Accurate evaluation of factor VIII activity of efanesoctocog alfa in the presence of emicizumab.

Background: Efanesoctocog is a B-domain-deleted, Fc-fusion FVIII linked to the D'D3 domain of VWF and two XTEN polypeptides, designed for an ultra-extended half-life for prophylaxis in hemophilia A, but also aiding in managing acute bleeding or surgery in patients on long-term emicizumab. However, no current laboratory method accurately measures FVIII levels in the presence of emicizumab. We hypothesized that the chromogenic (CSA) FVIII assay, specifically calibrated for efanesoctocog using bovine coagulation factors, could provide an accurate assessment of efanesoctocog activity.

A gain of function variant in RGS18 candidate for a familial mild bleeding syndrome.

Background: Inherited platelet diseases are bleeding disorders characterized by either defects in platelet count or platelet function, the latter being less common and very heterogeneous. Numerous gene variants associated with abnormal receptors, granules, and signaling pathways have been reported. Despite significant advancements in our understanding, many patients still lack a precise diagnosis.

Bioclinical features of haemophilia patients in Benin in 2023: Towards better care.

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.

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.

Multicenter evaluation of light transmission platelet aggregation reagents: communication from the ISTH SSC Subcommittee on Platelet Physiology.

Background: Light transmission aggregation (LTA) is used widely by the clinical and research communities. Although it is a gold standard, there is a lack of interlaboratory harmonization.

Objectives: The primary objective was to assess whether sources of activators (mainly adenosine diphosphate [ADP], collagen, arachidonic acid, epinephrine, and thrombin receptor activating peptide6) and ristocetin contribute to poor LTA reproducibility.

A French Real-World Evidence Study Evaluating the Efficacy, Safety, and Pharmacokinetic Parameters of rVIII-SingleChain in Patients with Hemophilia A Receiving Prophylaxis.

Background:  rVIII-SingleChain is a recombinant factor VIII (FVIII) with increased binding affinity to von Willebrand factor compared with other FVIII products. rVIII-SingleChain is indicated for the treatment and prevention of bleeding episodes in patients with hemophilia A.

Objectives:  To collect real-world evidence data from patients treated with rVIII-SingleChain to confirm the efficacy and safety established in the clinical trial program and carry out a population pharmacokinetic (PK) analysis.

Variable serotonin release assay pattern and specificity of PF4-specific antibodies in HIT, and clinical relevance.

Background: The diagnosis of heparin-induced thrombocytopenia (HIT) requires functional assays to demonstrate that platelet factor 4 (PF4)-specific antibodies activate platelets, typically when therapeutic heparin (H) concentrations are tested ("classical" pattern). Some HIT samples also activate platelets without heparin ("atypical" pattern), but with unclear clinical significance.

Objectives: We aimed to assess whether platelet activation pattern and some characteristics of PF4-specific antibodies were associated with the severity of HIT.

The deglycosylated form of 1E12 inhibits platelet activation and prothrombotic effects induced by VITT antibodies.

In order to improve the safety of COVID-19 vaccines, there is an urgent need to unravel the pathogenesis of vaccineinduced immune thrombotic thrombocytopenia (VITT), a severe complication of recombinant adenoviral vector vaccines used to prevent COVID-19, and likely due to anti-platelet factor 4 (PF4) IgG antibodies. In this study, we demonstrated that 1E12, a chimeric anti-PF4 antibody with a human Fc fragment, fully mimics the effects of human VITT antibodies, as it activates platelets to a similar level in the presence of platelet factor 4 (PF4). Incubated with neutrophils, platelets and PF4, 1E12 also strongly induces NETosis, and in a microfluidic model of whole blood thrombosis, it triggers the formation of large platelet/leukocyte thrombi containing fibrin(ogen).

What is the impact of blood pressure on neurological symptoms and the risk of ESKD in primary and secondary thrombotic microangiopathies based on clinical presentation: a retrospective study.

Background: The impact of blood pressure on neurological symptoms and risk of end-stage kidney disease (ESKD) is unknown in primary and secondary thrombotic microangiopathies (TMAs).

Methods: We measured baseline systolic (SBP) and diastolic (DBP) BP in consecutive 563 patients with adjudicated primary and secondary TMAs, and assessed its association with the risk of ESKD.

Results: Normal BP, grade 1, 2 and 3 hypertension were present in 243 (43.

Heparin-induced Thrombocytopenia Diagnosis: A Retrospective Study Comparing Heparin-induced Platelet Activation Test to C-serotonin Release Assay.

Laboratory confirmation of heparin-induced thrombocytopenia (HIT) is of crucial importance and remains challenging and relies on platelet functional assays highlighting the presence of heparin-dependent platelet-activating antibodies in patient serum or plasma. Platelet functional assays using washed platelets include the C-serotonin release assay (SRA), usually described as the gold standard, and the heparin-induced platelet activation assay (HIPA). Since its first comparison with SRA there has been no additional published study regarding HIPA diagnostic performances compared with SRA.

Multicentre evaluation of 5B9, a monoclonal anti-PF4/heparin IgG mimicking human HIT antibodies, as an internal quality control in HIT functional assays: Communication from the ISTH SSC Subcommittee on Platelet Immunology.

Background: Functional tests for the diagnosis of heparin-induced thrombocytopenia (HIT) exhibit variable performance.

Objectives: We evaluated in a multicenter study whether 5B9, a monoclonal anti-PF4/heparin IgG mimicking human HIT antibodies, could be used as an internal quality control.

Methods: 5B9 was sent to 11 laboratories in seven countries, and six initial concentrations ranging from 10 to 400 μg/mL were tested by heparin-induced platelet activation assay (HIPA), serotonin release assay (SRA), platelet aggregation test (PAT), flow cytometry (FC), or heparin-induced multiple-electrode aggregometry (HIMEA).

Infection in Patients with Suspected Thrombotic Microangiopathy Based on Clinical Presentation.

Background And Objectives: In contrast to shigatoxin-associated (STEC) causing hemolytic uremic syndrome, STEC-unrelated infections associated with thrombotic microangiopathy are less characterized.

Design, Setting, Participants, & Measurements: Our retrospective study in a four-hospital institution of 530 consecutive patients with adjudicated thrombotic microangiopathies during the 2009-2016 period studied STEC-unrelated infections' epidemiology and major outcomes (death, acute dialysis, and major cardiovascular events).

Results: STEC-unrelated infection was present in 145 of 530 (27%) patients, thrombotic microangiopathies without infection were present in 350 of 530 (66%) patients, and STEC causing hemolytic and uremic syndrome was present in 35 of 530 (7%) patients.

International multicenter, multiplatform study to validate Taipan snake venom time as a lupus anticoagulant screening test with ecarin time as the confirmatory test: Communication from the ISTH SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies.

Background: Lupus anticoagulant (LA) assays are compromised in anticoagulated patients, and existing strategies to overcome the interferences have limitations. The prothrombin-activating Taipan snake venom time (TSVT) screening test and ecarin time (ET) confirmatory test are innately insensitive to vitamin K antagonists (VKA) and direct factor Xa inhibitors (DFXaI).

Objectives: Validate standardized TSVT/ET reagents for LA detection, in a multicenter, multiplatform study.

Heparin-induced thrombocytopenia: Construction of a pretest diagnostic score derived from the analysis of a prospective multinational database, with internal validation.

Background: Diagnosis of heparin-induced thrombocytopenia (HIT) requires pretest probability assessment and dedicated laboratory assays.

Objective: To develop a pretest score for HIT.

Design: Observational; analysis of prospectively collected data of hospitalized patients suspected with HIT (ClinicalTrials.

Prospective evaluation of two specific IgG immunoassays (HemosIL AcuStar HIT-IgG and HAT45G ) for the diagnosis of heparin-induced thrombocytopenia: A Bayesian approach.

Introduction: The accurate diagnosis of heparin-induced thrombocytopenia (HIT) is essential to ensure adequate treatment and prevent complications. First step diagnosis test are immunoassays including enzyme-linked immunosorbent assays (ELISAs) and rapid immunoassays.

Methods: Using a Bayesian approach, we prospectively evaluated the performance of the IgG PF4/polyvinylsulfonate ELISA and a chemiluminescent immunoassay (CLIA), which are specific for IgG and use the same antigenic target to detect HIT antibodies.

Characterization of New Monoclonal PF4-Specific Antibodies as Useful Tools for Studies on Typical and Autoimmune Heparin-Induced Thrombocytopenia.

Background:  Heparin-induced thrombocytopenia (HIT) is typically caused by platelet-activating immunoglobulin G (IgG) antibodies (Abs) against platelet factor 4 (PF4) complexed with heparin (H). Much less frequent "autoimmune" HIT is distinguished from typical HIT by platelet activation without heparin and the presence of both anti-PF4/H and anti-PF4 IgG. We developed three murine monoclonal anti-PF4 Abs with a human Fc-part, 1E12, 1C12, and 2E1, resembling autoimmune HIT Abs.