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The assesment of trombocyte function by optical and impendance agregometry
Malíková, Lenka ; Stiborová, Marie (advisor) ; Poljaková, Jitka (referee)
Introduction: Platelets have an important role in the process of haemostasis in which they form blood clot generation. In some cases it is necessary to suppress activity of platelets by antiplatelet drugs to prevent life threatening states. Acetylsalicylic acid (ASA) and clopidogrel can influence the mechanism of primary haemostasis by inhibition of platelet function. This process has to be controlled. Clopidogrel is used for prevention of thrombotic states. The active form of clopidogrel is formed by cytochrome P450 3A4. Clopidogrel binds to the receptor P2Y12 instead of ADP, so platelets cannot be activated. The effect of clopidogrel is very variable. It is known that there is unresponsiveness to clopidogrel in 5-30 % patients. Acetylsalicylic acid acetylates cyclooxygenase and blocks the conversion of arachidonic acid to tromboxan A2, so platelets cannot be activated. ASA treatment is effective, but in some patients can appear so called aspirin resistance (AR). Possible unresponsiveness to the therapy is the reason why it is suitable to monitor antiplatelet therapy, which may be provided by various methods. Thesis target: To detect normal range in measurement of healthy control group, evaluate efficiency of clopidogrel and ASA and to determine which method (LTA - Light Transmission Aggregometry...
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Analysis of gene polymorphism of CYP 2C19 patients treated with clopidogrel
MAŠKOVÁ, Soňa
Clopidogrel is an antithrombotic medicament from the group of thienopyrids, used for the prevention of blood cloths by the patients with acute coronary syndrome, patients after an ischemic stroke, myocardial infarction or by the patients with proven lower limb ischemia. Clopidogrel is a "prodrug", which means that it needs to be metabolised into an active metabolite before it stars working. The cytochrome P450 2C19 plays the main role in the bioactivation of clopidogrel. Individual enzymes of cytochrome complex are coded by genes, which are polymorphic. The function of P450 2C19 can differ by individuals, from the reason of gene polymorphism, therefore the bioactivation of clopidogrel can differ as well. There are few alleles of cytochrome P450 CYP2C19, which are connected with different therapeutic reactions on the submission of clopidogrel. Individuals with the allele CYP2C19*17 have an increased concentration of active metabolite and are at a higher risk of bleeding complications. The carriers of CYP2C19*2 a CYP2C19*3 alleles have a decreased metabolisation of clopidogrel into an active metabolite, which leads to insufficient antiaggregate effect and to increased appearance of cardiovascular complications. The allele CYP2C19*1 is connected with a fully functioning metabolism. In the group of 512 patients, we detected 191 carriers of the genotype *1/*1, 79 carriers of the genotype *2/*1, 12 carriers of the genotype *2/*2, 1 carrier of the genotype *3/*1, 43 carriers of the genotype *17/*17, 146 carriers of the genotype *17/*1 and 40 carriers of the genotype *17/*2. The stratification of the patients according to genotype CYP2C19 has a significant meaning for adjusting the right treatment strategy and it is a prevention of stroke and the risk of bleeding.
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The assesment of trombocyte function by optical and impendance agregometry
Malíková, Lenka ; Stiborová, Marie (advisor) ; Poljaková, Jitka (referee)
Introduction: Platelets have an important role in the process of haemostasis in which they form blood clot generation. In some cases it is necessary to suppress activity of platelets by antiplatelet drugs to prevent life threatening states. Acetylsalicylic acid (ASA) and clopidogrel can influence the mechanism of primary haemostasis by inhibition of platelet function. This process has to be controlled. Clopidogrel is used for prevention of thrombotic states. The active form of clopidogrel is formed by cytochrome P450 3A4. Clopidogrel binds to the receptor P2Y12 instead of ADP, so platelets cannot be activated. The effect of clopidogrel is very variable. It is known that there is unresponsiveness to clopidogrel in 5-30 % patients. Acetylsalicylic acid acetylates cyclooxygenase and blocks the conversion of arachidonic acid to tromboxan A2, so platelets cannot be activated. ASA treatment is effective, but in some patients can appear so called aspirin resistance (AR). Possible unresponsiveness to the therapy is the reason why it is suitable to monitor antiplatelet therapy, which may be provided by various methods. Thesis target: To detect normal range in measurement of healthy control group, evaluate efficiency of clopidogrel and ASA and to determine which method (LTA - Light Transmission Aggregometry...
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