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Gene risk factors for reduced response to platelet inhibitory therapy identified

(Vienna, 29 December 2011) MedUni Vienna researchers have established that two gene factors increase the risk of further cardiovascular diseases despite therapy. A study headed by Thomas Gremmel and Sabine Steiner of the University Department of Internal Medicine II has determined that 2 gene variants slow down the effect of the platelet inhibitor clopidogrel that reduces the aggregation of blood platelets on the surface of the blood vessel. These factors can now be identified and the affected patients can be treated with an alternative platelet inhibitor.

At the Clinical Institute for Medical and Chemical Laboratory Diagnostics in the Department of Molecular Biology headed by Christine Mannhalter this method to identify gene variants had already been established last year. Its effect was now analysed in a study of 288 patients after vessel-opening procedures with stent implantations. “It could be shown that the carriers of certain gene variants of cytochrome 2C19 and cytochrome 2C9 had significantly more frequently a high residual platelet reactivity, which was equal to an insufficient inhibition of platelet aggregation“, explained Gremmel.

Clopidogrel inhibits the activation and aggregation of blood platelets on the surface of the blood vessels and hence the occurrence of renewed vascular occlusions in this area. The medication is often used in combination with Aspirin. In contrast to Aspirin, however, clopidogrel is a so-called “prodrug“, a less active pharmacological substance that changes only to an active substance by metabolising in the organism. This is caused by the cytochrome P450 enzyme system of the liver.

Earlier studies had shown that the platelet inhibitory effect of clopidogrel does vary considerably from person to person. The main factors identified are medication interaction, body weight and the age of the patient. The MedUni has now successfully achieved to identify gene risk factors too that are of significance during the treatment with clopidogrel and which can easily be counteracted. Says Gremmel: “The patients can be treated with an alternative platelet inhibitor that will not be influenced by the genetic variants of cytochrome 2C19 and cytochrome 2C9 in the inhibition of the platelet reactivity.“

The study was conducted in cooperation with the Clinical Department of Angiology, the Clinical Institute for Medical and Chemical Laboratory Diagnostics and the Thrombocytes Laboratory of the University Clinic of Blood Group Serology and Transfusion Medicine and has now been published in two renowned specialist magazines “International Journal of Cardiology“ and “Thrombosis Research“. 

Service: International Journal of Cardiology
"Influence of cytochrome 2C19 allelic variants on on-treatment platelet reactivity evaluated by five different platelet function tests." Thomas Gremmel, Christoph W. Kopp, Deddo Moertl, Daniela Seidinger, Renate Koppensteiner, Simon Panzer, Christine Mannhalter, Sabine Steiner. doi:10.1016/j.thromres.2011.11.019