Better increase in fibrin gel porosity by low dose than intermediate dose acetylsalicylic acid.
OBJECTIVE
To investigate the influence on plasma fibrin gel structure of low and intermediate doses of acetylsalicylic acid in healthy individuals. The influence of acetylsalicylic acid on thrombin formation, fibrinolytic capacity and plasminogen inhibitor-1 in plasma was also investigated.


METHODS
Nineteen subjects were treated with 75 mg and 11 with 320 mg acetylsalicylic acid daily; eight subjects received both doses. Fibrin gel structure was determined by a permeability technique yielding a porosity constant (Ks), and the thromboxane metabolite 11-dehydro-thromboxane B2 (TxM) was determined by an ELISA.


RESULTS
Acetylsalicylic acid increased fibrin porosity by 65% at 75 mg (P<0.001, n=19), whereas lower increases were found at 320 mg (+22%, P<0.05, n=11). One week after withdrawal Ks had essentially returned to baseline (ns). Urinary thromboxane metabolites were suppressed during treatment (-61%, P<0.001 at 75 mg, n=19; -46%, P<0.01 at 320 mg, n=11). The intra-individual comparison showed similar results (Ks +92%, TxM -62% at 75 mg; Ks +5%, TxM -52% at 320 mg). Fibrinolytic capacity, plasminogen inhibitor-1 levels and thrombin generation (in platelet-poor citrated plasma) were not influenced.


CONCLUSIONS
Low dose acetylsalicylic acid causes the greatest increase in fibrin gel porosity; this may well be of therapeutic importance.
Williams
S
S
Coagulation Research, Karolinska Institutet/Karolinska Hospital, Stockholm, Sweden.
Fatah
K
K
Hjemdahl
P
P
Blombäck
M
M
D000328:Adult; D000990:Antithrombin III / Q000378:metabolism; D001241:Aspirin / Q000008:administration & dosage* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005337:Fibrin / Q000187:drug effects / Q000378:metabolism*; D005342:Fibrinolysis / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D005782:Gels; D006801:Humans; D008297:Male; D010447:Peptide Hydrolases / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D016062:Porosity; D011446:Prospective Studies; D013931:Thromboxanes / Q000652:urine
D005343:Fibrinolytic Agents; D005782:Gels; D017395:Plasminogen Activator Inhibitor 1; D010975:Platelet Aggregation Inhibitors; D013931:Thromboxanes; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D005337:Fibrin; D010447:Peptide Hydrolases; D001241:Aspirin