Prediction of the international normalized ratio and maintenance dose during the initiation of warfarin therapy.

AIMS: A pharmacokinetic/pharmacodynamic model, with Bayesian parameter estimation, was used to retrospectively predict the daily International Normalized Ratios (INRs) and the maintenance doses during the initiation of warfarin therapy in 74 inpatients. METHODS: INRs and maintenance doses predicted by the model were compared with the actual INRs and the eventual maintenance dose. Cases with drugs or medical conditions interacting with warfarin or receiving concurrent heparin therapy were not excluded. As the study was retrospective, model predictions of the maintenance dose were not those that were administered. Mean prediction error (MPE) and percentage absolute prediction errors (PAPE) were used to assess the model predictions. RESULTS: INR MPE ranged from -0.07 to 0.06 and median PAPE from 10% to 20%. Dose MPE ranged from -0.7 to 0.17 mg and median PAPE from 16.7% to 37.5%. Accurate and precise dose predictions were obtained after 3 or more INR feedback's. CONCLUSIONS: This study shows that the model can accurately predict daily INRs and the maintenance dose in this sample of cases. The model can be incorporated into computer decision-support systems for warfarin therapy and may lead to improvement in the initiation of warfarin therapy.

Comparison of oral anticoagulant control by a nurse-practitioner using a computer decision-support system with that by clinicians.

With increasing work-loads in anticoagulant clinics different methods of service delivery need evaluation. The quality of anticoagulant control achieved by a nurse-practitioner using a computer decision-support system (CDSS) was compared with that achieved by trainee doctors without CDSS. Eighty-one out-patients (group A, therapeutic range 2-3) and 96 out-patients (group B, therapeutic range 3-4.5) were randomized to management by a nurse-practitioner or by trainee doctors (clinicians). Thirty-seven patients in group A and 50 patients in group B were randomized to be managed by the nurse-practitioner. In group A, patients in the nurse-practitioner group spent a longer time in the therapeutic range than those in the clinician group (60.7% compared with 51.6%). Dose suggestion acceptance in the nurse-practitioner group (88%) was higher compared with agreement between the CDSS and the clinicians (60%). In group B, patients in the clinician group spent a slightly longer time in the therapeutic range (70% compared with 67.6%). Acceptance of dose suggestion was lower in the nurse-practitioner group (67%) compared with agreement between the CDSS and the clinicians (73%). In conclusion, the CDSS can improve the quality of control of warfarin therapy by a nurse-practitioner over that by trainee doctors for the therapeutic range 2-3. Similar quality of control is achieved for the therapeutic range 3-4.5. The CDSS may be used by nurse-practitioners to achieve safe and effective anticoagulation in hospital-based or out-reach anticoagulant clinics.

Evaluation of a decision support system for initiation and control of oral anticoagulation in a randomised trial.

OBJECTIVE: To determine whether a computerised decision support system for initiation and control of oral anticoagulant treatment improves quality of anticoagulant control achieved by trainee doctors. DESIGN: Randomised controlled trial. SETTING: District general hospital in North London. SUBJECTS: 148 inpatients requiring start of warfarin treatment. INTERVENTIONS: Management by trainee doctors (to achieve therapeutic range of international normalised ratio of 2 to 3) with indirect assistance from computerised decision support system (intervention group) or without such assistance (control group). MAIN OUTCOME MEASURES: Median time to therapeutic range, stable dose, and first pseudoevent (excessive international normalised ratio after therapeutic range has been reached) and person time spent in the therapeutic range. RESULTS: 72 patients were randomised to the intervention group and 76 to control group. Median time to reach international normalised ratio of > or = 2 was not significantly different in the two groups (3 days). Median time to achieve a stable dose was significantly lower in intervention group than in controls (7 days v 9 days, P = 0.01) without excessive overtreatment or undertreatment with anticoagulant. Patients in intervention group spent greater proportion of time in therapeutic range, both as inpatients (59% v 52%) and outpatients (64% v 51%). CONCLUSION: The computerised decision support system was safe and effective and improved the quality of initiation and control of warfarin treatment by trainee doctors.

Validation of an algorithm for oral anticoagulant dosing and appointment scheduling.

Computer clinical decision-support systems require validation before clinical use. This study compared recommendations on warfarin dosage adjustment and timing of the next appointment made by an algorithm with those made by experienced and inexperienced clinicians. Data abstracted from the records of 125 patients seen regularly in the anticoagulant clinic were used. The algorithm recommended dose changes and next appointment for cases with INRs between 1.8 to 4.2 (therapeutic range 2.0-3.0) and between 2.3 to 5.3 (therapeutic range 3.0-4.5). Beyond these values the algorithm referred the cases to "see doctor'. Compared to experienced clinicians, the algorithm was better at "recognising' difficult patients than inexperienced clinicians (kappa = 0.43 and 0.32 respectively). There was no statistically significant difference between all decision makers in dosage recommendations for the non-difficult cases, but there was much more variation amongst the inexperienced clinicians. The interval recommendations were statistically different between and within the different decision-makers. The inexperienced clinicians tended to give relatively longer intervals for a given dose change. In conclusion, the algorithm performs better than inexperienced clinicians and as well as experienced clinicians for the non-difficult cases.

Life-threatening thrombotic and haemorrhagic problems associated with silent myeloproliferative disorders.

Myeloproliferative disorders are well recognized as being associated with haemorrhage and thrombosis. We describe two cases, one of life-threatening haemorrhage and the other of thrombosis, in patients with normal peripheral blood counts and films, both of whom went on to develop overt manifestations of myeloproliferative disorders (CGL and essential thrombocythaemia) more than a year after their first presentation.