New, direct thrombin and factor Xa inhibitors have been developed to reduce the well-established drawbacks of currently available anticoagulants such as a protracted duration of action and high inter- and intra-individual variation of dose-effect. New anticoagulants are noninferior and no less effective for thromboprophylaxis than low-molecular-weight heparins or vitamin K antagonists. They are currently administered at fixed doses without control of their effect on the clotting system. Whether they need monitoring cannot be answered because relevant data are lacking and present means of monitoring are inadequate. The individual response to a standard dose of (any) anticoagulantthe modern direct inhibitors includedis highly variable (approximate to 30%), and the clinical effect of all anticoagulants is not dose independent. Therefore a fixed dose that is optimal for the average patient is suboptimal for a fair percentage of patients that are low responders (risk of re-thrombosis) and dangerous for an equally high percentage of high responders (risk of bleeding). A better understanding of individual differences in the response, either low or high, to anticoagulants, irrespective of their mode of action, should be a primary objective for pharmacotherapy over the next decade.
- thrombin generation