PB1060 - Thrombin generation and fibrin clot structure in nephrotic patients with primary glomerular disorders

Tuesday, June 27, 2023

18:30 – 19:30 ET

Room: Exhibition

Co-Author(s)

JT

Jean Terrier

Junior consultant and research fellow
Clinical Pharmacology and Toxicology Service, Anesthesiology Pharmacology and Intensive Care Department, Geneva University Hospitals, Geneva, Switzerland
Geneva, Geneve, Switzerland
Rita Marchi

PhD
UNIGE
Geneva, Geneve, Switzerland
TT

Tomoko Takano

Professor - Department of Medicine, Division of Experimental Medicine
Division of Nephrology and research institute, Department of Medicine, McGill University Health Center, Montreal, QC, Canada
Montreal, Quebec, Canada
RS

Ratna Samanta

Associate Professor at McGill University
4Division of Nephrology, Department of Medicine, McGill University Health Center, Montreal, QC, Canada
Montreal, Quebec, Canada
SD

Sophie De Seigneux

Head of Division of Nephrology, Geneva University Hospitals
6Division of Nephrology, Geneva University Hospitals, Geneva, Switzerland
Geneva, Geneve, Switzerland
Alessandro Casini, MD

MD
Division of Angiology and Hemostasis, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland
Geneva, Geneve, Switzerland

Presenting Author(s)

Thomas A. Mavrakanas, MD, MSc

Assistant Professor of Medicine at McGill University
Division of Nephrology, Department of Medicine, McGill University Health Center and Research Institute, Montreal, QC, Canada
Montreal, Quebec, Canada

Background: Venous thromboembolic disease (VTE) is a well-known complication of the nephrotic syndrome (NS). The concept of selective or non-selective permeability of the glomerular barrier may explain the variable incidence of VTE in different types of glomerular disorders. There are currently no prospective data presenting in detail the hemostasis balance in different primary diseases of the nephrotic spectrum.

Aims: To assess the global hemostasis in patients with NS due to membranous nephropathy, primary focal segmental glomerulosclerosis (FSGS), IgA nephropathy (IgAN), or minimal change disease (MCD).

Methods: Patients with nephrotic range proteinuria and biopsy-proven glomerular disorders followed in the nephrology outpatient clinics at McGill University Health Centre and Geneva University Hospitals have been prospectively enrolled. Main exclusion criteria include partial or complete remission of proteinuria and active use of any anticoagulant medication. We evaluated thrombin generation by Calibrated Automated Thrombography and fibrin clot structure by turbidimetry, permeability and scanning electron microscopy. Patients with glomerular disorders and controls (commercial plasma) were compared using a Mann Whitney test at p = 0.05.

Results: We present here preliminary results from 8 patients with a primary glomerulopathy. Overall, thrombin generation was increased in patients with primary glomerulopathy, compared with controls (Figure 1). Fibrin clot properties indicate a thrombotic phenotype with an increased and faster fibrin polymerization, hypofibrinolysis, reduced permeability (data not shown), and thinner fibrin fibers, as shown in Figure 2.

Conclusion(s): Our results converge towards a pro-coagulant state at different levels of hemostasis in patients with NS due to primary glomerular disorders. To our knowledge, such a detailed study of global hemostasis has not been performed before and will allow us to better understand hemostatic balance in nephrotic patients.