International normalized ratio in anticoagulant therapy: understanding the issues

1997 ◽  
Vol 6 (2) ◽  
pp. 88-92 ◽  
Author(s):  
AL Severson ◽  
LR Baldwin ◽  
TG DeLoughery

Recently, a change in anticoagulation therapy occurred that is still partially ignored by the healthcare community. Understanding the controversy over the use of the internal normalized ratio in monitoring patients receiving warfarin therapy is important for nurses who provide care to these patients. Five questions related to current monitoring of patients treated with anticoagulants are addressed. Nurses must recognize the importance to their practice of changes in laboratory methods and move toward using the most useful measures available to influence patients' outcomes. The international normalized ratio is the most appropriate way to evaluate the effects of warfarin therapy. All healthcare providers should use this ratio as the standard in evaluating the effects of anticoagulation therapy.

2006 ◽  
Vol 76 (2) ◽  
pp. 65-74 ◽  
Author(s):  
Rebecca Couris ◽  
Gary Tataronis ◽  
William McCloskey ◽  
Lynn Oertel ◽  
Gerard Dallal ◽  
...  

Background: Changes in daily vitamin K intake may contribute to marked variations in the International Normalized Ratio (INR) coagulation index in patients receiving oral warfarin anticoagulant therapy, with potentially serious adverse outcomes. Thus, patients receiving warfarin therapy are routinely counseled regarding this drug-nutrient interaction and are instructed to maintain consistent vitamin K intakes, though little quantitative information about this relationship is available. Objective: To determine the quantitative impact of variability in dietary vitamin K1 (phylloquinone) intake, assessed by a validated patient self-monitoring instrument, on weekly INR in patients receiving warfarin anticoagulant therapy. Methods: A prospective dietary assessment study was conducted at the Massachusetts General Hospital in Boston. Sixty outpatients (37 males and 23 females) were selected with a mean age 60.3 ± 16.8 years, who began oral warfarin anticoagulant therapy within 14 days prior to their first clinic visit to an outpatient anticoagulation therapy unit. Exclusion criteria included more than 2 drinks of alcohol per day, inability to speak English, and concurrent disease states affecting warfarin therapy such as liver disease and terminal illness. Over the five-week study period, participants recorded daily intakes in specified amounts of all food items appearing on a validated dietary self-assessment tool. Concomitant use of prescription and/or non-prescription medications was also obtained. Concurrent daily warfarin dose and adherence to the drug regimen, concomitant use of prescription and/or non-prescription medications known to interact with warfarin, and weekly INR were obtained. Week-to-week changes in vitamin K intake, warfarin dose, and INR were determined and cross-correlated. Results: Forty-three patients (28 males and 15 females) completed the study and 17 dropped out. Pearson’s correlation coefficient revealed the variability in INR and changes in vitamin K intake were inversely correlated (r = –0.600, p < 0.01). Multiple regression analysis (r = 0.848) indicated that a weekly change of 714 mug dietary vitamin K significantly altered weekly INR by 1 unit (p < 0.01) and a weekly change of 14.5 mg warfarin significantly altered weekly INR by 1 unit (p < 0.01) after adjustment for age, sex, weight, height, and concomitant use of medications known to interact with warfarin. Conclusions: Patients taking warfarin and consuming markedly changing amounts of vitamin K may have a variable weekly INR with potentially unstable anticoagulant outcomes.


2019 ◽  
Vol 13 (18) ◽  
pp. 1599-1607
Author(s):  
Yide Cao ◽  
Ganyi Chen ◽  
Huangshu Li ◽  
Yafeng Liu ◽  
Zhonghao Tao ◽  
...  

Aim: To assess the relationship between the De Ritis ratio on admission and warfarin sensitivity in the initial 10 days of anticoagulation therapy. Methods: We retrospectively reviewed data from 906 patients who underwent heart valve replacement surgery. Results: A De Ritis ratio of 1.19 was identified as the optimal cutoff according to the ROC curve. Patients with a high De Ritis ratio achieved an international normalized ratio (INR) ≥4 more easily and earlier than those with a low De Ritis ratio in the initial 10 days of warfarin therapy. Multivariate analysis showed that a high De Ritis ratio was an independent predictor of an INR ≥4 (HR: 2.567; p < 0.001). Conclusion: A De Ritis ratio ≥1.19 on admission was significantly associated with an INR ≥4 in the initial 10 days of warfarin therapy among patients underwent heart valve replacement surgery.


2010 ◽  
Vol 23 (3) ◽  
pp. 194-204 ◽  
Author(s):  
Pamela J. White

Warfarin has long been the mainstay of oral anticoagulation therapy for the treatment and prevention of venous and arterial thrombosis. The narrow therapeutic index of warfarin, and the complex number of factors that influence international normalized ratio (INR) response, makes optimization of warfarin therapy challenging. Determination of the appropriate warfarin dose during initiation and maintenance therapy requires an understanding of patient factors that influence dose response: age, body weight, nutritional status, acute and chronic disease states, and changes in concomitant drug therapy and diet. This review will examine specific clinical factors that can affect the pharmacokinetics and pharmacodynamics of warfarin, as well as the role of pharmacogenetics in optimizing warfarin therapy.


Biomedicine ◽  
2021 ◽  
Vol 41 (3) ◽  
pp. 682-685
Author(s):  
Kanat kyzy Bazira ◽  
Nazgul Kinderbaeva ◽  
Gulnora Karataeva ◽  
Sabira Mamatova ◽  
Ulan Kundashev ◽  
...  

Introduction: Anticoagulant therapy can prevent adverse outcomes of Atrial fibrillation (AF), reducing the risk of stroke by 64% and death by 25%. The present study aimed to assess treatment adherence in elderly patients with non-valvular atrial fibrillation (NVAF) who were prescribed the vitamin K antagonist warfarin.   Materials and methods: In the present retrospective study, we analyzed the medical records of 202 elderly outpatients with NVAF aged between 65 and 74 years (mean ± SD: 68.7 ± 10.2 years).    Results: Problems associated with warfarin arose throughout the follow-up period. After 1 month of treatment, the number of patients taking warfarin had decreased to 71.3% of all patients; less than half of the patients (46%) were still taking the drug. In subsequent periods, the number continued to decrease; of all patients who had been prescribed warfarin with periodic international normalized ratio (INR) control, only 19 (9.4%) remained after 1 year. Our study revealed inadequate anticoagulation therapy in elderly patients, probably because most patients refused warfarin therapy because they could not control their INR. Moreover, significantly more rural residents than urban residents refused therapy (48 vs. 22; p < 0.05). Doctors underprescribed anticoagulants because they feared hemorrhagic complications in their patients.   Conclusion: The results of the present study showed that anticoagulants were underprescribed at the outpatient stage in centers of family medicine in our country. The main drug of choice for specialists remains warfarin, which only provides adequate therapy in a small number of patients (9.4%).


2002 ◽  
Vol 36 (10) ◽  
pp. 1554-1557 ◽  
Author(s):  
Cade B Jones ◽  
Susan E Fugate

OBJECTIVE: To report 4 cases of hypoprothrombotic response resulting from addition of levofloxacin therapy to chronic warfarin therapy and to review related literature to support or refute a warfarin—levofloxacin interaction. CASE SUMMARY: Four patients, 34–81 years old, were prescribed levofloxacin concomitantly with stable warfarin therapy. Three patients had a target international normalized ratio (INR) range of 2.0–3.0 and experienced an increase in INR to 3.5, 8.12, and 11.5 on days 11, 5, and 4 of a 10-day course of levofloxacin, respectively. The fourth patient experienced minor bleeding, with a slightly elevated INR on the second day of levofloxacin therapy that required up to a 19% warfarin dose reduction during levofloxacin treatment. DISCUSSION: An initial premarketing clinical trial concluded that levofloxacin had no effect on warfarin's pharmacokinetics and pharmacodynamic response. Two case reports have since documented an increase in INR in patients taking long-term warfarin on completion of levofloxacin therapy. Our case reports provide further evidence of a significant increase in INR observed during concomitant levofloxacin therapy. The proposed mechanism of this interaction is displacement of warfarin from protein binding sites, reduction in gut flora producing vitamin K, and decreased warfarin metabolism. CONCLUSIONS: Prolonged prothrombin response in patients undergoing chronic warfarin therapy has been well documented with many antibiotics, including fluoroquinolones. Recognition of newer antibiotics' effects on warfarin therapy is important to guide safe use and monitoring of anticoagulation therapy. Our case studies demonstrate significant elevations in INR values during and up to 1 day after levofloxacin therapy in patients undergoing stable warfarin therapy.


2003 ◽  
Vol 19 (4) ◽  
pp. 141-145 ◽  
Author(s):  
Shyam D Karki ◽  
Susan M Lander

Objective: To evaluate the warfarin management patterns in an academic nursing home and evaluate what predetermined factors are associated with variability in the international normalized ratio (INR). Setting: A 566-bed academic nursing home. Methods: A retrospective chart review of all residents receiving warfarin therapy for >3 consecutive months in a calendar year was conducted. Data were collected regarding the number of times the INR fluctuated during the follow-up period and the degree of fluctuation between each blood sampling. An INR that changed by 0.5–0.99 between samplings was classified as a small fluctuation; a change >0.99 was defined as a large fluctuation. The sample was divided into 2 groups, easy management and difficult management, based on variability in the INR. The easy-management group consisted of residents who had small fluctuations in the INR and who had INRs outside of the therapeutic range ≤10% of the time. The difficult- management group had large fluctuations in the INR, with the ratio outside of the therapeutic range >10% of the time. Results: Thirty-seven patients were taking warfarin (mean ± SD age 71 ± 14 y; mean number of medical illnesses 7.6 ± 3). The mean length of time of warfarin therapy was 10.6 ± 3.2 months. The average dose and INR were 4.0 ± 1.9 mg and 2.0 ± 0.3, respectively. No statistically significant differences were found between age, dose, or INR. For patients who had INR values exceeding the therapeutic range, there was no significant difference between the management groups in length of treatment, age, number of medical illnesses, number of high-risk factors, dose, average monthly INR, number of medication adjustments per year, albumin and creatinine levels, total number of medications, or number of routine medications known to interact with warfarin. The difficult-management group received more medications known to interact with warfarin than the easy-management group. These medications may have caused the INR to increase above the normal range (p = 0.003), as well as producing a large (p = 0.001) or small fluctuation (p = 0.0007) in the INR. Of all the interacting medications, 55% were antibiotics and 28% were analgesics. No statistically significant differences in outcome were seen between groups. Conclusions: Results of this study indicate that large variations (>0.99) in the INR may be due to newly prescribed medications that enhance the anticoagulant effect of warfarin. These variations may be minimized by closely monitoring the INR when a drug known to interact with warfarin is prescribed.


Blood ◽  
2009 ◽  
Vol 114 (5) ◽  
pp. 952-956 ◽  
Author(s):  
Daniel M. Witt ◽  
Thomas Delate ◽  
Nathan P. Clark ◽  
Chad Martell ◽  
Thu Tran ◽  
...  

For patients on warfarin therapy, an international normalized ratio (INR) recall interval not exceeding 4 weeks has traditionally been recommended. Less frequent INR monitoring may be feasible in stable patients. We sought to identify patients with stable INRs (defined as having INR values exclusively within the INR range) and comparator patients (defined as at least one INR outside the INR range) in a retrospective, longitudinal cohort study. Occurrences of thromboembolism, bleeding, and death were compared between groups. Multivariate logistic regression models were used to identify independent predictors of stable INR control. There were 2504 stable and 3569 comparator patients. The combined rates of bleeding and thromboembolism were significantly lower in stable patients. Independent predictors of stable INR control were age older than 70 years and the absence of comorbid heart failure and diabetes. Stable patients were significantly less likely to have target INR of 3.0 or higher or chronic diseases. We hypothesize that many patients demonstrating stable INR control could be safely treated with INR recall intervals greater than the traditional 4 weeks.


2000 ◽  
Vol 34 (5) ◽  
pp. 567-572 ◽  
Author(s):  
William E Dager ◽  
Jennifer M Branch ◽  
Jeffrey H King ◽  
Richard H White ◽  
Richard S Quan ◽  
...  

OBJECTIVE: To determine the effect of daily consultation by a team of hospital pharmacists on the accuracy and rapidity of optimizing warfarin therapy. DESIGN: Comparison of a historical control cohort with a prospective cohort matched for treatment indication. SETTING: A 400-bed university teaching hospital. PATIENTS: Sixty consecutive patients hospitalized in 1992 and starting warfarin for the first time, with anticoagulation therapy managed by physicians, were compared with 60 patients matched for warfarin indication hospitalized in 1995, but with anticoagulation therapy managed with pharmacy consultation. RESULTS: Pharmacist management of initial warfarin therapy resulted in a significant reduction in the length of hospitalization compared with physician dosing, from 9.5 ± 5.6 days to 6.8 ± 4.4 days (p = 0.009). The number of patients and patient-days with international normalized ratio (INR) values >3.5 were reduced by pharmacist dosing from 37 patients and 142 days to 16 patients and 29 days, respectively (p < 0.001). Similarly, the number of patients and patient-days with INR >6.0 were reduced from 20 patients and 50 days to two patients and six days, respectively (p < 0.001). There were six documented bleeding complications in 1992 compared with one in 1995 (p = 0.11). The mean INR at discharge was significantly lower in the pharmacy surveillance group, 2.6 ± 0.58, compared with the physician cohort, 3.3 ± 2.1 (p = 0.07). Readmissions after discharge due to bleeding or recurrent thrombosis were reduced from five (at 1 mo) and 10 (at 3 mo) to two and five readmissions, respectively, by pharmacist intervention (p = 0.43). The number of patients with concurrently prescribed drugs known to significantly interact with warfarin was significantly lower (6 vs. 13; p = 0.02) in the pharmacy surveillance group. CONCLUSIONS: Among patients starting warfarin for the first time, daily consultation by a pharmacist significantly decreased the length of hospital stay and the number of patients who received excessive anticoagulation therapy. These findings translate into improved quality of care and potentially significant cost savings.


2018 ◽  
Vol 96 (1) ◽  
pp. 42-48
Author(s):  
Mikhail V. Derugin ◽  
S. F. Zadvorev ◽  
A. G. Obrezan ◽  
A. E. Filippov ◽  
S. L. Grishaev

One of the most important problems in the modern coagulation is the issue of choosing the optimal drug for a long-term oral anticoagulation therapy. Research results of the last 5-10 years show that the reasonable choice between vitamin K antagonists (VKA) and non-vitamin K-dependent oral anticoagulants (NOAC) can be made. The following article describes the phenomenon of «labile INR» on warfarin therapy and describes its clinic and hereditary determinants. Our data about the clinical testing toassess the risk of "labile INR" based on the scale of the Russian populat ion demonstrate potential benefits from setting the scale into the clinic. It is shown that Clinical SAMe-TT2R2 scale correlates with the duration of achieving the target INR, and the patients with the SAMe-TT2R2 score of 4 or more are in the group of iatrogenic complications risks. The contribution of genetic and clinical factors to INR dynamics at the start of therapy in different groups of patients, according to their sensitivity to warfarin therapy and potential duration, is discussed in the article. The results obtained by the analysis of «labile INR» factors will help a doctor to make a choice of anticoagulant between the NOAC and VKA.


1992 ◽  
Vol 68 (02) ◽  
pp. 160-164 ◽  
Author(s):  
P J Braun ◽  
K M Szewczyk

SummaryPlasma levels of total prothrombin and fully-carboxylated (native) prothrombin were compared with results of prothrombin time (PT) assays for patients undergoing oral anticoagulant therapy. Mean concentrations of total and native prothrombin in non-anticoagulated patients were 119 ± 13 µg/ml and 118 ± 22 µg/ml, respectively. In anticoagulated patients, INR values ranged as high as 9, and levels of total prothrombin and native prothrombin decreased with increasing INR to minimum values of 40 µg/ml and 5 µg/ml, respectively. Des-carboxy-prothrombin increased with INR, to a maximum of 60 µg/ml. The strongest correlation was observed between native prothrombin and the reciprocal of the INR (1/INR) (r = 0.89, slope = 122 µg/ml, n = 200). These results indicated that native prothrombin varied over a wider range and was more closely related to INR values than either total or des-carboxy-prothrombin. Levels of native prothrombin were decreased 2-fold from normal levels at INR = 2, indicating that the native prothrombin antigen assay may be a sensitive method for monitoring low-dose oral anticoagulant therapy. The inverse relationship between concentration of native prothrombin and INR may help in identification of appropriate therapeutic ranges for oral anticoagulant therapy.


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