Antithrombin Deficiency

Researchers are evaluating the effects of TAK-330 compared with a standard treatment known as four-factor prothrombin complex concentrate (4F-PCC) for reversing anticoagulation caused by Factor Xa inhibitors in adults needing urgent surgery or invasive procedures. This Phase 3 trial aims to determine which treatment better controls bleeding during and after surgery in patients who require rapid reversal of blood thinning effects. Participants will be randomly assigned to receive either TAK-330 or the standard 4F-PCC treatment before surgery. TAK-330 is given as a single intravenous infusion of 25 international units per kilogram on the day of surgery, with an optional additional dose during surgery if needed, not exceeding a total dose of 50 IU/kg or 5,000 IU. The standard 4F-PCC is administered according to local protocols, with a possible additional dose during surgery under similar dosing limits. During the study, patients will be hospitalized and monitored closely. Researchers will assess bleeding control during surgery, blood product use, and adverse events up to 30 days after surgery. Follow-up contact will be conducted by phone or telehealth 30 days post-surgery. The main outcome measured is the percentage of participants achieving effective bleeding control at the end of surgery.

Researchers are investigating a new treatment for sepsis-induced coagulopathy, a condition where an infection causes an overactive immune response leading to harmful blood clots and low platelet levels. This condition can damage blood vessels and organs, sometimes resulting in death. The study aims to learn about the safety, suitable dose, and effects of the drug BAY 3389934 in patients receiving intensive care for sepsis-induced coagulopathy. Participants will receive BAY 3389934 as a continuous intravenous infusion over up to 96 hours. They will be divided into two groups: the first group receives a low starting dose which may be adjusted based on safety and tolerability, while the second group will receive a higher dose if the first group experiences no serious side effects. This phase 1 study focuses on carefully monitoring how the drug affects participants. During the approximately 28-day study period, doctors will collect blood and urine samples, perform physical exams, and monitor vital signs such as body temperature, blood pressure, and heart rate. Heart health will be assessed using electrocardiograms (ECG). Researchers will track any medical problems that occur during and after treatment to evaluate safety, including treatment-emergent adverse events and their severity. They will also measure blood clotting times from day 1 to day 6 to understand the drug’s effects.

Researchers are evaluating whether artificial intelligence (AI) models can accurately interpret ROTEM (Rotational Thromboelastometry) data and make treatment recommendations for adult patients undergoing elective cardiac or liver transplant surgery. This observational validation study aims to compare AI models' decisions to those of expert clinicians to see if AI can match expert-level interpretation in detecting coagulopathy types and suggesting treatments. The study uses de-identified ROTEM data collected during surgery, which is converted into clinical vignettes for review. AI models such as ChatGPT and Gemini analyze these standardized ROTEM parameters and recommend treatments following established ROTEM-guided transfusion protocols. Their outputs are compared to a panel of three clinical experts, forming the gold standard for diagnosis and treatment decisions. Participants will undergo standard ROTEM testing during their elective surgery. Researchers will evaluate agreement between AI and expert panels on whether treatment is needed and on the type of coagulopathy present. The study involves answering 14 structured clinical questions for each case, with results measured by accuracy and concordance metrics. No patient treatment is changed based on AI results, and all data is anonymized with informed consent obtained. The study timeline extends through December 2025.

Researchers are studying acute coronary syndrome (ACS), a condition caused by reduced blood flow to the heart, leading to heart tissue damage. This research focuses on understanding how stress and inflammation responses, shown by increased cortisol and C-reactive protein (CRP) levels, relate to changes in immune cells in the blood. The study aims to see how these factors predict clinical outcomes during hospital stays and after discharge in ACS patients. This is a prospective, observational study involving patients admitted with ACS to a coronary care unit over two years. Blood samples will be collected at admission to measure cortisol and CRP levels, along with counts of immune cells like leukocytes, neutrophils, lymphocytes, and eosinophils. Patients will receive usual medical care, and their clinical progress will be monitored through laboratory markers and medical records. After hospital discharge, participants will be followed up by telephone for six months. Participants will undergo baseline physical exams and electrocardiograms at admission, with regular blood tests to track heart damage markers and immune cell counts. Researchers will analyze these data to find links between immune responses, stress, inflammation, and patient outcomes. The primary outcome is cardiovascular death within one year, with secondary outcomes including heart attacks, strokes, revascularization procedures, and hospitalizations for unstable angina. The total study period includes two years of enrollment and six months of follow-up for each patient.

This research aims to evaluate the performance of the Perosphere ClotChek173 system, a hand-held, battery-operated blood coagulation device used at the point-of-care, in measuring whole blood clotting time (WBCT) in patients taking direct oral anticoagulants (DOACs) such as rivaroxaban or apixaban. The study focuses on characterizing how well this device can quantitatively assess clotting times in these patients compared to normal controls. Participants provide fresh whole blood samples taken at various times during the day to capture a range of clotting times rather than strict peak or trough measurements. The blood is loaded onto disposable cuvettes without biological reagents for testing with the Perosphere ClotChek173 device. This observational study collects these samples to analyze clotting times and device performance in relevant patient subgroups, including those with renal or hepatic impairments. During the study, participants will undergo venipuncture to provide non-citrated whole blood samples for the clotting time measurements. Researchers will evaluate the device's ability to distinguish between patients on rivaroxaban or apixaban and normal controls. Safety and patient history will be reviewed to ensure eligibility, and clotting times will be assessed on the day of sampling. The study is expected to run until June 2027, with participants involved in a single visit for sample collection and device evaluation.

Researchers are studying different dosages of tranexamic acid in adults undergoing elective cardiac surgery with cardiopulmonary bypass to understand how long the drug inhibits fibrinolysis, which helps prevent excessive bleeding. This trial aims to find the best dosage regimen by measuring clotting function and drug levels in the blood. The study is randomized and quadruple-masked to compare three dosing strategies and their impact on blood loss and related complications. Participants will be randomly assigned to one of three groups receiving tranexamic acid: a 10 mg/kg dose followed by a continuous infusion of 1 mg/kg per hour until surgery ends, a single 20 mg/kg dose, or a single 30 mg/kg dose given before surgery starts. Blood samples will be collected at multiple time points during and after surgery to perform ClotPro viscoelastic testing and measure tranexamic acid levels. If clotting inhibition decreases early, an additional 10 mg/kg dose is given. Throughout the study, researchers will collect detailed information including patient characteristics, surgery duration, anesthesia details, blood transfusions, bleeding amounts, and any adverse events. Postoperative care data such as mechanical ventilation duration, ICU and hospital stays, and mortality will also be tracked. The primary measurement is the duration of fibrinolysis inhibition as indicated by ClotPro results and its correlation with tranexamic acid blood levels. Secondary outcomes include bleeding, transfusion needs, seizures, thrombotic events, and length of recovery up to one year after surgery.

Researchers are evaluating how four different types of central venous catheters (CVCs) affect the body's blood clotting system. CVCs are thin tubes placed in large veins to give medications, fluids, or take secure blood samples, but they can sometimes cause blood clots, leading to serious health issues. This randomized controlled trial aims to compare the impact on coagulation caused by these commonly used catheters to better understand clot formation after catheter insertion. Participants will be randomly assigned to receive one of four different two-lumen central venous catheters, each made of polyurethane but with different sizes or coatings, including antimicrobial and silver ion-embedded options. Blood samples will be taken twice from each catheter: once immediately after insertion without flushing, and once after flushing with saline and discarding the initial blood. These samples will then be tested with rotational thromboelastometry (ROTEM) and other coagulation tests to compare clotting times and related markers between catheter types and within the overall group. During the study, participants will undergo catheter placement followed by blood sample collection at two specific times. The blood will be processed and analyzed shortly after collection to measure clotting times, clot strength, and various coagulation factors. The main outcome is the change in clotting time between the two samples. This information will help researchers identify how different catheters interact with blood clotting and could lead to safer catheter use and better prevention of clot-related complications. Participants will be monitored throughout the procedure and sample collection process, which is expected to last a short time after catheter insertion.

Researchers are investigating how the blood clotting and platelet function change in patients with end-stage heart failure who receive mechanical circulatory support devices such as percutaneous microaxial pumps (Impella), extracorporeal membrane oxygenators (ECMO), or Ventricular Assist Devices (VAD). The study aims to understand how these devices interact with the blood's clotting system and antithrombotic drugs to identify causes of clotting or bleeding complications and potential treatment targets. The study uses two innovative tests to evaluate platelet function: the Platelet Activity State (PAS) assay and the Thrombin Generation Test (TGT). These tests are performed at several points: before device implantation to establish baseline values, early after implantation during hospital stay, throughout long-term follow-up, and when complications or therapy changes occur. Alongside these tests, standard blood parameters related to coagulation and hemolysis are measured, and device function data such as pump speed and power use are recorded. Participants are monitored for up to 24 months with evaluations at 1, 3, 6, 12, 18, and 24 months after device implantation, as well as when any adverse events happen. Researchers track changes in platelet activity, coagulation markers, device parameters, and antithrombotic therapies. The study focuses on understanding how these factors relate to post-implant complications to improve patient care and device management.

Snakebites from Bothrops species are a significant health concern in French Guiana and Martinique, with envenomation causing severe local and systemic effects. This research aims to explore the role of plasma Willebrand factor activity and endothelial activation in patients bitten by Bothrops snakes in these regions. The study investigates how venom from different Bothrops species affects blood clotting and inflammation, potentially explaining distinct clinical outcomes like bleeding or thrombosis. Understanding these mechanisms could lead to more personalized treatment approaches for snakebite victims. Participants include patients with confirmed Bothrops snakebites from French Guiana and Martinique, divided into two groups of 15 each. Blood samples will be collected for research analysis alongside routine care, focusing on Willebrand factor activity before and after anti-venom treatment. The study does not involve new treatments but monitors biological markers related to coagulation and endothelial function to understand venom effects better. During the study, patients will have additional blood drawn at hospital admission and on days 1 and 8 to measure plasma Willebrand factor activity. Researchers will assess coagulation status and related biological changes while recording clinical signs of envenomation. The study is observational, with no experimental interventions, and participants are followed up during their hospital stay to gather data on venom effects and recovery. Total participation duration varies depending on clinical course but includes key blood sampling points within the first week.

Researchers are evaluating the incidence of thrombotic events and thromboembolic events in patients with congenital antithrombin deficiency who receive Atenativ during surgery or childbirth. This phase 3, open-label study aims to assess the safety, efficacy, and pharmacokinetics of Atenativ in these patients. The study includes both surgical patients and pregnant patients undergoing delivery, addressing an important need in managing this rare blood disorder during high-risk procedures. Participants receive Atenativ, an antithrombin concentrate, in two phases. In the pharmacokinetics (PK) phase, a single intravenous dose of 60 IU/kg is given to analyze how the drug behaves in the body. In the treatment phase, patients receive an initial intravenous loading dose followed by maintenance doses every 24 hours for about 2 to 7 days if undergoing surgery, or about 5 days if giving birth by caesarean section or delivery. Throughout the study, participants undergo regular blood tests to monitor coagulation parameters and drug levels up to 14 days after infusion, as well as safety monitoring for adverse events up to 30 days after treatment starts. Researchers closely track thrombotic event incidence up to 30 days post-treatment. Participants are involved in scheduled visits for drug administration, blood sampling, and clinical assessments to ensure thorough evaluation of Atenativ's effects and safety during and after treatment.