Paradoxical Thrombotic Effects of Aspirin: Experimental Study on 1000 Animals

Author(s): Christian Doutremepuich, Omar Aguejouf, Vanessa Desplat, Francisco X. Eizayaga.

Journal Name:Cardiovascular & Hematological Disorders-Drug Targets

Volume 10 , Issue 2 , 2010

Abstract:

Aspirin administration decreases the risk of vascular ischemic problems. However, aspirin withdrawal may temporarily increase this risk. Previous studies reported that high dilutions of aspirin might cause a pro-thrombotic effect. This paper studies the effect of the lower end of the aspirin dose-response curve, its possible mechanism and clinical implications.

Protocol: Wistar rats were distributed into 100 groups of 10 rats each. Aspirin was injected at 100 mg/kg, 1 mg/kg and at several different aspirin dilutions along with cyclooxygenase (COX) 1 (SC-560), COX 2 (NS-398) or both selective inhibitors simultaneously using a laser-induced thrombosis model.

Results: The higher doses of aspirin decreased thrombosis. An opposite trend was observed with the lowest doses. SC-560 produced an anti-thrombotic effect antagonized by the highest aspirin dilutions. NS-398 created a pro-thrombotic effect that was antagonized by aspirin at higher doses. Simultaneous inhibition of COX 1 and 2 produced changes similar to COX 1 inhibition.

Conclusion: COX 2 inhibition induced a pro-thrombotic effect that was antagonized by aspirin at 1 mg/kg or 100 mg/kg. The administration of the lowest aspirin doses induced a pro-thrombotic effect stronger than the antithrombotic effect of COX 1 selective inhibition. The mechanism of this last pro-thrombotic effect is induced by residual aspirin and is independent of COX 1 inhibition. This study may explain the cause of the paradoxical thrombo-embolic complications observed after aspirin discontinuation, an effect of residual aspirin rather than a rebound effect, and highlights the importance of low doses of substances as a barely studied source of side-effects.

Keywords: Aspirin, COX selective inhibitors, Thrombosis

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Article Details

VOLUME: 10
ISSUE: 2
Year: 2010
Page: [103 - 110]
Pages: 8
DOI: 10.2174/187152910791292510
Price: $58