TEG® 6s coagulation testing with a novel heparin neutralization cartridge: Technical validation and determination of normal reference ranges.

Objectives: We sought to establish normal reference ranges (NRRs) for a novel TEG 6s cartridge (TEG 6s Citrated: K, KH, RTH, FFH [Global Hemostasis]) (Haemonetics Corporation, Boston, MA, US).

Methods: Healthy volunteers (≥18 years of age) included in this single-arm study provided single samples of whole blood. Primary end points included TEG parameters in the citrated kaolin (CK), CK with heparinase (CKH), RapidTEG with heparinase (CRTH), and functional fibrinogen with heparinase (CFFH) assays.

Andexanet Alfa Neutralizes the Anticoagulant Effects of Unfractionated Heparin of Bovine, Ovine and Porcine Origin Almost as Protamine Sulfate.

Introduction: Andexanet alfa (AA) - zhzo, recombinant coagulation factor Xa, is an approved antidote for oral Xa inhibitors (apixaban and rivaroxaban). Unfractionated heparin (UFH) is commonly used for therapeutic, interventional, and surgical indications. Protamine sulfate (PrSO) is frequently used to neutralize UFH.

Syndecan-1 Level, a Marker of Endothelial Glycocalyx Degradation, Is Associated With Fetal Exposure to Chorioamnionitis and Is a Potential Biomarker for Early-Onset Neonatal Sepsis.

The goal of this investigation was to identify the association between Syndecan-1 (S1) serum levels in preterm newborns exposed to chorioamnionitis (CA) in utero and the potential of S1 as a biomarker of early-onset neonatal sepsis. A cohort of preterm newborns born <33 weeks gestational age was recruited. Within 48 hours of birth, 0.

Absolute pharmacokinetics of heparin in primates.

Heparin is a commonly used anticoagulant drug, derived from the tissues of animals including pigs, cows, and sheep. Measuring heparin concentration in plasma is challenging due to its complex molecular structure. Existing methods rely on measuring heparin's anticoagulant activity, which provides pharmacodynamic (PD) data but not pharmacokinetic (PK) data, measuring concentration over time.

Potency Adjusted Blended Heparin of Bovine, Ovine, and Porcine Heparin Exhibit Comparable Biologic Effects to Referenced Single-Sourced Porcine Heparin.

Bovine and ovine mucosa represent alternate anticoagulants to porcine mucosa for production of unfractionated heparin (UFH). Standardized heparins from various sources can be blended and potency adjusted, blended heparins exhibit comparable effects as single-sourced porcine UFH. This study evaluated the pharmacologic profile of blended heparin and compared their activities to that of single sourced porcine, ovine, and bovine heparins.

Enhanced Thrombin Formation in Patients With Ventricular Assist Devices Experiencing Bleeding: Insights From the Multicenter PREVENT Study.

The aim of this investigation was to characterize the hemostatic status of heart failure patients with implanted left ventricular assist devices (LVADs) to propose a mechanism associated with bleeding. Patients (n = 300) from 23 US hospitals were enrolled in the PREVENtion of HeartMate II Pump Thrombosis through Clinical Management (PREVENT) study. A biobank was established with serum and plasma samples prospectively collected from a cohort of 175 patients preimplant baseline (BL) and 3 months (3M) postimplant.

Differential Neutralization of Apixaban, Betrixaban, Edoxaban, and Rivaroxaban by Andexanet Alfa as Measured by Whole Blood Thromboelastographic Analysis.

Introduction: The available oral anti-Xa agents are routinely used for the management of thrombotic disorders. A molecularly modified recombinant coagulation FXa, also known as Andexanet Alfa (AA), that has been developed as an antidote to neutralize the bleeding effects of oral FXa inhibitors, such as Apixaban and Rivaroxaban.

Materials And Methods: This study utilized thromboelastography (TEG 5000 Hemostasis System), to investigate the neutralizing effects of AA at different concentrations of oral FXa inhibitors measuring such parameters as R-Time, K-Time, Angle, and Max Amplitude (MA).

The Multistage Antimalarial Compound Calxinin Perturbates Ca Homeostasis by Targeting a Unique Ion Channel.

Malaria elimination urgently needs novel antimalarial therapies that transcend resistance, toxicity, and high costs. Our multicentric international collaborative team focuses on developing multistage antimalarials that exhibit novel mechanisms of action. Here, we describe the design, synthesis, and evaluation of a novel multistage antimalarial compound, 'Calxinin'.

Inflammatory cytokines in robot-assisted thoracic surgery versus video-assisted thoracic surgery.

Background: Cytokines play a crucial role in the inflammatory response and are essential modulators of injury repair mechanisms. While minimally invasive operations have been shown to induce lower levels of cytokines compared to open thoracotomy, the inflammatory cytokine profile difference between video-assisted (VATS) and robotic-assisted thoracic surgery (RATS) techniques has yet to be elucidated.

Methods: In this prospective observational study of 45 patients undergoing RATS (n=30) or VATS (n=15) lung resection for malignancy, plasma levels of interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, vascular endothelial growth factor (VEGF), interferon (IFN)-γ, tumor necrosis factor (TNF)-α, monocyte chemo-attractant protein (MCP)-1, and endothelial growth factor (EGF) were measured before and after surgery via immunoassay.

Predictive Role of Blood Cellular Indices and Their Relationship with Endogenous Glycosaminoglycans as Determinants of Inflammatory Biomarkers in Pulmonary Embolism.

Introduction: In this study, we profiled the levels of blood cellular indices, endogenous glycosaminoglycans (GAGs) and inflammatory biomarkers in a cohort comprised of pulmonary embolism (PE) patients, to determine their inter-relationships. Identification of this relationship may provide insight to the complex pathophysiology of PE and the predictive role of blood cellular indices in acute PE patients.

Materials And Methods: Plasma samples from PE patients and healthy controls were analyzed for thrombo-inflammatory biomarkers (IL-2, IL-4, IL-6, IL-8, IL-10, VEGF, IFN-ɣ, TNF-α, IL-1α, IL-1β, MCP-1, EGF, D-dimer, CRP and MMP-9) using biochip array and ELISA methods.

Differential Neutralization of Unfractionated Heparin and Enoxaparin by Andexanet Alfa.

Introduction: Andexanet alfa (andexanet) is an approved antidote used to reverse the bleeding effects of Direct Oral Anticoagulant (Direct-Xa agents) agents because it reverses anti-Xa activity. Unfractionated heparin (UFH) and low molecular weight heparins (LMWHs) exhibit anti-Xa activity. The purpose is to investigate the neutralization of UFH and LMWH by andexanet in activated clotting time (ACT), thrombelastography (TEG), and anti-Xa due to the protamine sulfate shortage.

Potential Anti-SARS-CoV-2 Activity of Pentosan Polysulfate and Mucopolysaccharide Polysulfate.

With the increased prevalence of new SARS-CoV-2 variants of concern, such as Delta and Omicron, the COVID-19 pandemic has become an ongoing human health disaster, killing millions worldwide. SARS-CoV-2 invades its host through the interaction of its spike (S) protein with a host cell receptor, angiotensin-converting enzyme 2 (ACE2). In addition, heparan sulfate (HS) on the surface of host cells plays an important role as a co-receptor for this viral pathogen-host cell interaction.

An Update on the Status of Vaccine Development for SARS-CoV-2 Including Variants. Practical Considerations for COVID-19 Special Populations.

The progress in the development of various vaccine platforms against SARS-CoV-2 have been rather remarkable owing to advancement in molecular and biologic sciences. Most of the current vaccines and those in development focus on targeting the viral spike proteins by generating antibodies of varying spectrum. These vaccines represent a variety of platforms including whole virus vaccines, viral vector vaccines, nucleic acid vaccines representing RNA, DNA, and their hybrid forms.

Analysis of 3--Sulfated Heparan Sulfate Using Isotopically Labeled Oligosaccharide Calibrants.

The 3--sulfated glucosamine in heparan sulfate (HS) is a low-abundance structural component, but it is a key saccharide unit for the biological activities of HS. A method to determine the level of 3--sulfated HS is lacking. Here, we describe a LC-MS/MS based method to analyze the structural motifs.

Multiplex genome editing of mammalian cells for producing recombinant heparin.

Heparin is an essential anticoagulant used for treating and preventing thrombosis. However, the complexity of heparin has hindered the development of a recombinant source, making its supply dependent on a vulnerable animal population. In nature, heparin is produced exclusively in mast cells, which are not suitable for commercial production, but mastocytoma cells are readily grown in culture and make heparan sulfate, a closely related glycosaminoglycan that lacks anticoagulant activity.

An Update on the Pathogenesis of COVID-19 and the Reportedly Rare Thrombotic Events Following Vaccination.

Today the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a global health problem. After more than a year with the pandemic, although our knowledge has progressed on COVID-19, there are still many unknowns in virological, pathophysiological and immunological aspects. It is obvious that the most efficient solution to end this pandemic are safe and efficient vaccines.

Protamine Sulfate Neutralization Profile of Various Dosages of Bovine, Ovine and Porcine UFHs and Their Depolymerized Derivatives in Non-Human Primates.

Introduction: Currently used unfractionated heparins (UFHs) and low molecular weight heparins (LMWHs) are derived from porcine intestinal mucosa. However, heparins have also been manufactured from tissues of other mammalian species such as cow (Bovine) and sheep (Ovine). Protamine sulphate (PS) is an effective inhibitor of heparin and is used clinically to neutralize both LMWH and UFH.

Studies on Tissue Factor Pathway Inhibitor Antigen Release by Bovine, Ovine and Porcine Heparins Following Intravenous Administration to Non-Human Primates.

Unfractionated heparin (UFH) is a sulfated glycosaminoglycan that consists of repeating disaccharides, containing iduronic acid (or glucuronic acid) and glucosamine, exhibiting variable degrees of sulfation. UFHs release tissue factor pathway inhibitor (TFPI) which inhibits the extrinsic pathway of coagulation by inactivating factor Xa and the factor VIIa/TF complex. Most heparins used clinically are derived from porcine intestinal mucosa however, heparins can also be derived from tissues of bovine and ovine origin.

Comparative Anticoagulant and Thrombin Generation Inhibitory Profile of Heparin, Sulodexide and Its Components.

Introduction: Sulodexide represents a mixture of fast-moving heparin (FMH) and dermatan sulfate (DS) and has been used for the management of venous diseases such as DVT and related disorders. The purpose of this study is to compare sulodexide and its components with unfractionated heparin (UFH) to determine its suitability for the indications in which UFH is used.

Materials And Method: Active pharmaceutical ingredients (API) versions of sulodexide, FMH and DS were obtained from Alfasigma.

Protein C Pathway, Inflammation, and Pump Thrombosis in Patients With Left Ventricular Assist Devices.

Use of left ventricular assist devices (LVADs) for management of advanced heart failure is becoming increasingly common; however, device associated thrombosis remains an important cause of mortality in this patient population. We hypothesize that inflammation in LVAD implanted patients dysregulates the protein C pathway, creating a hypercoagulable state leading to thrombosis. Plasma samples from 22 patients implanted with the Thoratec HeartMate II LVAD were analyzed by commercial ELISAs.

Assay-Based Differentiation in the Neutralization Profile of Unfractionated Heparin, Enoxaparin, and Fondaparinux by Andexanet Alfa.

Andexanet alfa is a recombinant factor Xa decoy protein, designed to reverse bleeding associated with oral anti-Xa agents. Andexanet alfa is also reported to neutralize the effects of heparin-related drugs. This study focused on the neutralization profiles of unfractionated heparin (UFH), enoxaparin, and, a chemically synthetic pentasaccharide, fondaparinux by andexanet alfa.

Comparative Pharmacological Profiles of Various Bovine, Ovine, and Porcine Heparins.

Unfractionated heparin is the first anticoagulant drug and has been successfully used clinically for over 80 years. Heparin and its analogues are used during surgery and dialysis and are often used to coat indwelling catheters and other devices where the vascular system is exposed. Most of the heparins used clinically are derived from porcine intestinal mucosa.

Pharmacokinetic/pharmacodynamic assessment of a novel, pharmaceutical lipid-aspirin complex: results of a randomized, crossover, bioequivalence study.

Aspirin (acetylsalicylic acid, ASA) can lead to gastrointestinal mucosal injury through disruption of its protective phospholipid bilayer. A liquid formulation of a novel pharmaceutical lipid-aspirin complex (PL-ASA) was designed to prevent this disruption. We sought to determine the pharmacokinetic (PK)/pharmacodynamic (PD) characteristics of PL-ASA compared with immediate release aspirin (IR-ASA).

Reversal of Factor Xa Inhibitors by Andexanet Alfa May Increase Thrombogenesis Compared to Pretreatment Values.

Recombinant coagulation factor Xa (FXa), inactivated Zh-zo, also known as andexanet alfa (AA), is a modified version of human FXa that has been developed to neutralize FXa inhibitors. We studied the reversal effect of AA for these inhibitors in various anticoagulant and thrombin generation (TG) assays. Individual aliquots of normal human plasma containing 1 µg/mL of apixaban, betrixaban, edoxaban, and rivaroxaban, were supplemented with saline or AA at a concentration of 100 µg/mL.