Prothrombin Time International Research Articles

Association Between the Prothrombin Time-International Normalized Ratio and Concomitant Use of Antibiotics in Warfarin Users: Focus on Type of Antibiotic and Susceptibility of Bacteroides fragilis to Antibiotics.

The difference in type of antibiotics and susceptibility of Bacteroides fragilis to antibiotics may influence warfarin anticoagulation. However, these influences have not been clarified in clinical settings. This study aimed to investigate association the between the prothrombin time-international normalized ratio (PT-INR) and concomitant use of antibiotics in a real-world population of warfarin users. This was a single-center cohort study using data from health records and included patients who received β-lactams (BLs)/fluoroquinolones (FQs) during ongoing warfarin treatment (2011-2015) at Hamamatsu University Hospital in Japan. Antibiotics were categorized into those to which B fragilis is susceptible (BLsus, FQsus) and those to which it is not (BLnon, FQnon) and into those given orally (BLpo, FQpo) or intravenously (BLiv, FQiv). Outcomes were excessive PT-INR and changes in PT-INR, defined as the ratio (INR ratio) and difference (ΔINR) of maximum PT-INR and baseline PT-INR. Excessive PT-INR was graded as INR ratio of >1.5 or >2.5. A total of 1185 warfarin users were included. The proportion of INR ratio >2.5 in FQiv was higher than in BLiv (95% CI: 1.59-46.5). The proportions with an INR ratio of >1.5 in BLsus and FQsus were higher than in BLnon (1.72-14.1) and FQnon (1.05-9.36), respectively. ΔINR values in FQpo, FQiv, and FQsus were higher than those in BLpo, BLiv, and FQnon, respectively. Concomitant use of FQs, or of antibiotics to which B fragilis is susceptible is associated with higher risk of excessive anticoagulation. These findings would contribute to safe and proper antibiotic treatment in warfarin users.

The prognostic value of routine coagulation tests for patients with heat stroke

To evaluate the prognostic value of routine coagulation tests for patients with heat stroke. This was a multi-center retrospective study. Patients who arrived at the hospital <24h after the onset of Heat Stroke (HS) were included. The routine coagulation variables were detected within 24h after the onset, including the lowest platelet count (PLC). 60-day mortality rate was 20.9%. The median Prothrombin Time-International Normalized Ratio (PT-INR) of the non-surviving patients was significantly higher than that of the survivors (P<0.01). The median Activated Partial Thromboplastin Time (APTT) in non-surviving patients was significantly higher than in the surviving patients (P<0.01). A Cox regression analysis revealed that 60-day mortality was associated with PT-INR (P=0.032) and APTT (P=0.004). The optimal PT-INR point for predicting 60-day mortality rate was 1.7. The optimal APTT point for predicting 60-day mortality was 51.45. Patients with increased PT-INR (≥1.7) levels had, overall, a significantly reduced survival time (P<0.01). Patients with elevated APTT (≥51.45) also had a decrease in survival time (P<0.01). The prognostic scoring, with increased PT-INR (≥1.7) and prolonged APTT (≥51.45) at one point each, was also demonstrated to be useful in predicting 60-day mortality. Patients whose temperature fell to 38.9°C within 30min had significantly lower levels of PT-INR and APTT within 24h than those who took longer to cool down. A prolonged APTT and elevated PT-INR within 24h are independent prognostic factors of 60-day mortality in HS.

Role of Prothrombin time International normalized ratio and activated partial thromboplastin time in beta thalassemia major: A cross sectional study

Role of Prothrombin time International normalized ratio and activated partial thromboplastin time in beta thalassemia major: A cross sectional study - IJPO- Print ISSN No: - 2394-6784 Online ISSN No:- 2394-6792 Article DOI No:- 10.18231/j.ijpo.2019.047, Indian Journal of Pathology and Oncology-Indian J Pathol Oncol

Absence of Interactions between Denosumab and Warfarin in Women with Osteoporosis

The monoclonal antibody denosumab reduces bone resorption. Warfarin is an oral anticoagulant used in the prevention and treatment of thrombosis. To date, there have been no studies on the interaction between warfarin and denosumab. The aim of the present study was to assess the maintenance of the Prothrombin Time International Normalized Ratio (INR) in the therapeutic range (TTR) in women under treatment with warfarin and denosumab, in order to evaluate the pharmacological interference of denosumab. No variations of the median TTR were found after undergoing treatment with denosumab: this shows that the intake of denosumab does not require additional checks in anticoagulated patients.

Within-subject biological variation of activated partial thromboplastin time, prothrombin time, fibrinogen, factor VIII and von Willebrand factor in pregnant women.

During pregnancy, interpretation of results from coagulation parameters can be difficult as the physiological changes that occur may affect the biochemical parameters. The aim of this study was to describe the normal course of five coagulation parameters in healthy pregnancies, and to estimate the within-subject biological variation (CVI). Blood samples were obtained every 4th week during pregnancy and three samples after delivery in 20 healthy women and every 4th week during a 40-week period in 19 healthy non-pregnant women. Activated partial thromboplastin time (APTT), prothrombin time (PT), PT International Normalized Ratio (INR), fibrinogen, factor VIII clot (FVIII:C) and von Willebrand factor antigen (vWF:Ag) were analyzed. The physiological changes during pregnancy were compensated by transformation into multiples of the median (MoM) and it is natural logarithm (lnMoM) in order to establish a kind of steady state, and CVI was calculated from the standard deviation. During pregnancy, APTT, PT and INR remained unchanged or decreased, depending upon the reagent used, while fibrinogen, FVIII:C and vWF:Ag increased gradually until delivery. The CVI in pregnancy were 2.2 and 3.0% for APTT, 2.3 and 2.6% for PT, 2.2 and 2.3% for INR, 7.2% for fibrinogen, 12.2% for FVIII:C and 11.3% for vWF:Ag, and corresponded with the CVI in non-pregnant women. Transformation of coagulation parameters in healthy pregnancies to MoM is a tool to establish a kind of steady state. Although there is a physiological change in these coagulation parameters during pregnancy, the CVI after lnMoM transformation was comparable with the CVI of non-pregnant women.

Change in Prothrombin Time International Normalized Ratio due to Drug Interaction between Celecoxib and Warfarin

Change in Prothrombin Time International Normalized Ratio due to Drug Interaction between Celecoxib and Warfarin

A Bayesian decision support tool for efficient dose individualization of warfarin in adults and children

BackgroundWarfarin is the most widely prescribed anticoagulant for the prevention and treatment of thromboembolic events. Although highly effective, the use of warfarin is limited by a narrow therapeutic range combined with a more than ten-fold difference in the dose required for adequate anticoagulation in adults. An optimal dose that leads to a favourable balance between the wanted antithrombotic effect and the risk of bleeding as measured by the prothrombin time International Normalised Ratio (INR) must be found for each patient. A model describing the time-course of the INR response can be used to aid dose selection before starting therapy (a priori dose prediction) and after therapy has been initiated (a posteriori dose revision).ResultsIn this paper we describe a warfarin decision support tool. It was transferred from a population PKPD-model for warfarin developed in NONMEM to a platform independent tool written in Java. The tool proved capable of solving a system of differential equations that represent the pharmacokinetics and pharmacodynamics of warfarin with a performance comparable to NONMEM. To estimate an a priori dose the user enters information on body weight, age, baseline and target INR, and optionally CYP2C9 and VKORC1 genotype. By adding information about previous doses and INR observations, the tool will suggest a new dose a posteriori through Bayesian forecasting. Results are displayed as the predicted dose per day and per week, and graphically as the predicted INR curve. The tool can also be used to predict INR following any given dose regimen, e.g. a fixed or an individualized loading-dose regimen.ConclusionsWe believe that this type of mechanism-based decision support tool could be useful for initiating and maintaining warfarin therapy in the clinic. It will ensure more consistent dose adjustment practices between prescribers, and provide efficient and truly individualized warfarin dosing in both children and adults.Electronic supplementary materialThe online version of this article (doi:10.1186/s12911-014-0128-0) contains supplementary material, which is available to authorized users.

Development and Application of a Self-management Program based on Prothrombin INR Monitoring for Patients with Cardiac Valve Replacement

The purpose of this study was to develop and evaluate a self-management program based on INR monitoring for patients with cardiac valve replacement. This program was comprised of five weekly sessions based on Sousa's Enhance-Behavior Performance Model. The first session included individual teaching, and the other four sessions included Prothrombin Time International Normalized Ratios (PT INR) self-monitoring, telephone counseling and self-management checklist recording. Participants were patients who had cardiac valve replacement. They were randomly assigned to the experimental or control group. Sixteen in the experimental group participated in the self-management program and seventeen in the control group participated in general care. Self-management knowledge, self-efficacy, self-management behavior and PT INR were measured as dependent variables. Data were analyzed using Mann Whitney U-test, t-test and ANCOVA. The experimental group showed significantly higher post-test scores in self-management knowledge (t=5.86, p<.001), self-efficacy (F=18.32, p<.001), and self-management behavior (t=3.44, p=.002) compared to the control group. Also, the experimental group showed significantly higher frequency in maintaining the treatment range of PT INR compared to the control group (χ²=4.80, p=.028). The results of the research on the self-management program based on PT INR monitoring showed that it is effective in improving self-management knowledge, self-efficacy, and self-management behavior as well as maintaining treatment range of PT INR of patients with cardiac valve replacement.

(651) - Improving Prothrombin Time International Normalized Ratio (INR) Control in Left Ventricular Assist Device (LVAD) Patients with Computerized Decision Support

(651) - Improving Prothrombin Time International Normalized Ratio (INR) Control in Left Ventricular Assist Device (LVAD) Patients with Computerized Decision Support

Impact of prothrombin time–International Normalized Ratio on outcome of patients with septic shock receiving polymyxin B cartridge hemoperfusion

Although most patients with septic shock have a poor outcome, some may survive after blood purification treatment such as polymyxin B cartridge hemoperfusion (PMX). To explore the most significant characteristic associated with 28-day mortality in patients with septic shock receiving PMX. Between April 2006 and March 2008, 116 patients with septic shock who had received PMX in a prospectively collected multicenter collaborative study were enrolled. Uni- and multivariate analyses using the Cox proportional hazard model were performed to assess the most significant clinical characteristic that was associated with 28-day mortality. Among 33 clinicolaboratory characteristics, receiver operating characteristic (ROC) curve analyses selected 12 characteristics with recommended cutoff values such as HCO(3)(-) (≤19.8/>19.8; mEq/L), base excess (≤-5.35/>-5.35; mEq/L), diastolic blood pressure (≤48/>48 mmHg), mean arterial pressure (≤73/>73 mmHg), pH (≤7.29/>7.29), interleukin-6 (≤19,150/>19,150 pg/dL), prothrombin time-International Normalized Ratio (PT-INR; ≤2.05/>2.05), predictive value of Acute Physiology and Chronic Health Evaluation II (APACHE II; ≤0.4/>0.4), pyruvate (≤1.82/>1.82 mg/dL), APACHE II score (≤21/>21), acetate/pyruvate ratio (≤19/>19), and acetate (≤44.8/>44.8 mg/dL) on the basis of large area under the ROC curves for 28-day mortality. The results of uni- and multivariate analyses using these selected characteristics revealed that only PT-INR (≤2.05/>2.05; hazard ratio, 2.823; 95% CI, 1.243-6.412; P = .013) was associated with 28-day mortality. Survival curve analysis demonstrated a significant difference in 28-day mortality between patients with lower (≤2.05) and higher (>2.05) PT-INR (P < .001). Prolonged PT-INR is an independent risk factor for 28-day mortality in patients receiving PMX for septic shock.

Fondaparınux Versus Nadroparın for Preventıon of Venous Thromboembolısm After Electıve Hıp and Knee Arthroplasty

ObjectiveTo evaluate the efficacy and safety of fondaparinux compared with nadroparin for prevention of venous thromboembolism after arthroplasty. Patients and methodsOne hundred fifteen patients were randomized into 2 treatment groups. Patients were given fondaparinux in Group I and nadroparin in Group II. Measurements were performed on Days 1, 5, and 21. The wound area was assessed with a subjective visual analog scale. ResultsThe blood counts, clinical biochemical tests, and coagulation tests (ie, thrombin time, partial thromboplastin time, activated partial thromboplastin time, fibrinogen, prothrombin time–International Normalized Ratio, and antithrombin III activity) did not show statistically significant differences between Group I and Group II. In both study groups, anti-factor Xa activities increased significantly on the fifth and 21st day. The scores of the subjective visual analog scale showed significance on Day 21. ConclusionsOur results confirm the safety and efficacy of both fondaparinux and nadroparin for prophylaxis after major orthopedic surgery.

Study on Tooth Extraction in Patients Maintained on Oral Anticoagulant

We retrospectively reviewed and discussed hematostatic managements for tooth extraction in patients maintained on oral anticoagulant.From 2001 to 2007,109 patients maintained with oral anticoagulant treatment underwent a total of 143 occasions of tooth extraction in our department.At the time of tooth extraction, oral anticoaglant medication was maintained on 76 occasions (53%), and had been discontinued on 55 occasions (38%).Postoperative bleeding happened in 5 cases (9.1%)in patients without interruption of oral anticoagulant,and in 3 cases (3.9 %)in patients with interruption.There was no significant difference in the Prothrombin Time International Normalized Ratio (PT-INR)and in postoperative hemostatic procedures between them.The results of this study suggest that dental extraction can be performed without modification of oral anticoagulant treatment in cases where the PT-INR is less than 3.0.Strict local hemostatic procedures are necessary to prevent postoperative bleeding.Shinshu Med J 58 : 301―305, 2010 (Received for publication June 10,2010;accepted in revised form July 28,2010)

Plasma S/R ratio of warfarin co-varies with VKORC1 haplotype

We recently reported that the low-dose VKORC1*2 haplotype is an important genetic determinant for warfarin dose requirement and is associated with difficulties to attain stable therapeutic prothrombin time--International Normalized Ratio in patients undergoing anticoagulation therapy. The aim of this study was to investigate whether patients with VKORC1*2 compared with patients carrying high-dose haplotypes VKORC1*3 or VKORC1*4 had different warfarin S/R ratios in their plasma, and whether that was related to CYP2C9 variants CYP2C9*2 and CYP2C9*3 or other factors. Samples from patients previously haplotyped for VKORC1 and measured for plasma warfarin concentration were genotyped for the CYP2C9 variants CYP2C9*2 and CYP2C9*3. Nonparametric statistical analysis was performed to elucidate whether there was any significant difference in the warfarin S/R ratio between the two patient groups. Our result shows that there is a significant difference (P<0.01) in warfarin S/R ratios between VKORC1*2 and VKORC1*3 or VKORC1*4 patients. This difference did not originate from CYP2C9 variants CYP2C9*2 and CYP2C9*3. We speculate that VKORC1 haplotypes possibly are linked to some unidentified factors involved in the metabolic clearance of warfarin enantiomers. Dose-dependent variations in (S)-warfarin and (R)-warfarin clearance in these patients can also be a probable explanation for the difference in warfarin S/R ratios.

Poor Agreement among Prothrombin Time International Normalized Ratio Methods: Comparison of Seven Commercial Reagents

Prothrombin time (PT) has long been the most popular test for monitoring oral anticoagulation therapy. The International Normalized Ratio (INR) was introduced to overcome the problem of marked variation in PT results among laboratories and the various recommendations for patient care. According to this principle, all reagents should be calibrated to give identical results and the same patient care globally. This is necessary for monitoring of single patients and for application of the results of anticoagulation trials and guidelines to clinical practice. We took blood samples from 150 patients for whom oral anticoagulation had been prescribed. Plasmas were separated and PTs determined by use of seven commercial reagents and four calibrator sets. The differences in results were assessed by plotting, for each possible pair of methods, the differences in INR values for each sample against the mean INR value (Bland-Altman difference plots). Mean results differed significantly (P <0.001) for 17 of 21 possible paired comparisons of methods. Only two pairs of methods produced very similar results when assessed for problems of substantial differences in INR values; a significant, systematic increase in the difference with INR; and a significant systematic increase in the variation in difference with increasing INR values. The agreement among several (and perhaps most) commercial INR methods is poor. The failure of current calibration strategies may severely compromise both the monitoring of individual patients and the application of oral anticoagulation guidelines and trial results to clinical practice.

Importance of Device Evaluation for Point-of-Care Prothrombin Time International Normalized Ratio Testing Programs

To determine the accuracy of 2 commercially available point-of-care devices relative to plasma international normalized ratio (INR) values. Point-of-care INR testing was performed with the CoaguChek and ProTime 3 devices in consecutive patients attending an anticoagulation clinic between June 18, 2003, and August 6, 2003. Results were compared with plasma INRs using a sensitive thromboplastin (International Sensitivity Index, 1.0). Ninety-four patients agreed to participate in the study. Relative to the plasma INR, values were in agreement +/-0.4 INR unit 82% and 39% of the time for the CoaguChek and ProTime 3 devices, respectively. The mean +/- SD CoaguChek INRs were 0.2+/-0.31 unit lower, whereas ProTime 3 INRs were 0.8+/-0.68 unit higher than plasma INR values. Treatment decisions based on these data would have resulted in inappropriate dose adjustments 10% and 22% of the time for these 2 respective devices. Correlation with plasma was greater for the CoaguChek (r2=0.90) compared with the ProTime 3 device (r2=0.73). Optimal warfarin treatment requires accurate measurement of the INR. The choice of a point-of-care device for INR management depends on the reliability of INR data generated by the device.