Recurrent venous thromboembolism patients form clots with lower elastic modulus than those formed by patients with non‐recurrent disease

Stephen R Baker,Michal Zabczyk,Fraser L Macrae,Cédric Duval,Anetta Undas,Robert A.S Ariëns

doi:10.1111/jth.14402

Stephen R Baker, Michal Zabczyk + Show 4 more

Open Access

https://doi.org/10.1111/jth.14402

Copy DOI

Abstract

Essentials Venous thromboembolism (VTE) recurrence leads to decreased clot elastic modulus in plasma.Recurrent VTE is not linked to changes in clot structure, fiber radius, or factor XIII activity.Other plasma components may play a role in VTE recurrence.Prospective studies should resolve if clot stiffness can be used as predictor for recurrent VTE. SummaryBackgroundVenous thromboembolism (VTE) is associated with a high risk of recurrent events after withdrawal of anticoagulation.ObjectivesTo determine the difference in plasma clot mechanical properties between patients with recurrent VTE (rVTE) and those with non‐recurrent VTE (nrVTE).MethodsWe previously developed a system for determining clot mechanical properties by use of an in‐house magnetic tweezers system. This system was used to determine the mechanical properties of clots made from plasma of 11 patients with rVTE and 33 with nrVTE. Plasma was mixed with micrometer‐sized beads, and thrombin and calcium were added to induce clotting; the mixture was then placed in small capillary tubes, and clotting was allowed to proceed overnight. Bead displacements upon manipulation with magnetic forces were analyzed to determine clot elastic and viscous moduli. Fibrin clot structure was analyzed with turbidimetry and confocal microscopy. Factor XIII was measured by pentylamine incorporation into fibrin.ResultsClots from rVTE patients showed nearly two‐fold less elastic and less viscous moduli than clots from nrVTE patients, regardless of male sex, unprovoked events, family history of VTE, fibrinogen concentration, or body mass index. No differences were observed in clot structure, fibrinolysis rates, or FXIII levels.ConclusionUsing magnetic tweezers for the first time in patient samples, we found that plasma clots from rVTE patients showed a reduced elastic modulus and a reduced viscous modulus as compared with clots from nrVTE patients. These data indicate a possible role for fibrin clot viscoelastic properties in determining VTE recurrence.

Highlights

Venous thromboembolism (VTE), which encompasses deep vein thrombosis (DVT) and pulmonary embolism (PE), affects 0.1–0.3% of people per year [1,2]
Using magnetic tweezers for the first time in patient samples, we found that plasma clots from recurrent VTE (rVTE) patients showed a reduced elastic modulus and a reduced viscous modulus as compared with clots from non-recurrent VTE (nrVTE) patients
Studies in recent years have indicated that fibrin clot properties constitute a novel risk factor for both DVT and PE [6]

Summary

Introduction

Venous thromboembolism (VTE), which encompasses deep vein thrombosis (DVT) and pulmonary embolism (PE), affects 0.1–0.3% of people per year [1,2]. It is divided into two different categories, i.e. provoked and unprovoked (idiopathic); the latter is characterized by the patient having no history of cancer, surgery requiring general anesthesia, major trauma, plaster cast or recent hospitalization, including for pregnancy or delivery. Studies in recent years have indicated that fibrin clot properties constitute a novel risk factor for both DVT and PE [6] Clots from these patients have been shown to have thinner, more highly branched fibers, and are less porous and more resistant to lysis than clots from healthy controls. Clots made from PE patient plasma have been shown to develop viscoelastic properties at an accelerated rate as compared with clots made from DVT patients, interestingly, the final mechanical properties for these two patient groups were similar [10]

Objectives

Methods

Results

Discussion

Conclusion