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Background

Point-of-care devices (POCDs) for monitoring long-term oral anticoagulation therapy (OAT) may be a useful alternative to laboratory-based international normalized ratio [INR] testing and clinical management.

Purpose

To determine clinical outcomes of the use of POCDs for OAT management by performing a meta-analysis. Previous meta-analyses on POCDs have serious limitations.

Data sources

PubMed, the Cochrane Library, DIALOG, MEDLINE, EMBASE, BIOSIS Previews and PASCAL databases.

Study selection

Randomized controlled trials of patients on long-term OAT, comparing anticoagulation monitoring by POCD with laboratory INR testing and clinical management.

Data extraction

1) rates of major hemorrhage; 2) rates of major thromboembolic events; 3) percentage of time that the patient is maintained within the therapeutic range; 4) deaths. Outcomes were compared using a random-effects model. Summary measures of rates were determined. The quality of studies was assessed using the Jadad scale.

Data synthesis

Seventeen articles (16 studies) were included. Data analysis showed that POCD INR testing reduced the risk of major thromboembolic events (odds ratio [OR] = 0.51; 95% confidence interval [CI] 0.35–0.74), was associated with fewer deaths (OR = 0.58; 95% CI = 0.38–0.89), and resulted in better INR control compared with laboratory INR testing. No significant difference between the two management modalities with respect to odds ratios for major hemorrhage was found.

Limitations

Quality scores varied from 1 to 3 (out of a maximum of 5). Only 3 studies defined how thromboembolic events would be diagnosed, casting doubt on the accuracy of the reporting of thromboembolic events. The studies suggest that only 24% of patients are good candidates for self-testing and self-management. Compared with patients managed with laboratory-based monitoring, POCD patients underwent INR testing at a much higher frequency and received much more intensive education on OAT management.

Conclusions

The use of POCDs is safe and may be more effective than laboratory-based monitoring. However, most patients are not good candidates for self-testing and self-management. Patient education and frequency of testing may be the most important factors in successful PODC management. Definitive conclusions about the clinical benefits provided by self-testing and self-management require more rigorously designed trials.

Executive Summary

Subject of the Evidence-Based Analysis

The purpose of this evidence based analysis report is to examine the safety and effectiveness of point-of-care (POC) international normalized ratio (INR) monitoring devices for patients on long-term oral anticoagulation therapy (OAT).

Clinical Need: Target Population and Condition

Long-term OAT is typically required by patients with mechanical heart valves, chronic atrial fibrillation, venous thromboembolism, myocardial infarction, stroke, and/or peripheral arterial occlusion. It is estimated that approximately 1% of the population receives anticoagulation treatment and, by applying this value to Ontario, there are an estimated 132,000 patients on OAT in the province, a figure that is expected to increase with the aging population.

Patients on OAT are regularly monitored and their medications adjusted to ensure that their INR scores remain in the therapeutic range. This can be challenging due to the narrow therapeutic window of warfarin and variation in individual responses. Optimal INR scores depend on the underlying indication for treatment and patient level characteristics, but for most patients the therapeutic range is an INR score of between 2.0 and 3.0.

The current standard of care in Ontario for patients on long-term OAT is laboratory-based INR determination with management carried out by primary care physicians or anticoagulation clinics (ACCs). Patients also regularly visit a hospital or community-based facility to provide a venous blood samples (venipuncture) that are then sent to a laboratory for INR analysis.

Experts, however, have commented that there may be under-utilization of OAT due to patient factors, physician factors, or regional practice variations and that sub-optimal patient management may also occur. There is currently no population-based Ontario data to permit the assessment of patient care, but recent systematic reviews have estimated that less that 50% of patients receive OAT on a routine basis and that patients are in the therapeutic range only 64% of the time.

Overview of POC INR Devices

POC INR devices offer an alternative to laboratory-based testing and venipuncture, enabling INR determination from a fingerstick sample of whole blood. Independent evaluations have shown POC devices to have an acceptable level of precision. They permit INR results to be determined immediately, allowing for more rapid medication adjustments.

POC devices can be used in a variety of settings including physician offices, ACCs, long-term care facilities, pharmacies, or by the patients themselves through self-testing (PST) or self-management (PSM) techniques. With PST, patients measure their INR values and then contact their physician for instructions on dose adjustment, whereas with PSM, patients adjust the medication themselves based on pre-set algorithms. These models are not suitable for all patients and require the identification and education of suitable candidates.

Potential advantages of POC devices include improved convenience to patients, better treatment compliance and satisfaction, more frequent monitoring and fewer thromboembolic and hemorrhagic complications. Potential disadvantages of the device include the tendency to underestimate high INR values and overestimate low INR values, low thromboplastin sensitivity, inability to calculate a mean normal PT, and errors in INR determination in patients with antiphospholipid antibodies with certain instruments. Although treatment satisfaction and quality of life (QoL) may improve with POC INR monitoring, some patients may experience increased anxiety or preoccupation with their disease with these strategies.

Evidence-Based Analysis Methods

Research Questions

1. Effectiveness

Does POC INR monitoring improve clinical outcomes in various settings compared to standard laboratory-based testing?

Does POC INR monitoring impact patient satisfaction, QoL, compliance, acceptability, convenience compared to standard laboratory-based INR determination?

Settings include primary care settings with use of POC INR devices by general practitioners or nurses, ACCs, pharmacies, long-term care homes, and use by the patient either for PST or PSM.

2. Cost-effectiveness

What is the cost-effectiveness of POC INR monitoring devices in various settings compared to standard laboratory-based INR determination?

Inclusion Criteria

English-language RCTs, systematic reviews, and meta-analyses

Publication dates: 1996 to November 25, 2008

Population: patients on OAT

Intervention: anticoagulation monitoring by POC INR device in any setting including anticoagulation clinic, primary care (general practitioner or nurse), pharmacy, long-term care facility, PST, PSM or any other POC INR strategy

Minimum sample size: 50 patients Minimum follow-up period: 3 months

Comparator: usual care defined as venipuncture blood draw for an INR laboratory test and management provided by an ACC or individual practitioner

Outcomes: Hemorrhagic events, thromboembolic events, all-cause mortality, anticoagulation control as assessed by proportion of time or values in the therapeutic range, patient reported outcomes including satisfaction, QoL, compliance, acceptability, convenience

Exclusion criteria

Non-RCTs, before-after studies, quasi-experimental studies, observational studies, case reports, case series, editorials, letters, non-systematic reviews, conference proceedings, abstracts, non-English articles, duplicate publications

Studies where POC INR devices were compared to laboratory testing to assess test accuracy

Studies where the POC INR results were not used to guide patient management

Method of Review

A search of electronic databases (OVID MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library, and the International Agency for Health Technology Assessment [INAHTA] database) was undertaken to identify evidence published from January 1, 1998 to November 25, 2008. Studies meeting the inclusion criteria were selected from the search results. Reference lists of selected articles were also checked for relevant studies.

Summary of Findings

Five existing reviews and 22 articles describing 17 unique RCTs met the inclusion criteria. Three RCTs examined POC INR monitoring devices with PST strategies, 11 RCTs examined PSM strategies, one RCT included both PST and PSM strategies and two RCTs examined the use of POC INR monitoring devices by health care professionals.

Anticoagulation Control

Anticoagulation control is measured by the percentage of time INR is within the therapeutic range or by the percentage of INR values in the therapeutic range. Due to the differing methodologies and reporting structures used, it was deemed inappropriate to combine the data and estimate whether the difference between groups would be significant. Instead, the results of individual studies were weighted by the number of person-years of observation and then pooled to calculate a summary measure.

Across most studies, patients in the intervention groups tended to have a higher percentage of time and values in the therapeutic target range in comparison to control patients. When the percentage of time in the therapeutic range was pooled across studies and weighted by the number of person-years of observation, the difference between the intervention and control groups was 4.2% for PSM, 7.2% for PST and 6.1% for POC use by health care practitioners. Overall, intervention patients were in the target range 69% of the time and control patients were in the therapeutic target range 64% of the time leading to an overall difference between groups of roughly 5%.

Major Complications and Deaths

There was no statistically significant difference in the number of major hemorrhagic events between patients managed with POC INR monitoring devices and patients managed with standard laboratory testing (OR =0.74; 95% CI: 0.52- 1.04). This difference was non-significant for all POC strategies (PSM, PST, health care practitioner).

Patients managed with POC INR monitoring devices had significantly fewer thromboembolic events than usual care patients (OR =0.52; 95% CI: 0.37 - 0.74). When divided by POC strategy, PSM resulted in significantly fewer thromboembolic events than usual care (OR =0.46.; 95% CI: 0.29 - 0.72). The observed difference in thromboembolic events for PSM remained significant when the analysis was limited to major thromboembolic events (OR =0.40; 95% CI: 0.17 - 0.93), but was non-significant when the analysis was limited to minor thromboembolic events (OR =0.73; 95% CI: 0.08 - 7.01). PST and GP/Nurse strategies did not result in significant differences in thromboembolic events, however there were only a limited number of studies examining these interventions.

No statistically significant difference was observed in the number of deaths between POC intervention and usual care control groups (OR =0.67; 95% CI: 0.41 - 1.10). This difference was non-significant for all POC strategies. Only one study reported on survival with 10-year survival rate of 76.1% in the usual care control group compared to 84.5% in the PSM group (P=0.05).

Summary Results of Meta-Analyses of Major Complications and Deaths in POC INR Monitoring Studies

Patient Satisfaction and Quality of Life

Quality of life measures were reported in eight studies comparing POC INR monitoring to standard laboratory testing using a variety of measurement tools. It was thus not possible to calculate a quantitative summary measure. The majority of studies reported favourable impacts of POC INR monitoring on QoL and found better treatment satisfaction with POC monitoring. Results from a pre-analysis patient and caregiver focus group conducted in Ontario also indicated improved patient QoL with POC monitoring.

Quality of the Evidence

Studies varied with regard to patient eligibility, baseline patient characteristics, follow-up duration, and withdrawal rates. Differential drop-out rates were observed such that the POC intervention groups tended to have a larger number of patients who withdrew. There was a lack of consistency in the definitions and reporting for OAT control and definitions of adverse events. In most studies, the intervention group received more education on the use of warfarin and performed more frequent INR testing, which may have overestimated the effect of the POC intervention. Patient selection and eligibility criteria were not always fully described and it is likely that the majority of the PST/PSM trials included a highly motivated patient population. Lastly, a large number of trials were also sponsored by industry.

Despite the observed heterogeneity among studies, there was a general consensus in findings that POC INR monitoring devices have beneficial impacts on the risk of thromboembolic events, anticoagulation control and patient satisfaction and QoL (ES Table 2).

GRADE Quality of the Evidence on POC INR Monitoring Studies

CI refers to confidence interval; Interv, intervention; OR, odds ratio; RCT, randomized controlled trial.

Economic Analysis

Using a 5-year Markov model, the health and economic outcomes associated with four different anticoagulation management approaches were evaluated:

Standard care: consisting of a laboratory test with a venipuncture blood draw for an INR;

Healthcare staff testing: consisting of a test with a POC INR device in a medical clinic comprised of healthcare staff such as pharmacists, nurses, and physicians following protocol to manage OAT;

PST: patient self-testing using a POC INR device and phoning in results to an ACC or family physician; and

PSM: patient self-managing using a POC INR device and self-adjustment of OAT according to a standardized protocol. Patients may also phone in to a medical office for guidance.

The primary analytic perspective was that of the MOHLTC. Only direct medical costs were considered and the time horizon of the model was five years - the serviceable life of a POC device.

From the results of the economic analysis, it was found that POC strategies are cost-effective compared to traditional INR laboratory testing. In particular, the healthcare staff testing strategy can derive potential cost savings from the use of one device for multiple patients. The PSM strategy, however, seems to be the most cost-effective method i.e. patients are more inclined to adjust their INRs more readily (as opposed to allowing INRs to fall out of range).

Considerations for Ontario Health System

Although the use of POC devices continues to diffuse throughout Ontario, not all OAT patients are suitable or have the ability to practice PST/PSM. The use of POC is currently concentrated at the institutional setting, including hospitals, ACCs, long-term care facilities, physician offices and pharmacies, and is much less commonly used at the patient level. It is, however, estimated that 24% of OAT patients (representing approximately 32,000 patients in Ontario), would be suitable candidates for PST/PSM strategies and willing to use a POC device.

There are several barriers to the use and implementation of POC INR monitoring devices, including factors such as lack of physician familiarity with the devices, resistance to changing established laboratory-based methods, lack of an approach for identifying suitable patients and inadequate resources for effective patient education and training. Issues of cost and insufficient reimbursement strategies may also hinder implementation and effective quality assurance programs would need to be developed to ensure that INR measurements are accurate and precise.

Conclusions

For a select group of patients who are highly motivated and trained, PSM resulted in significantly fewer thromboembolic events compared to conventional laboratory-based INR testing. No significant differences were observed for major hemorrhages or all-cause mortality. PST and GP/Nurse use of POC strategies are just as effective as conventional laboratory-based INR testing for thromboembolic events, major hemorrhages, and all-cause mortality. POC strategies may also result in better OAT control as measured by the proportion of time INR is in the therapeutic range and there appears to be beneficial impacts on patient satisfaction and QoL. The use of POC devices should factor in patient suitability, patient education and training, health system constraints, and affordability.

Keywords

anticoagulants, International Normalized Ratio, point-of-care, self-monitoring, warfarin.

Abstract

Intracerebral haemorrhage (ICH) is the deadliest form of stroke, carrying a mortality rate between 30% and 55%, increasing to 67% in patients on oral anticoagulant therapy (OAT). Despite its relevant incidence, the treatment of ICH has been until recently a largely neglected item, addressed by only a few trials. Early treatment of ICH in non-anticoagulated patients with recombinant activated factor VII (rFVII) has been demonstrated to be able to limit the growth of the haematoma, but such a promising result requires further confirmations. In ICH patients receiving OAT a prompt reversal of the anticoagulant effect should be warranted in order to reduce the consequences of this dreadful adverse event. In clinical practice, however, just a small proportion of anticoagulated patients receive this treatment, probably because of the fear of thromboembolic complications. It is now time to check our way of thinking about ICH, regarding and treating it as a compelling medical emergency.

Background:

Oral anticoagulant therapy (OAT) is used to prevent/treat thromboembolism. Major bleeding is common in patients on OAT; eg, warfarin increases intracranial hemorrhage (ICH) risk.

Case:

A 71-year-old male on warfarin (to reduce stroke risk) presented at Accident and Emergency Minor Injuries Unit with headache after reportedly sounding ‘drunk’. On triage, the patient appeared lucid and well. However, International Normalized Ratio (INR) was 4.1. Head computed tomography (CT) indicated a large right-sided subdural hematoma. Prothrombin complex concentrate (PCC; Beriplex® P/N, CSL Behring) with vitamin K normalized the INR within minutes of administration. The patient underwent neurosurgery without complications, and was discharged after 5 days, with no residual neurological symptoms.

Conclusions:

ICH patients can present with no neurological signs. In OAT patients with headache, INR must be established; if ≥3.0, normalization of INR and head CT are essential. PCC is the best option to rapidly reverse anticoagulation and correct INR pre-surgery.

Background

Prothrombin Complex Concentrates (PCC) are administered to normalise blood coagulation in patients receiving oral anticoagulant therapy (OAT). Rapid reversal of OAT is essential in case of major bleeding, internal haemorrhage or surgery.

The primary end-point was to evaluate whether PCC in our hospital were being used in compliance with international and national guidelines for the reversal of OAT on an emergency basis. The secondary end-point was to evaluate the efficacy and safety of PCC.

Materials and methods

All patients receiving OAT who required rapid reversal anticoagulation because they had to undergo emergency surgery or urgent invasive techniques following an overdose of oral anticoagulants were eligible for this retrospective observational study.

Results

Forty-seven patients receiving OAT who needed rapid reverse of anticoagulation were enrolled in our study. The patients were divided in two groups: (i) group A (n=23), patients needed haemostatic treatment before neurosurgery after a head injury and (ii) group B (n=24), patients with critical haemorrhage because of an overdose of oral anticoagulants. The International Normalised Ratio (INR) was checked before and after infusion of the PCC. The mean INR in group A was 2.7 before and 1.43 after infusion of the PCC; in group B the mean INR of 6.58, before and 1.92 after drug infusion. The use of vitamin K, fresh-frozen plasma and red blood cells was also considered. During our study 22 patients died, but no adverse effects following PCC administration were recorded.

Discussion

In our study three-factor-PCC was found to be effective and safe in rapidly reversing the effects of OAT, although it was not always administered in accordance with international or national guidelines. The dose, time of administration and monitoring often differed from those recommended. In the light of these findings, we advocate the use of single standard protocol to guide the correct use of PCC in each hospital ward.

Dual antiplatelet treatment with aspirin and clopidogrel is the antithrombotic treatment recommended after an acute coronary syndrome and/or coronary artery stenting. The evidence for optimal antiplatelet therapy for patients, in whom long-term treatment oral anticoagulation is mandatory, is however scarce. To evaluate the safety and efficacy of the various antithrombotic strategies adopted in this population, we reviewed the available evidence on the management of patients receiving oral anticoagulation, such as a vitamin-k-antagonists, referred for coronary artery stenting.

Atrial fibrillation is the most frequent indication for oral anticoagulation. The need of starting antiplatelet therapy in this clinical scenario raises concerns about the combination to choose: triple therapy with warfarin, aspirin, and a thienopyridine being the most frequent and advised. The safety of this regimen appeared suboptimal because of an increased risk in hemorrhagic complications. On the other hand, the combination of oral anticoagulation and an antiplatelet agent is suboptimal in preventing thromboembolic events and stent thrombosis; dual antiplatelet therapy may be considered only when a high hemorrhagic risk and low thromboembolic risk are perceived. Indeed, the need for prolonged multiple-drug antithrombotic therapy increases the bleeding risks when drug eluting stents are used.

Since current evidence derives mainly from small, single-center and retrospective studies, large-scale prospective multicenter studies are urgently needed.

Background

Managing oral anticoagulant treatment (OAT) is a challenge for patients and primary care providers. It requires a high level of patient knowledge and adherence. Studies have shown that insufficient adherence and a low level of patient knowledge about OAT are primary causes for complications. This trial is the first to evaluate the long-term effects of a complex practice nurse-based patient education program in comparison to a patient brochure only.

Methods and design

This trial will be a cluster-randomized controlled trial in 22 general practices (GPs) recruiting 360 patients with OAT. GPs will be randomized into an intervention group or a control group. A baseline questionnaire will assess pre-existing knowledge about OAT. The patients in the intervention group will be educated by a complex education program which consists of a video, a brochure and individual training by a practice nurse. The video gives information about OAT, nutrition, and instructions about how to manage critical situations. The brochure repeats the content of the video. After 4 to 6 weeks, the intervention will be recapitulated. The control group will receive the brochure only. After 6 months, questionnaires will be used in both groups to assess patient knowledge about OAT as well as patients' subjective feelings of safety. Separately, we will evaluate patient records, looking for documented complications and the time spent in the therapeutic range.

Discussion

This trial will start in January 2011. This trial will evaluate the long-term effectiveness of a video-assisted education program on patients with OAT in comparison to a patient information brochure. Most previous studies have evaluated knowledge directly after an educational intervention. Our trial will look for long-term differences in basic knowledge of OAT. We expect that our complex patient education program effectively increases long-term basic knowledge about OAT. Although the population of our study is too small to observe differences in adverse effects, we expect to discover differences in secondary outcomes, such as the time spent in the therapeutic range.

Trial registration

Deutsches Register Klinischer Studien (German Clinical Trials Register): DRKS00000586

Universal Trial Number (UTN U1111-1118-3464)

Introduction

The oral anticoagulant therapy (OAT), used to prevent thrombosis, is associated with substantial avoidable hospitalization.

Aim

Identify the associations between chronic care management and the quality of OAT as suggested by the chronic care model (CCM) of Wagner.

Methods

Regression analysis with data of 61 thrombosis clinics and inductive analysis with 63 interviews with health care professionals of 23 thrombosis clinics.

Results

Results show substantial differences between regions in the quality of thrombosis care and the CCM activities. However, the variation in quality of care was not associated with the differences in CCM activities. The inductive analysis indicates that there are problems in the cooperation between caregivers. Several preferred CCM activities (e.g., multidisciplinary protocol) as well as the barriers to implement these activities (e.g., conflicting interests) were put forward by the health care professionals.

Conclusion

It can be concluded that there is variation in quality of thrombosis care between regions. This variation could not be explained by the observed differences in CCM activities. However, fragmentation is a major source of inefficiency according to health care professionals. The paper concludes with suggestions to improve chronic care management for thrombosis.

Background

Whether to continue oral anticoagulant therapy beyond 6 months after an “unprovoked” venous thromboembolism is controversial. We sought to determine clinical predictors to identify patients who are at low risk of recurrent venous thromboembolism who could safely discontinue oral anticoagulants.

Methods

In a multicentre prospective cohort study, 646 participants with a first, unprovoked major venous thromboembolism were enrolled over a 4-year period. Of these, 600 participants completed a mean 18-month follow-up in September 2006. We collected data for 69 potential predictors of recurrent venous thromboembolism while patients were taking oral anticoagulation therapy (5–7 months after initiation). During follow-up after discontinuing oral anticoagulation therapy, all episodes of suspected recurrent venous thromboembolism were independently adjudicated. We performed a multivariable analysis of predictor variables (p < 0.10) with high interobserver reliability to derive a clinical decision rule.

Results

We identified 91 confirmed episodes of recurrent venous thromboembolism during follow-up after discontinuing oral anticoagulation therapy (annual risk 9.3%, 95% CI 7.7%–11.3%). Men had a 13.7% (95% CI 10.8%–17.0%) annual risk. There was no combination of clinical predictors that satisfied our criteria for identifying a low-risk subgroup of men. Fifty-two percent of women had 0 or 1 of the following characteristics: hyperpigmentation, edema or redness of either leg; D-dimer ≥ 250 μg/L while taking warfarin; body mass index ≥ 30 kg/m2; or age ≥ 65 years. These women had an annual risk of 1.6% (95% CI 0.3%–4.6%). Women who had 2 or more of these findings had an annual risk of 14.1% (95% CI 10.9%–17.3%).

Interpretation

Women with 0 or 1 risk factor may safely discontinue oral anticoagulant therapy after 6 months of therapy following a first unprovoked venous thromboembolism. This criterion does not apply to men. (http://Clinicaltrials.gov trial register number NCT00261014)

Background

Heart failure (HF) patients show high morbidity and mortality rate with increased risk of malignant arrhythmia and thromboembolism. Anticoagulation reduces embolic event and death rates in HF patients with atrial fibrillation, but if antithrombotic therapy is beneficial in patients with HF in sinus rhythm is still debated.

Methodology and Principal Findings

We conducted a systematic review of prospective, randomized controlled trials (RCTs) to assess the efficacy and safety of oral anticoagulant therapies (OATs) compared to antiplatelet treatment in HF patients in sinus rhythm. MEDLINE, Web of Science, CENTRAL and Scopus databases were searched up to May 2012. Four RCTs were identified and a total of 3663 patients were included in the meta-analysis. Patients with both ischemic and non-ischemic HF were included. There was no significant difference in mortality (odds ratio (OR) 1.01, 95% confidence interval (CI) 0.86 to 1.19) between OATs group and antiplatelet drug group. OATs have reduced ischemic stroke risk (OR 0.49, 95% CI 0.32 to 0.74), but have increased major bleeding risk (OR 2.01, 95% CI 1.40 to 2.88) compared to antiplatelet treatment.

Conclusion

In HF patients in sinus rhythm OATs do not show a better risk-benefit profile compared to antiplatelet treatment in cardioembolism prevention. Warfarin and aspirin seem to be similar in reducing mortality. Warfarin reduces the incidence of ischemic stroke, but increases major bleedings. Thus, it is possible to speculate that aspirin prescription be indicated in patients with high risk of bleeding, whereas warfarin could be preferred in patients with high thromboembolic risk.

Background

Patients on oral anticoagulant therapy (OAT) require regular testing of the prothrombin time (PT) and the international normalised ratio (INR) to monitor their blood coagulation level to avoid complications of either over or under coagulation. PT/INR can be tested by a healthcare professional or by the patient. The latter mode of the testing is known as patient self-testing or home testing. The objective of this study was to elicit patients' perspectives and experiences regarding PT/INR self-testing using portable coagulometer devices.

Methods

Internet blog text mining was used to collect 246 blog postings by 108 patients, mainly from the USA and the UK. The content of these qualitative data were analysed using XSight and NVivo software packages.

Results

The key themes in relation to self-testing of OAT identified were as follows: Patient benefits reported were time saved, personal control, choice, travel reduction, cheaper testing, and peace of mind. Equipment issues included high costs, reliability, quality, and learning how to use the device. PT/INR issues focused on the frequency of testing, INR fluctuations and individual target (therapeutic) INR level. Other themes noted were INR testing at laboratories, the interactions with healthcare professionals in managing and testing OAT and insurance companies' involvement in acquiring the self-testing equipment. Social issues included the pain and stress of taking and testing for OAT.

Conclusions

Patients' blogs on PT/INR testing provide insightful information that can help in understanding the nature of the experiences and perspectives of patients on self-testing of OAT. The themes identified in this paper highlight the substantial complexities involved in self-testing programmes in the healthcare system. Thus, the issues elicited in this study are very valuable for all stakeholders involved in developing effective self-testing strategies in healthcare that are gaining considerable current momentum particularly for patients with chronic illness.

Background

Long-term oral anticoagulation treatment is associated with potential morbidity. Insufficient patient education is linked to poorly controlled anticoagulation. However the impact of a specific educational program on anticoagulation related morbidity remains unknown.

Objective

To evaluate the effect of an oral anticoagulation patient education program in reducing both hemorrhagic and recurrent thrombotic complications.

Design/Participants

We conducted a prospective, multicenter open randomized study, comparing an interventional group who received a specific oral anticoagulation treatment educational program with a control group. Eligible patients were older than 18 and diagnosed as having deep vein thrombosis or pulmonary embolism requiring therapy with a vitamin K antagonist for 3 months or more. Our primary outcome was the occurrence of hemorrhagic or thromboembolic events.

Results

During the 3-month follow-up the main outcome criteria were observed 20 times (6.6% of patients), 5 (3.1%) in the experimental and 15 (10.6%) in the control group. Consequently, in multivariate analysis, the cumulative risk reduction in the experimental group was statistically significant (OR 0.25, 95% CI 0.1 – 0.7,  < 0.01).

Conclusions

Patient education using an educational program reduced VKA-related adverse event rates.

Background

Oral anticoagulant therapy (OAT) with warfarin is the standard of stroke prevention in patients with atrial fibrillation. Approximately 30% of patients with cardioembolic strokes are on OAT at the time of symptom onset. We investigated whether warfarin exacerbates the risk of thrombolysis-associated hemorrhagic transformation (HT) in a mouse model of ischemic stroke.

Methods

62 C57BL/6 mice were used for this study. To achieve effective anticoagulation, warfarin was administered orally. We performed right middle cerebral artery occlusion (MCAO) for 3 h and assessed functional deficit and HT blood volume after 24 h.

Results

In non-anticoagulated mice, treatment with rt-PA (10 mg/kg i.v.) after 3 h MCAO led to a 5-fold higher degree of HT compared to vehicle-treated controls (4.0±0.5 µl vs. 0.8±0.1, p<0.001). Mice on warfarin revealed larger amounts of HT after rt-PA treatment in comparison to non-anticoagulated mice (9.2±3.2 µl vs. 2.8±1.0, p<0.05). The rapid reversal of anticoagulation by means of prothrombin complex concentrates (PCC, 100 IU/kg) at the end of the 3 h MCAO period, but prior to rt-PA administration, neutralized the exacerbated risk of HT as compared to sham-treated controls (3.8±0.7 µl vs. 15.0±3.8, p<0.001).

Conclusion

In view of the vastly increased risk of HT, it seems to be justified to withhold tPA therapy in effectively anticoagulated patients with acute ischemic stroke. The rapid reversal of anticoagulation with PCC prior to tPA application reduces the risk attributed to warfarin pretreatment and may constitute an interesting therapeutic option.

Background

Oral anticoagulant therapy (OAT) involves many health care disciplines. Even though collaboration between care professionals is assumed to improve the quality of OAT, very little research has been done into the practice of OAT management to arrange and manage the collaboration. This study aims to identify the problems in collaboration experienced by the care professionals involved, the solutions they proposed to improve collaboration, and the barriers they encountered to the implementation of these solutions.

Methods

In the Netherlands, intensive follow-up of OAT is provided by specialized anticoagulant clinics (ACs). Sixty-eight semi-structured face-to-face interviews were conducted with 103 professionals working at an AC. These semi-structured interviews were transcribed verbatim and analysed inductively. Wagner's chronic care model (CCM) and Cabana's framework for improvement were used to categorize the results.

Results

AC professionals experienced three main bottlenecks in collaboration: lack of knowledge (mostly of other professionals), lack of consensus on OAT, and limited information exchange between professionals. They mentioned several solutions to improve collaboration, especially solutions of CCM's decision support component (i.e. education, regular meetings, and agreements and protocols). Education is considered a prerequisite for the successful implementation of other proposed solutions such as developing a multidisciplinary protocol and changing the allocation of tasks. The potential of the health care organization to improve collaboration seemed to be underestimated by professionals. They experienced several barriers to the successful implementation of the proposed solutions. Most important barriers were the lack motivation of non-AC professionals and lack of time to establish collaboration.

Conclusions

This study revealed that the collaboration in OAT is limited by a lack of knowledge, a lack of consensus, and a limited information exchange. Education was identified as the best way to improve collaboration and considered a prerequisite for a successful implementation of other proposed solutions. Hence, the implementation sequence is of importance in order to improve the collaboration successfully. First step is to establish alignment regarding collaboration with all involved professionals to encounter the lack of motivation of non-AC professionals and lack of time.

ABSTRACT

Venous thromboembolism (VTE) remains a common disease with significant clinical impact upon our patients. Diagnostic challenges occur because of the nonspecific nature of the presenting symptoms. The advent of multidetector computed tomography, methods to stratify patients into VTE risks (low, intermediate, high) along with serological assays (D-dimers), have helped direct patients through proper workup and into conclusive diagnosis. In most cases, standard medical therapy for VTE is anticoagulation therapy (OAT). In situations where standard OAT is either contraindicated or complications result from that therapy, insertion of inferior vena cava (IVC) filters is considered. Recent reports suggest that although IVC filters are able to prevent pulmonary emboli (PE) in the short and intermediate term, there appear to be long-term consequences including excess recurrent deep venous thombosis (DVT and IVC/filter occlusions). Recognition of the time sequence of IVC filter benefits and complications has encouraged development of optional IVC filters, which can be left in place indefinitely or removed usually before certain time constraints. This article will attempt to address the timing of IVC filter placements to protect patients from significant PE.

To perform safe invasive procedures on patients on anticoagulation therapy, management of the patient's anticoagulation status is mandatory. For patients on anticoagulation therapy, a risk analysis of both the procedural risk of bleeding as well as the risk to the patient from discontinuing anticoagulation needs to be performed. For procedures at low risk of bleeding, the procedure may be performed with little change to the patient's anticoagulation regimen. For procedures with significant bleeding risk, however, anticoagulation will need to be held or reversed. Patients at high risk for thromboembolic complications will require bridging therapy if anticoagulation is to be withheld. In this article, a logical assessment of bleeding risk in patients undergoing procedures is presented, and a review of anticoagulation and risk is discussed.

Background

Antithrombotic treatment is a continuous therapy that is often performed in general practice and requires careful safety management. The aim of this study is to investigate whether a best-practice model that applies major elements of case management and patient education, can improve antithrombotic management in primary healthcare in terms of reducing major thromboembolic and bleeding events.

Methods

This 24-month cluster-randomized trial will be performed with 690 adult patients from 46 practices. The trial intervention will be a complex intervention involving general practitioners, healthcare assistants, and patients with an indication for oral anticoagulation. To assess adherence to medication and symptoms in patients, as well as to detect complications early, healthcare assistants will be trained in case management and will use the Coagulation-Monitoring List (Co-MoL) to regularly monitor patients. Patients will receive information (leaflets and a video), treatment monitoring via the Co-MoL and be motivated to perform self-management. Patients in the control group will continue to receive treatment as usual from their general practitioners. The primary endpoint is the combined endpoint of all thromboembolic events requiring hospitalization and all major bleeding complications. Secondary endpoints are mortality, hospitalization, strokes, major bleeding and thromboembolic complications, severe treatment interactions, the number of adverse events, quality of anticoagulation, health-related quality of life, and costs. Further secondary objectives will be investigated to explain the mechanism by which the intervention is effective: patients’ assessment of chronic illness care, self-reported adherence to medication, general practitioners’ and healthcare assistants’ knowledge, and patients’ knowledge and satisfaction with shared decision making.

Practice recruitment is expected to take place between July and December 2012. Recruitment of eligible patients will start in July 2012. Assessment will occur at three time points: baseline and follow-up after 12 months and after 24 months.

Discussion

The efficacy and effectiveness of individual elements of the intervention, such as antithrombotic interventions, self-management concepts in orally anticoagulated patients, and the methodological tool of case management, have already been extensively demonstrated. This project foresees the combination of several proven instruments, as a result of which we expect to profit from a reduction in the major complications associated with antithrombotic treatment.

Trial registration

Current Controlled Trials ISRCTN41847489

Background

Hematoma volume is a major determinant of outcome in patients with intracerebral hemorrhage (ICH). Accurate volume measurements are critical for predicting outcome and are thought to be more difficult in patients with oral anticoagulation-related ICH (OAT-ICH) due to a higher frequency of irregular shape. We examined hematoma shape and methods of volume assessment in patients with OAT-ICH.

Methods

We performed a case–control analysis of a prospectively identified cohort of consecutive patients with ICH. We retrospectively reviewed 50 consecutive patients with OAT-ICH and 50 location-matched non-OAT-ICH controls. Two independent readers analyzed CT scans for hematoma shape and volume using both ABC/2 and ABC/3 methods. Readers were blinded to all clinical variables including warfarin status. Gold-standard ICH volumes were determined using validated computer-assisted planimetry.

Results

Within this cohort, median INR in patients with OAT-ICH was 3.2. Initial ICH volume was not significantly different between non-OAT-ICH and OAT-ICH (35 ± 38 cc vs. 53 ± 56 cc, P = 0.4). ICH shape did not differ by anticoagulation status (round shape in 10% of OAT-ICH vs. 16% of non-OAT-ICH, P = 0.5). The ABC/3 calculation underestimated median volume by 9 (3–28) cc, while the ABC/2 calculation did so by 4 (0.8–12) cc.

Conclusions

Hematoma shape was not statistically significantly different in patients with OAT-ICH. Among bedside approaches, the standard ABC/2 method offers reasonable approximation of hematoma volume in OAT-ICH and non-OAT-ICH.

Recognition of the risk of thromboembolic phenomena to patients in the postsurgical period has resulted in the practice of administering prophylactic anticoagulant agents to those patients who are at high risk for this complication. Institution of a perioperative anticoagulant or antithrombotic protocol needs to be considered when a regional anesthetic is proposed as part of, or as the total, anesthetic management of the patient. This article reviews current data on the risks involved in the use of neuraxial regional anesthesia in the care of surgical patients in whom prophylactic thromboembolic anticoagulant therapy is planned. Guidelines are established to help the physician minimize the risks of a neuraxial hematoma forming, monitor the patient for this complication, and optimally treat him or her if a hematoma were to occur.

Elderly people represent a patient population at high thromboembolic risk, but also at high hemorrhagic risk. There is a general tendency among physicians to underuse anticoagulants in the elderly, probably both because of underestimation of thromboembolic risk and overestimation of bleeding risk. The main indications for anticoagulation are venous thromboembolism (VTE) prophylaxis in medical and surgical settings, VTE treatment, atrial fibrillation (AF) and valvular heart disease. Available anticoagulants for VTE prophylaxis and initial treatment of VTE are low molecular weight heparins (LMWH), unfractionated heparin (UFH) or synthetic anti-factor Xa pentasaccharide fondaparinux. For long-term anticoagulation vitamin K antagonists (VKA) are the first choice and only available oral anticoagulants nowadays. Assessing the benefit-risk ratio of anticoagulation is one of the most challenging issues in the individual elderly patient, patients at highest hemorrhagic risk often being those who would have the greatest benefit from anticoagulants. Some specific considerations are of utmost importance when using anticoagulants in the elderly to maximize safety of these treatments, including decreased renal function, co-morbidities and risk of falls, altered pharmacodynamics of anticoagulants especially VKAs, association with antiplatelet agents, patient education. Newer anticoagulants that are currently under study could simplify the management and increase the safety of anticoagulation in the future.

Background

Anticoagulation management services (AMSs) are widely used for anticoagulation management in many countries. Our AMS is a pharmacist-run ambulatory clinic with a physician advisory committee that manages patients referred with complicated anticoagulation histories. This paper assesses the adequacy of anticoagulation, rates of anticoagulant-related events and associated health care resource utilization for patients before and after referral to our AMS.

Methods

Consecutive patients referred to the AMS with 4 months of prior anticoagulation management who also had anticoagulation management for 4 months within the AMS were included in the evaluation. The primary endpoint was adequacy of anticoagulation (target international normalized ratio [INR] ± 0.5). Secondary outcomes included adverse events requiring an emergency department (ED) visit or hospital stay. These were classified by International Classification of Diseases (ICD) codes as thromboembolic, hemorrhagic, or non-anticoagulant related. Health care system resource consumption data were collected as number of hours spent in an ED and hospitalization costs.

Results

A total of 125 patients were included: 57.6% were male, with a mean age of 62.9 (standard deviation [SD]) ± 15.0 years. Indications for warfarin therapy were atrial fibrillation (40.0%), mechanical valve replacement (24.0%) and venous thromboembolism (19.2%). The adequacy of anticoagulant control was significantly greater during AMS care compared with the period before referral; patients were in the target INR range 66.5% versus 48.8% of the time, respectively (95% confidence interval [CI] 13.4%–22.0%; p < 0.0001). The relative risk of a thromboembolic event before referral to AMS care was 17.6 (95% CI 6.0–51.9; p < 0.0001), while the relative risk of a hemorrhagic event before AMS care was 1.6 (95% CI 0.7–3.7; p = 0.25). During AMS care, savings included 572 hours in the ED and Cdn$122,145.40 in hospitalization costs.

Conclusions

A pharmacist-directed, physician-supported AMS program achieved significantly better INR control and reduced rates of thromboembolic complications compared with standard care. Resource utilization was substantially reduced during AMS care.

Aim

In order to avoid the complications associated with thromboembolic disease, patients with this condition typically are placed on long-term anticoagulant therapy. This report compares bleeding complications in this patient population by level of achieved INR.

Materials and Methods

During the 6-year period between January 1997 and January 2003, 386 patients with venous thromboembolism of the lower extremities were admitted to the Cardiovascular Surgery Outpatient Clinic of Alsancak State Hospital. Of the 386 patients, 198 (51.2%) were women, and the average age was 52.3 years. All diagnoses of venous thromboembolism were confirmed by means of Doppler ultrasonography. Further investigation showed occult neoplasms in 22 (5.6%) of the cases. We excluded the patients with occult disease, and the remaining 364 constituted our study population.

Results

Oral anticoagulation was standardized at 6 months' duration in all cases. We divided the patients into two groups. Group I consisted of 192 patients (52.7%) with INR values between 1.9 and 2.5; Group II comprised 172 patients with INR values between 2.6 and 3.5. Complications in each group were assessed and compared. The minor hemorrhage rate was 1.04% in Group I and 4.06% in Group II. The major hemorrhage rate was also 1.04% in Group I and was 6.3% in Group II. We determined that the complication rates for both minor and major hemorrhage were significant in patients with INR values above 2.5.

Conclusion

Oral anticoagulation must be followed closely in patients with venous thromboembolism. Higher INR levels are associated with significant increases in hemorrhage and associated complications. INR values of 2.0 to 2.5 are sufficient for long-term anticoagulant therapy, ensuring ideal anticoagulation levels and minimizing the complication rate.

Background

Warfarin is an oral anticoagulant (OAT) that needs active management to ensure therapeutic range. Initial management is often carried out as an inpatient, though not requiring inpatient facilities. This mismatch results in financial costs which could be directed more efficaciously. The extent of this has previously been unknown. Here we aim to calculate the potential number of bed nights which may be saved among those being dose optimized as inpatients and examine associated factors.

Methods

A 6 week prospective audit of inpatients receiving OAT, at Cork University Hospital, was carried out. The study period was from 11th June 2007 to 20th July 2007. Data was collected from patient's medications prescription charts, medical record files, and computerised haematology laboratory records. The indications for OAT, the patient laboratory coagulation results and therapeutic intervals along with patient demographics were analysed. The level of potentially avoidable inpatient nights in those receiving OAT in hospital was calculated and the potential cost savings quantified. Potential avoidable bed nights were defined as patients remaining in hospital for the purpose of optimizing OAT dosage, while receiving subtherapeutic or therapeutic OAT (being titred up to therapeutic levels) and co-administered covering low molecular weight heparin, and requiring no other active care. The average cost of €638 was taken as the per night hospital stay cost for a non-Intensive Care bed. Ethical approval was granted from the Ethical Committee of the Cork Teaching Hospitals, Cork, Ireland.

Results

A total of 158 patients were included in the audit. There was 94 men (59.4%) and 64 women (40.6%). The mean age was 67.8 years, with a median age of 70 years.

Atrial Fibrillation (43%, n = 70), followed by aortic valve replacement (15%, n = 23) and pulmonary emboli (11%, n = 18) were the commonest reasons for prescribing OAT. 54% had previously been prescribed OAT prior to current admission.

It was confirmed that, there are potentially avoidable nights in patients receiving OAT. The majority of this group were those being commenced on OAT for the first time (p = 0.00002), in the specialities of Cardiology, Cardiothoracic surgery and Care of the Elderly. The potential number of bed nights to be saved is 13 per week for the hospital or 1.1 bed nights per 10,000 general hospital admissions. These were predominantly weekday nights. The estimated cost of avoidable inpatient OAT dose optimization was approximately €8300 per week.

Conclusion

With rising costs and the increasing demands for acute hospital beds, alterations to inpatient management for this group of patients should be considered. Alternatives include increasing the size of current anticoagulation clinics, introduction of POCT (point of care testing) devices and increased GP management. POCT can be justified based upon the publication by Gardiner et al, who showed that 87% of patients find self testing straightforward, 87% were confident in the result they obtained using the devices and 77% preferred self testing.

Evidence-based care recommendations and standardized protocols improve outcomes. In addition, anticoagulant management has been recognized by The Joint Commission (TJC) as an opportunity for improving patient safety. A National Patient Safety Goal requiring a standardized process for patients receiving anticoagulants was established by TJC. This requirement provided an opportunity to apply evidence-based care recommendations to the issue of safe anticoagulant use. To meet TJC requirement, the following searchable clinical question was drafted: “In children receiving anticoagulation therapy, what are the appropriate dosing, laboratory monitoring, timing, and dosing adjustments for warfarin, unfractionated heparin, and low-molecular-weight heparin to prevent coagulation-related complications?” The team used the Appraisal of Guidelines Research and Evaluation Collaboration (AGREE) instrument to evaluate the quality and relevance of identified guidelines in answering the clinical question. Best Evidence Statements (BESts) were developed for each of the medications (warfarin, low-molecular-weight heparin, and unfractionated heparin). BESts provide the format for the presentation of recommendations, discussion, and methods for point-of-care providers seeking synthesized evidence to guide care decisions. The primary goal of developing and implementing these statements was to standardize the use of anticoagulants and to prevent unsafe practices. A secondary goal was to ensure accessibility of the BESts throughout our organization, including the electronic medical record, various internal division home pages, and our organization's external website. The anticoagulant BESts developed at our organization show how an interprofessional approach to patient care results in the development of evidence-based care recommendations. The BESts were developed to standardize care associated with the use of anticoagulants and to provide dosing and monitoring parameters to ensure safe care to all patients receiving these medications. The development of evidence-based care recommendations can be accomplished with a focused interprofessional team dedicated to providing the safest possible care to patients.

Introduction. Dental treatment performed in patients receiving continuous oral anticoagulant drug therapy is becoming increasingly common in dental offices. For these patients it is imperative to carry out careful anamnesis, as well as a multiprofessional clinical evaluation with regard to the risk and control of hemorrhagic or thromboembolic episodes. Objectives and Material and Methods. The aim is to evaluate postextraction hemorrhagic or thromboembolic episodes in patients who have been on anticoagulant medications for an uninterrupted period of 48 months. Results. Among the 108 patients evaluated, 215 extractions were performed in which there was only one case of postoperative bleeding. Warfarin was used by 98 patients; Warfarin associated with salicylic acetic acid by 9 patients and salicylic acetic acid in only 1 patient. As regards the serologic tests performed, International Normalized Ratio (INR) ranged from 0.8 to 4.9, with a mean of 3.15. Conclusion. Extractions in patients on oral anticoagulants must be performed in the least traumatic manner possible. It is not necessary to stop anticoagulant therapy to perform extractions. Local hemostasis techniques, such as obliterative sutures alone are sufficient to prevent hemorrhagic complications.