title: 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.
authors.affiliation: Centre for Heart and Chest Research, Department of Medicine, Monash University and Monash Medical Centre, Melbourne, Victoria, Australia. roger.peverill@med.monash.edu.au
authors.forename: R E
authors.initials: RE
authors.lastname: Peverill
authors.forename: R W
authors.initials: RW
authors.lastname: Harper
authors.forename: T E
authors.initials: TE
authors.lastname: Gan
authors.forename: J J
authors.initials: JJ
authors.lastname: Smolich
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005263:Femoral Artery / Q000378:metabolism; D005268:Femoral Vein / Q000378:metabolism; D006325:Heart Atria / Q000378:metabolism; D006439:Hemodynamics; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D008946:Mitral Valve Stenosis / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism*; D011516:Prothrombin / Q000378:metabolism*; D013917:Thrombin / Q000096:biosynthesis*
chemical_list: D010446:Peptide Fragments; D011498:Protein Precursors; C029733:prothrombin fragment 1; C044183:prothrombin fragment 2; D011516:Prothrombin; D013917:Thrombin