Original ArticleEffects of Acetylsalicylic Acid on Increase of Fibrin Network Porosity and the Consequent Upregulation of FibrinolysisHe, Shu MD, PhD*; Bark, Niklas MD, PhD†; Wang, Haiyao MD, PhD†; Svensson, Jan MD, PhD†; Blombäck, Margareta MD, PhD*†Author Information From the *Department of Clinical Sciences, Danderyd Hospital; and †Department of Molecular Medicine and Surgery-Coagulation Research, Karolinska Institutet, Stockholm, Sweden. Received for publication July 15, 2008; accepted November 5, 2008. Supported by funds from Karolinska Institutet, the Swedish Society of Medicine, the Magnus Bergvall Foundation, and a donation by Brita Benjaminsson. The authors report no conflicts of interest. Reprints: Shu He, MD, PhD, Coagulation Research, L2-5 Karolinska University Hospital, S-171 76 Stockholm, Sweden (e-mail: email@example.com). Journal of Cardiovascular Pharmacology: January 2009 - Volume 53 - Issue 1 - p 24-29 doi: 10.1097/FJC.0b013e3181953e0f Buy Metrics Abstract Our earlier study in vivo showed that a lower dose of acetylsalicylic acid (ASA) brought greater enhancement in fibrin gel permeability (Ks) than a higher dose. To assess whether this finding related to modifications of fibrinogen clotting property by ASA, purified fibrinogen was incubated with ASA and/or salicylic acid (SA). The fibrinogen product was examined. Fibrinogen “clotting time” was not affected. Shortening of fibrin clot “lysis time” paralleled the increase of fibrin network porosity demonstrated by measurements of liquid permeability (Ks), fibrin fiber thickness, and 3-dimensional microscopic image, in a low ASA concentration-dependent way. Ks levels were not altered by SA alone but significantly decreased in samples treated by both where the concentrations were low for ASA and high for SA. In conclusion, ASA at the concentrations used did not influence the rate of fibrinogen gelation by thrombin. However, assembly of fibrin monomers was most probably altered, leading to enhancement of fibrin fiber thickness. A looser network was constructed by the thicker fibrin fibers, which benefits fibrinolysis. According to the known mechanism that SA interferes with ASA in preventing acetylation of platelet's proteins, an explanation for the low ASA concentration-dependent effects on fibrin network structure may be that fewer molecules of SA-the hydrolytic product of ASA-are generated from lower doses of ASA, which block acetylation of fibrinogen to a smaller extent and thus more significantly impair fibrin formation. © 2009 Lippincott Williams & Wilkins, Inc.