Self-management of oral anticoagulation therapy--methodological and clinical aspects

Abstract

Oral anticoagulation therapy (OAT) with coumarins (vitamin K-antagonists) is prescribed for both prophylactic and therapeutic use to patients at increased risk of thromboembolism. OAT has a narrow therapeutic index, and monitoring is based on the International Normalized Ratio (INR) conventionally determined on citrated plasma obtained by venepuncture. Based on the INR measurements, health care providers determine the appropriate dose of coumarins (e.g. warfarin (Marevan). Optimised management of OAT improves the quality of treatment. Patient self-management (PSM) is a new concept where the patient takes an active part in his or her own treatment. PSM in OAT implies that the patient analyses a drop of blood using a portable coagulometer (INR-monitor). The coagulometer displays the INR, which the patient uses for coumarins dosage. It is still not clarified which subset of patients (in terms of indication for OAT, age, co-morbidity etc.) that potentially will benefit from PSM, and how large this potential effect is. A precondition for a correct dosage of coumarins is a correct estimation of the INR, and the method and apparatus used for providing the INR measurements is in this context essential. The coagulometers used for PSM have not been investigated adequately in terms of precision and agreement, so this is warranted. INR has proven adequate for adjusting dosages. It is doubtful that the level of INR reflects the overall haemostatic capacity or thrombotic potential of individual patients. Measurement of continuous calibrated automated thrombin generation (CAT) and coagulation factors activities may serve as a more sensitive and global haemostatic parameter and potentially with better performance in predicting risk of complications in patients on OAT. We found that the clotting activity of coagulation factors II, VII, IX, and X and CAT exhibited no variability over a 6-week period. The activity of the coagulation factors and CAT was significantly associated with the INR, so these two tests can be used concomitantly and/or interchangeably with the INR. Approximately 50% of the total variability of the coagulation factor activities and CAT was reflected by the INR, whereas the remaining variability was within the subject (patient). Coagulation factor activities and CAT can therefore potentially be used to provide further information to the risk of bleeding and thromboembolism, since almost 50% of the variability within the subject is not displayed in the INR value. Yet it remains uncertain if this method can predict complications in individual patients on OAT. Larger clinical trials with a longer follow-up period, preferably using clinical endpoints, are needed in order to draw any firm conclusions regarding the clinical consequences. However, measurement of coagulation factor activities and CAT may improve measurement of coagulation activity in patients prescribed OAT beyond the parameters currently clinically available. The CoaguChek S and XS coagulometers used for PSM were found to have an adequate precision. Regarding the accuracy, the INR measurements tended to be lower on the coagulometers, compared with the laboratory. A large proportion of the measurements on the coagulometers deviated more than 15% from the laboratory measurements. However, only one laboratory was used for comparison and the original WHO method (gold standard) for estimating INR was not used. Furthermore, the inherent limitations of the INR have to be taken into consideration, and the results have to be viewed in this context. The accuracy of the coagulometers seems in this respect acceptable and they can be used in a clinical setting. However, external quality control is essential. In the observational studies, it was found that PSM was feasible and provides satisfactory treatment quality for various indications and in a wide range of patient age. In a randomised controlled trial, using a documented blinded composite endpoint, PSM was found to provide a treatment quality that was at least as good as that provided by conventional management. Additionally it was found, that training and implementation of PSM lead to a smaller variance in INR measurements, a higher median INR and a higher dose of coumarins compared to that obtained for conventionally managed patients. Further evidence was provided in a systematic review and meta-analysis, where it was documented, that PSM appears at least as good as and possibly better than conventional management in highly selected patients.