|Beythien Ch et al.|
Influence of Aspirin Ingestion on In-Vitro Formation and Lysis of Platelet-Fibrin-Thrombi
Journal of Clinical and Basic Cardiology 2001; 4 (3): 231-233
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Keywords: Aspirin, Kardiologie, Plättchen, Plättchenaggregation, Thrombolyse, aspirin dosage, cardiology, platelet aggregation, platelets, thrombolysis
Introduction: Aspirin is successfully used in primary and secondary prevention of myocardial infarction and in combination with plasminogen activators in lysis. Since the optimal dose is still unknown, we developed an in-vitro model to investigate dose dependent influence of aspirin ingestion on formation of combined platelet-fibrin-thrombi and lysis, in-vitro thromboxane A2-synthesis, thrombus histology, and platelet aggregation parameters. Methods: Thrombi were induced by adding CaCl2 (final concentration 10 mmol/l) and collagen (1 mg/l) to platelet rich plasma (250 platelets per nl) of healthy non-smoking volunteers. In a cross-over design, doses of none, 20, 50, 100 or 500 mg of aspirin per day were administered for one week. After thrombus aging for 10 (TA10) or 30 min (TA30) thrombolysis over 30 min with urokinase (100, 500 or 2000 IU/ml) was performed. Results: Depending on increasing aspirin doses, thrombus formation time was prolonged from 292 to 354 seconds; no aspirin vs 500 mg (p < 0.001). Initial thrombus weight of TA10 decreased from 18.5 ± 1.4 to 14.7 ± 1.7 mg (p < 0.001). This was also true for TA30; 15.1 ± 1.1 reduced to 12.4 ± 1.3 mg (p < 0.001). After 30 min of lysis with 2000 IU urokinase final thrombus weight of TA10 was lower than of TA30; no aspirin 5.2 ± 1.3 vs 500 mg 5.5 ± 0.9 mg (p < 0.01) and 7.0 ± 1.8 vs 6.3 ± 1.0 mg (p < 0.05), respectively. Lysis efficacy of urokinase 500 and 2000 IU showed no significant differences, 100 IU/ml had minor lysis efficacy. Inhibition of in-vitro thromboxane synthesis increased from 0 to 99.7 % (p < 0.001). Aggregation rate decreased from 114 ± 20 to 60 ± 12 %/min, extent of aggregation decreased from 86 ± 5 to 62 ± 11 %, and lag time increased from 49 ± 14 to 68 ± 23 sec (p < 0.0001 each). Conclusion: Corresponding to increasing aspirin doses, thrombus formation time was prolonged, initial thrombus weight was reduced, and lysis was less effective. Urokinase 100 IU/ml induced only minor thrombus weight reduction, 500 and 2000 IU/ml showed comparable results. Lysis of TA30 was less efficacious. Aggregation rate decreased, extent of aggregation decreased, and lag time increased. In our in-vitro model the optimal dose for aspirin was between 50 and 100 mg per day.