regression with age, sex, and invasive mechanical ventilation (IMV) duration, and FVIII (correlated with DLCOc%) as covariates. Most CBCs and coagulation biomarkers had median values within the normal range. However, only 21% (15/70) of patients achieved full normalization of all biomarkers. Compared to acute COVID-19, hemoglobin, PT%, and AT increased, while leukocytes, fibrinogen, FVIII, and D-dimer decreased. Despite decreased levels, FVIII remained elevated in 46% (31/68), leukocytes in 26% (18/70), and D-dimer in 27% (18/67) at 6 months. A weak negative correlation (r = -0.37, p = .036) was found between DLCOc% and FVIII. Multivariable analysis revealed a weak, independent association between DLCOc% and FVIII. Excluding patients with anticoagulation therapy, FVIII no longer correlated with DLCOc%, while AT showed a moderate correlation with DLCOc%. Only a few patients had normal CBC and coagulation biomarker values 6 months after critical COVID-19. A weak negative correlation between DLCOc% and FVIII suggests that deranged coagulation activity may be associated with reduced diffusing capacity.

Discordance between aPTT and anti-Xa in monitoring heparin anticoagulation in mechanical circulatory support.

It is unclear whether activated partial thromboplastin time (aPTT) or anti-Xa is more accurate for monitoring heparin anticoagulation in mechanical circulatory support (MCS) patients. This study investigates the relationship between aPTT and anti-Xa in MCS patients and identifies predictors of discordance. aPTT and anti-Xa were simultaneously measured in a prospective cohort of MCS patients receiving unfractionated heparin at a tertiary academic medical centre. Therapeutic aPTT and anti-Xa levels were 60-100s and 0.3-0.7IU/mL, respectively, and concordance was defined as both levels being subtherapeutic, therapeutic, or supratherapeutic. To identify predictors of discordance, both a machine learning random forest model and a multivariate regression model were applied to patient demographics, device type, and 14 laboratory variables; 23001 pairs of simultaneously measured aPTT/anti-Xa were collected from 699 MCS patients. aPTT and anti-Xa were concordant in 35.5% of paired observations and discordant in 64.5% (aPTT>antiXa 61.5%; aPTT<antiXa 3.0%). Discordance with a high aPTT relative to anti-Xa (aPTT>antiXa) was associated with high INR, eGFR, and total bilirubin, as well as low platelets, haemoglobin, pre-albumin, white blood cell count, and haptoglobin. Total artificial heart and durable ventricular assist devices were more likely to be associated with aPTT>anti-Xa than temporary MCS devices. aPTT and anti-Xa were frequently discordant in MCS patients receiving heparin anticoagulation. Clinical conditions common in MCS patients such as concurrent warfarin use, malnutrition, haemolysis, and thrombocytopenia, as well as durable type of MCS devices were associated with a high aPTT relative to anti-Xa.

Prophylactic use of standardized extract of propolis of Apis mellifera (EPP-AF®) reduces lung inflammation and improves survival in experimental lethal sepsis

Ethnopharmacological relevanceSepsis poses one of the biggest public health problems, necessitating the search for new therapeutic alternatives. For centuries, propolis has been widely used in folk medicine to treat various inflammatory and infectious diseases. Given its extensive use, it has excellent potential as an adjuvant treatment for patients with sepsis. ObjectiveThis study evaluated prophylactic treatment with standardized propolis extract (EPP-AF®) and followed the prognosis of sepsis induced by ligation and cecal ligation and puncture (CLP). MethodsInitially, for survival assessment, Swiss mice were separated into five groups: Sham (false operated), control (PBS), ATB (received antibiotic, 8 mg/kg), P10 (received EPP-AF®, 10 mg/kg), and P100 (received EPP-AF®, 100 mg/kg). The animals received PBS, antibiotic, or EPP-AF® by the subcutaneous route 6 h before the CLP procedure. Animal survival was assessed every 12 h for five days when all of them were euthanized. ResultsWe show that the treatment with EPP-AF® significantly increased the life expectancy of animals with sepsis compared to the control group. Interestingly, prophylactic treatment with EPP-AF® showed no effect on the number of colony-forming units in the peritoneum, blood, or lung. However, there was a decrease in cellular influx in the peritoneum. This alteration was unrelated to the number of bone marrow cells or the differential counting of peripheral blood cells. The coagulogram remained unchanged, including the number of platelets and prothrombin time-activated partial thromboplastin time. However, the inflammatory infiltrate and bleeding in the lung tissue were lower in the animals that received EPP-AF®. ConclusionThus, it was possible to conclude that prophylactic treatment with EPP-AF® preserved the lung parenchyma, resulting in an increased lifespan of mice with sepsis. It can be a helpful adjuvant in prophylactic treatment with antibiotics in presurgical conditions.

A retrospective study of the prevalence of isolated prolongation of activated partial thromboplastin time in the preoperative setting

BackgroundIsolated 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.MethodsPreoperative 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.ResultsOverall, 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.ConclusionsWe 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.

DNA base editing corrects common hemophilia A mutations and restores factor VIII expression in in vitro and ex vivo models

BackgroundReplacement and nonreplacement therapies effectively control bleeding in hemophilia A (HA) but imply lifelong interventions. Authorized gene addition therapy could provide a cure but still poses questions on durability. FVIIIgene correction would definitively restore factor (F)VIII production, as shown in animal models through nuclease-mediated homologous recombination (HR). However, low efficiency and potential off-target double-strand break still limit HR translatability. ObjectivesTo correct common model single point mutations leading to severe HA through the recently developed double-strand break/HR-independent base editing (BE) and prime editing (PE) approaches. MethodsScreening for efficacy of BE/PE systems in HEK293T cells transiently expressing FVIII variants and validation at DNA (sequencing) and protein (enzyme-linked immunosorbent assay; activated partial thromboplastin time) level in stable clones. Evaluation of rescue in engineered blood outgrowth endothelial cells by lentiviral-mediated delivery of BE. ResultsTransient assays identified the best-performing BE/PE systems for each variant, with the highest rescue of FVIII expression (up to 25% of wild-type recombinant FVIII) for the p.R2166∗ and p.R2228Q mutations. In stable clones, we demonstrated that the mutation reversion on DNA (∼24%) was consistent with the rescue of FVIII secretion and activity of 20% to 30%. The lentiviral-mediated delivery of the selected BE systems was attempted in engineered blood outgrowth endothelial cells harboring the p.R2166∗ and p.R2228Q variants, which led to an appreciable and dose-dependent rescue of secreted functional FVIII. ConclusionOverall data provide the first proof-of-concept for effective BE/PE-mediated correction of HA-causing mutations, which encourage studies in mouse models to develop a personalized cure for large cohorts of patients through a single intervention.

Rare bleeding disorders in Egyptian females presented with heavy menstrual bleeding: single-center study

BackgroundHeavy menstrual bleeding is an important health problem in women of reproductive age and is also one of the most common symptoms in women with bleeding disorders. Data about the frequency of rare bleeding disorders are limited, and population-based studies are lacking, so we aimed to determine the frequency of rare bleeding disorders among women presented with heavy menstrual periods that cannot be attributed to obvious problems.MethodsComplete blood count and bleeding profiles include activated partial thromboplastin time, prothrombin time, factor VIII activity assay, ristocetin cofactor activity, von Willebrand antigen assay, platelet aggregation tests and other factor assays in 100 out of 300 females presented with unexplained heavy menstrual period, pictorial bleeding assessment chart (PBAC) > 100 as a screening tool for heavy menstrual periods, and or International Society of Thrombosis and Hemostasis-Bleeding Assessment Tool (ISTH-BAT) > 6.ResultsA total of 300 women with heavy menstrual periods without an obvious explained cause were included in our study. Among them, we found 100 (30%) females with a mean PBAC of 234 ± 147 and mean ISTH-BAT of 9 ± 5 denoting HMB may be due to underlying bleeding disorders. Among them, the most common diagnosis was VWD in 30 (30%). Other disorders were as follows: 28 (28%) cases with clotting factor deficiencies, 24 (24%) cases were found to have platelet dysfunction, and in 18% of our studied cases, we did not find a clear cause of their bleeding disorders (unknown).ConclusionRare bleeding disorders are not uncommon and require comprehensive hemostatic evaluation as well as simple tools like PBAC and ISTH-BAT questionnaires for the identification of females presented with unexplained HMB.

Elevated plasma levels of factor VIII enhance arterial thrombus formation on erosive smooth muscle cell-rich neointima but not normal intima in rabbits

BackgroundPlaque erosion, a type of coronary atherothrombosis, involves superficial injury to smooth muscle cell (SMC)-rich plaques. Elevated levels of coagulation factor VIII (FVIII) correlate with an increased ischemic heart disease risk. FVIII may contribute to thrombus formation on eroded plaques. AimsWe aimed to elucidate the role of elevated FVIII in arterial thrombus formation within SMC-rich neointima in rabbits. Methods and resultsWe assessed the effect of recombinant human FVIII (rFVIII) on blood coagulation in vitro and platelet aggregation ex vivo. An SMC-rich neointima was induced through balloon injury to the unilateral femoral artery. Three weeks after the first balloon injury, superficial erosive injury and thrombus formation were initiated with a second balloon injury of the bilateral femoral arteries 45 min after the administration of rFVIII (100 IU/kg) or saline. The thrombus area and contents were histologically measured 15 min after the second balloon injury. rFVIII administration reduced the activated partial thromboplastin time and augmented botrocetin-induced, but not collagen- or adenosine 5′-diphosphate-induced, platelet aggregation. While rFVIII did not influence platelet-thrombus formation in normal intima, it increased thrombus formation on SMC-rich neointima post-superficial erosive injury. Enhanced immunopositivity for glycoprotein IIb/IIIa and fibrin was observed in rFVIII-administered SMC-rich neointima. Neutrophil count in the arterial thrombus on the SMC-rich neointima correlated positively with thrombus size in the control group, unlike the rFVIII group. ConclusionsIncreased FVIII contributes to thrombus propagation within erosive SMC-rich neointima, highlighting FVIII's potential role in plaque erosion-related atherothrombosis.

Bivalirudin Monitoring in Pediatric Ventricular Assist Device and Extracorporeal Membrane Oxygenation: Analysis of Single-Center Retrospective Cohort Data 2018-2022.

The activated partial thromboplastin time (aPTT) is the most frequently used monitoring assay for bivalirudin in children and young adults on mechanical circulatory support including ventricular assist devices (VADs) and extracorporeal membrane oxygenation (ECMO). However, intrinsic variability of the aPTT complicates management and risks bleeding or thrombotic complications. We evaluated the utility and reliability of a bivalirudin-calibrated dilute thrombin time (Bival dTT) assay for bivalirudin monitoring in this population. Retrospective analysis of clinical data (including aPTT, dilute thrombin time [dTT]) and results of residual plasma samples from VAD patients were assessed in two drug-calibrated experimental assays. One assay (Bival dTT) was validated for clinical use in VAD patients, and subsequently used by clinicians in ECMO patients. Pearson correlation and simple linear regression were used to determine R2 correlation coefficients between the different laboratory parameters using Statistical Package for Social Sciences (Armonk, NY). ICUs at Cincinnati Children's Hospital Medical Center. Children on VAD or ECMO support anticoagulated with bivalirudin. None. One hundred fifteen plasma samples from 11 VAD patients were analyzed. Both drug-calibrated experimental assays (anti-IIa and Bival dTT) showed excellent correlation with each other ( R2 = 0.94) and with the dTT ( R2 = 0.87), but poor correlation with aPTT ( R2 = 0.1). Bival dTT was selected for validation in VAD patients. Subsequently, clinically ordered results (105) from 11 ECMO patients demonstrated excellent correlation between the Bival dTT and the standard dTT ( R2 = 0.86) but very poor correlation with aPTT ( R2 = 0.004). APTT is unreliable and correlates poorly with bivalirudin's anticoagulant effect in ECMO and VAD patients. A drug-calibrated Bival dTT offers superior reliability and opportunity to standardize results across institutions. Additional studies are needed to determine an appropriate therapeutic range and correlation with clinical outcomes.

Assessing the Utility of the Aspartate Aminotransferase to Platelet Ratio Index (APRI) as a Noninvasive Indicator for Liver Cirrhosis.

Background Of liver-related disorders, cirrhosis is currently the leading cause of death and has become a significant global public health concern. Aspartate aminotransferase to platelet ratio index (APRI), a newer prognostic modality, is a very effective noninvasive diagnostic for identifying advanced liver fibrosis. Methods A prospective observational study was conducted among individuals with liver disease, 100 casesand 100 controls for two years. All the sociodemographic details, clinical features of the patients, and clinical findings such as prothrombin time (PT), liver function tests, kidney function tests, and total blood count were recorded using a pretested semi-structured questionnaire. Results According to our survey results, 48% of the participants were between the ages of 40 and 60.Regarding aPTT (activated partial thromboplastin time) and liver function test characteristics (serum glutamic-oxaloacetic transaminase(SGOT), serum glutamic pyruvic transaminase (SGPT)), we showed a substantial difference between the patients and controls.Regarding the APRI distribution, we also found a statistically significant variation between the research groups. When we compared the validity of APRI scores in diagnosing cirrhosis, we discovered that the ideal cutoff value of APRI was determined to be 3.99, with sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 33%, 86%, 70%, and 56%, respectively. The area under the receiver operating characteristic (ROC) curve for APRI in detecting cirrhosis was also 0.693. Conclusion Thus, our study results conclude that APRI is a crucial noninvasive prognostic tool that can be utilized to prognostize liver cirrhosis.