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

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

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

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

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

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

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

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

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

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

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

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

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]

Objective Methods Results Conclusions Coagulation assessment in traumatic brain injury (TBI) typically relies upon laboratory‐based standard coagulation tests (SCTs), including the activated partial thromboplastin time (aPTT), INR and platelet count. Rotational thromboelastometry (ROTEM) sigma is an alternative point‐of‐care assay; however, its role in isolated TBI is under‐evaluated. The present study aims to assess the prognostic utility of ROTEM sigma in isolated TBI.ROTEM sigma analysis was performed during the initial evaluation of patients presenting to the Royal Adelaide Hospital between February 2022 and 2023 with radiographically demonstrated traumatic intracranial haemorrhage and GCS ≤14. Patients with concomitant severe extracranial injury, or who received blood products or antifibrinolytic therapy prior to sample collection were excluded.Thirty‐six patients had blood samples analysed with ROTEM, 25 of these patients were also evaluated with paired SCTs. Twenty‐two per cent (8/36) of patients with isolated TBI had a hypocoaguable ROTEM profile, and this was associated with an increased incidence of head injury‐related death (50% [4/8] vs 11% [3/28], P = 0.03). Median diagnostic turn‐around‐times were shorter for ROTEM parameters compared to SCT counterparts: EXTEM clotting time (CT) versus INR (20 vs 63 min, P < 0.01), and INTEM CT versus aPTT (21 vs 63 min, P < 0.01). EXTEM CT, FIBTEM CT and INR values had similar performance in predicting head injury‐related death, area under the receiver operator curves were 0.8, 0.8 and 0.7, respectively.ROTEM sigma expedites the detection of clinically significant coagulopathy in isolated TBI. EXTEM and FIBTEM CT values are more rapidly attainable than INR and comparable in predicting head injury‐related death. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Donor‐derived dengue infections present significant challenges to organ transplantation, particularly in endemic regions like Singapore. Although primarily transmitted by Aedes mosquitoes, dengue can also be transmitted through organ transplantation, occasionally with fatal outcomes. This study aims to evaluate the outcomes and evolution of dengue screening protocols for potential deceased donors in Singapore from 2006 to 2022.Initially, screening was done via dengue immunoglobulin M (IgM), targeting donors with specific clinical criteria (thrombocytopenia, drop in platelet count, prolonged prothrombin time/partial thromboplastin time, and discretion of the transplant team), later transitioning to blood dengue reverse transcription‐polymerase chain reaction (RT‐PCR) in 2007 with similar criteria, and subsequently universal screening in 2016. In 2021, urine dengue RT‐PCR was added following a case of donor‐derived dengue infection from an aviremic but viruric donor.Out of 431 potential deceased donors, 395 (91.6%) underwent dengue screening, with six (1.5%) testing positive for dengue. In 2006, three positive screens were identified: two through dengue IgM and one via blood dengue RT‐PCR; subsequent years saw one positive screen each in 2007, 2008, and 2019 via blood dengue RT‐PCR. Potential deceased donors with a positive blood dengue screen were rejected as solid organ and tissue donors. Those with negative blood dengue RT‐PCR but positive urine dengue RT‐PCR would be rejected as kidney donors, but the use of other organs and tissues was at the discretion of the transplantation team.The optimal screening protocol remains uncertain, but our findings suggest that a universal screening strategy utilizing both blood and urine dengue RT‐PCR could be considered in dengue‐endemic countries. [ABSTRACT FROM AUTHOR]

Introduction Method Results Conclusion It is recommended to use two chronometric assays of different principles for the diagnosis of lupus anticoagulant (LA), consisting in diluted Russell Viper Venom Time (dRVVT) and activated Partial Thromboplastin Time (aPTT). Yet, there are only a few integrated aPTT assays; this study aims to evaluate one of them: Cephen LS/Cephen (Hyphen Biomed).249 samples of patients were included in this study. Normal reference ranges were determined with platelet‐poor plasma (PPP) from healthy blood donors. Performances were then evaluated by comparing Cephen LS/Cephen test results to the results of the laboratory's reference assay for the diagnosis of LA and to clinical data, both on non‐anticoagulated and anticoagulated patients' samples (Unfractioned heparin (UFH), Low Molecular Weight Heparin (LMWH), Vitamin K Antagonists (VKA) and apixaban). Interference of UFH, LMWH and VKA were also evaluated thanks to spiking experiment of increasing heparin concentrations or factor deficiency.Cephen LS/Cephen test had 48.6% sensitivity towards LA. Although UFH and VKA seemed to interfere with this assay and were likely to cause false negative, LMWH and apixaban did not.Finally, combination of Cephen LS/ Cephen with dRVVT had 89.0% sensitivity.Cephen LS/Cephen seems relevant for LA diagnosis, in combination with dRVVT, and might be used in patients undergoing LMWH or apixaban therapy. [ABSTRACT FROM AUTHOR]

Introduction: An investigation of the suitability of reagents for measuring FVIII products in a one‐stage clotting assay (OSA) showed variations in their FVIII activity (FVIII:C). Most studies have focused on the activated partial thromboplastin time (APTT) reagent rather than FVIII‐deficient plasma (F8DP), even though the APTT‐based OSA is comprised of APTT reagents and factor‐deficient plasma. Aim: A single‐centre study was conducted to clarify variations in measurements of FVIII products in an OSA using a total of 12 reagent combinations, including four APTT reagents and three types of F8DP. Methods: FVIII:C in nine types of FVIII product‐spiked plasma was measured using an OSA with four different APTT reagents and three types of F8DP. Results: F8DP‐dependent variations were found in addition to differences derived from APTT reagents. Variations in target recovery (TR) were observed for NovoEight®, Eloctate®, and Jivi®. Reduced TR for Jivi was found only for Pathromtin SL in combination with congenital F8DP (F8DP‐3). This lower TR was not observed with alternative manufacturing lots of F8DP‐3. The reduced TR for Jivi might be related to impaired contact activation due to lower factor XI activity in F8DP‐3. Conclusion: In addition to APTT reagents, variations in F8DPs used for OSAs can also affect FVIII:C results. F8DPs as well as the APTT reagent used for OSA should be chosen with caution, and laboratories should evaluate reagents for F8DPs as they currently do for APTT reagents, especially when lot changes occur. [ABSTRACT FROM AUTHOR]

Background: Clot based assays used for lupus anticoagulant (LAC) detection are typically interpreted in a qualitative fashion and may not reflect LAC potency. In this cross‐sectional study, we describe a method for quantifying the LAC titer using serial (dependent) two‐fold dilutions in normal pooled plasma. Methods: Serial dilutions of 51 residual plasma samples from 50 patients were tested using the Russell's viper venom screening time (DRVVT) and activated partial thromboplastin screening time (APTT) methodologies. The measured clotting times and the corresponding dilution factors were then used to derive a four‐parameter logistic model. The LAC titer for each patient was interpolated as the sample dilution that corresponds to the upper reference interval limit of the corresponding assay. Results: Calculated APTT and DRVVT LAC titers displayed a strong linear correlation (R2 = 0.84) between each other, but not with the degree of prolongation of the APTT/DRVVT screening time in the neat undiluted samples. Using data driven partitioning, patients could be grouped into low (<10) or high (≥10) DRVVT LAC titer. There were no significant differences in anticardiolipin (aCL) or anti‐beta 2 glycoprotein 1 (aB2GPI) antibody levels or prevalence of thromboembolic events between low and high LAC titer groups. In contrast, antiphosphatidylserine/prothrombin (aPS/PT) IgM antibody levels, but not IgG, were significantly higher in the high LAC titer group. Conclusions: The degree of prolongation of the APTT/DRVVT screening time is not correlated with the LAC titer. Only aPS/PT IgM antibodies levels were strongly correlated with the LAC titers. Additional studies are warranted to determine clinical implications of high LAC titers. [ABSTRACT FROM AUTHOR]

Background: Having faster plasma thawing devices could be beneficial for transfusion services, as it may improve the rapid availability of thawed plasma for bleeding patients, and it might remove the need to have extended pre‐thawed plasma: thus, reducing unnecessary plasma wastage. Study Design and Methods: The aims of this study were to assess (a) the thawing times and (b) in vitro haemostatic quality of thawed plasma using Barkey Plasmatherm V (PTV) at 37 and 45°C versus Barkey Plasmatherm Classic (PTC) at 37 and 45°C, Sarstedt Sahara‐III Maxitherm (SS‐III) at 37°C and Helmer Scientific Thermogenesis Thermoline (TT) at 37°C. Haemostatic quality was assessed using LG‐Octaplas at three different time points: baseline (5 min), 24 and 120 h after thawing. Results: The thawing time (SD) of 2 and 4 units was significantly different between different thawers. PTV at 45°C was the fastest method for both 2 and 4 units (7.06 min [0.68], 9.6 min [0.87], respectively). SS‐III at 37°C being the slowest method (24.69 min [2.09] and 27.18 min [4.4], respectively) (p = < 0.05). Baseline measurements for all assays showed no significant difference in the prothrombin time, fibrinogen, FII, FV, protein C activity or free protein S antigen between all methods tested. However, at baseline PTV (both 37°C and 45°C) had significantly higher levels of FVII, FVIII and FXI and shortened activated partial thromboplastin time. Discussion: PTV was the quickest method at thawing plasma at both 37 and at 45°C. The haemostatic quality of plasma thawed at 45 versus 37°C was not impaired. Thawing frozen plasma at 45°C should be considered. [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]

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]

Introduction: Non‐factor replacement therapies are emerging as prophylactic treatment options in haemophilia A or B (HA/HB) with and without inhibitors. Concizumab is an anti‐tissue factor pathway inhibitor (TFPI) monoclonal antibody preventing factor (F)Xa inhibition and enhancing thrombin generation. Based on experience with other non‐factor therapies and extended half‐life products, there is a focus on potential interference with common clinical coagulation assays used to monitor patients treated with concizumab. Aim: To evaluate the impact of concizumab on standard clinical coagulation assays. Methods: Plasma samples (normal, HA/HB with/without inhibitors) in the presence/absence of added concizumab (250–16,000 ng/mL) were analysed in clinical assays including activated partial thromboplastin time (aPTT), prothrombin time (PT), FVIII and FIX one‐stage clot and chromogenic substrate assay, assays for detecting FVIII or FIX inhibitors and other assays for coagulation factors. Results: Concizumab did not impact PT assays, but resulted in a small shortening of aPTT (up to 5 s in haemophilia plasma and 0.4 s in normal plasma). Concizumab had no, or only a minor impact on FVIII and FIX activity assays or Bethesda inhibitor assays. FXI and FXII activity in normal plasma, as measured by single factor aPTT‐based assay, was significantly increased in the presence of concizumab (+11% each). This was also the case for FVII and FX measured by PT‐based assays using plasma with 25% of FVII or FX (+64% and +22%, respectively). Conclusion: The presence of concizumab did not, or only slightly, influence the outcome of standard clinical coagulation assays relevant for HA and HB. [ABSTRACT FROM AUTHOR]

Introduction: Diagnosing hemophilia B (HB) carrier status is important to manage bleeding in carriers and to prevent bleeding in potential offspring. Without a family history of hemophilia, diagnosing HB carrier status is challenging. Genetic testing is the gold‐standard, however it is reserved for individuals with a high suspicion of carrier status. Aims: To describe the distribution of activated partial thromboplastin time (aPTT) and factor IX coagulant (FIX:C) levels in HB carriers and assess the ratio of FIX:C to other Vitamin K dependent factors (FII:C, FVII:C, FX:C) as an indicator of HB carrier status. Methods: In this retrospective, single‐centre cohort study, subjects were included if they were obligate or genetically proven HB carriers. Distributions of aPTT and FIX:C were described and the relationship between FIX:C levels in carriers and severity of familial HB was analysed. Ratios of FIX:C to FII:C, FVII:C, FX:C were calculated. Results: Seventy‐two female HB carriers (median age: 34 years; IQR 24–43) were included. Median aPTT and FIX:C levels were 33.0 s [IQR 30.0–37.0] and 57 IU/dL [IQR 43–74]. Fifteen carriers (21%) had mild HB (FIX:C levels of 10–40 IU/dL). FIX:C levels trended higher in carriers of mild HB versus carriers of moderate/severe HB. In six carriers, the median ratio of FIX:C to other Vitamin K dependent factors was 0.44, with 92% of ratios being ≤ 0.75. Conclusion: aPTT and FIX:C levels were unreliable in diagnosing HB carrier status. A low ratio of FIX:C to other Vitamin K dependent factors may be a useful marker of HB carrier status. [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]

Recent studies have suggested the use of insects to enhance various bioactivities in the treatment of many diseases or as alternative sources of nutrients. White‐spotted flower chafer (Protaetia brevitarsis seulensis; PBS) extract, which is used for medicinal purposes, appears to be effective in improving blood circulation. However, few studies have investigated the efficacy of PBS extract in improving blood circulation. Here, we investigated the effects of PBS extract on serum cholesterol metabolites (total cholesterol, high‐density lipoprotein cholesterol, and low‐density lipoprotein cholesterol) and anticoagulant activities (prothrombin time [PT], activated partial thromboplastin time [aPTT], and fibrinogen [Fib]) in very‐high‐fat diet (VHFD)‐induced hyperlipidemic rats. The experimental groups comprised a control group that was not treated with PBS and five PBS treatment groups (50, 100, 150, 200, and 250 mg/kg) in a randomized complete block design. In the efficacy evaluation for health functionality to reduce cholesterol levels, no beneficial effects on serum cholesterol metabolites were observed in the control and PBS treatment groups. In addition, the cholesterol data indicated that the effect of the PBS extract was not related to antioxidant activity. Moreover, the PT, aPPT, and Fib values were prolonged by increasing the PBS extract concentration, and PBS extract concentrations of 150–250 mg/kg were recommended for the VHFD model based on the anticoagulant activity. In conclusion, the PBS extract can be used in a potential therapeutic strategy for improving anticoagulant activity rather than improving the serum cholesterol profile. [ABSTRACT FROM AUTHOR]

Introduction: The Thai National Guidelines for Hemostatic Laboratory Testing were established in 2018. The guidelines recommend that the 20‐min whole blood clotting time (20WBCT) method be used to diagnose/monitor snake bites. The aim of this study was to survey members of the Thailand National External Quality Assessment Scheme (NEQAS) for Blood Coagulation to investigate the use of 20WBCT testing compared between the 2021 post‐guideline and 2007 pre‐guideline periods. Methods: In July 2021, questionnaires were sent from the Faculty of Medicine Siriraj Hospital, Mahidol University to 521 Thailand NEQAS for Blood Coagulation member laboratories to survey their WBCT practices. Current WBCT practices were compared with pre‐guideline WBCT practices, and chi‐square test (x2) was used to test for differences between groups. Results: Ninety‐seven (18.6%) of 521 surveys were returned. Seventy‐one laboratories (73.2%) reported knowing about 20WBCT from the Thai national guidelines. The reported average frequency of overall WBCT testing in 2021 was 12.4 times/month. The proportion of laboratories that reported using the 20WBCT test increased from 2.0% in 2007 to 46.4% in 2021 (p < 0.001), and the indications for performing WBCT were virtually unchanged from 2007 to 2021. The proportion of laboratories that reported having problems with WBCT testing decreased from 32.7% in 2007 to 16.5% in 2021. Conclusion: Despite our findings that almost three‐quarters of respondent laboratories reported knowing about 20WBCT testing from the WBCT guidelines, and that WBCT‐specific problems decreased significantly from 2007 to 2021, more work and training is needed to improve WBCT guideline dissemination, understanding, and adherence in Thailand. [ABSTRACT FROM AUTHOR]

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 toxicity of inhaled particulate air pollution perseveres even at lower concentrations than those of the existing air quality limit. Therefore, the identification of safe and effective measures against pollutant particles‐induced vascular toxicity is warranted. Carnosol is a bioactive phenolic diterpene found in rosemary herb, with anti‐inflammatory and antioxidant actions. However, its possible protective effect on the thrombotic and vascular injury induced by diesel exhaust particles (DEP) has not been studied before. We assessed here the potential alleviating effect of carnosol (20 mg/kg) administered intraperitoneally 1 h before intratracheal (i.t.) instillation of DEP (20 μg/mouse). Twenty‐four hours after the administration of DEP, various parameters were assessed. Carnosol administration prevented the increase in the plasma concentrations of C‐reactive protein, fibrinogen, and tissue factor induced by DEP exposure. Carnosol inhibited DEP‐induced prothrombotic effects in pial microvessels in vivo and platelet aggregation in vitro. The shortening of activated partial thromboplastin time and prothrombin time induced by DEP was abated by carnosol administration. Carnosol inhibited the increase in pro‐inflammatory cytokines (interleukin‐6 and tumor necrosis factor α) and adhesion molecules (intercellular adhesion molecule‐1, vascular cell adhesion molecule‐1, E‐selectin, and P‐selectin) in aortic tissue. Moreover, it averted the effects of DEP‐induced increase of thiobarbituric acid reactive substances, depletion of antioxidants and DNA damage in the aortic tissue. Likewise, carnosol prevented the decrease in the expression of nuclear factor erythroid 2‐related factor 2 (Nrf2) and heme oxygenase‐1 (HO‐1) caused by DEP. We conclude that carnosol alleviates DEP‐induced thrombogenicity and vascular inflammation, oxidative damage, and DNA injury through Nrf2 and HO‐1 activation. [ABSTRACT FROM AUTHOR]

Background: Severe fever with thrombocytopenia syndrome (SFTS) is a zoonotic infectious disease caused by the severe fever with thrombocytopenia syndrome virus (SFTSV). Endemic in East Asia, SFTS is characterized by an exceptionally high mortality rate. Presently, there is no established treatment for SFTS, particularly for patients in critical condition. In this study, we collected and analyzed laboratory and clinical data from 92 critically ill patients with SFTS treated at Weihai Municipal Hospital between 2019 and 2022. We hope that our study will provide some hints for the treatment of critically ill patients with SFTS. Methods: A total of 92 critically ill patients with SFTS were included in this study. Of these patients, 45 received treatment with therapeutic plasma exchange (TPE) and ribavirin (referred to as the TPE group), while the remaining patients received only ribavirin (referred to as the non‐TPE group). Clinical and laboratory parameters were analyzed retrospectively. Results: The results showed significant improvements in multiple laboratory parameters following treatment with TPE and ribavirin, including white blood cell and neutrophil count, lactate dehydrogenase, creatine kinase isoenzyme‐MB, prothrombin time, activated partial thromboplastin time, D‐Dimer, serum sodium and copies of virus genomes. The combination of TPE with ribavirin demonstrated a significant reduction in mortality rates, with a mortality rate of 20.0% in the TPE group compared to 40.4% in the non‐TPE group (P = 0.033). Conclusions: Our findings suggest that critically ill patients with SFTS who received TPE and ribavirin experienced improvements in both clinical and laboratory parameters. These results indicate that TPE combined with ribavirin may represent a promising novel therapeutic approach for managing critically ill patients with SFTS. However, comparative studies of large sample size or randomized clinical trials are warranted to confirm the effectiveness of this combination therapy in the treatment of severe SFTS cases. [ABSTRACT FROM AUTHOR]

This article discusses the effectiveness and safety of upadacitinib, a selective JAK1 inhibitor, for pediatric patients with moderate-to-severe atopic dermatitis (AD) who did not respond to dupilumab treatment. The study included 12 patients aged 6-14 who had failed conventional topical corticosteroid treatment and had a history of poor response to dupilumab. Significant improvements were observed in various clinical endpoints, including Eczema Area and Severity Index (EASI), Numerical Rating Scale (NRS), and Children's Dermatology Life Quality Index (CDLQI). Adverse events were generally mild, with acne being the most common. Infections were reported in 25% of patients, highlighting a potential risk for younger patients. One serious adverse event of appendicitis was reported, although a direct causal relationship with upadacitinib remains unclear. Routine laboratory monitoring is important for detecting and managing adverse events. One patient developed vitiligo during treatment, which may be attributed to the common coexistence of AD and vitiligo rather than being an adverse effect of upadacitinib. The study acknowledges limitations such as the small sample size and lack of a control group, emphasizing the need for long-term follow-up to assess the sustained efficacy and safety of upadacitinib in pediatric patients. [Extracted from the article]

Summary: Prolonged coagulation times, such as activated partial thromboplastin time (APTT) and thrombin time (TT), are common in patients infected with severe fever with thrombocytopenia syndrome virus (SFTSV) and have been confirmed to be related to patient's poor outcome by previous studies. To find out the reason for prolonged coagulation time in patients with SFTSV infection, and whether it predicts haemorrhagic risk or not. Seventy‐eight consecutive patients with confirmed SFTSV infection were enrolled in this prospective, single‐centre, observational study. Several global and specific coagulation parameters of these patients on admission were detected, and the haemorrhagic events during hospitalization and their outcomes were recorded. Most of the enrolled patients had prolonged APTT (82.1%) and TT (80.8%), normal prothrombin time (83.3%) and intrinsic coagulation factors above haemostatic levels (97.4%). The heparin‐like effect was confirmed by a protamine neutralization test and anti‐Xa activity detection in most patients. Interestingly, the APTT and TT results were significantly positively correlated with the levels of endothelial markers and viral load, respectively. The APTT was independently associated with the haemorrhage of patients. The prolonged APTT and TT of SFTS patients may mainly be attributed to endogenous heparinoids and are associated with increased haemorrhagic risk. [ABSTRACT FROM AUTHOR]

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

Invasive pulmonary aspergillosis (IPA) is a life‐threatening complication in patients with severe fever with thrombocytopenia syndrome (SFTS), yet SFTS‐associated IPA (SAPA)'s risk factors remain undefined. A multicenter retrospective cohort study across Hubei and Anhui provinces (May 2013–September 2022) utilized least absolute shrinkage and selection operator (LASSO) regression for variable selection. Multivariable logistic regression identified independent predictors of SAPA, Cox regression highlighted mortality‐related risk factors. Of the 1775 screened SFTS patients, 1650 were included, with 169 developing IPA, leading to a 42‐day mortality rate of 26.6% among SAPA patients. Multivariable logistic regression revealed SAPA risk factors including advanced age, petechia, hemoptysis, tremor, low albumin levels, elongated activated partial thromboplastin time (APTT), intensive care unit (ICU) admission, glucocorticoid usage, intravenous immunoglobulin (IVIG) and prolonged hospital stays. Cox regression identified predictors of 42‐day mortality, including ecchymosis at venipuncture sites, absence of ICU admission, elongated prothrombin time (PT), vasopressor and glucocorticoid use, non‐antifungals. Nomograms constructed on these predictors registered concordance indexes of 0.855 (95% CI: 0.826–0.884) and 0.778 (95% CI: 0.702–0.854) for SAPA onset and 42‐day mortality, respectively. Lower survival rates for SAPA patients treated with glucocorticoids (p < 0.001) and improved 14‐day survival with antifungal therapy (p = 0.036). Improving IPA management in SFTS‐endemic areas is crucial, with effective predictive tool. [ABSTRACT FROM AUTHOR]

Objective: Unilateral biportal endoscopic (UBE) surgery has recently been used as a minimally invasive procedure for the treatment of lumbar spinal stenosis and is associated with less perioperative blood loss. However, perioperative hidden blood loss (HBL) may be neglected during UBE. This study aimed to examine the volume of HBL and discuss the influential risk factors for HBL during unilateral biportal endoscopic surgery. Methods: From January 2022 to August 2022, 51 patients underwent percutaneous unilateral biportal endoscopic surgery for lumbar spinal stenosis at the Department of Spinal Surgery of the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University and were enrolled in this study. The data included general indicators (age, sex and body mass index [BMI]), underlying disease (hypertension and diabetes), laboratory test results (prothrombin time [PT], activated partial thromboplastin time [APTT], fibrinogen [Fbg]), and preoperative and postoperative hematocrit and hemoglobin), related imaging parameters (severity of intervertebral disc [IVD] degeneration and soft tissue thickness of the interlaminar approach), number of operated vertebrae and operation time. Total blood loss (TBL) and HBL during surgical procedures were measured via the Gross formula. Influential factors were further analyzed by multivariate linear regression analysis and t‐tests. Results: The mean HBL was 257.89 ± 190.66 mL for single‐operation patients and 296.58 ± 269.75 mL for two‐operation patients. Patients with lower PT (p = 0.044), deeper tissue thickness (p = 0.047), and diabetes mellitus were determined to have more HBL during UBE. The operation time might also be an important factor (p = 0.047). However, sex (p = 0.265), age (p = 0.771/0.624), BMI (p = 0.655/0.664), APTT (p = 0.545/0.751), degree of degenerated IVD (p = 0.932/0.477), and hypertension (p = 0.356/0.896) were not related to HBL. Conclusion: This study determined the different influential factors of HBL during UBE. PT, tissue thickness, and diabetes mellitus are the independent risk factors that affect HBL incidence. Long PT may decrease the volume of HBL within a certain range. Tissue thickness and diabetes mellitus can lead to an increased volume of HBL. [ABSTRACT FROM AUTHOR]

Introduction: The mainstay of acute pulmonary embolism (PE) treatment is anticoagulation. Timely anticoagulation correlates with decreased PE‐associated mortality, but the ability to achieve a therapeutic activated partial thromboplastin time (aPTT) with unfractionated heparin (UFH) remains limited. Although some institutions have switched to a more accurate and reproducible test to assess for heparin's effectiveness, the anti‐factor Xa (antiXa) assay, data correlating a timely therapeutic antiXa to PE‐associated clinical outcomes remains scarce. We evaluated time to a therapeutic antiXa using intravenous heparin after PE response team (PERT) activation and assessed clinical outcomes including bleeding and recurrent thromboembolic events. Methods: This was a retrospective cohort study at NYU Langone Health. All adult patients ≥18 years with a confirmed PE started on IV UFH with >2 antiXa levels were included. Patients were excluded if they received thrombolysis or alternative anticoagulation. The primary endpoint was the time to a therapeutic antiXa level of 0.3–0.7 units/mL. Secondary outcomes included recurrent thromboembolism, bleeding and PE‐associated mortality within 3 months. Results: A total of 330 patients with a PERT consult were identified with 192 patients included. The majority of PEs were classified as sub massive (64.6%) with 87% of patients receiving a bolus of 80 units/kg of UFH prior to starting an infusion at 18 units/kg/hour. The median time to the first therapeutic antiXa was 9.13 hours with 93% of the cohort sustaining therapeutic anticoagulation at 48 hours. Recurrent thromboembolism, bleeding and mortality occurred in 1%, 5% and 6.2%, respectively. Upon univariate analysis, a first antiXa <0.3 units/ml was associated with an increased risk of mortality [27.78% (5/18) vs 8.05% (14/174), p = 0.021]. Conclusion: We observed a low incidence of recurrent thromboembolism or PE‐associated mortality utilizing an antiXa titrated UFH protocol. The use of an antiXa based heparin assay to guide heparin dosing and monitoring allows for timely and sustained therapeutic anticoagulation for treatment of PE. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of frunexian (formerly known as EP‐7041 and HSK36273) injection, a small molecule inhibitor of activated coagulation factor XI (FXIa), in healthy Chinese adult volunteers. This study was a randomized, placebo‐ and positive‐controlled, sequential, ascending‐dose (0.3/0.6/1.0/1.5/2.25 mg/kg/h) study of 5‐day continuous intravenous infusions of frunexian. Frunexian administration exhibited an acceptable safety profile with no bleeding events. Steady state was rapidly reached with a median time ranging from 1.02 to 1.50 h. The mean half‐life ranged from 1.15 to 1.43 h. Frunexian plasma concentration at a steady state and area under the concentration–time curve exhibited dose‐proportional increases. The dose‐escalation study of frunexian demonstrated its progressively enhanced capacities to prolong activated partial thromboplastin time (aPTT) and inhibit FXIa activity. The correlations between PK and PD biomarkers (aPTT/baseline and FXI clotting activity/baseline) were described by the two Emax models, with the EC50 values of 8940 and 1300 ng/mL, respectively. Frunexian exhibits good safety and PK/PD properties, suggesting it is a promising candidate for anticoagulant drug. [ABSTRACT FROM AUTHOR]

The inhibition of coagulation factor XI (FXI) presents an attractive approach for anticoagulation as it is not expected to increase the risk of clinically relevant bleeding and is anticipated to be at least as effective as currently available anticoagulants. Fesomersen is a conjugated antisense oligonucleotide that selectively inhibits the expression of FXI. The article describes three clinical studies that investigated the safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of fesomersen after subcutaneous (s.c.) injection to healthy participants. The studies included participants from diverse ethnic backgrounds (Caucasian, Japanese, and Chinese). Fesomersen demonstrated good safety and tolerability in all three studies. No major bleeding events were observed. After single‐dose s.c. injection, fesomersen was rapidly absorbed into the systemic circulation, with maximum fesomersen‐equivalent (fesomersen‐eq) concentrations (Cmax) in plasma observed within a few hours. After reaching Cmax, plasma fesomersen‐eq concentrations declined in a biphasic fashion. The PD analyses showed that the injection of fesomersen led to dose‐dependent reductions in FXI activity and increases in activated partial thromboplastin time (aPTT). The maximum observed PD effects were reached between Day 15 and 30, and FXI activity and aPTT returned to near‐baseline levels by Day 90 after a single dose. The PK/PD profiles after a single injection were similar among the various ethnic groups. Collectively, the study results suggest that fesomersen has a favorable safety profile and predictable and similar PK and PD profiles across Chinese, Japanese, and Caucasian participants. [ABSTRACT FROM AUTHOR]

To explore the association and impact between viral myocarditis and mortality in patients with severe fever with thrombocytopenia syndrome. A dynamic analysis was conducted between fatal group and nonfatal group regarding the daily epidemiology data, clinical symptoms, and electrocardiogram (ECG), echocardiogram, and laboratory findings. Outcomes of patients with and without viral myocarditis were compared. The association between viral myocarditis and mortality was analyzed. Among 183 severe fever with thrombocytopenia syndrome patients, 32 were in the fatal group and 151 in the nonfatal group; there were 26 (81.25%) with viral myocarditis in the fatal group, 66 (43.70%) with viral myocarditis in the nonfatal group (p < 0.001), 79.35% of patients had abnormal ECG results. The abnormal rate of ECG in the fatal group was 100%, and in the nonfatal group was 74.83%. Univariate analysis found that the number of risk factors gradually increased on Day 7 of the disease course and reached the peak on Day 10. Combined with the dynamic analysis of the disease course, alanine aminotransferase, aspartate aminotransferase, creatine kinase, creatine kinase fraction, lactate dehydrogenase, hydroxybutyrate dehydrogenase, neutrophil count, serum creatinine, Na, Ca, carbon dioxide combining power, amylase, lipase, activated partial thromboplastin time and thrombin time had statistically significant impact on prognosis. The incidence of fever with thrombocytopenia syndrome combined with viral myocarditis is high, especially in the fatal group of patients. Viral myocarditis is closely related to prognosis and is an early risk factor. The time point for changes in myocarditis is Day 7 of the course of the disease. [ABSTRACT FROM AUTHOR]

This article discusses a rare bleeding disorder called combined factor V and factor VIII deficiency (F5F8D). The disorder is characterized by reduced levels of both factor V and factor VIII, leading to mild-to-moderate bleeding. F5F8D is caused by genetic variations in the LMAN1 or MCFD2 genes, which are involved in the transport of these factors in the body. The article presents a case study of a 1-year-old boy with F5F8D and describes the identification of a pathogenic variant in the MCFD2 gene. The study highlights the importance of genetic counseling and segregation studies in non-consanguineous patients with homozygous variants. [Extracted from the article]

The present study aimed to investigate the preventive role of Protaetia brevitarsis seulensis (P. brevitarsis) larvae in the κ‐carrageenan‐induced rat tail thrombosis model, in comparison with that of heparin. Thrombosis was induced in Sprague–Dawley (SD) rats by intraperitoneal injection with a dose of 30 mg/kg κ‐carrageenan after receiving oral pretreatment with P. brevitarsis larvae at doses of 300 or 900 mg/kg. The control group was only given physiological saline for 7 days without the administration of κ‐carrageenan. The results indicate that pretreatment with P. brevitarsis larvae at 300 or 900 mg/kg not only significantly reduced the average length of the thrombus but also markedly decreased the fibrinogen levels and serum P‐selectin in a dose‐dependent manner (P < 0.05). However, there were no notable effects on the blood clotting times, such as prothrombin time (PT) and activated partial thromboplastin time (aPTT). Moreover, the histological analysis of tail tissues treated with P. brevitarsis larvae supported the serum biochemical findings, thereby providing evidence of enhanced blood circulation. Based on these results, it was concluded that P. brevitarsis larvae had a positive effect on preventing thrombosis in vivo through the reduction of fibrinogen and P‐selectin levels, suggesting potential applications for thrombosis prevention. [ABSTRACT FROM AUTHOR]

Introduction: Haemophilia B (HB) is an X‐linked hereditary bleeding disorder characterized by coagulation factor IX (FIX) deficiency. To improve the quality of life of patients and adherence to treatment, recombinant factor concentrates modified to extend their half‐life have been developed, called extended half‐life factors (EHL: extended half‐life). Nonacog beta pegol (N9‐GP) is a glycopegylated recombinant human FIX molecule that has a half‐life of 93 h with a single dose and has shown a higher recovery percentage than other molecules. To diagnose and monitor the treatment of haemophiliac patients, FIX activity is determined with the one‐stage clotting assay (OSA) and/or the chromogenic assay. The objective of this work, carried out in three centres, was to measure the recovery of N9‐PG with 10 different activated partial thromboplastin time (APTT) reagents on three platforms, in samples spiked in vitro with N9‐GP, at four different concentration levels. Methods: It was measured the recovery of N9‐GP with 10 different APTT reagents (polyphenol, ellagic acid, silice dioxide, colloidal silica as APTT activator on three platforms, in sample spiked in vitro with N9‐GP. Results: The results show heterogeneity in the activity of N9‐GP measured by OSA with the different APTT reagents when the calibrations were performed with the specific calibrator of each coagulometer. A recovery percentage between 87% and 108% was obtained only with polyphenol and ellagic acid as activator in the three platforms evaluated. The other reagents studied overestimate or underestimate, with no clear profile. When a calibration curve was performed with a calibrator prepared from the N9‐GP vial, all APTT reagents met the established recovery requirement. Conclusion: APTT reagents with polyphenol or ellagic acid as activator would be the only ones appropriate when using the commercially available OSA with specific calibrator to monitor patients treated with N9‐GP. [ABSTRACT FROM AUTHOR]

Bleeding complications following thrombolytic treatment for acute myocardial infarction (AMI) are not infrequent, among which intracranial hemorrhage is commonly reported. In contrast, retroperitoneal hematoma following the administration of thrombolytics is rarely reported in the literature. We are reporting a case of a middle‐aged man, who presented with left‐sided chest pain and was diagnosed with acute coronary syndrome with anterior wall ST elevation AMI. The patient was administered with thrombolytic drugs, including streptokinase and heparin. Percutaneous coronary intervention in the form of Coronary angioplasty with stent insertion was done to the left anterior descending artery, given coronary artery disease. The blood investigations showed elevated activated partial thromboplastin time and prothrombin time. The patient developed vomiting, altered sensorium, and left‐sided weakness, and a non‐contrast computerized tomography brain was done, which showed acute hemorrhage involving the right frontal lobe with intraventricular extension, so the ventricular drain was placed. The patient developed cardiac arrest and died on the third day. On autopsy examination, the brain showed subarachnoid hemorrhage, intraparenchymal hemorrhage over the right frontal lobe, and clotted blood in all the ventricles. A retroperitoneal hematoma of around 1500 cc was seen over the left side of the peritoneal cavity. This case highlights that although intracranial hemorrhage is a known complication after administrating thrombolytic therapy, clinicians should also be aware of the possibility of retroperitoneal hemorrhage. This case emphasizes the value of an autopsy in determining the cause of death in such situations. [ABSTRACT FROM AUTHOR]

Background: Severe COVID‐19 causes acute inflammation, which is complicated by venous thromboembolism events (VTE). However, it is unclear if VTE risk has evolved over time since the COVID‐19 outbreak. Aims: To determine markers of thrombo‐inflammation and rates of symptomatic VTE in patients hospitalised for COVID‐19 in a metropolitan hospital in Sydney, Australia. Methods: A retrospective, single‐centre, cohort study was performed by reviewing electronic medical records of consecutive patients admitted to Royal Prince Alfred Hospital between March 2020 and September 2021. This period included three waves of COVID‐19 outbreaks in Australia with the ancestral, alpha and delta variants. Standard coagulation assays and inflammatory markers were recorded over 4 weeks. Results: A total of 205 patients were consecutively admitted during the study period. Activated partial thromboplastin time, neutrophil count and C‐reactive protein (CRP) were significantly increased in patients hospitalised in the intensive care unit (ICU) compared with non‐ICU patients. The use of anti‐inflammatory medication increased in 2021 compared with 2020. The mortality rate was 7.3% in our cohort. Ninety‐four per cent of patients received anticoagulation with 6.3% of patients developing VTE. Conclusion: We observed lower rates of VTE compared to the internationally reported rate for the same period. We conclude that in the setting of controlled hospital admission rate and standard anticoagulation guidelines, COVID‐19 resulted in similar thrombo‐inflammatory response and VTE rates over the first 1.5 years of the pandemic. [ABSTRACT FROM AUTHOR]

Introduction: Structural and chemical modifications of factor VIII (FVIII) products may influence their behaviour in FVIII activity assays. Hence, it is important to assess the performance of FVIII products in these assays. Efanesoctocog alfa is a new class of FVIII replacement therapy designed to provide both high sustained factor activity levels and prolonged plasma half‐life. Aim: Evaluate the accuracy of measuring efanesoctocog alfa FVIII activity in one‐stage clotting assays (OSAs) and chromogenic substrate assays (CSAs). Methods: Human plasma with no detectable FVIII activity was spiked with efanesoctocog alfa or a full‐length recombinant FVIII product comparator, octocog alfa, at nominal concentrations of 0.80 IU/mL, 0.20 IU/mL, or 0.05 IU/mL, based on labelled potency. Clinical haemostasis laboratories (N = 35) tested blinded samples using in‐house assays. Data from 51 OSAs (14 activated partial thromboplastin time [aPTT] reagents) and 42 CSAs (eight kits) were analyzed. Results: Efanesoctocog alfa activity was reliably (±25% of nominal activity) measured across all concentrations using OSAs with Actin FSL and multiple other aPTT reagents. Under‐ and overestimation of FVIII activity occurred with some reagents. No specific trend was observed for any class of aPTT activators. A two‐ to three‐fold overestimation was consistently observed using CSAs and the OSA with Actin FS as the aPTT reagent across evaluated concentrations. Conclusion: Under‐ or overestimation occurred with some specific OSAs and most CSAs, which has been previously observed with other modified FVIII replacement products. Efanesoctocog alfa FVIII activity was measured with acceptable accuracy and reliability using several OSA methods and commercial plasma standards. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Acquired hemophilia A (AHA) can present as life‐threatening bleeding during the postpartum period. Prompt treatment allows patients with AHA to achieve complete remission and have normal subsequent pregnancies. Acquired hemophilia A (AHA) is a rare bleeding disorder caused by the production of autoantibodies against factor VIII (FVIII). AHA can present with severe bleeding, especially in postpartum patient. We report a 38‐year‐old woman who presented in an emergency department with severe postpartum hemorrhage 2 weeks after cesarean section. Her investigation showed an isolated prolongation of partial thromboplastin time (PTT), low factor VIII assay and a factor VIII inhibitor test, resulting in abnormal Bethesda units which consistent with AHA. This case report highlights the importance of early diagnosis and treatment of AHA. With timely and appropriate management, most patients can achieve a good outcome. [ABSTRACT FROM AUTHOR]

Objective: To determine the characteristics of canine freeze‐dried plasma (cFDP) as it is serially diluted with sterile water. Design: In vitro experimental study. Setting: Government blood and coagulation research laboratory. Animals: cFDP from a commercial manufacturer. Interventions: Ten units of cFDP were reconstituted to 100%, 90%, 80%, 70%, 60%, 50%, and 40% of the recommended volume with sterile water. The resultant solutions were analyzed for coagulation factor activity (factors II, V, VII, VIII, IX, X, and XII as well as antithrombin), fibrinogen concentration, prothrombin time, activated partial thromboplastin time, viscosity, osmolality, and kaolin‐activated thromboelastography. Measurements and Main Results: Viscosity, osmolality, and turbidity properties of plasma were increased in a reconstitution volume‐dependent manner, with the 40% suggested volume generating approximately 2‐fold increases in each. Similarly, factor activity levels and fibrinogen concentration increased by approximately 2‐fold over this range in a concentration‐dependent manner. Prothrombin time declined from 11.4 seconds at 100% volume to 10.9 seconds at 70% before increasing to 11.9 seconds at 40%. Activated partial thromboplastin time increased exponentially from 21.8 seconds at 100% rehydration to 100.0 seconds at 40%. R‐time on TEG increased from 3.1 to 13.9 minutes at 50% rehydration, while alpha angle declined from 61.3° to 24.7° over the same range, and the maximum amplitude initially increased from 13.2 mm at 100% water to 18.6 mm at 70% water before dropping back down to 14.6 mm at 50% water. No clotting was observed with 40% rehydration. Conclusions: The creation of hyperosmotic plasma from cFDP appears feasible with preservation of concentrated coagulation factors, although there are some unexplained effects that happen to coagulation functions at the highest concentrations tested using only 40%–50% of recommended rehydration volume. Further studies are needed to evaluate the hyperosmotic product in vivo. [ABSTRACT FROM AUTHOR]

Crimean–Congo hemorrhagic fever (CCHF) is a severe viral disease. The scientific literature is growing, emphasizing the significance of the interleukin (IL)‐36 family in the proinflammatory signaling pathway. However, to date, no research has explored the potential of IL‐36 family members as biomarkers in CCHF. This study aims to bridge this gap by evaluating IL‐36α, IL‐36β, and IL‐36γ levels in CCHF patients and healthy controls and investigating their association with disease severity and prognosis. Sixty confirmed CCHF patients and 29 healthy controls were enrolled in this case‐control study. Serum levels of IL‐36α, IL‐36β, and IL‐36γ were measured using enzyme‐linked immunosorbent assays. Significantly higher levels of IL‐36α and IL‐36β were observed in CCHF patients compared to healthy controls (p < 0.05). However, no statistically significant changes were found in IL‐36γ levels between the two groups. Among the CCHF patients, those who did not survive exhibited significantly elevated IL‐36α and IL‐36γ levels compared to survivors (p < 0.01). Positive correlations were identified between IL‐36α and IL‐36γ levels with activated partial thromboplastin time, and D‐dimer (p < 0.01). Conversely, platelet levels showed a negative correlation with IL‐36α and IL‐36γ levels (p < 0.01). The increased levels of IL‐36α, IL‐36β, and IL‐36γ in patients indicate their participation in proinflammatory reactions in CCHF patients. Understanding the role of IL‐36 family members in CCHF pathogenesis could offer valuable insights into disease progression and facilitate the development of targeted therapeutic strategies. [ABSTRACT FROM AUTHOR]

The purpose of this study was to analyse the risk factors for sepsis in patients with trauma and develop a new scoring system for predicting sepsis in patients with trauma based on these risk factors. This will provide a simple and effective early warning method for the rapid and accurate detection and evaluation of the probability of sepsis in patients with trauma to assist in planning timely clinical interventions. We undertook a retrospective analysis of the clinical data of 216 patients with trauma who were admitted to the emergency intensive care unit of the emergency medicine department of the Hebei Medical University Third Hospital, China, between November 2017 and October 2022. We conducted a preliminary screening of the relevant factors using univariate logistic regression analysis and included those factors with a p value of <0.075 in the multivariate logistic regression analysis, from which the risk factors were screened and assigned, and obtained a total score, which was the sepsis early warning score. The incidence of sepsis in patients in the intensive care unit with trauma was 36.9%, and the mortality rate due to sepsis was 19.4%. We found statistically significant differences in several factors for patients with sepsis. The risk factors for sepsis in patients with trauma were the activated partial thromboplastin time, the New Injury Severity Score, growth differentiation factor‐15 levels, shock, mechanical ventilation and the Acute Physiology and Chronic Health Evaluation II score. The area under the receiver operating characteristic curve of the sepsis early warning score for predicting sepsis in patients with trauma was 0.725. When the cutoff value of the early warning score was set at 5.0 points, the sensitivity was 69.9% and the specificity was 60.3%. The incidence of sepsis in patients with trauma can be reduced by closely monitoring patients' hemodynamics, implementing adequate fluid resuscitation promptly and by early removal of the catheter to minimize the duration of unnecessary invasive mechanical ventilation. In this study, we found that the use of the sepsis early warning score helped in a more accurate and effective evaluation of the prognosis of patients with trauma. [ABSTRACT FROM AUTHOR]

Summary: Factor XI deficiency is a rare disorder with an unpredictable bleeding tendency. Here, we report the successful use of the sonic estimation of elasticity via resonance sonorheometry for guiding the management of haemostasis in a patient with a severe factor XI deficiency in repeated revision hip surgeries. Regardless of an administration of fresh frozen plasma, a significant haemorrhage occurred at the first of three hip surgeries. The repeat application of fresh frozen plasma normalised the prolonged activated partial thromboplastin time and the resonance sonorheometry clot time values; the factor XI activity increased to a sufficient level. No significant bleeding occurred in the second and third hip surgery. Using a resonance sonorheometry guided approach in haemostasis management has the potential to improve safety for patients with factor XI deficiency undergoing surgery by ensuring sufficient clotting and preventing side effects. [ABSTRACT FROM AUTHOR]