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

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. Summary Background Venous thromboembolism ( VTE ) is associated with a high risk of recurrent events after withdrawal of anticoagulation. Objectives To determine the difference in plasma clot mechanical properties between patients with recurrent VTE (r VTE ) and those with non‐recurrent VTE (nr VTE ). Methods We 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 r VTE and 33 with nr VTE . 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. Results Clots from r VTE patients showed nearly two‐fold less elastic and less viscous moduli than clots from nr VTE 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. Conclusion Using magnetic tweezers for the first time in patient samples, we found that plasma clots from r VTE patients showed a reduced elastic modulus and a reduced viscous modulus as compared with clots from nr VTE patients. These data indicate a possible role for fibrin clot viscoelastic properties in determining VTE recurrence.

Effect of anticoagulants on fibrin clot structure: A comparison between vitamin K antagonists and factor Xa inhibitors

“…The kinetic profile of polymerizing fibrin clots was investigated by turbidity, using a standardized protocol as previously described 30 . In brief, plasma was diluted to a final ratio of 1 in 6 in TBS and loaded onto 384‐well plates (Thermo Fisher Scientific, Altrincham, UK) in triplicates.…”

“…The kinetic profile of polymerizing fibrin clots was investigated by turbidity, using a standardized protocol as previously described. 30…”

Clot Structure and Implications for Bleeding and Thrombosis

“…The role of clot mechanics in disease recurrence has been examined in recurrent VTE patients versus nonrecurrent VTE patients. 56 In these studies, a magnetic tweezer system was used to quantify clot mechanics, such as clot elastic and viscous moduli, through bead displacement. Patients with recurrent thrombi showed less elastic and less viscous moduli than clots from nonrecurrent thrombi regardless of a host of other factors.…”

Factor XIII and Fibrin Clot Properties in Acute Venous Thromboembolism

“…Available data indicate that FXIII levels/activity are not associated with the risk of recurrent VTE. No differences in plasma FXIII levels were observed among 11 patients with recurrent VTE and 33 non-recurrent VTE subjects in the study by Baker et al [ 48 ], which was associated with no differences found in fibrin clot structure or fibrinolysis rates.…”