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. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial As the study did not involve any new drug, biological product or a device, it was not registered with any clinical trial registry. ### Funding Statement None ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: F.1/IEC/MAMC/85/04/2021/No.485 I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The authors confirm that the data supporting the findings of this study are available within the article.