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

Background Patients of severe mitral stenosis (MS) in normal sinus rhythm (NSR) with left atrial appendage (LAA) inactivity and associated left atrial spontaneous echo contrast (LASEC) develop left atrial (LA) or LAA thrombus. But unlike atrial fibrillation (AF), oral anticoagulants (OAC) are not routinely prescribed in this subset of patients. Aim To assess local (LA) and systemic levels of procoagulants (PF1+2: prothrombin fragment 1+2; TAT-III: thrombin antithrombin III), PAI-1 (plasminogen activator inhibitor-1) and fibrinogen, in patients of severe MS in NSR with LAA inactivity and associated LASEC with healthy controls. Methods 35 patients of severe MS with valve suitable for balloon mitral valvuloplasty, along with 35 healthy volunteers were enrolled. All patients underwent transthoracic and transesophageal echocardiography to assess severity of MS, LAA activity, grade of LASEC, and exclude the presence of LA or LAA clot. Peripheral venous and LA blood samples were analysed for levels of procoagulants. Results Baseline characteristics like age and sex were comparable in both groups. Most of the patients in our study were either in NYHA II (n=13, 37.1%) or NYHA III functional class (n=21, 60%) and had grade 3+ (n=17;48.57%) or grade 4+ (n =15;42.86%) LASEC. Levels of PF1+2 {patient vs control, 9017(6228-10963.5) pg/mL vs 1790(842.3-2712) pg/mL, p<0.0001)}, TAT-III {patient vs control, 39(5.45-74.85) ng/ml vs 2.80(1.6-6.5) ng/mL, p<0.0001}, PAI-1 {patient vs control, 26.09±8.18 ng/ml vs 8.05 ± 3.53ng/ml. p<0.0001)}and fibrinogen (3.48± 0.89g/L vs 3.01± 0.53g/L, p=0.029) were significantly higher in LA of patients as compared to controls. Similarly, systemic levels of PF1+2, TAT-III, PAI-1 and fibrinogen were significantly higher in patients as compared to controls. However, systemic level of D-dimer was similar in both groups. Conclusion Both local and systemic levels of procoagulants were significantly raised in patients of severe MS in NSR with LAA inactivity and associated grade 3+ or 4+ LASEC, suggestive of a hypercoagulable state similar to that reported in patients of AF. Hence, we feel that OAC should be administered routinely in this subgroup of patients to prevent thrombus formation until there is improvement in LA and LAA function following valvuloplasty or mitral valve surgery. Clinical Perspective What’s new? Patients of severe MS in NSR with LAA inactivity and associated LASEC are prone to develop LA or LAA thrombus. However, the ACC/AHA 2020 guidelines on valvular heart disease still do not recommend oral anticoagulants in this subset of patients. We carried out an adequately powered study to assess the level of procoagulants in patients of severe MS in NSR with associated LASEC (LASEC being a marker of stasis). What are the clinical implications? Both local and systemic levels of procoagulants were significantly raised in patients of severe MS in NSR with LAA inactivity and associated grade 3+ or 4+ LASEC as compared to controls, suggestive of a hypercoagulable state similar to that reported in patients of AF. We feel that OAC should be administered routinely in this subgroup of patients of rheumatic MS in NSR to prevent thrombus formation until there is improvement in LA and LAA function following valvuloplasty or MV surgery.