Effects of balloon mitral valvuloplasty on systemic and regional left atrial levels of prothrombin fragment 1+2 in mitral stenosis

Abstract

A proportion of mitral stenosis patients with left atrial spontaneous echo contrast but without thrombus exhibit a regional hypercoagulable state, characterized by increased left atrial levels, but normal venous levels, of prothrombin fragment 1+2 (F1+2), a marker of thrombin generation. Valve dilatation by balloon mitral valvuloplasty has beneficial effects on left atrial spontaneous echo contrast, but its effect on left atrial thrombin generation is unknown. We examined the effects of balloon mitral valvuloplasty on venous and left atrial levels of F1+2 in 37 patients with mitral stenosis, divided into those with normal (group 1; n=22) and those with increased (group 2; n=15) regional left atrial thrombin generation, as described previously. The mitral valve area increased by a similar degree after the valvuloplasty procedure in the two groups. In group 1, the venous (P<0.005) and left atrial (P<0.0005) levels of F1+2 increased similarly after valvuloplasty, and as a result the left-atrial-venous F1+2 difference was unchanged. The venous F1+2 level also increased after valvuloplasty in group 2 (P<0.005); however, in contrast with group 1, the left atrial level decreased (P<0.03) and as a result the left-atrial-venous difference fell (P<0.05). These results show that balloon mitral valvuloplasty results in an immediate increase in thrombin generation, but a decrease in the left-atrial-venous F1+2 difference, in patients with increased left atrial thrombin generation. The divergent changes in venous and left atrial levels of F1+2 further highlight the limitations of assessing regional changes in coagulation activity by measuring venous levels of coagulation markers.

Effects of balloon mitral valvuloplasty on systemic and regional left atrial levels of prothrombin fragment 1+2 in mitral stenosis

“…Contrary to the assertion of Li-Saw-Hee and Lip that thrombogenesis in cardiac disease is likely to be a generalized process, we believe that there is now abundant evidence from our group [1][2][3][4] and others [5][6][7] which supports the existence of a localized increase in left atrial coagulation activity in mitral stenosis. Moreover, this coagulation activation is not primarily due to atrial fibrillation as it is also observed in patients with sinus rhythm who have left atrial spontaneous echo contrast [1,7].…”

“…While this does not completely exclude a residual effect of warfarin in our study, our previous finding of no difference in venous or left atrial F1j2 levels between patients who had or had not been on warfarin prior to the valvuloplasty procedure [1], suggests that any such effect was likely to have been small. Furthermore, any minor suppression of coagulation activity by warfarin would have been present at the beginning of the procedure and does not explain the changes in F1j2 levels occurring after balloon mitral valvuloplasty [4].…”

“…We recently reported [4] a study of PBMV in 16 patients with mitral stenosis, all of whom had chronic atrial fibrillation and all of whom had been taking warfarin previously, which was stopped and restarted in a consistent manner. We found a significant increase in plasma levels of soluble P-selectin, an index of platelet activation, immediately post-PBMV and at 24 h, which was also associated with a significant increase in von Willebrand-factor levels, an index of endothelial damage\ dysfunction, at 24 h after PBMV.…”

“…The question raised by Li-Saw-Hee and Lip of the possible effects of preceding warfarin therapy on coagulation activity is an important one, particularly given our prior observation that warfarin therapy suppressed increases in left atrial coagulation activity [2]. However, a feature of our study design was to only include patients without any prolongation of their INR at the beginning of the procedure [4]. While this does not completely exclude a residual effect of warfarin in our study, our previous finding of no difference in venous or left atrial F1j2 levels between patients who had or had not been on warfarin prior to the valvuloplasty procedure [1], suggests that any such effect was likely to have been small.…”

Assessment of Coagulation Factors in Patients of Severe Rheumatic Mitral Stenosis in Sinus Rhythm With Left Atrial Appendage Inactivity

“…Studies have shown that relieving the obstruction across the MV by valvuloplasty decreases the left atrial afterload, leading to improvements in LA/LAA contractility, 34,35 decrease in stasis 36,37 and decrease in the level of procoagulants. 38,39…”