Wide variation in thrombin generation in patients with atrial fibrillation and therapeutic International Normalized Ratio is not due to inflammation.
Atrial fibrillation (AF) is a common cardiac arrhythmia with a 5-20% annual risk of stroke. Warfarin reduces this risk by at least 60%. Despite adequate anticoagulation within the target International Normalized Ratio (INR) range of 2.0-3.0, some patients still experience thrombotic and bleeding events. It is now possible to assess the intensity of anticoagulation with automated thrombin generation (TG) tests, such as the calibrated automated thrombogram (CAT). These tests were compared and an inverse relationship was found between the INR and CAT in 143 elderly AF patients. There was equally good correlation between the concentration of factors II, VII, IX and X and the INR and TG parameters. The peak thrombin was most strongly associated with the concentration of prothrombin fragment 1 + 2 in plasma. There was wide variability in TG parameters in patients with identical INR values, sometimes up to a fourfold difference. This TG variability in individuals with the same INR is not due to inflammation, at least when the latter is measured as the concentration of factor VIII coagulant activity, von Willebrand factor antigen, high sensitivity C-reactive protein and fibrinogen. It was concluded that, although the TG and INR were closely correlated there was wide variability in peak thrombin and endogenous thrombin potential in patients within the INR therapeutic range, the cause of which remains unclear.
Royal Free Hospital, Haemophilia Centre & Thrombosis Unit, London, UK. alexander.gatt@royalfree.nhs.uk
A
A
Gatt
J J
JJ
van Veen
A
A
Bowyer
A M
AM
Woolley
P
P
Cooper
S
S
Kitchen
M
M
Makris
D000328:Adult; D000368:Aged; D001281:Atrial Fibrillation / Q000097:blood* / Q000150:complications; D001779:Blood Coagulation Factors / Q000378:metabolism; D001780:Blood Coagulation Tests / Q000379:methods; D015331:Cohort Studies; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000150:complications; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D011498:Protein Precursors / Q000097:blood; D011516:Prothrombin; D012016:Reference Values; D013917:Thrombin / Q000096:biosynthesis*
D001779:Blood Coagulation Factors; D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; D011498:Protein Precursors; C036309:fibrin fragment D; C029733:prothrombin fragment 1; C044183:prothrombin fragment 2; D011516:Prothrombin; D013917:Thrombin