Endogenous thrombin potential (ETP) in plasma from patients with AMI during antithrombotic treatment.
BACKGROUND
The beneficial impact of warfarin in preventing new events after AMI is well established. Decrease in thrombin generation seems to be the key element in anticoagulant treatment.


OBJECTIVE
The aims were to investigate the effect of warfarin and platelet inhibition on thrombin generation, assessed by the endogenous thrombin potential (ETP), and study the relation between coagulation parameters and ETP in patients with AMI.


METHODS
In the present sub-study of the WARIS II trial, patients with AMI were randomly assigned to treatment with aspirin 160 mg/d (n=57), aspirin 75 mg/d and warfarin (INR 2.0-2.5) (n=68) or warfarin (INR 2.8-4.2) (n=61). Fasting blood samples were collected from patients at discharge from hospital and after 6 weeks treatment.


RESULTS
Correlation analyses showed that both ETP and peak thrombin levels were significantly correlated with Factor VII Ag (r=0.38 and 0.36 respectively, p<0.01 for both) and with F1+2 (r=0.26 and 0.23 respectively, p=0.01 for both) at baseline. Antithrombotic treatment for 6 weeks caused a highly significant inhibition of ETP in patients treated with warfarin (-28%+/-5%, p<0.001), and patients treated with aspirin/warfarin (-24%+/-8%, p=0.04). Similarly, peak thrombin levels were reduced in patients treated with warfarin (-18%+/-7%, p=0.049) and aspirin/warfarin (-19%+/-5%, p=0.029), whereas an increase (12%+/-4%, p=0.029) occurred during aspirin treatment alone. F1+2 levels decreased by 64% and 58% in the warfarin and aspirin/warfarin groups, respectively (p=0.001 for both).


CONCLUSIONS
In patients with AMI, warfarin significantly reduced the endogenous thrombin generation and the potential to generate thrombin in plasma ex vivo, whereas aspirin alone had no effect on thrombin generation in vivo or ex vivo, assessed by ETP.
Brodin
E
E
Center for Atherothrombotic Research in Tromsø (CART), Department of Medicine, Institute of Clinical Medicine, University of Tromsø, 9037 Tromsø, Norway. ellenb@fagmed.uit.no
Seljeflot
I
I
Arnesen
H
H
Hurlen
M
M
Appelbom
H
H
Hansen
J B
JB
D000925:Anticoagulants / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D001780:Blood Coagulation Tests; D004359:Drug Therapy, Combination; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D013917:Thrombin / Q000378:metabolism*; D014859:Warfarin / Q000627:therapeutic use*
D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors; D014859:Warfarin; D013917:Thrombin; D001241:Aspirin