Impaired fibrinolysis in degenerative mitral and aortic valve stenosis

Anetta Undas,Bogusław Kapelak,Piotr Mazur,Joanna Natorska,Grzegorz Grudzień,Jacek Myć,Krzysztof Plens,Dariusz Plicner

doi:10.1007/s11239-018-1687-1

Abstract

Valvular heart disease is associated with an increased thromboembolic risk. Impaired fibrinolysis was reported in severe aortic stenosis (AS). Little is known about fibrinolysis in mitral stenosis (MS). We sought to compare fibrinolysis impairment in AS and MS. We studied 121 individuals scheduled for elective aortic valve (AV) or mitral valve (MV) surgery for AS (n = 76) or MS (n = 45), in order to compare fibrinolysis impairment. Fibrinolytic capacity was assessed by determination of clot lysis time (t50%) and fibrinolysis inhibitors, including plasma plasminogen activator inhibitor-1 (PAI-1) antigen (PAI-1:Ag) and activity, thrombin-activatable fibrinolysis inhibitor (TAFI) antigen and activity. Prolonged t50% (+ 29%), elevated TAFI activity (+ 12%), TAFI:Ag (+ 21%), and PAI-1:Ag (+ 84%) were observed in patients with MS, compared with those with AS. t50% Correlated with mean and maximal MV gradients (r = 0.43, p < 0.0001 and r = 0.39, p < 0.0001, respectively), but not with AV gradients. Mean and maximal MV gradients correlated with TAFI activity and PAI:Ag. Patients with permanent atrial fibrillation (AF; 35 with MS and 5 with AS) had longer t50% (by 22%, p = 0.0002) and higher PAI-1:Ag (by 74%, p < 0.0001) than the remainder. In the whole group, postoperative drainage volumes correlated inversely with PAI-1:Ag (r = − 0.22, p = 0.02). MS is associated with more pronounced impairment of global fibrinolytic capacity than AS at the stage of surgical intervention, which is in part driven by AF. Our findings suggest that hypofibrinolysis might be implicated in the progression of MS and its thromboembolic complications.

Highlights

Degenerative mitral stenosis is associated with more pronounced impairment of global fibrinolytic capacity than aortic stenosis at the stage of surgical intervention
Mitral stenosis (MS) patients were in higher New York Heart Association class, had mildly decreased left ventricular systolic function, and demonstrated higher values of INR and APTT (Table 1.)
Our results suggest that different groups of patients might require a different antifibrinolytic regimen for optimal outcomes, with adjustment according to the diagnosis-dependent activity of fibrinolysis

Summary

Introduction

Degenerative mitral stenosis is associated with more pronounced impairment of global fibrinolytic capacity than aortic stenosis at the stage of surgical intervention. The research on AS is most frequently focused on calcification, in 2013 our group documented impaired fibrinolysis in 74 patients with severe AS, evidenced by prolonged plasma fibrin clot lysis time (CLT) and increased plasma plasminogen activator inhibitor-1 (PAI-1), as compared to controls [10]. PAI-1 expression is found in as many as in 69% of the human AS valves [12] Another fibrinolysis inhibitor, thrombin activatable fibrinolysis inhibitor (TAFI), which cleaves C-terminal lysine and arginine residues from partially degraded fibrin, thereby attenuating efficient plasminogen activation, has been shown to be elevated in AS patients [13]. Clinical relevance of varying levels of circulating fibrinolysis inhibitors in VHD is unclear due to the paucity of data It has been reported in a study on 28 individuals with severe MS that blood coagulation activation and fibrinolytic activity assessed using plasma D-dimer levels were increased in MS, compared with controls [14]. Marin et al showed impaired fibrinolysis in 24 MS patients, compared with 18 controls, as reflected by elevated PAI-1 (both in patients with atrial fibrillation [AF] and in sinus rhythm), without assessment of the overall fibrinolytic plasma capacity [15]

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Discussion

Conclusion