The Prevalence of Nontherapeutic and Dangerous International Normalized Ratios Among Patients Receiving Warfarin in the Emergency Department

Saint Luke's Hospital (NY, USA), New York, New York, United States
Annals of emergency medicine (Impact Factor: 4.68). 09/2006; 48(2):182-9, 189.e1. DOI: 10.1016/j.annemergmed.2005.12.010
Source: PubMed


We determine the prevalence of nontherapeutic and coagulopathic international normalized ratios (INRs) among patients receiving warfarin and presenting to an emergency department (ED). As a secondary goal, we aim to determine whether a simple decision aid composed of physical examination and historical features could be predictive of INR greater than 5.
This was a prospective, observational study at 2 associated urban academic centers from February 2003 through May 2004, using a convenience sample of patients identified by direct questioning and contemporaneous medical record review in the ED as receiving long-term warfarin therapy. Inclusion criteria were warfarin therapy and self-reported compliance. Patients were enrolled by trained researchers. The primary outcome measure was the percentage of patients within appropriate therapeutic range for their condition according to accepted national guidelines. Descriptive statistics were used, and multivariate regression analysis was performed to identify associations.
One thousand nineteen patients were enrolled. INR values were obtained in 77% (782/1019) of patients. Of these patients, 72% (95% confidence interval 67% to 76%) were outside the desired range. Values were less than 2 in 43% of patients and greater than 3 in 29% of patients. INR greater than 5 was present in 11% (86/782) of patients, and 40% (34/86) of these patients exhibited gross bleeding. Emergency therapy was administered in 12% (96/782) of patients: fresh frozen plasma in 7% of patients, heparin in 5% of patients. Intracranial hemorrhage was found in 12 patients, 5 with INR greater than 3. Ischemic stroke or venous thromboembolism occurred in 51 patients known to be receiving warfarin specifically for prevention of the event that occurred. Of these patients, 49% (25/51) had INR less than 2. Regression analysis indicated no sensitive or specific constellation of features, though 2 factors were associated with INR greater than 5: gross hemorrhage (P=.006) and increasing duration of therapy (P=.047).
The prevalence of undesirable INR in the ED is higher than in warfarin populations previously studied, and a significant number of nontherapeutic levels were associated with thromboembolism, stroke, or hemorrhage. Given the prevalence and established danger of subtherapeutic and supratherapeutic levels, a low threshold should be maintained for testing and addressing INR levels in patients receiving warfarin in the ED.

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    • "Many patients admitted to the emergency department (ED) use anticoagulants, mostly vitamin K antagonists (VKA). Newman et al. [1] showed that the majority of patients in the ED using VKA had a sub- or supra-therapeutic international normalized ratio (INR). Chronic anticoagulation is associated with an increased risk of bleeding, which is related to the degree of anticoagulation, e.g., the height of the INR [2]. "
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    ABSTRACT: Background: Co-fact©, prothrombin complex concentrate, is used for restoring the international normalized ratio (INR) in patients on vitamin K antagonists (VKA) presenting with acute bleeding. In this prospective cohort study, we evaluated whether adequate INR values were reached in ED patients using the Sanquin (Federation of Dutch Thrombosis Services) treatment protocol. Methods: We evaluated this protocol for two target INR groups: group 1, target INR ≤ 1.5 (for life-threatening bleeding/immediate intervention); group 2, target INR 1.6-2.1 (in cases of a minor urgent surgery or serious overdosing of anticoagulant). We specifically wanted to identify both under- and over-treated patients. Reversing VKA anticoagulation therapy to unnecessarily low INR values may involve thrombotic risks. Apart from this risk, the patient is also administered an excess amount of the drug. This means unnecessary costs and may present problems with restoring an anticoagulated state at a later time. Results: In our cohort, the Sanquin dosing protocol was followed for 45/60 patients. It appeared that out of the 41 patients in group 1 (target INR ≤ 1.5), 35 (85%) achieved the goal INR. This occurred more often than for the 19 patients in group 2 (target INR 1.6-2.1), where only 6 (32%) achieved the goal INR. Using the protocol resulted in a positive trend toward better INR reversal in group 1. In group 2, no relation between using the protocol and achieving the desired INR value was detected. Physicians ignoring the proposed dose of Co-fact© prescribed significantly less Co-fact© (even when correcting for patient weight). It appeared that patients in group 1 had a significantly lower baseline INR than patients in group 2. Group 2 patients, on the other hand, had a baseline INR > 7.5 in 53% of the cases. Conclusion: In our cohort, for most patients in INR group 2 treated with Co-fact©, the achieved INR value was outside the desired range of 1.6-2.1. The supra-therapeutic range of baseline INR in group 2 may have contributed to the different kind of bleeding witnessed in this patient group. Our results support the idea that treatment of patients on vitamin K antagonists with Co-fact© could benefit from a slightly different approach, taking into account the INR value to which the patient needs to be reversed.
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    ABSTRACT: This study's aims were to evaluate patient knowledge of safe warfarin practices early in treatment, and to pilot a nursing telephone follow-up enhancement to a pharmacy-facilitated discharge. Forty-two randomized patients in either "enhanced follow-up" or "treatment as usual" groups completed the study. Enhanced treatment resulted in significant improvement in warfarin knowledge (86% versus 71%). In critical safety related knowledge questions even larger improvements were present (∼96% compared to ∼77%). The hypothesis that non-adherence generating rehospitalization is a function of poorer knowledge was not supported as there were no warfarin-related readmissions during the study. The study supports the use of enhanced follow up and the need for larger studies to delineate what patient knowledge prevents rehospitalization and cost effective educational efforts.
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    ABSTRACT: Patients taking anticoagulants orally over the long term have international normalized ratios (INRs) outside the individual therapeutic range more than one-third of the time. Improved anticoagulation control will reduce hemorrhagic and thromboembolic event rates. To gauge the potential effect of improved anticoagulation control, we undertook to determine the proportion of anticoagulant-associated events that occur when INRs are outside the therapeutic range. We conducted a meta-analysis of all studies that assigned hemorrhagic and thromboembolic events in patients taking anticoagulants to discrete INR ranges. We identified studies using the MEDLINE (1966-2006) and EMBASE (1980-2006) databases. We included studies reported in English if the majority of patients taking oral anticoagulants had an INR range with a lower limit between 1.8 and 2 and an upper limit between 3 and 3.5, and their INR at the time of the hemorrhagic or thromboembolic event was recorded. The final analysis included results from 45 studies (23 that reported both hemorrhages and thromboemboli; 14 that reported hemorrhages only; and 8, thromboemboli only) involving a median of 208 patients (limits of interquartile range [25th-75th percentile] 131-523 subjects; total n = 71 065). Of these studies, 64% were conducted at community practices; the remainder, at anticoagulation clinics. About 69% of the studies were classed as having moderate or high quality. Overall, 44% (95% confidence interval [CI] 39%-49%) of hemorrhages occurred when INRs were above the therapeutic range, and 48% (95% CI 41%-55%) of thromboemboli took place when below it. The mean proportion of events that occurred while the patient's INR was outside the therapeutic range was greater for studies with a short mean follow-up (< 1 yr). Between-study heterogeneity was significant (p < 0.001). Improved anticoagulation control could decrease the likelihood of almost half of all anticoagulant-associated adverse events.
    Full-text · Article · Jun 2007 · Canadian Medical Association Journal
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