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Accuracy, reproducibility and clinical utility of the CoaguChek S portable international normalized ratio monitor in an outpatient anticoagulation clinic.

The accuracy and reproducibility of the CoaguChek S, and its clinical agreement with conventional laboratory international normalized ratio (INR) determination, were evaluated in an outpatient anticoagulation clinic setting. Forty-three patients provided 248 paired INR measurements for analysis. The paired results were highly correlated (r = 0.90). The mean coefficient of variation for the CoaguChek S for a random sample of 21 patients with three repeated tests each, was 4%. Clinical applicability was also measured by discrepant INR values, as defined in the literature by expanded and narrow agreement, and by INR values resulting in a different clinical decision by a blinded haematology registrar. Expanded agreement and narrow agreement between the two INR values occurred 90 and 88% of the time, respectively. The stricter criteria set down by the clinician resulted in 73% of paired results producing the same dosage decision. The CoaguChek S displayed good correlation with laboratory determination of INR and compared relatively well with expanded and narrow clinical agreement criteria.

Ambulatory Care Facilities↗

[Relationship between prothrombin time international normalized ratio and thrombo test (%)].

OBJECTIVES: The optimal therapeutic range for laboratory evaluation of oral anticoagulant therapy is now defined by the prothrombin time international normalized ratio (PT-INR). However, the thrombo test (TT), an alternative method to measure intensity of anticoagulation, is also currently used throughout Japan. The relationship between PT-INR and TT (%) has yet to be clarified. This study investigated the relationship between PT-INR and TT (%). METHODS: The PT-INR and TT (%) were simultaneously measured of 505 consecutive samples from patients treated with warfarin in our hospital. Fourteen functions were used for regression analyses: a fractional function (Y = a/X + b), a square root function (Y = aX0.5 + b), a natural logarithmic function (Y = a.lnX + b), a power series function (Y = aXb), a quotient function (Y = abX), and polynomial functions [Y = anXn + an - 1Xn - 1 +......+ a1X1 + b, (1 < or = n < or = 9)]. The results were confirmed by the same methods in 383 samples and 296 samples from another two laboratories. RESULTS: The power series function showed the most significant (p < 0.0001) and highest adjusted R2 (0.858) correlation, with a regression formula of TT (%) = e4.48 (PT-INR)-2.09 in our laboratory. Using the same analyses, the power series function also showed the most significant and highest adjusted R2 in samples from the other two laboratories. CONCLUSIONS: This study showed that a power series function is the most appropriate for expressing the relationship between PT-INR and TT (%) among the 14 functions. The function between PT-INR and TT (%) is mainly derived from the relationship between TT (%) and TT (sec). Both internal validity and external validity confirmed the relationship between PT-INR and TT (%).

Aged↗

[Increased acceptance of the International Normalized Ratio (INR) as a monitoring parameter of oral anticoagulation therapy in Germany. GELIA Study Group].

In 1994 the German Cardiac Society recommended the International Normalized Ratio (INR) instead of "Quick's test" for the long-term management of oral anticoagulation therapy. Parallel cardiac surgical centers in Germany and Switzerland started patient recruitment for the GELIA study (German Experience with Low Intensity Anticoagulation). By the end of 1996, 862 consecutive patients with mechanical heart valve replacement had been enrolled. According to the protocol of the GELIA study, intensity of anticoagulation, methods used to control the oral anticoagulation therapy as well as other factors relevant for the anticoagulation management are reported every three months. The so far accumulated data material of the GELIA study seemed, therefore, appropriate to analyze potential changes in the acceptance of INR during the time period 1993-1996. Potential differences in the anticoagulation management were analyzed separately according to the time of enrollment of patients and changes during the follow up period, e. g., a switch from "Quick's test" to INR. Taking the time of enrollment into account, the percentage of patients who had INR-controlled oral anticoagulation therapy increased from 0% (1993), 14.3% (1994), 63.2% (1995) to 74.2% in 1996. During the follow up, there was a change from "Quick's test" to INR controls in 7 patients (1994; 2.1%), 67 patients (1995; 10.5%) and 142 patients (1996; 17.3%) with a consequent increase of INR controlled patients to a total of 34.2% in 1994, 52.0% in 1995, and 73.9% in 1996.

Administration, Oral↗

Optimal intensity of international normalized ratio in warfarin therapy for secondary prevention of stroke in patients with non-valvular atrial fibrillation.

OBJECTIVE: To determine optimal intensity of international normalized ratio (INR) of warfarin therapy for the prevention of ischemic events in patients with non-valvular atrial fibrillation (NVAF), we evaluated the risk of severe recurrent stroke, systemic embolism and major hemorrhagic complications according to INR and age. METHODS: We carried out the National Cardiovascular Center (NCVC) NVAF Secondary Prevention Study and analyzed data with those of Japanese Nonvaluvular Atrial Fibrillation-embolism Secondary Prevention Cooperative Study to elucidate relationships of major stroke and hemorrhage with INR and age. In both studies, all patients with cardioembolic stroke were given warfarin, monitored with INR every month, and followed up for primary endpoints of stroke and embolism to other parts of the body, and for secondary endpoints of major hemorrhagic complications requiring blood transfusion or hospitalization. We regarded ischemic stroke with NIH stroke scale (NIHSS) score > or = 10 or systemic embolism as a major ischemic event and ischemic stroke with NIHSS score <10 as a minor ischemic event. There were 203 patients enrolled in total (152 men and 51 women). We investigated the relationship of occurrence of the events with INR and age, and calculated the incidence rates of major and minor ischemic events and major hemorrhagic events. RESULTS: During the mean follow-up of 653 days, major ischemic stroke and systemic embolism occurred in only 4 patients with INR <1.6, minor ischemic stroke in 10 patients with INR 1.50-2.66, and major hemorrhage in 9 patients with INR 2.30-3.56. Patients with major ischemic or hemorrhagic events were significantly older than those without any events (75+/-4 years vs. 67+/-7 years, p<0.001 unpaired t test). Incidence rates of any events at INR < or = 1.59, 1.60-1.99, 2.00-2.59 and > or = 2.60 were 8.6%, 3.8%, 4.9%, and 25.7%/year, respectively. CONCLUSIONS: Major ischemic or hemorrhagic events occur often in the elderly NVAF patients, in whom an INR value of between 1.6 and 2.6 seems optimal to prevent such events.

Aged↗

Comparison of a daily fixed 2.5-mg warfarin dose with a 5-mg, international normalized ratio adjusted, warfarin dose initially following heart valve replacement.

Patients starting oral anticoagulant therapy after heart valve replacement initially require a lower target international normalized ratio (INR) (2.0, range 1.5 to 2.6) because of a higher risk of bleeding until pericardial wires are removed. In a previous retrospective analysis, we observed a higher sensitivity to warfarin in these patients compared with nonsurgical patients. In a randomized clinical trial, we compared a fixed, lower dose of warfarin (2.5 mg) with the standard treatment consisting of a 5-mg loading dose, then adjusted to the target INR during the first 5 days of anticoagulation. INRs were measured daily, but the fixed dose was only modified on day 3 if the INR was <1.5 or >3.0. One hundred ninety-seven patients were considered eligible for the study. The 2 groups were well matched according to age, gender, body mass index, concomitant treatments, and type of valves implanted. The proportion of INRs >2.6 during the study period was 42.5% in the 5-mg group and 26.2% in the 2.5-mg group (p <0.05), and the proportion of INRs >3.0 on day 3 was 23.9% and 9.5% (p <0.05), respectively. In the 2.5-mg group, 35.7% of patients had an INR <1.5 on day 3 and had the dose increased (vs 3.5%, p <0.001); however, in the 5-mg group, 95.6% had the initial dose reduced, 49.6% had the dose withheld for at least 1 day, and the mean dose during the 5 days of study was 3.08 mg. Average time to achieve therapeutic range was higher in the 2.5-mg group (2.72 vs 1.98 days, p <0.0001), but the approach to the targeted INR was more regular, and the gap between target and mean INR on day 5 was smaller. There were no bleeding or thromboembolic complications in either group. Thus, a lower loading dose of warfarin in patients after heart valve replacement reduces excessive anticoagulation and offers a more regular achievement of the therapeutic target by reducing the number of dose adjustments. Daily monitoring of the INR is still recommended.

Aged↗

Effect of low-dose aspirin on the international normalized ratio variability in patients with mechanical heart valve prostheses.

An increased risk of bleeding is associated with a more intense oral anticoagulation, a greater international normalized ratio (INR) variability and the use of aspirin. We studied the INR variability of patients (n = 121) with modern heart valves who had been prospectively randomized to receive acenocoumarol at a targeted INR of 2.4-3.6 plus aspirin 100 mg/day or acenocoumarol alone at the same dosage, to evaluate whether aspirin influences variability and thus the risk of bleeding. Variability was similar in patients with no events regardless of the use of aspirin. A statistically significantly higher variability was observed in patients with bleeding events independently of the use of aspirin. Nevertheless, the concomitant use of aspirin in patients with a high variability should be monitored closely and thoroughly.

Acenocoumarol↗

Has the Quick or the Owren prothrombin time method the advantage in harmonization for the International Normalized Ratio system?

Prothrombin time (PT) is the most commonly used coagulation test in health care. We sought here to compare two major PT methods (Quick and Owren) for harmonization of International Normalized Ratio (INR) results. We measured PT with an ACL 7000 analyser. We used three Owren and three Quick reagents for PT, and estimated the International Sensitivity Index (ISI) for each reagent using two local and two manufactured ISI calibrator sets. The coagulation time was measured using five different normal plasmas to assess variation for every reagent and both methods. We studied the analytical bias for every reagent and both methods at INR = 1.0 and INR = 2.5. The mean percentage coefficient of variation of the Owren reagent ISI was 2.40% and that of the Quick reagent ISI was 12.85%. The mean percentage coefficient of variation of normal plasma seconds for the Owren method was 2.54% and that for Quick was 4.02%. The absolute error at INR = 1.0 and INR = 2.5 was 0.00 and 0.04 INR for Owren, and 0.01 and 0.16 INR for Quick. The Owren PT method has the advantage over the Quick PT method in ISI calibration, normal plasma variation, within-run analytical variation and absolute error at INR = 2.5. The INR system is more demanding on analytical quality than earlier units (Ratio,%). The data would indicate that the Owren PT method has advantages over the Quick PT method in harmonization of the INR system.

Calibration↗

Poor agreement among prothrombin time international normalized ratio methods: comparison of seven commercial reagents.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Administration, Oral↗

Accuracy of international normalized ratio determined by portable venous-blood coagulation monitor versus a central laboratory.

BACKGROUND: The CoaguChek is a portable monitor unit for measuring the international normalized ratio (INR). The purpose of the study was to evaluate the accuracy of a portable prothrombin time (PT) monitor (CoaguChek, Roche Diagnostics, Mannheim, Germany) compared with the laboratory method. MATERIAL AND METHOD: Paired venous blood INRs were performed in 220 consecutive outpatient tests mainly in anticoagulated (n = 210) and non-anticoagulated (n = 10) individuals. Accuracy was evaluated in 220 tests by parallel assessment of INRs (CoaquChek and laboratory). Accuracy was determined using statistic regression analysis and clinical agreement (expanded and narrow criteria). Agreement in dual INR measurement also was evaluated as a function of increasing INR. RESULTS: The CoaguChek significantly correlated with the laboratory measurement (r = 0.89). The proportion of dual INR measurements that satisfied the clinical relevant expanded, and narrow agreement criteria was 90 per cent and 86 per cent respectively. Eighty-two per cent of all dual measurements were within 0.5 INR units. The accuracy of the portable monitor was greatest for INR values less than 3.0; above this INR level the portable monitor overestimated laboratory INR values. CONCLUSIONS: The CoaguChek is an accurate alternative to laboratory assessment of INR at values < 3.0. The authors suggest the use of the monitor in non anticoagulated patients or anticoagulated patients at values less than 3, as most physicians in Thailand prefer lower INR than in Western countries.

Aged↗

Inaccuracy of international normalized ratio (INR) measurements and suggestions for improved WHO guidelines for calibration of reference preparations--a statistical study.

Numerous empirical studies show that the accuracy of international normalized ratio (INR) measurements is unsatisfactory and worse than generally expected. We demonstrate that a plausible reason for this large inaccuracy is a conventional calibration procedure of reference preparations with (i) an erroneous assumption that the line relating logarithmic prothrombin times (log PTs) of patients passes through the mean log PT of the 'normal' population (mean normal PT); (ii) non-perceived interactions between patients and PT systems; and (iii) systematic exclusions of 'outliers'. The same conventional procedure also results in serious overestimation of the accuracy of INR measurements, thus leading to a false sense of security in oral anticoagulant therapy. In an example with data from WHO guidelines, we show that the systematic overprediction of INR (which is believed to be 0) may be as large as 5%, when prediction is performed under the conventional WHO model. Under the same model the CV of the predicted vs. the true INR is believed to be only about 1% when it in reality is more than 4%. We suggest that the conventional calibration procedure is modified in order to reduce the twofold negative impact of lower true accuracy and overestimated reported accuracy on oral anticoagulant therapy and to allow for an unambiguous definition of true INR values.

Calibration↗

Prediction of the international normalized ratio and maintenance dose during the initiation of warfarin therapy.

AIMS: A pharmacokinetic/pharmacodynamic model, with Bayesian parameter estimation, was used to retrospectively predict the daily International Normalized Ratios (INRs) and the maintenance doses during the initiation of warfarin therapy in 74 inpatients. METHODS: INRs and maintenance doses predicted by the model were compared with the actual INRs and the eventual maintenance dose. Cases with drugs or medical conditions interacting with warfarin or receiving concurrent heparin therapy were not excluded. As the study was retrospective, model predictions of the maintenance dose were not those that were administered. Mean prediction error (MPE) and percentage absolute prediction errors (PAPE) were used to assess the model predictions. RESULTS: INR MPE ranged from -0.07 to 0.06 and median PAPE from 10% to 20%. Dose MPE ranged from -0.7 to 0.17 mg and median PAPE from 16.7% to 37.5%. Accurate and precise dose predictions were obtained after 3 or more INR feedback's. CONCLUSIONS: This study shows that the model can accurately predict daily INRs and the maintenance dose in this sample of cases. The model can be incorporated into computer decision-support systems for warfarin therapy and may lead to improvement in the initiation of warfarin therapy.

Adult↗

Effect of lepirudin on the international normalized ratio.

BACKGROUND: Many patients receiving direct thrombin inhibitor (DTI) therapy require transition to warfarin. This transition may be complicated by DTI-induced elevations in the international normalized ratio (INR). While the effect of argatroban on the INR has been characterized, data assessing the effect of lepirudin on the INR are limited. OBJECTIVE: To evaluate the effect of lepirudin on the INR. METHODS: Patients receiving lepirudin therapy between January 2000 and May 2001 were identified using the pharmacy database, and a retrospective chart review was conducted. Patients were included for analysis if they had paired activated partial thromboplastin time (aPTT) and INR data while receiving lepirudin monotherapy. RESULTS: Fifty-three paired aPTT and INR data points from 8 patients receiving lepirudin monotherapy were collected. The Organon MDA 180 instrument was used for aPTT and prothrombin time (PT) determination. Organon MDA Platelin L reagent was used for the aPTT and Organon Simplastin L reagent was used for the PT. The international sensitivity index (ISI) of the Simplastin L thromboplastin was 2.0. The mean +/- SD lepirudin dose was 0.05 +/- 0.04 mg/kg/h. Linear regression was used to identify the INRs that correspond to a therapeutic aPTT value of 45-75 seconds (1.5-2.5 times mean laboratory normal of 30 sec). The correlation between aPTT and INR was 0.77. An aPTT of 45-75 seconds with lepirudin correlated to an INR of 1.6-3.2. CONCLUSIONS: Based on laboratory results, when using a thromboplastin with an ISI of 2, lepirudin appears to elevate the INR in the absence of warfarin.

Aged↗

Bleeding and recurrent thrombosis in definite antiphospholipid syndrome: analysis of a series of 66 patients treated with oral anticoagulation to a target international normalized ratio of 3.5.

BACKGROUND: Prolonged anticoagulation is the treatment of choice for patients with thrombosis and the antiphospholipid syndrome. However, there is still debate about the optimum intensity of anticoagulation. METHODS: The study included 66 patients with antiphospholipid syndrome (Sapporo criteria) and previous thrombosis. All were receiving oral anticoagulation to a target international normalized ratio of 3.5. Every patient was individually interviewed to recall major bleeding and thrombotic episodes during the previous 12 months. RESULTS: Patients were mainly women and white. The rate of major bleeding was 6 cases per 100 patient-years (95% confidence interval [CI] 1.6-15.0). The rate of intracranial bleed was 1.5 per 100 patient-years (95% CI, 0.04-8.4). None of the bleeding episodes was fatal. The rate of thrombotic recurrences was 9.1 cases per 100 patient-years (95% CI, 3.3-19.6). Most recurrences took place in the same vascular bed as the original thrombosis. Age, time receiving anticoagulant therapy, primary vs secondary antiphospholipid syndrome, positivity for anticardiolipin antibodies, positivity for lupus anticoagulant, previous arterial thrombosis, previous stroke, previous venous thrombosis, and previous thrombocytopenia were not predictive of bleeding events. However, the risk of thrombotic recurrences was independently higher in patients who were receiving anticoagulation for longer periods. CONCLUSIONS: The risk of intracranial and fatal bleeding in patients with definite antiphospholipid syndrome and previous thrombosis treated with oral anticoagulation to a target international normalized ratio of 3.5 is similar than in groups of patients treated to lower target ratios. The risk of thrombotic recurrences, even during anticoagulation, was high. Most recurrences took place in the same territory as original thromboses.

Adolescent↗

Effect of age on international normalized ratio at the time of major bleeding in patients treated with warfarin.

STUDY OBJECTIVES: Because the risk of major bleeding associated with warfarin increases with increasing international normalized ratio (INR) as well as with advanced age, we evaluated the association between age and INR in patients with major bleeding events related to anticoagulation with warfarin. DESIGN: Retrospective record review. SETTING: Two university-affiliated anticoagulation clinics. PATIENTS: Sixty-six patients (mean age 61.2 yrs, range 21-90 yrs) receiving warfarin therapy who experienced major bleeding, defined as bleeding requiring hospitalization, during a 20-month index period. MEASUREMENTS AND MAIN RESULTS: In patients aged 65 years or older, the mean INR at the time of a major bleeding event was significantly lower than that in patients younger than 65 years (INR 3.1 vs 4.2, respectively; p=0.01). For every 1-year increase in age, mean INR at the time of a major bleeding event decreased by 0.03 (p=0.02). CONCLUSION: Patients aged 65 years or older experience warfarin-related major bleeding events at a mean INR 1.1 units lower (95% confidence interval -1.9 to -0.27) than patients younger than 65 years. Older patients may require more aggressive management of overanticoagulation to minimize the risk of major bleeding.

Adult↗

Use of lyophilized calibrant plasmas for simplified international normalized ratio determination with a human tissue factor thromboplastin reagent derived from cultured human cells.

BACKGROUND: For monitoring of treatment with oral anticoagulants, the clotting time obtained in the prothrombin time (PT) test is transformed to the International Normalized Ratio (INR) with use of a system-specific International Sensitivity Index (ISI). The calibrant plasma procedure (CPP) is an alternative approach to INR calculation based on the use of a set of lyophilized plasmas with assigned INRs. METHODS: With the CPP, a linear relationship is established between log(PT) and log(INR), using orthogonal regression. CPP was validated for Simplastin HTF, a new human tissue factor reagent derived from cultured human cells. CPP precision was assessed as the CV of the slope of the regression line. The accuracy of the CPP was determined by comparing the INR obtained with the CPP with that obtained with the established ISI-based reference method. INRs of the calibrants were assigned by different routes: by manufacturer (consensus labeling) or by use of Simplastin HTF or International Reference Preparations (IRPs; rTF/95 or RBT/90). RESULTS: The mean CV of the CPP regression slope ranged from 1.0% (Simplastin HTF reagent-specific INR) to 2.4% (INR assigned with rTF/95). INRs calculated with the CPP were similar to those obtained with the reference method, but when the routes for assigning INRs to the calibrant plasmas were compared, the mean difference in INR between CPP and the reference method was smaller with Simplastin HTF reagent-specific values. In several (but not all) cases, this difference was significant (P <0.05, t-test). CONCLUSION: CPP can be used for local INR determination, but better precision and accuracy are obtained with reagent-specific INRs compared with INR assignment by consensus labeling or IRP.

Calibration↗

Influence of storage time and temperature on international normalized ratio (INR) levels and plasma activities of vitamin K dependent clotting factors.

We designed this study to assess the effect of storage time and temperature on the international normalized ratio (INR) levels and plasma activities of vitamin K-dependent, clotting factors. A total of 100 subjects, comprising 34 healthy controls, 33 patients with liver cirrhosis and 33 patients on long-term coumarin therapy were enrolled. After centrifugation of collected specimens, aliquots of plasma were stored at room temperature (20 -22 degrees C), refrigerated at 2-6 degrees C and frozen at -40 degrees C. Determinations of INR and plasma activities of clotting factors II, VII, IX and X were performed immediately after sampling (0 time) and after 6, 12 and 24 h. We found no significant change of either INR levels or plasma activity of any of the studied clotting factors up-to 24 h at different studied temperatures (p >0.05). Our data demonstrates that clinical specimens for determination of INR levels and plasma activities of factors II, VII, IX and X are acceptable for testing for up-to 24 h whatever may be the temperature of storage.

Anticoagulants↗

Interpretation of serial measurements of international normalized ratio for prothrombin times in monitoring oral anticoagulant therapy.

Despite careful monitoring of oral anticoagulant treatment (OAT), some international normalized ratio (INR) for prothrombin time values will fall outside the therapeutic range. Considerable changes in serial INR results from OAT patients may be caused by random fluctuation alone, and, for statistical reasons, a fraction of the INR values will fall outside therapeutic range and interfere with dose adjustments. On the basis of therapeutic intervals and statistical evaluation of reference changes, we suggest and discuss an alternative method for interpretation of serial INR measurements. Retrospective evaluation of serial measurements of INR from OAT patients revealed an "overshooting" phenomenon. When a dose was adjusted on the basis of insignificant change in INR value, the subsequent INR value generally fell in the opposite direction. If a further change of dose was initiated because of the new INR value, a similar course in the opposite direction was observed. This "ping-pong" effect renders patients in a fluctuating state of anticoagulation and may introduce increased risk of complications. The suggested method provides an objective criterion for dose adjustments in OAT, which should reduce patients' risk.

Anticoagulants↗

Reemergence of the International Normalized Ratio for the standardization of prothrombin time.

A survey of physicians demonstrated that half had knowledge of the International Normalized Ratio (INR) but none used the value for monitoring their patients because it was not available from the Coagulation Laboratory. The Laboratory then provided the INR value at a physician's request. A six month review of prothrombin time (PT) results showed that only the physicians from the Cardiology Clinic and the Hematology Clinic employed the INR for monitoring their patients. General Medical and Surgical, Vascular, and Orthopedic Clinics continued to use the PT in seconds. This dichotomy allowed the unique opportunity to compare variability of PT in patients followed by INR and those followed by PT in seconds. Inpatients on daily monitoring were used as the standard for close control. During a six month period, laboratory reports from all patients having regular PTs and/or INRs recorded were analyzed for mean level of PT maintained, variability between individual PTs in any given patient, and instances when the PT changed > or = 5 seconds (sec) or increased to > or = 30 sec. Physicians intended to keep the PTs between 16 and 19 sec (INR 2.0 to 3.0). Results showed statistically significantly lower values of PT, less variation in values of PT and a smaller fraction of patients with changes in PT of > or = 5 sec in the group followed by INR. This group was comparable to the inpatient group but significantly different from the outpatient group followed by PT in sec.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Monitoring↗