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Biochemistry of Aspirin

Activated and aggregated thrombocytes play a key role in the pathogenesis of cardiovascular diseases. After transformation of arachidonic acid into prostaglandin H2 by cyclooxygenase-1 (COX-1), activated thrombocytes synthesize thromboxane A2 (TxA2), a potent vasoconstrictor that also induces platelet aggregation. TxA2 has a short half-life in plasma and is rapidly turned into thromboxane B2 (TxB2). TxB2 is further transformed into 11-dehydro-thromboxane B2 (11dhTxB2) and a large number of other TxB2 metabolites that are secreted via the kidneys. Since 11dhTxB2 is a stable TxA2 metabolite, it is an in vivo indicator of thrombocyte activity.

Clinical significance of Aspirin

Aspirin (acetylsalicylic acid) has an important role in the antithrombotic therapy for cardiovascular disease. It has long been known, that aspirin has a anticoagulatory effect. It works by acetylation and irreversible inhibition of COX-1, meaning inhibition of TxA2 synthesis and its metabolites. Low doses of aspirin can block more than 95% of the COX-1 activity and reduces the events in subjects with cardiovascular diseases with more than 25%. A method for monitoring the effect of aspirin is to measure the stable TxA2 metabolites in urine, such as 11dhTxB2. The test works by measuring the effect of given aspirin on its inhibitory effect on COX-1 via 11dhTxB2. Since the effect of aspirin has large individual variations, many subjects receive a too low dose, which does not sufficiently inhibit platelet function. It is estimated that 10-20% of subjects on aspirin treatment have recurrent thrombotic events. This phenomenon is called aspirin resistance. Dependent on method used and population screened, between 5-57% of aspirin users have a low response to typical dosages.

Clinical or Research use of Aspirin

The possibility to monitor the effect of aspirin treatment facilitates giving correct dosages and helps protect the subject. An optimal dosage adjustment is necessary, since an ineffective dose increases the risk of further thrombotic events. Moreover, an excessive dosage is associated with an elevated risk of bleeding.

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