Low-intensity warfarin reduces thrombin generation and fibrin turnover, but not low-grade inflammation, in men at risk of myocardial infarction.
In the Thrombosis Prevention Trial (TPT), low-intensity warfarin reduced the risk of first coronary events only when the achieved international normalized ratio (INR) was > or =1.4. To validate the likely mechanism of action of low-intensity warfarin we measured its effects on plasma markers of thrombin generation, fibrin turnover and low-grade inflammation in TPT participants. D-dimer and prothrombin fragment F1.2 levels were lower at INRs > or =1.4 (P = 0.02 and 0.03 respectively); levels fell as INR increased (P for trend 0.04 and 0.002 respectively). C-reactive protein did not vary with INR. The efficacy of warfarin is related to reductions in thrombin generation and fibrin turnover.
MacCallum
Peter K
PK
Wolfson Institute of Preventive Medicine, Barts and The London, Queen Mary's School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, UK. p.k.maccallum@qmul.ac.uk
Rudnicka
Alicja R
AR
Rumley
Ann
A
Meade
Tom W
TW
Lowe
Gordon D O
GD
D000925:Anticoagulants / Q000008:administration & dosage*; D003328:Coronary Thrombosis / Q000097:blood; D005337:Fibrin / Q000378:metabolism*; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood*; D010446:Peptide Fragments / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D012307:Risk Factors; D013917:Thrombin / Q000378:metabolism*; D014859:Warfarin / Q000008:administration & dosage*
D000925:Anticoagulants; D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; C036309:fibrin fragment D; D014859:Warfarin; C044183:prothrombin fragment 2; D011516:Prothrombin; D005337:Fibrin; D013917:Thrombin