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BACKGROUND & AIMS: Despite several recent international guidelines, no consensus exists on the bleeding risk nor haemostatic parameter thresholds that define the safety of invasive procedures in patients with cirrhosis. The aim of this study was to establish a position paper on the bleeding risk associated with invasive procedures in patients with cirrhosis among the experts involved in various guidelines. METHODS: All experts involved in recent guidelines on the management of invasive procedures in patients with cirrhosis were invited to classify 80 procedures as high risk or low risk with respect to bleeding. Procedures were considered high risk when the estimated risk of major bleeding was 1.5% or more, or when even minor bleeding might lead to significant morbidity or death. The experts were also asked to choose safety thresholds for laboratory test values at which elective invasive procedures could be safely performed. The predetermined threshold considered as consensus was ≥75% agreement. RESULTS: Fifty-two experts participated in the study. Out of 80 procedures, a consensus opinion was reached for 52 procedures (65%): 17 procedures were classified as high risk, primarily interventional endoscopic procedures, percutaneous organ biopsies, or procedures involving the central nervous system; and 35 as low risk, primarily diagnostic procedures. The lowest platelet counts at which performance of a low-risk procedure or a high-risk procedure/surgery were deemed acceptable were 30 × 109/L and 50 × 109/L, respectively. Experts did not believe that international normalised ratio should be considered before performing low-risk procedures; 71% also indicated that it should not be considered before performing high-risk procedures. CONCLUSIONS: This experience-based classification may be helpful to refine future study designs and to guide clinical decision making regarding invasive procedures in patients with cirrhosis. IMPACT AND IMPLICATIONS: Several risk classifications and management guidelines for invasive procedures in patients with cirrhosis have been proposed, but with conflicting recommendations. By providing a position paper, based on the opinion of a broad panel of experts, on the bleeding risk associated with 52 invasive procedures in patients with cirrhosis, this survey will help to provide a framework for future study design. The consensus on platelet count, international normalised ratio, fibrinogen and activated partial thromboplastin time identified in this survey will inform physicians regarding the laboratory test values considered acceptable by the experts prior to the performance of an elective invasive procedure in patients with cirrhosis.

Introduction: 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). Method: 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. Results: 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. Conclusion: 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]

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]

It is common practice in laboratories to store biological samples in ultra-low temperature (ULT) freezers. There is growing interest in raising the temperature of ULT freezers in order to save energy and reduce expenses, as energy conservation becomes increasingly important and sustainable laboratory practices gain popularity. In our laboratory, plasma samples are stored for three months for diagnostic purposes. We therefore took the opportunity to investigate the effect of two different storage temperatures (−70 °C vs −80 °C), on activated partial thromboplastin time (APTT), factor VIII (FVIII), international normalized ratio (INR) and factor VII (FVII) measurements on paired plasma samples collected from 26 individuals after three months of storage. Automated coagulation analysers CS-5100 and ACL TOP were used to perform the tests. We found no consistent difference between the two storage temperatures for any of the four coagulation parameters (all p-values > 0.05). We conclude that the temperature of ULT freezers used to store plasma samples for APTT, FVIII, INR, and FVII measurements can be safely increased from −80 to −70 °C without affecting the stability of the samples. [ABSTRACT FROM AUTHOR]

Background Clot waveform analysis can be used to evaluate clot formation profiles. This waveform can be obtained from activated partial thromboplastin time (APTT) assays without additional reagents and shows different patterns in hemophilia patients with coagulation factor VIII (F VIII) deficiency or abnormality. Objective To determine the clot wave pattern and its process in clot formation phases (pre-coagulation, coagulation, and post-coagulation) in normal and hemophilia A subjects, analyze for possible correlations between clot wave parameters and F VIII activity, and obtain the pattern of coagulation curves in hemophilia subjects as a step to assess clot waveform analysis as a possible screening tool for hemophilia. Methods In this cross-sectional study, we performed clot wave analysis in 145 adult and pediatric subjects with hemophilia to obtain the clot wave pattern in this condition. Clot wave analysis was also done in 160 subjects with normal hemostasis to obtain reference clot wave parameters. Results In this study, the starting point of coagulation phase in normal subjects was between 30-40 seconds, with a shorter pre-coagulation phase and steeper slope. Hemophilia patients had a longer pre-coagulation phase and flatter slope, especially in severe hemophilia A patients, who had longer and more variable coagulation starting points (P

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]

Glioblastomas are among the most malignant tumors which, despite aggressive treatment, currently have an abysmal prognosis. These lesions are known to cause local and systemic perturbations in the coagulation system, leading to neoangiogenesis and a high risk of venous thromboembolism. Indeed, there have been multiple proposals of the coagulation system being a possible target for future treatment of these patients. However, nonselective anticoagulant therapy has proven suboptimal and leads to a significant increase of intracranial hemorrhage. Thus, recognizing factors that lead to hypercoagulation is considered paramount. Hyperglycemia is a well-known prothrombotic factor, a fact that has received little attention in neuro-oncology. We previously hypothesized that patients with brain tumors could be highly susceptible to iatrogenic glycemia dysregulation. Here, we analyzed the connection between glycated hemoglobin (HbA1c) and the routine coagulation markers (D-dimers, prothrombin time and activated partial thromboplastin time [aPTT]) in patients with de novo intracranial glioblastomas. Included in this study were 74 patients who were operated on in 2 hospitals: Clinical Hospital Dubrava, Zagreb, Croatia; University Hospital Center Split, Split, Croatia; and University Hospital de la Princesa, Madrid, Spain. We found a significant inverse correlation between HbA1c and aPTT (ρ = –0.379; P = 0.0009). We also found a significant inverse correlation between Ki67 immunoreactivity and aPTT (ρ = –0.211; P = 0.0082). No connection was found between HbA1c and D-dimers or prothrombin time. Our results suggest that patients with hyperglycemia, with a more proliferative glioblastoma, could in fact have their coagulation profile significantly disrupted, primarily through the intrinsic coagulation pathway. Such findings could have great clinical importance. Further research in this area could help to elucidate the vicious connection between glioblastomas and coagulation and to combat this deadly disease. [ABSTRACT FROM AUTHOR]

Le bilan d'hémostase standard (taux de prothrombine [TP] et temps de céphaline avec activateur [TCA]) est très couramment prescrit mais son interprétation peut poser problème pour les cliniciens. Nous rappelons ici les bases de la démarche diagnostique devant ces tests. Seule une connaissance très basique de la cascade de la coagulation est nécessaire pour identifier les dosages de facteurs de la coagulation à prescrire et interpréter les résultats. En cas de déficit en plusieurs facteurs, on s'orientera vers une insuffisance hépatocellulaire, une coagulation intravasculaire disséminée ou une carence en vitamine K. Devant la baisse d'un seul facteur de la coagulation, nous rappelons les différentes causes de déficits acquis et évoquons brièvement les caractéristiques des différents déficits congénitaux qui relèvent généralement d'une prise en charge spécialisée. L'anticoagulant circulant de type lupique est une cause fréquente et généralement bénigne d'allongement du TCA à connaître, ne devant pas faire craindre un risque hémorragique. Une bonne connaissance de la démarche diagnostique devant une anomalie du TP ou du TCA permet généralement de débrouiller les situations les plus courantes. The standard hemostasis workup [quick time (QT), and activated partial thrombin time (APTT)] is very commonly prescribed but its interpretation is often difficult for practitioners who are not specialized in hemostasis. Here, we review the principles of the diagnostic approach to these tests. Only a very basic knowledge of the coagulation cascade is necessary to identify which clotting factor tests to prescribe and to interpret the results. Deficiency in several clotting factors suggests liver dysfunction, disseminated intravascular coagulation (DIC) or vitamin K deficiency. If a single factor is deficient, we review the different causes of acquired deficiencies and briefly discuss the characteristics of the different congenital defects, which generally require specialized management. Lupus anticoagulant is a common and generally benign cause of prolonged APTT to be aware of, which is not related to a hemorrhagic risk. A good knowledge of the diagnostic approach to abnormal QT or APTT generally allows the resolution of the most common situations. [ABSTRACT FROM AUTHOR]

Background This study was conducted to compare whole blood clotting time (20 minutes) with PT and APTT as early markers for hematotoxicity identification in snake bites. Early anti-snake venom administration can prevent hematotoxic consequences. Methods This study involved 94 patients who presented to the Department of General Medicine at the Karnataka Institute of Medical Sciences, KIMS Hospital, Hubballi, with a history ofsnakebites and characteristic clinical signs and symptoms. The study was conducted over a two-year period, from December 2020 to December 2022. The institutional ethics committee approved the study, and the participants provided written informed consent. Results Out of the 92 patients who had WBCT20 performed at admission, only 28 had positive results; the test's sensitivity in this study was 30.43%, and it missed 43% of cases with VICC. Additionally, two patients had normal coagulation profiles, and in both cases, WBCT20 was negative. These results indicate that WBCT20 has a high specificity of 100% in this study, as well as 100% PPV, 3.03% NPV, and 31.91% diagnostic accuracy. In contrast to previous research, the WBCT20 test's sensitivity, NPV, and diagnostic accuracy were low. There was also a significant likelihood that the coagulopathy in the cases would go unnoticed, which could delay ASV administration and raise the death and morbidity rates from snake bites. Conclusion In tertiary care hospitals managing instances of hematotoxic snake bites when PT-INR and APTT tests are feasible, prothrombin time is a very beneficial blood study in making an early diagnosis of coagulopathy compared to whole blood clotting tests. [ABSTRACT FROM AUTHOR]

Background- Sepsis is a severe, life-threatening condition resulting from an abnormal and uncontrolled immune response to infection, posing a significant global health challenge. Blood coagulation disorders are significant complications in sepsis, often exacerbating the severity of the condition. The APACHE II (Acute Physiology and Chronic Health Evaluation II) score is a widely used severity-of-disease classification system that provides valuable prognostic information in critically ill patients. This study aims to investigate the relationship between various blood coagulation parameters and the severity of sepsis as assessed by the APACHE II score. Materials And Methods- A descriptive cross-sectional hospital-based study was conducted in the Department of General Medicine at Mahatma Gandhi Medical College & Hospital, Jaipur, on patients admitted to the ICU diagnosed with sepsis according to Sepsis-3 criteria. Blood coagulation parameters, including platelet count, PT, aPTT, D-dimer, and fibrinogen levels, were monitored and compared to assess the severity of sepsis using the APACHE II score. Results- The study included 168 sepsis patients aged 18 to 65 years. The mean APACHE II score was 29.08, with a significant correlation between age and APACHE II scores (p<0.001). The study found 68.5% of patients in a hypo-coagulation state and 31.5% in a hyper-coagulation state. Significant correlations were observed between APACHE II scores and PT, aPTT, D-dimer, and platelet count. Conclusions- The study highlights the critical role of blood coagulation disorders in the pathophysiology of sepsis and their correlation with disease severity as assessed by the APACHE II score. Routine monitoring of coagulation parameters in sepsis patients is essential, and incorporating these parameters into the APACHE II scoring system could provide a more comprehensive assessment of sepsis severity, aiding in better prognostication and treatment planning. [ABSTRACT FROM AUTHOR]

Evidence supporting anticoagulation with unfractionated heparin (UFH) in patients with an intra-aortic balloon pump (IABP) to prevent limb ischaemia remains limited, while bleeding risks remain high. Monitoring heparin in this setting with anti-factor Xa (anti-Xa) is not previously described. The study objective is to describe the incidence of thromboembolic and bleeding events with the use of UFH in patients with an IABP utilising monitoring with both anti-Xa and activated partial thromboplastin time (aPTT). This is a retrospective study of adults who received an IABP and UFH for ≥24 hours. Electronic medical records were reviewed for pertinent data. The primary outcome was the incidence of limb ischaemia during IABP. Secondary outcomes included myocardial infarction, thrombus on IABP, or stroke. Exploratory outcomes included any venous thromboembolism and bleeding events. Of 159 patients, 88% received an IABP for cardiogenic shock and median duration of IABP support was 118 hours (interquartile range, 67–196). Limb ischaemia occurred in four of 159 patients (2.5%). Strokes occurred in 3.8% of the cohort, and bleeding events occurred in 33%. Despite anticoagulation use in all patients, 11% experienced a venous thromboembolism, with most identified upon asymptomatic screening with concern for heparin-induced thrombocytopenia. We found no differences in outcomes that occurred with a hybrid anti-Xa and aPTT versus aPTT monitoring alone. We observed a high rate of thrombotic and bleeding complications with the use of UFH in patients with an IABP. Use of anti-Xa versus aPTT for monitoring was not associated with complications. These data suggest safer anticoagulation strategies are needed in this setting. • Utilization of unfractionated heparin titrated to therapeutic aPTT and/or anti-Xa in patients requiring hemodynamic support with an IABP may not be required for all. • Patient characteristics, such as increased thromboembolic or bleeding risk, should be assessed and careful consideration of anticoagulation goals should be determined at the bedside. • Given a paucity of data, evaluation of heparin monitoring with anti-Xa during IABP support requires further investigation. • Further research is needed to understand optimal goals of anticoagulation therapy if utilized, specifically if therapeutic levels are necessary or if prophylactic goals can be targeted to reduce the risk of bleeding without increasing thromboembolic events in patients supported with an IABP. [ABSTRACT FROM AUTHOR]

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

Objective To investigate the influence of the dead space in disposable blood sampling needle on activated partial thromboplastin time (APTT), FVIII level and pharmacokinetic (PK) profiles in children with hemophilia.Methods Children (

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

Chen Lin,1 Jing Wang,2 Kexin Cai,2 Yuqing Luo,2 Wensi Wu,1 Siming Lin,2 Zhihong Lin,2 Shaodan Feng2 1Department of Emergency, The Third Affiliated People’s Hospital, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, People’s Republic of China; 2Department of Emergency, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of ChinaCorrespondence: Zhihong Lin; Shaodan Feng, Department of Emergency, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of China, Tel +86 59187981975, Email fzlinzh@163.com; sdfeng@fjmu.edu.cnPurpose: To address the critical mortality rates among sepsis-associated acute kidney injury (SA-AKI) patients, early prognosis is vital. This study investigates the relationship between coagulation indices and the 28-day mortality rate in patients with SA-AKI.Patients and Methods: This study was a retrospective cohort analysis including patients with SA-AKI admitted to the First Hospital of Fujian Medical University as a training cohort (n = 119) and patients admitted to the Third People’s Hospital of Fujian University of Traditional Chinese Medicine as a validation cohort (n = 51). We examined the relationship between coagulation indices and 28-day mortality in SA-AKI, the cumulative mortality at different activated partial thromboplastin time (APTT) levels, and the nonlinear relationship between APTT and 28-day mortality. Receiver operating characteristic curves were plotted, and the area under the curve was calculated to assess the predictive power of APTT. Finally, subgroup analyses were performed to assess the robustness of the association.Results: Overall, 119 participants with a mean±standard deviation age of 70.47± 15.20 years were included in the training cohort: 54 died, 65 survived. According to univariate and multivariate COX regression analyses, APACHE II score, CRP level, Lac level, and APTT level were independent risk factors for 28-day adverse prognosis. After controlling for some variables, an elevated baseline APTT (≥ 37.7 s) was associated with an elevated risk of 28-day mortality (HR, 1.017; 95% CI, 1.001– 1.032), and Kaplan–Meier analyses further confirmed the increased mortality in the group with a higher APTT. The same results were shown when the validation cohort was analyzed (HR, 1.024; 95% CI, 0.958– 1.096). Subgroup analyses showed the stability of the association between APTT and poor prognosis in SA-AKI.Conclusion: In essence, APTT elevation is synonymous with increased 28-day mortality rates, indicating a poor prognosis in SA-AKI scenarios.Keywords: APTT, prognosis, retrospective studies, critical illness

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

Unfractionated heparin is a widely used anticoagulant in critically ill patients. It has a well-established safety profile and remains an attractive option for clinicians due to its short half-life and reversibility. Heparin has a unique pharmacokinetic profile, which contributes to significant inter-patient and intra-patient variability in effect. The variability in anticoagulant effect combined with heparin's short half-life mean close monitoring is required for clinical efficacy and preventing adverse effects. To optimize heparin use in critically ill patients, effective monitoring assays and dose adjustment strategies are needed. This paper explores the use of heparin as an anticoagulant and optimal approaches to monitoring in critically ill patients. Conventional monitoring assays for heparin dosing have significant limitations. Emerging data appear to favor using anti-Xa assay monitoring for heparin anticoagulation, which many centers have successfully adopted as the standard. The anti-Xa assay appears have important benefits relative to the aPTT for heparin monitoring in critically ill patients, and should be considered for broader use. [ABSTRACT FROM AUTHOR]

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

Antisense oligonucleotides (ASOs) are a therapeutic modality for incurable diseases. However, systemic injection of gapmer-type ASOs causes class-related toxicities, including prolongation of activated partial thromboplastin time (aPTT) and thrombocytopenia. We previously reported that cholesterol-conjugated DNA/RNA heteroduplex oligonucleotides (Chol-HDOs) exhibit significantly enhanced gene-silencing effects compared to ASOs, even in the central nervous system, by crossing the blood-brain barrier. In the present study, we initially evaluated the effect of the HDO structure on class-related toxicities. The HDO structure ameliorated the class-related toxicities associated with ASOs, but they remained to some extent. As a further antidote, we have developed artificial cationic oligopeptides, L-2,4-diaminobutanoic acid oligomers (DabOs), which bind to the phosphates in the major groove of the A-type double-helical structure of HDOs. The DabO/Chol-HDO complex showed significantly improved aPTT prolongation and thrombocytopenia in mice while maintaining gene-silencing efficacy. Moreover, the conjugation with DabOs effectively prevented cerebral infarction, a condition frequently observed in mice intravenously injected with high-dose Chol-HDO. These approaches, combining HDO technology with DabOs, offer distinct advantages over conventional strategies in reducing toxicities. Consequently, the DabO/HDO complex represents a promising platform for overcoming the class-related toxicities associated with therapeutic ASOs.

Fanchun Yang, Qingying Wang, Rui Ma, Fangzhen Deng, Jie Liu Department of Obstetrics and Gynecology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Jie Liu, Department of Obstetrics and Gynecology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, No. 301, Yanchang Zhong Road, Shanghai, People’s Republic of China, Email Liujie1997@tongji.edu.cnObjective: Adenomyosis patients are in a hypercoagulable state, and studies have shown that carbohydrate antigen125 (CA125) may relate to the hypercoagulability and thrombosis of patients with adenomyosis, but there is still a lack of clarity regarding the changes in CA125-related coagulation indicators. This study was to explore the changes and influencing factors of CA125-related coagulation parameters in patients with adenomyosis.Methods: Retrospective observational study conducted on 200 patients with adenomyosis (AM group), 240 patients with uterine leiomyoma (LM group) and 81 patients with cervical intraepithelial neoplasia (CIN)-III (control group), of which the coagulation parameters were detected by clinical blood sample collection and statistical method analysis and informed consent was obtained.Results: The level of CA125 in the AM group was significantly higher than that in the LM group and control group. However, thrombin time (TT) shortened in the AM group when compared with the LM and control group. Activated partial thromboplastin time (APTT) in the AM group was shorter than in the control group. Multivariate logistic regression analysis found that adenomyosis was associated with CA125 level (OR=323.860, 95% CI 90.424– 1159.924, P< 0.001), APTT (OR=1.295, 95% CI 1.050– 1.598, P=0.016), TT (OR=0.642, 95% CI 0.439– 0.938, P=0.022), menorrhagia (OR=7.363, 95% CI 2.544– 21.315, P< 0.001), dysmenorrhea (OR=22.590, 95% CI 8.185– 62.347, P< 0.001). Correlation analysis revealed that APTT (r= − 0.207) and TT (r = − 0.174) were negatively correlated with the level of CA125.Conclusion: The shortening of CA125-related APTT and TT indicates that it is meaningful to detect coagulation parameters of patients with elevated CA125 levels early, dysmenorrhea and menorrhagia, and maybe further discover the hypercoagulability and prevent the occurrence of thrombus in adenomyosis.Keywords: adenomyosis, coagulation parameters, hypercoagulability, CA125, APTT, TT

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]

Background: Risk assessment of vascular thrombosis in SLE patients with the presence of antiphospholipid antibodies (aPL) remains a challenge. The adjusted global antiphospholipid syndrome score (aGAPSS) has been validated and used to predict aPL-related thrombosis in SLE patients in some countries. Relevant data of aGAPSS in thrombotic evaluation in SLE population from China has not been reported. We aim to validate aGAPSS in thrombosis assessment in Chinese patients with SLE and to explore the correlations of aGAPSS with routine laboratory parameters and their clinical significance as well. Methods: A total of 166 consecutive SLE patients were retrospectively analyzed. Multivariate logistic regression analysis was performed to examine the impact of multiple cardiovascular risk factors and laboratory parameters in recurrent thrombosis risk in SLE. ROC was conducted to explore the discriminative ability of aGAPSS and platelet (PLT), activated partial thromboplastin time (APTT), alone or in combination. Results: Significantly higher value of aGAPSS was seen in SLE patients with vascular thrombosis. ROC curve indicated that aGAPSS of 3.5 or more had the best diagnostic accuracy for the prediction of aPL-related thrombosis in SLE patients. PLT with cutoff of 187.5 x 109/L and APTT with 37.5 seconds were predictors of aPL-related thrombosis as well. The combination of aGAPSS with PLT and APTT improved AUC compared to aGAPSS alone. Conclusions: The aGAPSS could predict the risk of aPL-related vascular thrombosis in SLE patients from China. The combination of aGAPSS with PLT and APTT was first time proved to have better predictive performance in thrombosis risk assessment in SLE. [ABSTRACT FROM AUTHOR]

Copyright of Al-Mustansiriyah Journal for Pharmaceutical Sciences is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high lethality. This study aimed to determine whether prolonged activated partial thromboplastin time (APTT) predicted SFTS mortality. Methods: SFTS patients were enrolled from 6 hospitals in the north China. Subjects were divided into training cohort and 5 externally validation cohorts. The least absolute shrinkage and selection operator Cox regression model was performed to screen potential prognostic factors. Risk factors were analyzed using multivariable regression models. Prognostic models were established by Cox regression and random survival forest (RSF) methods, and evaluated regarding discrimination, validity and clinical benefit. Time-dependent receiver operating characteristic (ROC) curve was used to evaluate the predictive effectiveness of variables. Results: 1332 SFTS cases were included, in which 211 patients died. Six potential prognostic factors were screened, and pulse, breath, APTT and aspartic transaminase (AST) were independently associated with mortality in both training cohort (Yantai, N = 791) and external validation cohort (N = 541). APTT was steadily correlated with the fatality (HR: 1.039–1.144; all P

Gauri Metkar , Shalaka Saraf Background: Snakebite is a potentially life-threatening emergency that can be treated effectively. Snake envenomation can cause hematologic and coagulation abnormalities. In this respect, tests such as prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (aPTT) are commonly used. The present study aimed to determine the value of coagulation parameters in the prognostication of snakebite patients. Methods: This prospective descriptive observational study examined the coagulation parameters, including PT, INR, and aPTT, in consecutive cases of snake envenomation admitted to a tertiary health care hospital from October 2019 to August 2021. The correlation of coagulation parameters with each other and with prognostic indicators (ie, the number of days spent in the intensive care unit [ICU], the requirement of anti-snake venom [ASV], fresh frozen plasma [FFP], and the total number of blood products) was studied. Results: A total of 58 patients with snakebite were studied. The majority were males (69%). The highest proportion of patients belonged to the age group of 16-40 years (60%). The correlation of coagulation parameters with each other was statistically significant. The correlation of coagulation parameters with prognostic indicators (ie, the total number of ASV vials administered, the total number of days in the ICU, the total number of FFP units administered, and the total number of blood components administered) was statistically significant. Conclusion: Coagulation parameters (PT, INR, and aPTT) are essential laboratory investigations for treatment monitoring and can be used effectively for the prognostication of snakebite patients. In cases where the coagulation profile of snakebite patients shows abnormalities, conducting repeated coagulation studies at intervals of 12 hours can contribute to improved prognostication.

Background: Hepatitis B virus is a growing problem worldwide leading to increasing incidences of life-threatening complications of which liver diseases play a major part of it. Materials and Methods: To evaluate these effects in Sudanese patients, a cross-sectional study was carried out in Wad Medani teaching hospital from October 2020 to February 2021 for assessing the effect of the disease on the coagulation profile. Patients were randomly selected according to inclusion and exclusion criteria. 2.5ml of blood samples were collected from each patient in tri-sodium citrate containers, and then semi-automated Coatron M4 was used to estimate Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT) after calibrated and controlled setting according to the manufacturer’s instructions. SPSS (version 25) was used to analysed data. Results: A total of 100 hepatitis B virus patients were included in the study, with males representing (79%) and females were (21%), their age were between 18 to 60 years. The study results showed PT prolonged in (98%) of the study population and only (2%) were normal. regarding the APTT (99%) of them had prolonged results (more than the upper normal), and the remaining (1%) was normal. Also, the study results showed there were slight statistically insignificant differences in coagulation profile in hepatitis B virus patients according to gender, age group, family history, and duration of the disease. Conclusion: hepatitis B infection had a great effect on Coagulation profiles. Therefore, it is recommended on the basis of these results to request PT, INR, and APTT as routine works up for hepatitis B virus patients.

Fucosylated glycosaminoglycans (FGs) derived from sea cucumbers exhibit potent intrinsic Xase (iXase) inhibition, anticoagulation, and antithrombosis. Plasma activated partial thromboplastin time (APTT), a widely used screening test worldwide, is crucial for evaluating anticoagulant efficacy. However, the applicability of these commercially available APTT reagents for assessing anticoagulation of FGs remains unreported. In this study, we investigated the disparity between ellagic acid and colloidal silica APTT reagents in evaluating anticoagulation of dHG-5 and dHLFG-4, two depolymerized FGs, and elucidated the underlying rationale. The results demonstrated that dHG-5 and dHLFG-4 exhibited heightened sensitivity to the ellagic acid APTT reagent both in vitro and in vivo, and did not significantly affect the activation of APTT reagents for plasma. In addition, both ellagic acid and colloidal silica APTT reagents inhibited the anti-iXase of dHG-5 and dHLFG-4, and the inhibition of the ellagic acid APTT reagent was less pronounced compared to the colloidal silica APTT reagent. These findings suggest that the reduced impact of the ellagic acid APTT reagent on the anti-iXase activity of dHG-5 and dHLFG-4 is responsible for the increased sensitivity in plasma APTT analysis. This study offers valuable insights into the characteristics of two APTT reagents applied for assessing the anticoagulant activity of FG-related compounds. [ABSTRACT FROM AUTHOR]

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

The editorial discusses the potential inclusion of activated partial thromboplastin time (APTT) in thrombophilia screening, highlighting the complexity of thrombophilia as a predisposition to thrombosis due to various molecular abnormalities. The cost-effectiveness of comprehensive thrombophilia screening remains controversial, especially in asymptomatic populations with higher thrombosis risk. The study by Radišić Biljak et al. explores the causes of shortened APTT, emphasizing the importance of considering elevated factor VIII levels as a potential risk factor for venous thromboembolism. The editorial underscores the need for further research to determine the clinical utility of APTT in detecting elevated coagulation factors and managing thrombotic risk. [Extracted from the article]

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

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

As several plants have anticoagulant activity, Calotropis procera has been investigated "in vitro" in this study. Hot and cold water, ethanol, and methanol extracts of these plant leaves were prepared to final concentrations of 100, 50, and 25 mg/ml. In vitro, PT and aPTT assays were conducted on normal platelet poor plasma blood samples of 20 healthy volunteers by a digital coagulation analyzer. Results showed that all evaluated extracts prolonged both PT and aPTT at 100 and 50 mg/ml concentrations. The highest effect on PT was observed for ethanol and methanol extracts by recording 128.52±24.45 sec and 105.99±17.76 sec at 100mg/ml concentrations, respectively. The high effect on aPTT was observed for all evaluated extracts by recording 420 ±0.00 sec at 100mg/ml concentration. So they could have an inhibitory effect on the clotting factors in the intrinsic and extrinsic pathways and those in the common pathway. While at 25 mg/ml concentrations, they prolonged PT only, 16.63±1.78 sec, 15.34±0.97 sec, 16.19±1.32 sec, and 16.02±1.37 sec for hot water extract, cold water extract, ethanol extract, and methanol extract, respectively. Suggesting their inhibitory effect was on the extrinsic pathway tissue clotting factors. On the contrary, they demonstrated a decreasing effect on aPTT at a concentration of 25 mg/ml, recording zero aPTT, affecting the intrinsic pathway. Moreover, compared with the positive heparin control, only the alcoholic extracts at 100 mg/ml concentration showed a similar anticoagulant effect on PT (P>0.05). While all evaluated plant extracts at a concentration of 100 mg/ml revealed similar bioactivity on aPTT (P>0.05). Still, all evaluated extracts' anticoagulant and procoagulant activity need in vivo clarification. [ABSTRACT FROM AUTHOR]

Pneumatic tube system (PTS) is a transport medium that is widely used in hospitals. The samples transported via PTS would get vibrations due to changing air velocity and pressure. This unstable pressure could cause pre-analytic errors in laboratory measurements. It happened because it damages erythrocytes and lymphocytes and causes haemolysis. It has been demonstrated that these changes can alter the quality of samples and induce haemolysis by leading primarily to increase in lactate dehydrogenase (LDH) concentrations, and potassium concentration. Haemolysis is dined as the release of intracellular components of erythrocytes and other blood cells into the extracellular space of blood. It can also affect the results of in vitro platelet function test. Incorrect test results can affect the diagnosis and the treatment for patients Every hospital that uses PTS are advised to validate and investigate that PTS has the possibility of haemolysis and impacts laboratory results of blood specimens. The purpose of the study was to validate and know comparison between use courier transport with using PTS on the results of routine haematology tests, PPT, APTT, and potassium. This research was experimental research by using posttest without control. The research used statistical test which was paired t-test. The research was conducted at the Integrated Clinical Laboratory Installation of the Gadjah Mada University Academic Hospital in August – October 2020 with 30 preoperative patients. Data were analysed with Prism GraphPad 8 software. There was no significant difference between WBC, RBC, Hb, HCT, MCV, MCH, MCHC, PPT, and APTT. Moreover, there was a significant difference between the results of PLT and potassium in the samples transported via PTS and delivered by courier transport.

Hemostasis markers associated with tumors have been widely studied. However, the associations between the coagulation factors and papillary thyroid carcinoma (PTC) prognosis remain unclear. The aim of the present study was to investigate these associations.

Purpose The goal of this study was to evaluate the correlation of anti–factor Xa (anti-Xa) and activated partial thromboplastin time (aPTT) measures with heparin dosing in adult patients on extracorporeal membrane oxygenation (ECMO) support. Methods This was a retrospective cohort study evaluating adult patients managed on ECMO for at least 24 hours who received unfractionated heparin for systemic anticoagulation and were monitored per protocol using anti-Xa and/or aPTT coagulation assays. The primary outcome was the correlation between aPTT and anti-Xa measures. The secondary outcomes included, but were not limited to, the number of hemorrhagic and thrombotic events. Results Twenty-seven patients were included in this study. In the 227 events where both laboratory values were collected, a weak correlation was found between anti-Xa and aPTT (Spearman's correlation coefficient = 0.4, P = 0). In the 12 hemorrhagic events that occurred, aPTT was collected for only 10 events. Fifty percent of those events were associated with supratherapeutic aPTT, while none of the hemorrhagic events were associated with a supratherapeutic anti-Xa level. Two thrombotic events occurred, one of which had subtherapeutic anti-Xa and aPTT and the other of which had neither an anti-Xa nor aPTT measure on the day the event occurred. Conclusion In a population of patients on ECMO, many of whom had coronavirus disease 2019 (COVID-19), there was a weak association between aPTT and anti-Xa measures. Hemorrhagic evens were more common than thrombotic events; however, a relationship between these events and aPTT or anti-Xa levels was not determined. The applicability of these findings to an ECMO population without COVID-19 is unknown and will require further study. [ABSTRACT FROM AUTHOR]

Copyright of Kocatepe Veterinary Journal / Kocatepe Veteriner Dergisi is the property of Afyon Kocatepe University, Faculty of Veterinary Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The laboratory diagnosis of antiphospholipid syndrome (APS) requires the measurement of solid-phase antibodies to cardiolipin or β2-Glycoprotein-I and the search for lupus anticoagulant (LA). The diagnosis of patients whilst on anticoagulation is impaired by the difficult interpretation of results, at least for LA, owing to the fact that prolongations of clotting times induced by LA superimpose those induced by anticoagulants. This is a matter of concern as treating physicians very often need to know the APS status of their patients to make a decision on secondary antithrombotic prophylaxis. This article aims to review the effect brought about by anticoagulants on APS diagnosis and discuss the options that can be used to overcome such an effect. [ABSTRACT FROM AUTHOR]

Background: The literature regarding alterations in the coagulation profile in pediatric acute appendicitis (PAA) is scarce and mainly limited to retrospective studies. Evidence on the diagnostic yield of coagulation parameters is limited to fibrinogen. Patients and Methods: This is a prospective study with 151 patients divided into two groups: patients with nonsurgical abdominal pain (NSAP) in whom the diagnosis of PAA was excluded (n = 53) and patients with a confirmed diagnosis of PAA (n = 98). In 93 patients (62%), a coagulation study was obtained at the time of diagnosis and international normalized ratio (INR), activated partial thromboplastin time (aPTT), d-dimer, platelets, mean platelet volume, and platelet-to-lymphocyte ratio were analyzed. The PAA group was further classified into complicated (n = 19) and non-complicated PAA (n = 40). Quantitative variables were compared between groups using the Mann-Whitney U test. Diagnostic performance of the coagulation profile was evaluated with the area under the receiver operating characteristic (ROC) curves. Results: Patients with NSAP had lower median levels of INR, fibrinogen and d-dimer than those with PAA. Moreover, patients with complicated PAA had higher median values of INR and fibrinogen. None of the patients needed specific treatment for the correction of coagulopathy. Fibrinogen was the parameter with the highest diagnostic yield for distinguishing between NSAP and PAA (area under the curve [AUC], 0.74; 95% confidence interval [CI], 0.65–0.85), as well as between complicated versus non-complicated PAA (AUC, 0.71; 95% CI, 0.57–0.86). Conclusions: This study found a moderate extrinsic pathway coagulopathy in patients with PAA, especially in complicated PAA. Fibrinogen is a parameter with moderate diagnostic yield for the diagnosis of PAA. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy of hematological parameters to predict severity of COVID-19 patients. Method: This was a cross-sectional comparative study conducted at Central Park Teaching Hospital, Lahore in COVID ward and COVID ICU between April 23, 2021 to June 23, 2021. Patients of all ages and both genders with positive PCR admitted in the COVID ward and ICU during this time span of two months were included in the study. Data was collected retrospectively. Results: This study included 50 patients with male to female ratio of 1.38:1. Though males are more affected by COVID-19 but the difference is not statistically significant. The mean age of the study population was 56.21 and the patients in the severe disease group have higher age. It was observed that in severe/critical group the mean values of total leukocyte count 21.76×103 μI (p-value= 0.002), absolute neutrophil count 71.37% (p-value=0.045), neutrophil lymphocyte ratio (NLR) 12.80 (p-value=0.00) and PT 11.9 seconds (p-value=0.034) and the difference was statistically significant. While in severe/critical group, the mean values of hemoglobin 12.03g/dl (p-value=0.075), lymphocyte count 28.41% (p-value=0.8), platelet count 226×103 μI (p-value=0.67) and APTT 30.7 (p-value=0.081) and the difference was not significantly different between groups. Conclusion: It can be concluded from the study that total leucocyte count, absolute neutrophil count and neutrophil lymphocyte ratio can predict in-hospital mortality and morbidity in COVID-19 patients. [ABSTRACT FROM AUTHOR]

Background: The initiation of extracorporeal membrane oxygenation (ECMO) is associated with complex inflammatory and coagulatory processes, raising the need for systemic anticoagulation. The balance of anticoagulatory and procoagulant factors is essential, as therapeutic anticoagulation confers a further risk of potentially life-threatening bleeding. Therefore, our study aims to systematize and analyze the most recent evidence regarding anticoagulation monitoring and the thromboembolic events in patients receiving veno-arterial ECMO support. Methods: Using the PRISMA guidelines, we systematically searched the Scopus and PubMed databases up to October 2022. A weighted effects model was employed for the meta-analytic portion of the study. Results: Six studies comprising 1728 patients were included in the final analysis. Unfractionated heparin was used for anticoagulation, with an activated partial thromboplastin time (aPTT) monitoring goal set between 45 and 80 s. The majority of studies aimed to investigate the incidence of adverse events and potential risk factors for thromboembolic and bleeding events. None of the authors found any association of aPTT levels with the occurrence of thromboembolic events. Finally, the most frequent adverse events were hemorrhage (pooled 43%, 95% CI 28.4; 59.5) and any kind of thrombosis (pooled 36%, 95% CI 21.7; 53.7), and more than one-half of patients did not survive to discharge (pooled 54%). Conclusions: Despite the tremendous development of critical care, aPTT-guided systemic anticoagulation is still the standard monitoring tool. We did not find any association of aPTT levels with thrombosis. Further evidence and new trials should clarify the true incidence of thromboembolic events, along with the best anticoagulation and monitoring strategy in veno-arterial ECMO patients. [ABSTRACT FROM AUTHOR]

Based on WHO data, there is about 14% average of patients who suffer from a severe level of Covid-19 disease and 5% of patients admitted to the ICU (Intensive Care Unit) are known to have symptoms of thromboembolism and coagulopathy disorders. The current management of Covid-19 therapy requires heparin. This research aims to find out the accuracy of the heparin regimen, to determine the improvement of the patient's clinical condition, the side effects of heparin based on clinical response, to analyze the relationship between the accuracy of the therapeutic regimen and the improvement of the patient's clinical condition, and also to know the incidence of side effects after heparin use. The type of this research was descriptive-analytic with a cohort design with retrospective data collection. The data were collected by taking medical records at PKU Muhammadiyah Gamping Hospital Yogyakarta. Moreover, the data were collected including heparin therapy regimens with subjective condition and patient objective during the therapy. The data obtained were analyzed by using univariate analysis technique and bivariate analysis technique. The results showed there were 61 patients who fulfilled the inclusion criteria. The evaluation of the accuracy the heparin therapy regimen obtained 95.08% correct results and 4.92% incorrect results. The analysis result of the accuracy the therapeutic regimen showed a significant relationship with clinical improvement with parameters APTT number (p=0.006; RR=0.155; CI = 0.085-0.283). Whereas, there was not found a significant relationship between the accuracy of the therapeutic regimen with the incidence of side effects (p>0.05). [ABSTRACT FROM AUTHOR]

Purpose The activated partial thromboplastin time (aPTT) is a coagulation assay commonly utilized for monitoring therapeutic heparin anticoagulation. aPTT methods based on optical detection are vulnerable to spectral interference from hemolysis, icterus, lipemia, and other substances. Intravenous lipid emulsions of primarily 20% have been shown to interfere with multiple clinical laboratory assays, including those measuring aPTT by optical methods, but there is limited data on propofol's effect. The primary objective of this study was to determine the rate of interference of propofol with aPTT measurements in patients receiving both propofol and intravenous heparin. Methods A retrospective observational cohort study of intensive care unit patients who received concomitant propofol and heparin infusions (N = 38 patients) and whose heparin therapy was monitored by aPTT (N = 531 aPTTs) was conducted. Review of the electronic medical record was completed to obtain relevant clinical and laboratory data, while the laboratory information system was queried for analytical interference with the aPTT assay. Results A total of 109 aPTTs (21%) spanning 21 patients (55%) had documented aPTT interference. All 21 patients had at least one aPTT requiring ultracentrifugation prior to reporting, and 12 aPTTs from 4 patients were unreportable due to interference. Patients with and without aPTT interference received similar doses of propofol. None of the cases of aPTT interference were caused by hemolysis or hyperbilirubinemia. Conclusion A potential medication-assay interaction was observed in approximately half of patients who received concomitant propofol and heparin infusions and had aPTT measured for anticoagulation management. Sample ultracentrifugation removes the optical interference in most cases but significantly prolongs aPTT reporting and delays appropriate adjustments to heparin dosing. [ABSTRACT FROM AUTHOR]

Biopharmaceuticals have become increasingly attractive therapeutic agents and are often PEGylated to enhance their pharmacokinetics and reduce their immunogenicity. However, recent human clinical trials have demonstrated that administration of PEGylated compounds can evoke anti-PEG antibodies. Considering the ubiquity of PEG in commercial products and the presence of pre-existing anti-PEG antibodies in patients in large clinical trials evaluating a PEG-modified aptamer, we investigated how anti-PEG antibodies effect the therapeutic activities of PEGylated RNA aptamers. We demonstrate that anti-PEG antibodies can directly bind to and inhibit anticoagulant aptamer function in vitro and in vivo. Moreover, in parallel studies we detected the presence of anti-PEG antibodies in nonhuman primates after a single administration of a PEGylated aptamer. Our results suggest that anti-PEG antibodies can limit the activity of PEGylated drugs and potentially compromise the activity of otherwise effective therapeutic agents.

Regular measurement of fibrinogen as dose guidance in catheter directed thrombolysis (CDT) for acute limb ischaemia (ALI) has recently been dropped from European guidelines based on inconsistent literature. This study aimed to determine whether low fibrinogen levels and high activated partial thromboplastin time (APTT) are associated with an increased major bleeding risk during CDT. All consecutive patients treated with CDT for ALI in two Dutch hospitals between January 2004 and April 2021 were analysed retrospectively. Patients were treated with two dosing regimens (low dose: 50 000 IU/hour; high dose: 100 000 IU/hour) of urokinase and, after 2018, with a single low dose regimen of alteplase (rtPA) due to urokinase manufacturing problems. The incidence of major bleeding and associated APTT and fibrinogen levels were reviewed from patient charts. Of the 443 included cases, 277 underwent CDT with urokinase and 166 with rtPA. The incidence of major bleeding in the whole cohort was 7%. Patients with a fibrinogen levels < 1.0 g/L developed more major bleeding than those in whom the fibrinogen level did not drop below 1.0 g/L (15% vs. 6%; p =.041). Systemic heparinisation during CDT or high (> 80 seconds) APTT were not significantly associated with major bleeding. Angiographic success (47% vs. 72%; p =.003) and 30 day amputation free survival (53% vs. 82%; p <.001) were lower for cases with major bleeding. Older age (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.02 – 1.11), cardiac history (OR 3.35, 95% CI 1.39 – 8.06), high dose regimens (≥ 75 000 IU/hour urokinase; OR 2.67, 95% CI 1.18 – 6.04), and fibrinogen values < 1.0 g/L (OR 5.59, 95% CI 1.98 – 15.77) were independent predictors for major bleeding during CDT. High dose thrombolytic regimens and fibrinogen levels of ≤ 1.0 g/L are associated with more major bleeding during thrombolytic therapy. Major bleeding significantly worsened the clinical outcome. A prospective comparative study is needed to assess the benefit of monitoring fibrinogen levels. [ABSTRACT FROM AUTHOR]

The in vitro anticoagulant action of proteases secreted by the micromycete Aspergillus ochraceus L-1 and contained in snakes' venoms (Protac® and RVV-X® preparations) was studied. The severity of the action was shown of micromycete protease in relation to plasmas of humans and warm-blooded animals, as well as human plasmas deficient in certain factors of the hemostasis system, in comparison with snake proteases in reactions with chromogenic peptide substrates of activated protein C and factor X as well as using the activated partial thromboplastin time (APTT) test. The optimal time of preincubation of the micromycete A. ochraceus L-1 protease with human blood plasma (3 min) and the concentration of the chromogenic peptide substrate of activated protein C (from 0.1 to 0.5 mg/mL) necessary for the correct determination of protein C with its help was determined. [ABSTRACT FROM AUTHOR]