Conventional Anticoagulant Therapy
Conventional antithrombotic therapy is the mainstay of anticoagulant therapy that have been used for over 40 years in the treatment of thrombosis before newer agents become available. It includes unfractionated heparin, low-molecular-weight heparins (LMWHs) and vitamin K antagonists. Unfractionated heparin is a glucosaminoglycan which through binding to antithrombin accelerates thrombin inhibiton. It is administered parenterally and has an immediate start of action and a variable half-life related to the dose administered. Heparin causes prolongation of the aPTT which is the assay used to monitor its anticoagulant activity although lately anti-Xa activity assay has also been used for this purpose. The main adverse event of heparin treatment is haemorrhage. Other non-haemorrhagic serious adverse events are heparin-induced thrombocytopenia and osteoporosis. Heparin can be completely and rapidly reversed by the use of protamine sulphate. LMWHs are fragments of unfractionated heparin and act via the same mechanism. LMWHs have replaced unfractionated heparin in most indications of use because their pharmacokinetic properties allow them to be administered once or twice daily without need for routine monitoring of their anticoagulant activity. However, in situations such as renal failure, obesity and pregnancy, where clearance of the drug is altered, monitoring is required and the anti-Xa activity is the recommended test. LMWHs have the same adverse events as unfractionated heparin but to a lesser extend owing to decreased binding to platelets and osteoblasts. Protamine only partially reverses their anticoagulant effect. Vitamin K antagonists were the only orally administered anticoagulant agents until recently. They act through inhibition of the reduced form of vitamin K production which is necessary for anticoagulant factors II, VII, IX, X carboxylation and activation. Their many interactions with other drugs, foods and comorbid conditions render the stability of the anticoagulant response difficult and frequent monitoring is needed. The PT test is the most common test used to monitor VKA therapy and it is expressed as INR, a standardized ratio of patient PT to normal PT. The lower and higher INR values beyond which the incidence of adverse events increases is defined as the therapeutic range. For most indications of VKAs the therapeutic range of INR must be 2,0-3,0. The most serious adverse event of VKAs is bleeding, with the rate increasing as the INR rises >5. When reversal of anticoagulant effect is needed vitamin K is administered and in major bleeding vitamin K along with prothrombin complex concentrates (PCC) or FFP is recommended.
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