Increased left atrial thrombin generation in mitral stenosis is not reflected in arterial prothrombin fragment 1+2 levels

Abstract

A proportion of patients with mitral stenosis have increased left atrial thrombin generation, with elevated left atrial but normal peripheral venous levels of prothrombin fragment 1+2 (F1+2). Whether this pattern of left atrial and venous F1+2 levels is related to limited spillover of F1+2 from the left atrium into the systemic circulation, or to washout of increased left atrial F1+2 production into the arterial circulation with subsequent systemic clearance, is unclear. We examined the relationship between arterial and venous F1+2 levels in mitral stenosis patients without left atrial thrombus. The study group comprised 36 patients with either a normal (n=29) or prolonged (n=7) international normalized ratio (INR; a measure of clotting time) who were undergoing percutaneous balloon mitral valvuloplasty. Baseline arterial and venous blood samples were collected at the beginning of the valvuloplasty procedure, and left atrial and venous samples were collected after trans-septal puncture. The left atrial F1+2 level exceeded the corresponding venous level in patients with a normal INR (P<0.03); however, baseline arterial and venous F1+2 levels were similar. Arterial and venous F1+2 levels were also similar in the subgroup of patients with evidence of a regional increase in left atrial thrombin generation, and were not different from arterial and venous F1+2 levels in patients without such an increase. Baseline arterial and venous F1+2 levels were both lower in the presence of a prolonged INR. Thus the pattern of increased left atrial but normal venous F1+2 levels in mitral stenosis is due to limited spillover from the left atrium into the systemic circulation.

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

“…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].…”

“…mia has been associated with a hypercoagulable state, with abnormalities of haemostasis, platelets and endothelial dysfunction, which are independent of aetiology and underlying structural heart disease, and are altered by antithrombotic therapy and cardioversion [3]. We were pleased to note that Peverill et al [1] only found a reduction in left atrial F1j2 levels in the patients with increased regional left atrial thrombin generation who were in sinus rhythm, and not among the patients who were in atrial fibrillation, which is in keeping with the highly prothrombotic or hypercoagulable state in this arrhythmia.…”

“…Based on the ability of mitral valvuloplasty to improve flow in the left atrium and cause a reduction or resolution of left atrial spontaneous echo contrast [18], the central hypothesis of our study was that balloon dilatation of the mitral valve would have a beneficial effect on increased left atrial coagulation activity [3]. Contrary to the contention of Li-Saw-Hee and Lip, no such benefit was anticipated (nor seen) in patients without an increase in left atrial coagulation activity prior to valvuloplasty.…”

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

“…However, the conclusion that mitral valve dilatation produced a sustained decrease in left atrial coagulation activity is confounded by two major factors. Secondly, the assumption of Yamamoto et al [7] that arterial F1j2 levels are representative of left atrial levels may not be correct, and has not been confirmed in a subsequent study [27]. Secondly, the assumption of Yamamoto et al [7] that arterial F1j2 levels are representative of left atrial levels may not be correct, and has not been confirmed in a subsequent study [27].…”

Left atrial thrombin generation and prothrombin fragment 1+2

“…Peverill and colleagues [1] recently reported differences in levels of prothrombin fragment 1j2 (F1j2) in blood obtained from the left atrium, the femoral artery and the femoral vein from 36 patients with mitral stenosis. They aimed (i) to compare arterial and venous levels of F1j2 in patients with normal clotting times, (ii) to examine and compare the relationship between arterial and venous levels of F1j2 in patients with and without increased left atrial thrombin generation, and (iii) to compare the relationship between arterial and venous levels of F1j2 in patients with a prolonged or a normal international normalized ratio (INR).…”