title: Aspirin acetylates fibrinogen and enhances fibrinolysis. Fibrinolytic effect is independent of changes in plasminogen activator levels.
abstract: In addition to its antiplatelet effect, aspirin has been reported to have fibrinolytic and hypoprothrombinemic effects. The objective of this study was to investigate possible mechanisms underlying the enhanced fibrinolysis after aspirin. Five healthy subjects received 650 mg of aspirin every 12 hr for 5 days. Blood samples were collected before aspirin (control), and immediately before (0 hr) and 2 hr after (2 hr) the last dose for determinations of clot lysis time, time course of thrombin-induced fibrin aggregation, tissue plasminogen activator activity, intrinsic pathway fibrinolytic activity, plasminogen, fibrinogen, aspirin and salicylic acid, and the coagulation tests activated partial thromboplastin time, thrombin time and prothrombin time. Clot lysis time was shorter after aspirin, control: 9.1 +/- 12.4 min (mean +/- S.D.); 0 hr: 4.6 +/- 4.0 min; 2 hr: 5.7 +/- 6.2 min (P: .04) and the fibrin aggregation curves showed increased relative absorbance at 10 min, control: 8.4 +/- 2.2; 0 hr: 11.2 +/- 0.2; 2 hr: 13.3 +/- 5.4 (P: .02). Control values of tissue plasminogen activator (0.11 +/- 0.04 IU/ml), intrinsic pathway fibrinolytic activity (2.20 +/- 0.54 IU/ml), plasminogen (10.9 +/- 1.0 mg/dl), fibrinogen (288 +/- 37 mg/dl) and the coagulation tests were not different from those after aspirin. Aspirin concentration was below detection limits at 0 hr and 1.63 +/- 0.97 micrograms/ml at 2 hr, whereas salicylic acid concentration was 55.0 +/- 35.8 and 136 +/- 71.9 micrograms/ml at 0 and 2 hr, respectively. In vitro studies using fibrinogen-free plasma and added acetylated fibrinogen showed an inverse relationship between the extent of acetylation and clot lysis time.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: T D
authors.initials: TD
authors.lastname: Bjornsson
authors.forename: D E
authors.initials: DE
authors.lastname: Schneider
authors.forename: H
authors.initials: H
authors.lastname: Berger
mesh_terms: D000107:Acetylation; D001241:Aspirin / Q000097:blood / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D005260:Female; D005337:Fibrin / Q000502:physiology; D005340:Fibrinogen / Q000378:metabolism*; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D008297:Male; D010960:Plasminogen Activators / Q000097:blood; D012016:Reference Values
chemical_list: D005337:Fibrin; D005340:Fibrinogen; D010960:Plasminogen Activators; D001241:Aspirin