Urgent call to the European Commission to simplify and contextualize IVDR Article 5.5 for tailored and precision diagnostics.

The European Commission (EC) started targeted evaluations and public consultations regarding the EU IVDR 2017/746 to assess its effectiveness, efficiency, relevance, and EU-added value. The goal is to identify implementation challenges and unintended consequences, experienced by either IVD-manufacturers that put CE-IVDs on the EU market or by medical laboratories that establish and operate in-house-IVDs (IH-IVDs) in their healthcare institution (network). Based on stakeholder feedback the EC aims to be informed about potential regulatory revisions by late 2025.

Overview of laboratory diagnostics for immediate management of patients presenting to the emergency department with acute bleeding.

Acute, life-threatening bleeding is a relatively common but critical presentation in the emergency department (ED), needing immediate assessment and intervention to reduce morbidity and mortality. Rapid identification of the bleeding source, evaluation of hemostatic function, and timely initiation of resuscitation are essential components of early management. Laboratory diagnostics plays a central role in this process, enabling clinicians to stratify the risk, guide therapeutic decisions, and predict outcomes.

Impact of asundexian on a panel of coagulation assays.

Background: During the last few years, the small, oral, activated factor XI inhibitor, asundexian, has been investigated in different cardiovascular disorders. However, little is known about its impact on laboratory coagulation assays.

Objectives: To describe the effects of asundexian on a panel of laboratory coagulation assays.

Clinical Laboratories Need More Information About Commercially Available Reagents to Prepare for the IVDR: A Call From the ICSH.

Introduction: According to the new In Vitro Diagnostic Medical Device Regulation (EU) (IVDR) an In Vitro Medical Device (IVD) is considered as a laboratory developed test (LDT) if used outside of intended use. It is therefore essential that the information given by the manufacturer about the intended use is clear, precise, and well documented. For now, the only source of information for laboratories is the instructions for use (IFU).

Effect of heparins, direct oral anticoagulants, and factor XII/factor XI inhibitors on catheter-initiated thrombin generation in platelet-rich plasma: an in vitro study.

Background: Invasive endovascular procedures often require anticoagulation to prevent device-associated thrombosis. High doses of unfractionated heparin (UFH) are the gold standard. The efficacy of factor (F)XII(a) and FXI(a) inhibitors remains unexplored.

Management of bleeding and invasive procedures in patients treated with anti-factor XI(a) anticoagulants: proposals from the French Working Group on Perioperative Haemostasis and French Society of Thrombosis and Haemostasis.

Background: Several anti-FXI(a) agents with distinct mechanisms of action and pharmacological properties are currently under clinical development. While these anticoagulants are not yet available, there is a need to address bleeding risk management for patients already enrolled in phase III trials. These patients may face elective or unplanned invasive procedures and bleeding events in anticipation of marketing authorization.

Prediction of Lymphoma Aggressiveness Using Machine Learning Algorithms.

Introduction: Lymph nodes are essential to diagnose lymphoid neoplasms, metastases, and infections. Some lymphomas, particularly aggressive non-Hodgkin lymphomas (NHL), need urgent diagnosis. Combining lymph node cytology (LNC) and flow cytometry (FC) with other rapidly available parameters through multivariable predictive models could offer valuable diagnostic information while waiting for anatomopathological results.

Results of an international survey on the management of therapeutic intensity unfractionated heparin: communication from the SSCs of the ISTH.

Background: Unfractionated heparin (UFH) remains the anticoagulant of choice in critically ill patients. However, its laboratory monitoring and clinical management are particularly challenging.

Objectives: Our objective was to describe current practices and variations among centers of the ISTH.

Guidance-Based Appropriateness of Hemostasis Testing in the Acute Setting.

In this review, we aim to highlight the extent of inappropriate hemostasis testing and provide practical guidance on how to prevent it. We will focus on the acute setting, including but not limited to the emergency department and intensive care unit. To this end, we will first discuss the significance of inappropriateness, in the general context of laboratory medicine.

Prevention of perioperative venous thromboembolism: 2024 guidelines from the French Working Group on Perioperative Haemostasis (GIHP) developed in collaboration with the French Society of Anaesthesia and Intensive Care Medicine (SFAR), the French Society of Thrombosis and Haemostasis (SFTH) and the French Society of Vascular Medicine (SFMV) and endorsed by the French Society of Digestive Surgery (SFCD), the French Society of Pharmacology and Therapeutics (SFPT) and INNOVTE (Investigation Network On Venous ThromboEmbolism) network.

Background: Any surgical procedure carries a risk for venous thromboembolism (VTE), albeit variable. Improvements in medical and surgical practices and the shortening of care pathways due to the development of day surgery and enhanced recovery after surgery, have reduced the perioperative risk for VTE.

Objective: A collaborative working group of experts in perioperative haemostasis updated in 2024 the recommendations for the Prevention of perioperative venous thromboembolism published in 2011.

Management of Therapeutic-intensity Unfractionated Heparin: A Narrative Review on Critical Points.

Nowadays, unfractionated heparin (UFH) use is limited to selected patient groups at high risk of both bleeding and thrombosis (patients in cardiac surgery, in intensive care unit, and patients with severe renal impairment), rendering its management extremely challenging, with many unresolved questions despite decades of use. In this narrative review, we revisit the fundamental concepts of therapeutic anticoagulation with UFH and address five key points, summarizing controversies underlying the use of UFH and discussing the few recent advances in the field: (1) laboratory tests for UFH monitoring have significant limitations; (2) therapeutic ranges are not well grounded; (3) the actual influence of antithrombin levels on UFH's anticoagulant activity is not well established; (4) the concept of UFH resistance lacks supporting data; (5) scarce data are available on UFH use beyond acute venous thromboembolism. We therefore identified key issues to be appropriately addressed in future clinical research: (1) while anti-Xa assays are often considered as the preferred option, we call for a vigorous action to improve understanding of the differences between types of anti-Xa assays and to solve the issue of the usefulness of added dextran; (2) therapeutic ranges for UFH, which were defined decades ago using reagents no longer available, have not been properly validated and need to be confirmed or reestablished; (3) UFH dose adjustment nomograms require full validation.

Revisiting the Environmental Impact of Inappropriate Clinical Laboratory Testing: A Comprehensive Overview of Sustainability, Economic, and Quality of Care Outcomes.

Background: The use of laboratory resources has seen a substantial increase in recent years, driven by automation and emerging technologies. However, inappropriate use of laboratory testing, encompassing both overuse and underuse, poses significant challenges.

Content: This review explores the complex interplay between patient safety, economic, and environmental factors-known as the "triple bottom line" or "3Ps" for people, profit, and planet-associated with inappropriate use of laboratory resources.

Is lupus anticoagulant testing with dilute Russell's viper venom clotting times reliable in the presence of inflammation?

Background: Testing for lupus anticoagulant (LA) is not recommended in case of inflammation as C-reactive protein (CRP) can interfere with the phospholipids present in the activated partial thromboplastin time test used to detect an LA. However, the potential interference of an acute phase protein (ie, CRP) in LA testing using the dilute Russell's viper venom (DRVV) test is poorly studied.

Objectives: To study the effect of inflammation, as evidenced by increased CRP levels, on DRVV tests.

Mepacrine Flow Cytometry Assay for the Diagnosis of Platelet δ-granule Defects: Literature Review on Methods-Towards a Shared Detailed Protocol.

Accurate assessment of platelet secretion is essential for the diagnosis of inherited or acquired platelet function disorders and more specifically in identifying δ-storage pool disease. Mepacrine, a fluorescent dye, specifically accumulates in platelet δ-granules. The mepacrine flow cytometry (mepacrine FCM) assay has been used for more than half a century in the clinical laboratory as a diagnostic tool for platelet δ-granule disorders.

Comparison of assays measuring extracellular vesicle tissue factor in plasma samples: communication from the ISTH SSC Subcommittee on Vascular Biology.

Background: Scientific and clinical interest in extracellular vesicles (EVs) is growing. EVs that expose tissue factor (TF) bind factor VII/VIIa and can trigger coagulation. Highly procoagulant TF-exposing EVs are detectable in the circulation in various diseases, such as sepsis, COVID-19, or cancer.

Hemostasis Testing in the Emergency Department: A Narrative Review.

Routine laboratory screening is typically performed at initial evaluation of the vast majority of presentations to the emergency department (ED). These laboratory results are crucial to the diagnostic process, as they may influence up to 70% of clinical decisions. However, despite the usefulness of biological assessments, many tests performed are inappropriate or of doubtful clinical relevance.

The use of 1E12, a monoclonal anti-platelet factor 4 antibody, to improve the diagnosis of vaccine-induced immune thrombotic thrombocytopenia.

Background: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a complication of adenoviral-based vaccine against SARS-CoV-2 due to prothrombotic immunoglobulin (Ig) G antibodies to platelet factor 4 (PF4) and may be difficult to distinguish from heparin-induced thrombocytopenia (HIT) in patients treated with heparin.

Objectives: We assessed the usefulness of competitive anti-PF4 enzyme immunoassays (EIAs) in this context.

Methods: The ability of F(ab')2 fragments of 1E12, 1C12, and 2E1, 3 monoclonal anti-PF4 antibodies, to inhibit the binding of human VITT or HIT antibodies to PF4 was evaluated using EIAs.