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

Peverill, Roger E.; HARPER, Richard W.; GAN, T. Eng; Smolich, Joseph J.

doi:10.1042/cs19990244

Cited by 4 publications

(8 citation statements)

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“…First, patients in the study were on full-dose oral anticoagulation before and after the valvuloplasty procedure, and results may therefore have been influenced by the well-recognized effect of warfarin to reduce coagulation activity [23][24][25][26]. 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].…”

Section: Discussionmentioning

confidence: 97%

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

et al. 2000

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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.

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Section: Discussionmentioning

confidence: 97%

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

et al. 2000

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“…Although they provide some data of levels of D-dimer, these alone are insufficient to be able to put the changes in F1j2 into a perspective of the wider field of coagulation and fibrinolysis. While Peverill et al [1] suggest that peripheral blood sampling may perhaps underestimate the degree of haemostatic activation in the left atrium, the process of thrombogenesis is unlikely to be confined to the left atrium itself in cardiovascular disease, and is likely to be a more generalized process. Indeed, levels of F1j2 can also be influenced by sampling methods [3].…”

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confidence: 91%

“…For example, the division of patients into ' normal ' and ' prolonged ' INR by Peverill et al [1] resulted in the latter group having only seven subjects. It is unclear why Peverill et al [1] chose an INR of 1n2 as the divider, when a better analysis would have been to compare groups above and below the median INR.…”

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confidence: 97%

“…from 0.92 nmol\l to approx. 1.28 nmol\l in the left atrium (as, indeed, reported by Peverill et al [1]), with a power of 0.80 and P 0.05, then the minimum number of patients can be calculated [2]. The simple finding of significance (or not) at P 0n05 is no demonstration of an actual difference, especially if many measurements have been made on the same small group of subjects.…”

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confidence: 97%

“…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).…”

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Left atrial thrombin generation and prothrombin fragment 1+2

Blann

Lip

2000

Clinical Science

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CORRESPONDENCELeft atrial thrombin generation and prothrombin fragment 1+2: authors’ reply

Peverill

Smolich

2001

Clinical Science

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We are pleased to respond to the recently published comments of Blann and Lip [1] regarding statistical and methodological aspects of our study [2] and the interpretation of our findings. As clearly stated in the Introduction, the purpose of our study was to determine if the observed lack of elevation in venous levels of prothrombin fragment 1j2 (F1j2) in mitral stenosis patients with increased left atrial F1j2 levels [3] was due to limited spillover of this coagulation marker into the arterial circulation or its rapid clearance by systemic tissues, an explanation which was implied by the results of a recent study from Yamamoto et al. [4]. Pivotal to the discrimination between these two possibilities was the comparison between arterial and venous F1j2 levels, since similar levels would be consistent with limited spillover, whereas greater arterial than venous levels would be indicative of rapid systemic clearance. Our finding that arterial and venous levels of F1j2 were similar, even in the subgroup of patients with a clearcut increase in left atrial thrombin generation, therefore suggests that the association of increased left atrial with normal venous F1j2 levels in mitral stenosis is principally due to limited spillover of F1j2 from the left atrium into the systemic circulation.Blann and Lip [1] have questioned our subdivision of subjects based on ' externally applied criteria ', but it is important to emphasize that such subdivisions were based on clear rationales. First, the grounds for subdividing the total group on the basis of the international normalized ratio (INR) was our previous evidence that a prolonged INR ( 1.2) was associated with suppression of left atrial coagulation activation [5]. Indeed, the potential confounding effects of a prolonged INR were evident, despite the relatively small numbers in the prolonged INR group, as there were significantly lower arterial and venous levels of F1j2 in this group compared with those with a normal INR. Secondly, subdivision of patients into those with and without increased left atrial thrombin generation was based on a statistical comparison between left atrial and venous F1j2 levels, and has been previously described in detail [3].We can reassure Blann and Lip [1] that the basic issues regarding statistical power and methods which they have raised were considered in both the design and analysis of our study. With respect to the power of the study to detect a difference in venous and arterial levels of F1j2, analysing the 29 subjects with an INR in the normal range, our study had 95 % power to detect a difference of 0.5 nmol\l between the arterial and venous F1j2 levels, a difference which is approx. 50 % of that reported by Yamamoto et al. [4]. Moreover, the 95 % confidence interval for the difference between the arterial and venous F1j2 level was quite narrow (k0.07 to 0.14 nmol\l). Nor was there any difference in the results of this analysis dependent on whether a paired t test or non-parametric test was performed (P l 0.52 and P l 0.87 respectively). Fi...

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

Cited by 4 publications

References 20 publications

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

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

Left atrial thrombin generation and prothrombin fragment 1+2

CORRESPONDENCELeft atrial thrombin generation and prothrombin fragment 1+2: authors’ reply

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