Overanticoagulation on coumarin anticoagulants

Most of the extensive research on oral anticoagulant therapy has focussed on its pharmacological- and biochemical action, prothrombin time calibration, optimal therapeutic intensity and hemorrhagic complications. However, whlle the risks of overanticoagulation are clear, its treatment and determinants have received little attention. Therefore, the aim of this thesis was to study aspects of overanticoagulation on coumarin anticoagulants among outpatients of an anticoagulation clinic. Overanticoagulation was defined as an INR:>6.0, since at this INR-value the risk of hemorrhage sharply increases (28, 41). Chapter 2 relates to the treatment of overanticoagulation and describes the course of the INR in response to oral vitamin K1 in overanticoagulated patients. Chapter 3 concerns the incidence of and risk factors for overanticoagulation and includes five studies. Chapter 3.1 focusses on characteristics of anticoagulant therapy and comorbidlty associated with overanticoagulation, chapters 3.2 and 3.3 on drug interactions as a cause of overanticoagulation, and chapters 3.4 and 3.5 on lifestyle and diet as risk factors for overanticoagulation. The levels of the vitamin K-dependent pro- and anticoagulant proteins in overanticoagulated patients are evaluated in chapter 4. In chapter 5, several measures of the quality of oral anticoagulant therapy, among which the occurrence of overanticoagulation are compared between phenprocoumon and acenocoumarol. Finally, in chapter 6 the main findings are presented, methodological issues and implications for oral anticoagulant therapy are discussed. and recommendations for future resecuch cue given.

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