Disease relevance of International Normalized Ratio

• In a randomized, double-blind, placebo-controlled trial, we assessed the efficacy and safety of adding aspirin (100 mg per day) to warfarin treatment (target international normalized ratio, 3.0 to 4.5) in 370 patients with mechanical heart valves or with tissue valves plus atrial fibrillation or a history of thromboembolism [1].
• CONTEXT: Warfarin is highly effective in preventing thromboembolism, but increases the risk of hemorrhage, particularly at an international normalized ratio (INR) greater than 4 [2].
• I examined the degree of factor deficiency for a given INR in patients with liver disease and controls receiving stable-dose warfarin [3].
• Bleeding complications were hemorrhagic stroke, major extracranial bleeding, and false aneurysm. "Optimal" anticoagulation was defined as an INR in the target range for at least 70% of the follow-up time [4].
• We conclude that, in patients with liver failure, INR fails to yield a PT expression independent of the thromboplastin used and only activity percentage expression may provide a common international scale of PT reporting [5].

Psychiatry related information on International Normalized Ratio

• There was no correlation between alcohol consumption and severity of hepatotoxicity (mean INR and the serum creatinine levels over the first 7 days after the overdose) [6].
• Increase in international normalized ratio after smoking cessation in a patient receiving warfarin [7].
• Warfarin (dose-adjusted to a target INR of 2.0-3.0) has been well established to reduce this risk of stroke by 68% (95% CI 50-79%), while aspirin provides a risk reduction of 21% (95% CI 0-38%) [8].

High impact information on International Normalized Ratio

• METHODS: In a multicenter, double-blind, randomized trial, we compared the effect of warfarin (at a dose adjusted to produce an international normalized ratio of 1.4 to 2.8) and that of aspirin (325 mg per day) on the combined primary end point of recurrent ischemic stroke or death from any cause within two years [9].
• Of the 902 patients enrolled, 5 were later excluded because they had congenital protein C deficiency; 443 were randomly assigned to receive six weeks of oral anticoagulant therapy with a targeted international normalized ratio (INR) of 2.0 to 2.85, and 454 were randomly assigned to receive six months of such therapy [10].
• Acetaminophen ingestion was independently associated in a dose-dependent manner with having an INR greater than 6.0 (P for trend <.001) [2].
• The rate of events was similar between sexes, coumarin type, size of enrolling centre, and target INR [11].
• These proteins were also found in the cell lines AR42J, BON, RIN, and INR [12].

Chemical compound and disease context of International Normalized Ratio

• The Model for End-Stage Liver Disease (MELD) consists of serum bilirubin and creatinine levels, International Normalized Ratio (INR) for prothrombin time, and etiology of liver disease [13].
• METHODS: Serial assays of APTT, international normalized ratio, heparin levels, and functional levels of prothrombin (factor II) and factors VII and X were performed in 24 patients with acute venous thromboembolism who were treated with concomitant continuous intravenous heparin and warfarin [14].
• METHODS: We undertook a pooled analysis of 7329 patients with nonvalvular atrial fibrillation from the Stroke Prevention Using Oral Thrombin Inhibitor in Atrial Fibrillation III and V trials to compare bleeding outcomes in patients who received ximelagatran, 36 mg twice daily, or warfarin sodium (target international normalized ratio, 2.0-3.0) [15].
• BACKGROUND: The risk of hemorrhage when coumarin anticoagulants are used sharply increases when the international normalized ratio (INR) is > or = 6 [16].
• Fluindione inhibited thrombus formation on TF-coated coverslips in a dose-dependent manner by 50% and 80% at INR 1.5 to 2.0 and INR 2.1 to 3.0, respectively (P<0.05) [17].

Biological context of International Normalized Ratio

• To evaluate whether patients could be reliably monitored with a less intense regimen, we anticoagulated patients with warfarin for several months using a target INR range of 1.3 to 1.6 as determined by prothrombin time (PT) using a sensitive thromboplastin (Dade IS, International Sensitivity Index [ISI] = 1.3) [18].
• Associations between a pharmacodynamic index (reduction in factor VII activity and international normalized ratio [INR] change) and several genetic polymorphisms (VKORC1: -4931T>C, -4451C>A, -2659G>C, -1877A>G, -1639G>A, 497C>G, 1173C>T, and CYP2C9*3) were investigated using haplotype and univariate analyses [19].
• Analysis of transcriptional regulation of the alpha FR gene have revealed two promoter regions, P1 and P4, flanking exons 1 and 4, respectively, and a requirement for three SP1 sites and an INR element for optimal P4 activity [20].
• During capecitabine treatment, the effect of warfarin on the baseline corrected AUC of the International Normalized Ratio (INR) increased by 2.8 times (90% CI, 1.33 to 5.70), with the maximum observed INR value almost doubling [21].
• Reporter gene assays confirm that the region of the AM promoter containing the INR is the target of Myc-mediated repression [22].

Anatomical context of International Normalized Ratio

• The eosinophil count before allergen challenge was low in 79.5% of positive INR and in 76.5% of negative INR, whereas it was high in 20.5% of positive INR and in 23.5% of negative INR [23].
• Using "reagent-specific" calibration procedures, relatively homogeneous INR were obtained for the fresh coumarin plasmas, whatever type of calibrant was used [24].
• Peak serum aspartate aminotransferase, bilirubin levels, and international normalized ratio after LDLT were significantly higher in the H Group, as was mean ascitic fluid volume [25].
• Fifteen patients with differentiated thyroid cancers and continued international normalized ratio (INR)-adjusted therapy with coumarin derivates were included in this retrospective analysis [26].
• Hemoglobin, hematocrit, thrombocyte count, prothrombin time, activated partial thromboplastin time, international normalized ratio, arterial pH, von Willebrand factor, viscosity, platelet aggregation, and bleeding time were measured 1 h pre-, intra-, and postanesthesia [27].

Associations of International Normalized Ratio with chemical compounds

• INTERVENTION: Patients were randomly assigned to receive enoxaparin (30 mg subcutaneously every 12 hours) or adjusted-dose warfarin (international normalized ratio, 2.0 to 3.0) [28].
• RESULTS: In 68 of 71 patients (96%), oral vitamin K1 lowered the INR from between 5.0 and 10.0 to less than 5.0 without inducing resistance to further anticoagulation [29].
• RESULTS: The mean INR was 2.75 (range, 2.02 to 3.81) at baseline and increased to 8.04 (range, 5.32 to 20.0) after methylprednisolone administration [30].
• Elevated international normalized ratio associated with trovafloxacin [31].
• 0. Genetic analyses for CYP2C9 (*2 and *3 alleles) and VKORC1 (-1639 polymorphism) were performed and venous INR and plasma R- and S-warfarin concentrations determined [32].

Gene context of International Normalized Ratio

• DESIGN AND METHODS: CYP2C9 genotyping was performed in 325 acenocoumarol-treated patients (INR target between 2.0 and 3.0) and in an additional group of 84 patients with repeated bleeding [33].
• Dual promoters initiate hASH1 transcription, with the predominant site being an evolutionarily conserved initiator (INR) element [34].
• We cloned the promoter region of the murine mac25 gene and found five repeats of CCAAT sequences, four Sp1 sites, a TATA-like sequence, and an initiator (INR) sequence [35].
• By contrast, no significant changes were observed in CRP (2.2+/-0.7 vs. 1.7+/-0.7 mg/l), WCC (7.2+/-0.5 vs. 6.8+/-0.5 10(9) cells/l), APTR (0.91+/-0.02 vs. 0.93+/-0.02), INR (0.92+/-0.01 vs. 0.91+/-0.01), vWF (103+/-8 vs. 102+/-9 U/dl), and VIII:C (120+/-8 vs. 107+/-8 U/dl) levels [36].
• Unexpectedly, we found relatively high levels of functional protein S in a group of patients on long-term warfarin therapy whose INR ranged from 1.1 to 3 [37].

Analytical, diagnostic and therapeutic context of International Normalized Ratio

• Two large clinical trials have demonstrated that fixed-dose oral ximelagatran, 36 mg twice daily, administered without coagulation monitoring, prevents stroke and systemic embolic events in patients with nonvalvular AF as effectively as well-controlled, adjusted-dose warfarin (international normalized ratio 2.0 to 3.0) [38].
• Length of stay in intensive care unit, postoperative hospital stay, laboratory results (bilirubin, INR, and LFTs), morbidity, and the different types of grafts in the 3 different periods were compared [39].
• CONCLUSIONS: Older age itself and not as a marker for polypharmacy or increased number of medical conditions is associated with lower requirements for warfarin and a greater hemoglobin decrease postoperatively even when the proportion of time the INR fell within the therapeutic range is controlled [40].
• METHODS: We randomly assigned 1279 patients 3 days after total hip replacement surgery to fixed-dose subcutaneous low-molecular-weight heparin (reviparin sodium, 4200 anti-Xa IU) or adjusted-dose oral anticoagulant (international normalized ratio, 2-3; acenocoumarol) for a 6-week period [41].
• Design: Population-based cohort study in a sample of the Rotterdam Study. SUBJECTS: All patients who were treated with acenocoumarol or phenprocoumon in the study period from April 1, 1991 through December 31, 1998 and for whom INR data were available [42].

References