Accelerated fibrin clot degradation is associated with arterial thromboembolism in patients following venous thrombosis: a cohort study

Sandra Mrozinska,Elżbieta Broniatowska,Ewa Wypasek,Anetta Undas

doi:10.1038/s41598-021-00411-6

Abstract

Several lines of evidence have suggested that patients following venous thromboembolism (VTE) are at higher risk of arterial thromboembolism (ATE). Prothrombotic fibrin clot characteristics were reported in individuals with cardiovascular risk factors. We investigated whether specific fibrin clot properties measured after 3–4 months of anticoagulation characterize VTE patients with subsequent ATE. We enrolled 320 patients following VTE aged below 70 years (median age, 46). Ten patients were lost to follow-up. ATE occurred in 21 individuals after a median 54 (31–68) months during a follow-up of 87.5 months (incidence 0.94%; 95% confidence interval [CI], 0.59–1.4 per patient-year). Patients with ATE had faster fibrin clot degradation, reflected by maximum rate of D-dimer increase during plasma clot lysis induced by tissue-type plasminogen activator (D-Drate) at baseline. Clot permeability, turbidimetric variables, clot lysis time, and thrombin generation were unrelated to ATE. Univariable Cox proportional hazards analysis showed that age, diabetes, and D–Drate were risk factors for subsequent ATE. Increased D–Drate (by 0.001 mg/L/min; hazard ratio, 1.08; 95% CI 1.02–1.14) was an independent predictor of ATE after adjustment for potential confounders. Faster fibrin clot degradation at 3 months since VTE may increase the risk of ATE among VTE patients during follow-up.

Highlights

Several lines of evidence have suggested that patients following venous thromboembolism (VTE) are at higher risk of arterial thromboembolism (ATE)
Looking for prothrombotic mechanisms involved in the pathophysiology of both ATE and VTE, it has been demonstrated that fibrin clots generated from plasma of patients with VTE are characterized by the so-called prothrombotic fibrin clot phenotype, defined as formation of denser fibrin clot networks evidenced by low permeability and reduced susceptibility to lysis, which can predict the risk of recurrent VTE18–21
Fourteen patients (4.5% of the whole group) had myocardial infarction (MI), 6 (1.9%) had ischemic stroke and 1 patient was diagnosed with peripheral arterial disease complicated with acute popliteal artery occlusion

Summary

Introduction

Several lines of evidence have suggested that patients following venous thromboembolism (VTE) are at higher risk of arterial thromboembolism (ATE). Faster fibrin clot degradation at 3 months since VTE may increase the risk of ATE among VTE patients during follow-up. Looking for prothrombotic mechanisms involved in the pathophysiology of both ATE and VTE, it has been demonstrated that fibrin clots generated from plasma of patients with VTE are characterized by the so-called prothrombotic fibrin clot phenotype, defined as formation of denser fibrin clot networks evidenced by low permeability and reduced susceptibility to lysis, which can predict the risk of recurrent VTE18–21. Cardiovascular risk factors including smoking, diabetes, higher blood pressure, and positive family history have been shown to be associated with prothrombotic fibrin clot characteristics[18,22,24,25,26]

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