Coagulation activity is increased in the left atrium of patients with mitral stenosis—I

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Coagulation Activity Is Increased in the Left Atrium of Patients With Mitral S t e n o s i s ~ l I read the study by Yamamoto et al. (I) with immense interest. However, their conclusion of activation of the coagulation system in the left atrium even during anticoagulation may be incorrect. We do not know thc severity of pulmonary hypertension in the patients studied. Although the authors found no correlation of elevated fibrinopeptide A (FPA) levels with either chronic atrial fibrillation or severity of mitral stenosis, no attempt at correlation with severity of pulmonary hypertension was made. There is evidence to suggest activation of the coagulation system in pulmonary hypertension, both in primary (2) and seconda U pnlmonaU hypertension (3), although controversy also exists (4). To my knowledge, no studies have been done to date on FPA or thrombin anti-thrombin III (TAT) activity and pulmonary hypertension secondary to mitral stenosis. The coaguhttion activation in the present study suggests an activation in the pulmona~ circuit rather than the left atrium, contra U to the suggestion by the authors. If this hypothesis is correct, particularly if the FPA levels decrease after correction of mitra[ stcnosis, pulmonaU hypertension with mitral stenosis may itself be a risk factor for coagulation. Hencc, there is an argument for early definitive therapy for mitral stenosis to better control or correct the coagulation abnormality. The TAT levels in the present study were not significantly clcvatcd in the left atrium, although they correlated with the FPA levels. This difference could have resulted from the influence of different blood sampling techniques. Significantly lower TAT levels are measured in blood samples taken from central cathcters than those with blot~d samples obtained from direct venipunctures (5). The TAT levels measured in the left atrium in the present study may thus be artifactually low, when the TAT levels are in fact significantly clcwtlcd in patients with mitral stcnosis. Congratulations for the wonderful study. MUMTAZ A. SIDDIQU1, MD. MR('P The Graduate ftov~ital Philadelphia. Penn.svk'ania 19144 References 1. Yamamoto K, lkeda U, Seino Y. ct al. ( oagulation activity is increased in the lea atinun of patients with mitral stcnosis. J Am Coil Cardiol 1~)95;25:1ti7 12. 2. Eisenberg PR, kucore C. Kaufman 1.. Sobe/ BE. JatlL' AS. Rich S. Fibrinopeptide A/cwls indicative o[ pulmonary vascular thromb~sis in patients with primary pnlmonary hypertension. Circulation 1990:82:841 7. 3. Nakstad B, Lyberg T, Skjonsberg Ott. Bore NP. I.ocal activation nf the coagulation and fibrinolysis systems in lung disease Thromb Res Iqttl):57:g27-38. 4. Schulman LL. Grossman BA, Owcn J. Platclct acti',ation and fihrmopcptide tnrmation in pulmonary hypertension. Chest I q93:1(14:1hq{)-3. 5, Harrier G. Schinzel H, Ehrenthal W, ct al. Influence of blood sampling from vcniptinettncs and catheter systems on serial deterniinations ol prothrombm actiwltion fragment I ~2 and thrombin-antithrombin I11 complex. Ann Hemalnl ]tJ%:(g:121 5.

Coagulation Activity Is Increased in the Left Atrium of Patients With Mitral S t e n o s i s ~ l I We read with interest the reporl by Yamamoto et al. ( I ) on coagulation activity in patients with mitral stenosis. In this interesting study. various coagulation markers in 12 patients were compared with those 15 normal subjects. Eleven of the 12 patients were in alrial fibrillation, but the heart

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rhythm of the normal control subjects was not stated (we assume that they were in sinus rhythm) (1). However, patients with atrial fibrillation who are not receiving any antithrombotic therapy are known to demonstrate abnormalities in coagulation factors, consistent with a prothrombotic or hypercoagulable state, that may contribute to the high risk of stroke and thromboembolism in such patients. For example, patients with atrial fibrillation who are not receiving any antithrombotic therapy demonstrate an elevation in plasma levels of fibrinogen, fibrin D-dimer, von Willebrand factor antigen and betathromboglobulin compared with control subjects in sinus rhythm, and this finding is independent of any underlying structural heart disease (2-4). There was also no relation to left atrial size or ventricular function (3). In addition, all patients in the study by Yamamoto et al. (1) had received warfarin therapy for 3 months. The introduction of warfarin therapy normalizes certain markers of thrombogenesis, such as fibrin D-direct and beta-tbromboglobulin; although other markers, such as yon Willebrand factor antigen and fibrinogen, remain unchanged (3,4). It is therefore not surprising that Yamamoto et al. (1) found no significant differences in levels of D-dimer and beta-thromboglobulin betwecn their patients (taking warfarin) and control subjects and that von Willebrand factor antigen levels remained significantly elevated. A better assessment of hypercoagulablc state in mitral stenosis would have been to compare patients with mitra[ stenosis in sinus rhythm (and not on any antithrombotic therapy) and matched healthy control subjects in sinus rhythm (who are also not receiving any therapy). However, whether such a study is feasible remains debatable because most patients with significant mitral stenosis should be started on antithrombotic therapy, in view of the risk of developing atrial fibrillation and thromboembolism. GREGORY Y. H. LIP, MD, MBCHB, MRCP, DFM JOHN ZARIFIS, MD UmvemO' Departmentof MedMne ('it)' Ho.?#tal Birmingham BIg 7QH, England, UnitedKingdom References I. ", amamoto K, [keda U. Sein(~ Y, et al. Coagulation activi B' is increased in the [eft atrium of patients wilh mimil stenosis. J Am Cnll Cardiol 1995;25:1[)7-12. 2. Kumagai K, l='ukunami M, Ohmori M, Kitabatake A, Kamada T, Hoki N. Increased intracardinwiscular clotting in patients with chronic atrial fibrillation. J Am Coil Cardiol 199(1:J,3:377-81). 3. Lip GYH. kowe GDO, Rumley A. Dunn FG. Increased markers of thrombogenesis in chronic atrial fibrillation: effects of warfarin therapy. Br Heart J. In press, 4. Lip GYH. l.ip PL. Zarilis J, et al. Fibrin D-dimer and beta-thromboglobulin as markers of thrombngcnesis and plateiet activation in atrial fibrillation: effects of warfarin and aspirin. ('lin Sci. In press.

Reply Wc very much appreciate the interest of Siddiqui in our recent study on coagulation activity in the left atrium of patients with mitral stcnosis (1). Siddiqui raises two issues with regard to our study. The first is the possibility of increased coagulability in the pulmonary circuit rather than in the left atrium of patients with mitral stenosis. We therefore ewtluated the correlation of elevated fibrinopeptide A (FPA) and thrombin-antithrombin III complex (TAT) levels in the left atrium of the patients in relation to the severity of pulmonary hypertension. However, the levels of these biochemical markers did not correlate well with the mean pulmonary artery pressure (FPA: r - 0.47, p 0.13: TAT: r - 0.41, p - 0.19). As pointed out by