الفهرس | Only 14 pages are availabe for public view |
Abstract • The term aspirin resistance exclusively refers to situations in which aspirin is unable to inhibit COX-1- dependent TxA2 production and the corresponding TxA2- dependant platelet functions while the term treatment failure should be applied in other situations. • Polymorphism within the P2Y12 receptor or the CYP3A4 genes are the predominant genetic factors associated with clopidogrel resistance. Patient non compliance ,under dosing, drug interactions increased ADP release and up regulation of P2Y12 independent pathway are other potential factors contributing to the clopidogrel treatment failure. • Antithrombin (AT) deficiency is the predominant factor influencing heparin resistance, however AT independent factors have been reported • Val29Leu, Ala41Ser, Arg58Gly, Val66Met, Leu128Arg, Val45Ala and the most recently discovered Asp36Tyr mutations within VKORC-1 gene complex are predominatly associated with inherited warfarin resistance while acquired resistance could be attributed to herbal, food and drug interactions . • Resistance to thrombolytic therapy could be attributed to structural changes of fibrin, elevated levels of PAI-1 and the development of antibodies particularly for streptokinase. • Dose escalation or the use of an alternative agent to the ineffective one is the recommended strategy to overcome the problem of resistance to the antithrombotic therapy. |