Warfarin monitoring and interference by lupus anticoagulant in patients with antiphospholipid syndrome.

INTRODUCTION: Patients with antiphospholipid syndrome (APS) receive vitamin K antagonists, which warrants international normalized ratio (INR) monitoring. Research has indicated that presence of lupus anticoagulant (LA) can interfere with INR results obtained by point-of-care testing (POCT) devices. We aimed to investigate whether a systematic difference exists between POCT-INR and plasma-INR in patients with APS. MATERIALS AND METHODS: We compared 291 paired POCT- and plasma-INR results from 52 LA-positive APS patients receiving warfarin with each patient having a minimum of three paired measurements of paired POCT-INR (CoaguChek, Roche Diagnostics) and plasma-INR. Agreement limits were considered satisfactory if differences were within ±0.4 INR for plasma-INR < 2.0, within ±20% for plasma-INR 2.0 to 3.5, within ±20% for plasma-INR > 3.5 to 4.5, within ±25% for plasma-INR > 4.5 to 6.0 and within ±30% for plasma-INR > 6.0. RESULTS: A strong positive correlation was found between POCT- and plasma-INR, Spearman's rho (95% CI) = 0.72 (0.65-0.78), p < 0.001. The average bias was 0.1 INR (3.7%), p < 0.001. 79% of paired INR results met the agreement limits with 67% of the diverging POCT-INRs being from a subset of five patients, who had consistently higher POCT- than plasma-INR. CONCLUSIONS: The majority of LA-positive APS patients had no clinically significant difference between POCT-INR and plasma-INR. However, in a subset of patients, clinically significant systematic differences were found. Consequently, systematic comparison of a minimum three paired POCT- and plasma-INR results is recommended before implementing POCT-INR monitoring in LA-positive APS patients.

International normalised ratio (INR) measured on the CoaguChek S and XS compared with the laboratory for determination of precision and accuracy.

Oral anticoagulation therapy is monitored by the use of international normalised ratio (INR). Patients performing self-management estimate INR using a coagulometer, but studies have been partly flawed regarding the estimated precision and accuracy. The objective was to estimate the imprecision and accuracy for two different coagulometers (CoaguChek S and XS). Twenty-four patients treated with coumarin were prospectively followed for six weeks. INR's were analyzed weekly in duplicates on both coagulometers, and compared with results from the hospital laboratory. Statistical analysis included Bland-Altman plot, 95% limits of agreement, coefficient of variance (CV), and an analysis of variance using a mixed effect model. Comparing 141 duplicate measurements (a total of 564 measurements) of INR, we found that the CoaguChek S and CoaguChek XS had a precision (CV) of 3.4% and 2.3%, respectively. Regarding analytical accuracy, the INR measurements tended to be lower on the coagulometers, and regarding diagnostic accuracy the CoaguChek S and CoaguChek XS deviated more than 15% from the laboratory measurements in 40% and 43% of the measurements, respectively. In conclusion, the precision of the coagulometers was found to be good, but only the CoaguChek XS had a precision within the predefined limit of 3%. Regarding analytical accuracy, the INR measurements tended to be lower on the coagulometers, compared to the laboratory. A large proportion of measurement of the coagulometers deviated more than 15% from the laboratory measurements. Whether this will have a clinical impact awaits further studies.

Quality of oral anticoagulant therapy in patients who perform self management: warfarin versus phenprocoumon.

BACKGROUND: The quality of oral anticoagulant therapy may be related to which type of coumarin is used. The aim was to investigate whether phenprocoumon or warfarin provide the highest quality of oral anticoagulant therapy in patients who manage the therapy themselves. METHODS AND RESULTS: In a cohort study 519 patients on self managed oral anticoagulant therapy were included. Quality control parameters, were, the percentage of time spent in the therapeutic range and the variability in the patients' INR values. Time within therapeutic INR target range in the patient group treated respectively with warfarin and phenprocoumon was 70.2% and 74.0% (P = 0.008).The median variance in the warfarin group was 0.35 (95% CI (0.32-0.38)) and 0.29 (95% CI (0.25-0.33)) in the phenprocoumon group (P = 0.0004). CONCLUSION: Phenprocoumon provides a higher percentage of time spent in therapeutic INR interval and a lower variation of INR-values compared with warfarin.

Self- versus conventional management of oral anticoagulant therapy: effects on INR variability and coumarin dose in a randomized controlled trial.

BACKGROUND: Comparison of self-management of oral anticoagulant therapy versus conventional management has been hindered by use of different methods. We tested the hypothesis that there is no difference in the International Normalized Ratio (INR) variability, INR level, and coumarin dose among patients randomized to conventional management versus self-management. METHODS: The study design included uniform analysis of blinded control blood samples in both treatment arms. Ninety-two patients were randomly assigned to either self-management of oral anticoagulant therapy (including a teaching program for self-management followed by 6 months of independent self-management) or 6 months of conventional management. The endpoints were the variance (median square of the standard deviation) of the INR value, the median INR-value (using a blinded control sample analyzed monthly by a reference laboratory), and the coumarin dose. RESULTS: Self-management was associated with a statistically significant smaller variance in INR values, a higher median INR value, and a higher dose of warfarin compared with conventional management. No difference was found in the group of patients using phenprocoumon. CONCLUSION: Training and implementation of patient self-management leads to a smaller variance in INR values, a higher median INR value and a higher dose of coumarin compared with results obtained for conventionally managed patients.

Self-management versus conventional management of oral anticoagulant therapy: A randomized, controlled trial.

BACKGROUND: The efficacy of self-managed oral anticoagulant therapy has been addressed in few randomized, controlled trials, which have provided inconsistent results. The aim of this study was to compare the quality of self-managed oral anticoagulant therapy with conventional management. METHODS: This was a pragmatic, open-label, randomized, controlled trial where 100 patients receiving long-term oral anticoagulant therapy referred to a Danish clinic for self-management was randomized to either self-management of oral anticoagulant therapy (including a teaching program of self-management followed by 6 months of self-management) or 6 months of conventional management. The primary endpoint was an intention-to-treat analysis of a composite score combining the variance (median square of the standard deviation) of the International Normalized Ratio (INR) value (using a blinded control sample analyzed monthly by a reference laboratory), death, major complications, or discontinuation from the study. Secondary endpoints - assessed in per-protocol analyses - were the variance of the INR value (using the blinded control sample) and time within therapeutic INR target range using the standard INR values from the coagulometer and laboratory measurement. RESULTS: There was no significant difference in the primary endpoint between the self-management and conventional management groups (composite score 0.16 vs. 0.24, respectively, p=0.09). Self-management was significantly better (0.16 vs. 0.24, p=0.003) with regard to the variance in a per-protocol analysis. The difference in time within therapeutic INR target range was not significantly better (78.7% vs. 68.9%, p=0.14) using self-management. CONCLUSION: The quality of self-management of oral anticoagulant therapy is at least as good as that provided by conventional management.

Self-Management of Anticoagulant Therapy in Mechanical Heart Valve Patients: A Matched Cohort Study.

BACKGROUND: Patient-self-management (PSM) of oral anticoagulant therapy with vitamin K antagonists for mechanical heart valves has demonstrated efficacy in randomized controlled trials. However, the effectiveness of PSM in clinical practice has only been investigated in small trials. Our aim was to evaluate the effectiveness of PSM of oral anticoagulant therapy in mechanical heart valve patients. METHODS: We conducted a matched cohort study: cases were patients with a mechanical heart valve performing PSM affiliated with Aarhus University Hospital or Aalborg University Hospital, Denmark, in the period 1996 to 2012 (n = 615). Prospectively registered patient data were obtained from databases at two hospitals, and cross linkage between these databases and national patient registries provided detailed information on comorbidities and events. Control patients were matched (on sex, date of birth, year of first valve surgery, and grouped valve position) in a ratio of 5:1 (n = 3,075) with patients receiving conventional management who were randomly selected within the match group. The effectiveness and safety was estimated using major bleeding and thromboembolic events and death as outcomes. RESULTS: We observed low event rates in the PSM group. After 5 years, PSM was associated with a lower risk of all-cause mortality compared with conventional management (adjusted hazard ratio of 0.49, 95% confidence interval: 0.34 to 0.71). The hazard ratios for thromboembolism and major bleeding were 0.91 (95% confidence interval: 0.66 to 1.24) and 0.83 (95% confidence interval: 0.56 to 1.22). CONCLUSIONS: Owing to superior clinical effectiveness, self-managed oral anticoagulant therapy may potentially improve the standard of care for patients with mechanical heart valves.

Patient-specific errors in agreement between International Normalized Ratios measured by a whole blood coagulometer and by a routine plasma-based method.

We applied a new statistical method to improve comparisons between systems measuring prothrombin time (PT) by splitting disagreement into systematic errors, which can be eliminated, and random errors, which can not. We found that the disagreement between International Normalized Ratio (INR) measurements based on plasma and whole blood was significantly patient-dependent.

Precision of INR measured with a patient operated whole blood coagulometer.

INTRODUCTION: The objective of the present study was to evaluate the precision of a portable whole blood coagulometer (CoaguChek S) in the hands of self-managing patients on oral anticoagulant therapy (OAT). MATERIALS AND METHODS: Fifteen patients on self-managed OAT performed measurements of INR by two types of portable whole blood coagulometers (CoaguChek and CoaguChek S) at home for 10 weeks. RESULTS: The coefficient of variation (CV) of INRs determined at home by CoaguChek S by patients on self-managed OAT was 5.5% (95% confidence limits: 4.9%, 6.1%). The biological CV of INR within and between patients was 15.0% and 14.7%, respectively. CONCLUSION: The precision of CoaguChek S is satisfactory.

Mechanical heart valve patients can manage oral anticoagulant therapy themselves.

OBJECTIVES: Thromboembolism and anticoagulant related bleeding are still the most common complications in mechanical heart valve patients. Management of the oral anticoagulant therapy is therefore a key determinant for these clinical complications. We hypothesize that patients selected to self-managed oral anticoagulant therapy have a better treatment quality than patients in conventional oral anticoagulant therapy. The aim of this study was to assess the time within the therapeutic International Normalized Ratio (INR) target range and the incidence of clinical complications in our group of patients, and compare these data with published data on conventional management. METHODS: Mechanical heart valve patients (N=94) with a mean age of 47.6 years (range 4.2-76.6 years) were trained in home blood analysis of INR using a CoaguChek home coagulometer and coumarin dosage adjustment. After training, the patients were followed by weekly INR measurements. The therapeutic range was a target INR +/-0.5. The indications for initiating oral anticoagulant therapy were: aortic valve (N=62), mitral valve (N=29), tricuspid valve (N=1) and multiple valves (N=2). RESULTS: The mean observation time was 2.1 years (range 0.04-6.2 years), and the total number of patient-years was 197. The patients were within the therapeutic INR target range for a median of 76.0% (range 32.1-100.0%) of the time. There were two major thromboembolic events and five major bleedings events, comprised of two deep vein thromboses (both in the same patient), four episodes of epistaxis and one case of gastrointestinal bleeding. All the events required short hospitalization, and after treatment all the patients were discharged from the hospital without any sequelae or other complications. Using published work as references the expected number of major thromboembolic and bleeding complications in conventional management was four and 12, respectively. CONCLUSIONS: Self-management of oral anticoagulant therapy provides a good treatment quality for mechanical heart valve patients. We therefore consider self-management of oral anticoagulant therapy as an equally as good or potentially better treatment option for selected patients compared to conventional management.

Oral anticoagulation therapy in children: successfully controlled by self-management.

BACKGROUND: Children with congenital heart disease and who are on oral anticoagulation therapy present special challenges due to, for example, rapid fluctuations in international normalized ratio (INR) values, interruption in daily life due to frequent hospital/doctor visits, and difficulties and pain to the child in the performance of venipuncture. We hypothesize that oral anticoagulation therapy can be successfully controlled by self-management for this subset of patients. The aim of this study was to assess the treatment quality of self-managed oral anticoagulation therapy as the proportion of time within the therapeutic INR target range in children with congenital heart disease. METHODS: Children (N = 22) with a mean age of 10.6 years (range, 1.8-18.6 years) and their parents were trained in home blood analysis of INR and in coumarin dosage adjustment. After training, the children were monitored by weekly INR measurements. The therapeutic range in target INR values was +/-0.5. The indications for initiating oral anticoagulation therapy were the presence of a mechanical heart valve (n = 16) and total cavopulmonary connection (n = 6). The children had no physical restrictions. RESULTS: The mean observation time was 3.6 years (range, 0.9-5.8 years), and the total number of patient-years was 75.4. The patients were within the therapeutic INR target range for a median of 73.1% (range, 30.3%-91.0%) of the observation time. Two children died for reasons not related to the oral anticoagulation therapy. None of the patients experienced thromboembolic or bleeding complications requiring doctor intervention. CONCLUSION: Self-management of oral anticoagulation therapy is safe and provides a good quality of treatment for selected children with congenital heart disease.

[Self-management of oral anticoagulant therapy in children with congenital heart defects]. / Selvstyring af peroral antikoagulationsbehandling hos børn med medfødte hjertesygdomme.

INTRODUCTION: Self-management of oral anticoagulation has been shown to produce a better quality of treatment than conventional management when assessed in selected adults. We have extended the concept of self-management to include children with congenital cardiac disease on the hypothesis that it is also possible in this subset of patients. Our aim was to assess the quality of self-management in children with congenital cardiac disease. MATERIAL AND METHODS: We trained 14 children aged from 2.2 to 15.6 years, with a mean age of 9.7 years, and their parents, in domiciliary analysis of the international normalised ratio (INR) and the necessary dose adjustment of the oral anticoagulant therapy. The curriculum for training covered 27 weeks, and the patients and their parents were followed up for a period of up to 31 months by weekly measurement of the INR values obtained. RESULTS: The patients were observed over a mean of 547 days (range: 214-953 days). They were within the therapeutic targeted range of the INR for a median of 65.5% of the time (range: 17.6-90.4%. None of the patients experienced thromboembolic or bleeding complications requiring doctoral intervention. All the patients and their parents expressed full satisfaction with the treatment. DISCUSSION: Self-management of oral anticoagulation provides a good quality of treatment and is safe and feasible in selected children with congenital cardiac disease.

Sex differences in treatment quality of self-managed oral anticoagulant therapy: 6,900 patient-years of follow-up.

BACKGROUND: Patient-self-management (PSM) of oral anticoagulant therapy with vitamin K antagonists has demonstrated efficacy in randomized, controlled trials. However, the effectiveness and efficacy of PSM in clinical practice and whether outcomes are different for females and males has been sparsely investigated.The objective is to evaluate the sex-dependent effectiveness of PSM of oral anticoagulant therapy in everyday clinical practice. METHODS: All patients performing PSM affiliated to Aarhus University Hospital and Aalborg University Hospital, Denmark in the period 1996-2012 were included in a case-series study. The effectiveness was estimated using the following parameters: stroke, systemic embolism, major bleeding, intracranial bleeding, gastrointestinal bleeding, death and time spent in the therapeutic international normalized ratio (INR) target range. Prospectively registered patient data were obtained from two databases in the two hospitals. Cross-linkage between the databases and national registries provided detailed information on the incidence of death, bleeding and thromboembolism on an individual level. RESULTS: A total of 2068 patients were included, representing 6,900 patient-years in total. Males achieved a significantly better therapeutic INR control than females; females spent 71.1% of the time within therapeutic INR target range, whereas males spent 76.4% (p<0.0001). Importantly, death, bleeding and thromboembolism were not significantly different between females and males. CONCLUSIONS: Among patients treated with self-managed oral anticoagulant therapy, males achieve a higher effectiveness than females in terms of time spent in therapeutic INR range, but the incidence of major complications is low and similar in both sexes.

[Self-management versus conventional management of oral anticoagulant therapy: a randomized controlled trial]. / Selvstyret versus konventionel oral antikoagulansbehandling: et randomiseret studie - sekundaerpublikation.

The efficacy of self-managed oral anticoagulant therapy has been addressed in few randomized controlled trials, which have provided inconsistent results. The aim of this study was to compare the quality of self-managed oral anticoagulant therapy with conventional management. One hundred patients were randomly assigned to the two treatment regimens, and it was found that the quality of self-management of oral anticoagulant therapy was at least as good as the treatment provided by conventional management. Self-management is therefore a valid management option in selected patients.