Target International Normalized Ratio Range Research Articles

Role of Thrombophilia in Deciding on the Duration of Anticoagulation

It is now possible to identify hereditary risk factors in a substantial percentage of patients presenting with a venous thrombotic event. Discovery of the factor V Leiden and prothrombin G20210A mutations has greatly increased the percentage of patients in whom venous thrombosis can be attributed to hereditary thrombophilia. There is considerable uncertainty, however, as to how this information should be used in patient management. Although prolonged anticoagulation at an international normalized ratio (INR) of 2 to 3 is highly effective in preventing thrombotic recurrences, this benefit is partially offset by the risk of major bleeding and the inconvenience associated with oral vitamin K antagonists. Although low-intensity anticoagulation at a target INR of 1.5 to 2 has recently been shown to be effective in preventing recurrent venous thromboembolism after 3 to 6 months of treatment at an INR of 2 to 3, it has not been demonstrated to reduce the risk of major bleeding complications. A decision as to the overall benefit of extended anticoagulation therefore continues to require clinical assessment of an individual patient's risk of recurrence in the absence of treatment and the risk of bleeding at the chosen INR target range.

Warfarin Anticoagulation and Outcomes in Patients With Atrial Fibrillation: A Systematic Review and Metaanalysis

To examine the relationship between international normalized ratio (INR) and outcomes (major bleeding events and strokes) in patients with atrial fibrillation (AF) receiving anticoagulation with warfarin. A systematic review and metaanalysis of studies published in the English language between January 1, 1985, and October 30, 2002, was performed. MEDLINE (PubMed), Current Contents, and relevant reference lists were searched. Studies enrolling patients with nonvalvular AF receiving warfarin anticoagulation were eligible for inclusion if they reported stroke and/or major bleeding events in relation to INR, or time spent in therapeutic range. The risk of bleeds in overanticoagulated patients (INR > 3) and the risk of strokes in underanticoagulated patients (INR < 2) were assessed. Twenty-one studies (6,248 patients) met all inclusion criteria. Of the 21 studies, a target conventional INR of 2 to 3 was used in 9 studies. An INR < 2, compared with an INR > or = 2, was associated with an odds ratio (OR) for ischemic events of 5.07 (95% confidence interval [CI], 2.92 to 8.80). An INR > 3, compared with an INR < or = 3, was associated with an OR for bleeding events of 3.21 (95% CI, 1.24 to 8.28). On average, in the four studies with a target INR range of 2 to 3, patients with AF receiving warfarin spent 61% of time within, 13% of time above, and 26% below the therapeutic range. Available evidence indicates that in patients with nonvalvular AF, the risk of ischemic stroke with insufficient warfarin anticoagulation (INR < 2), and the risk of bleeding events with overanticoagulation (INR > 3) are significantly higher relative to patients with AF maintained within the recommended INR of 2 to 3. However, the published data are sparse, heterogeneous, and primarily reported from clinical trials. More studies evaluating clinical outcomes in relation to INR are needed, especially in a real-world setting.

CV4 EVALUATION OF SURVIVAL AND ISCHAEMIC AND THROMBOEMBOLIC EVENT RATES IN PATIENTS WITH NONVALVULAR ATRIAL FIBRILLATION IN THE GENERAL POPULATION WHEN TREATED AND UNTREATED WITH WARFARIN

Objective: To compare survival and adverse outcome of patients with non-valvar atrial fibrillation (NVAF) treated with or without warfarin. Design: Record linkage method to identify patients with a previous hospital diagnosis of atrial fibrillation and to link these patients to international normalised ratio (INR) test results and mortality data. Setting: Cardiff and the Vale of Glamorgan, Wales. Main outcome measures: Mortality, specifically from ischaemic and thromboembolic events. Results: 6108 patients were identified with NVAF, of whom 36.4% received warfarin. Mean survival in the warfarin and non-warfarin groups was 52.0 months and 38.2 months, respectively (p < 0.001), and 14.4 months (p < 0.001) after adjustment for confounding factors. Warfarin treated patients in the upper quartile of INR control had significantly longer survival (57.5 months) than did those in the lowest quartile of control (38.1 months, p < 0.001). The risk of stroke in the warfarin group when treated was lower than that in the non-warfarin group (relative rate (RR) 0.74, p < 0.001). The risk of death from ischaemic stroke was lower in the warfarin group (RR 0.43, p < 0.001). The risk of all ischaemic and embolic events in the warfarin group was lower when they were taking warfarin (RR 0.74, p < 0.001). The risk of bleeding in the warfarin group when treated was greater (RR 1.78, p = 0.001). Conclusions: Patients with NVAF within the recommended target INR range of 2.0–3.0 survive longer and have reduced morbidity. Probably too few people are anticoagulated with warfarin in NVAF.

Results of an open-label, prospective study of anticoagulant therapy for atrial fibrillation in an outpatient anticoagulation clinic

Objective: The goal of this study was to investigate the complications and control of warfarin treatment in patients with nonvalvular atrial fibrillation (NVAF) newly referred to an outpatient anticoagulation clinic. Methods: This study included new patients with NVAF who were referred to an anticoagulation clinic for warfarin therapy over a recruitment period of 21 months. To reflect real-world clinical practice, patient selection for anticoagulation and patient management were left to the referring physicians, who were blinded to their patients' participation in the study. Patients were interviewed in person at the first clinic visit and then by telephone every 4 to 6 weeks. They were questioned about any bleeding or thromboembolic events. Results: A total of 402 patients were included (100% of all new referrals over 21 months). The mean (SD) age was 72.3 (10.3) years, and 224 (56%) patients were men. The mean (SD) international normalized ratio (INR) was 2.4 (0.31). Patients were followed up for a mean (SD) of 19 (8.1) months (range, 1.0–31.0 months). They spent a mean (SD) 66% (18.3) of time in the target range of INR (ie, 2.0–3.0). Annual event rates were 1.7% (95% CI, 0.4%–3.0%) for major bleeding, 16.6% (95% CI, 13.0%–20.2%) for minor bleeding, 1.2% (95% CI, 0.1%–2.3%) for ischemic stroke, and 0.3% (95% CI, 0.2%–0.8%) for transient ischemic attacks. There were no cases of hemorrhagic stroke or fatal bleeding. Variability of INR and number of medications were identified as risk factors for bleeding ( P = 0.03 and P = 0.001, respectively). There was no significant association between age and bleeding. Conclusions: Based on this analysis, the risks of long-term oral anticoagulation therapy in an outpatient anticoagulation clinic appear to reflect the results of clinical trials. Rates of ischemic stroke, major bleeding, and anticoagulation control were comparable. There was no age-related risk of complications.

Sustained intake of paracetamol (acetaminophen) during oral anticoagulant therapy with coumarins does not cause clinically important INR changes: a randomized double-blind clinical trial

Paracetamol (acetaminophen) is routinely advised when non-steroidal anti-inflammatory drugs (NSAID) are necessary during oral anticoagulant treatment (OAT) because it has no relevant effect on the primary hemostasis. However, in a recent case-control study a dose-related effect was observed of paracetamol intake on the International Normalized Ratio (INR) values making its use controversial during OAT. Our objectives were to determine the effect of paracetamol on the INR values during OAT independent of underlying illness. A double-blind randomized controlled trial in which 31 out-patients on coumarin oral anticoagulant therapy with phenprocoumon, aged 18-70 years, with a planned treatment duration of more than 12 weeks, and an INR target range of 2.5-3.5, were included. Patients were randomized for placebo (10 patients), paracetamol 1500 mg daily (11 patients) or paracetamol 3000 mg daily (10 patients) for 14 days during the stable phase of coumarin OAT and INR values at day 1, 8, 15, 22 and 29 were measured. At day 8 a mean rise of 0.46 INR was seen in both paracetamol groups compared to placebo. At day 15 there was no difference between placebo and paracetamol 1500 mg daily, and a small mean rise of 0.22 INR in the paracetamol 3000 mg daily group. The sustained use of paracetamol (acetaminophen) during oral anticoagulant therapy in itself does not provoke clinically relevant INR changes. Any important INR rise will predominantly be the result of the illness necessitating the intake of this medication. A difference has to be made between those patients taking paracetamol (acetaminophen) for pain relief or as an antipyretic during infectious diseases.

Mechanical heart valve patients can manage oral anticoagulant therapy themselves.

Thromboembolism and anticoagulant related bleeding are still the most common complications in mechanical heart valve patients. Management of the oral anticoagulant therapy is therefore a key determinant for these clinical complications. We hypothesize that patients selected to self-managed oral anticoagulant therapy have a better treatment quality than patients in conventional oral anticoagulant therapy. The aim of this study was to assess the time within the therapeutic International Normalized Ratio (INR) target range and the incidence of clinical complications in our group of patients, and compare these data with published data on conventional management. Mechanical heart valve patients (N=94) with a mean age of 47.6 years (range 4.2-76.6 years) were trained in home blood analysis of INR using a CoaguChek home coagulometer and coumarin dosage adjustment. After training, the patients were followed by weekly INR measurements. The therapeutic range was a target INR +/-0.5. The indications for initiating oral anticoagulant therapy were: aortic valve (N=62), mitral valve (N=29), tricuspid valve (N=1) and multiple valves (N=2). The mean observation time was 2.1 years (range 0.04-6.2 years), and the total number of patient-years was 197. The patients were within the therapeutic INR target range for a median of 76.0% (range 32.1-100.0%) of the time. There were two major thromboembolic events and five major bleedings events, comprised of two deep vein thromboses (both in the same patient), four episodes of epistaxis and one case of gastrointestinal bleeding. All the events required short hospitalization, and after treatment all the patients were discharged from the hospital without any sequelae or other complications. Using published work as references the expected number of major thromboembolic and bleeding complications in conventional management was four and 12, respectively. Self-management of oral anticoagulant therapy provides a good treatment quality for mechanical heart valve patients. We therefore consider self-management of oral anticoagulant therapy as an equally as good or potentially better treatment option for selected patients compared to conventional management.

Evaluation of the clinical and economic impact of a brand name-to-generic warfarin sodium conversion program.

Substitution of generic warfarin initially was discouraged because of concerns regarding therapeutic failure or toxicity. Although subsequent research with AB-rated (i.e., bioequivalent) warfarin did not confirm initial concerns, the issue is not settled for all clinicians. We sought to provide additional information regarding the clinical and economic impact of warfarin conversion by analyzing a real-life sample of patients receiving long-term anticoagulation therapy who were switched from brand name to generic warfarin. Patients who had been taking warfarin for at least 180 days and had received uninterrupted oral anticoagulation 90 days before and 90 days after switching to generic warfarin were included. The switch date was based on the first time generic warfarin was dispensed from our pharmacies. The primary end point was the calculated amount of time each patient's international normalized ratio (INR) values were within the patient-specific target INR range in the 90 days before and after the switch. Data regarding adverse events and medical resource utilization were also collected. Pharmacoeconomic analyses were performed. The analysis included 2299 patients. The overall difference in calculated time INR values were below (22.6% before vs 26.1% after switch, p<0.0001) and within (65.9% before vs 63.3% after switch, p=0.0002) the therapeutic INR range was statistically but not clinically significant. Only 28.0% of patients experienced a change in therapeutic INR control of 10% or less, 33.1% experienced INR control that improved by greater than 10%, and 38.9% experienced INR control that worsened by more than 10%. The difference in total treatment costs associated with brand name and generic warfarin was 3128 dollars/100 patient-years in favor of the generic product. Sensitivity analyses revealed that cost savings associated with warfarin conversion in this health care system were highly dependent on the difference between warfarin costs and cost of treating anticoagulation-related adverse events. Most of these patients were successfully switched from brand name to generic warfarin. However, supplemental INR monitoring is warranted when one warfarin product is substituted for another to allow timely detection of those patients who experience significant changes in anticoagulation response.

Cardiology patient pages. Pulmonary embolism and deep vein thrombosis.

The heart pumps oxygenated blood through the aorta to smaller arteries. After the blood supplies nutrients to vital organs, it returns through veins for reoxygenation in the lungs (Figures 1 and 2⇓). Blood clots called deep vein thrombi (DVT) often develop in the deep leg veins. Pulmonary embolism (PE) occurs when clots break off from vein walls and travel through the heart to the pulmonary arteries. The broader term venous thromboembolism (VTE) refers to DVT, PE, or to a combination of both. Figure 1. The arterial (red) and venous systems (blue) are depicted. The left ventricle (LV) ejects oxygenated blood into the aorta, which circulates blood to vital organs. Deoxygenated blood travels through the venous system to the right atrium, right ventricle, and pulmonary artery. Adapted with permission from MediClip, Clinical Cardiopulmonary Images 1997, CCP01026.TIF, Williams & Wilkins, Baltimore, Md. Figure 2. Deoxygenated blood returns to the heart and lungs for reoxygenation. SVC indicates superior vena cava; IVC, inferior vena cava; RA, right atrium; RV, right ventricle; and PA, pulmonary artery. Adapted with permission from MediClip, Clinical Cardiopulmonary Images 1997, CATHRHT.TIF, Williams & Wilkins, Baltimore, Md. VTE poses a public health threat with an estimated incidence in the United States of 250 000 to 2 million cases per year. Predisposition to VTE arises from acquired conditions, inherited disorders, or both. Many of the acquired risk factors can be modified, thus lessening the likelihood of PE or DVT. Long-haul air travel is the most talked-about risk factor for PE. Other acquired risk factors include obesity, …

Intensity of oral anticoagulation after implantation of St. Jude Medical mitral or multiple valve replacement: lessons learned from GELIA (GELIA 5)

Aims The purpose of the present analysis was to determine survival rate, and risk for thromboembolic and bleeding complications after mechanical heart valve replacement with St. Jude Medical mechanical heart (bileaflet) valves under differing regimens of postoperative anticoagulation. Method In the randomized German Experience with Low Intensity Anticoagulation (GELIA) study, 553 patients after mitral valve replacement and 158 patients after double valve replacement with a St. Jude Medical prosthesis were randomly assigned to three groups for postoperative oral anticoagulation: group A, target International Normalized Ratio (INR) range 3·0–4·5; group B, target INR range 2·5–4·0; and group C, target INR range 2·0–3·5. Results The various anticoagulation regimens had no significant impact on risk for bleeding or thromboembolism, or cumulative survival rate after mitral valve replacement. However, less intensive anticoagulation (target INR range 2·0–3·5) was associated with a significant decrease in cumulative survival rate after combined valve replacement, although analysis confirmed that 54% of these deaths were not valve related. Conclusion The results suggest that in terms of low-intensity anticoagulation an INR of 2·0–3·5 after mitral valve replacement and of 2·5–4·0 after double valve replacement (aortic and mitral) may be recommended when using the St. Jude Medical bileaflet prosthetic valve.

Intensity of oral anticoagulation after implantation of St. Jude Medical aortic prosthesis: analysis of the GELIA Database (GELIA 4)

Aims No prospective studies exist that define the ideal target International Normalized Ratio (INR) with respect to anticoagulation-related complications and survival rates after valve replacement with mechanical prostheses. The purpose of the present analysis is to determine optimal levels of anticoagulation for St. Jude Medical mechanical aortic prostheses (St. Jude Medical, Inc., St. Paul, MN, U.S.A.). Method Patients who received a St. Jude Medical mechanical prosthesis were randomized to three ranges of INR for postoperative oral anticoagulation: stratum A, INR 3·0–4·5; stratum B, INR 2·5–4·0; and stratum C, INR 2·0–3·5. This intent-to-treat analysis is based on the assigned range, not the actual range. Results In total, 2024 patients with aortic valves were included in the German Experience with Low Intensity Anticoagulation (GELIA) study, with 672, 677 and 675 patients in strata A, B and C, respectively. The percentages of patients who achieved an INR within their target range in each stratum are as follows: 43·3% in stratum A; 62·8% in stratum B; and 75·9% in stratum C. Patients who self-managed their anticoagulation therapy achieved an INR within their target range more often than did those who were managed by conventional methods. No statistically significant differences in adverse event rates were identified between strata. Conclusion A target INR range of 2·0–3·5 is preferable to the usual 3·0–4·5 range in reducing the number of severe bleeding complications in patients implanted with a St. Jude Medical prosthesis. Self-management of INR may result in better achievement of target INR levels.

Self-management of Oral Anticoagulant Therapy for Mechanical Heart Valve Patients

Objective - Self-management of oral anticoagulant therapy (OAT) has shown good results on a short-term basis. We hypothesize that self-management of OAT provides a better quality of treatment than conventional management also on a long-term basis. The aim of this study was to assess the quality of self-management of OAT in patients with mechanical heart valve prostheses on a 4-year perspective in a prospective, non-randomized study. Design - Twenty-four patients with mechanical heart valves and on self-managed OAT were followed for up to 4 years. A matched, retrospectively selected group of conventionally managed heart valve patients (control group) was used as reference. Results -The median observation time was 1175 days (range: 174-1428 days). The self-managed patients were within therapeutic INR target range for a mean of 78.0% (range: 36.1%-93.9%) of the time compared with 61.0% (range 37.4%-2.9%) for the control group. Conclusion - Self-management of OAT is a feasible and safe concept for selected patients with mechanical heart valve prostheses also on a long-term basis. It provides at least as good and most likely better quality of anticoagulant therapy than conventional management assessed by time within the therapeutic International Normalized Ratio (INR) target range.

Dosing practices of physicians for anticoagulation with warfarin during inpatient rehabilitation.

To determine the percentage of international normalized ratios (INRs) maintained within the therapeutic range for patients receiving chronic anticoagulation treatment with warfarin during inpatient rehabilitation. A consecutive, 4-month, retrospective chart review of all patients receiving oral anticoagulation treatment was conducted in a large academic rehabilitation center. The percentage of INRs within and out of the therapeutic range, frequency of blood samples, length of therapy, and warfarin dose prescribed by physicians were calculated. A total of 181 patients receiving chronic anticoagulation treatment were identified. A total of 3,709 blood samples were analyzed. In 74 patients, the primary physician recommended a therapeutic range (Group 1). In the remaining 107 patients, no therapeutic range was specified, and a target INR range of 2.0-3.0 was assumed (Group 2). In Group 1, the INRs were in the recommended range in 38.2% of all blood samples. In Group 2, 37.6% of all blood drawn was within an INR range of 2.0-3.0. Statistical analysis showed that no better accuracy was obtained when the INR range was predefined by a physician (Group 1) or assumed to be in the 2.0-3.0 range (Group 2; P = 0.839). Despite frequent physician monitoring, this study demonstrates the difficulty in maintaining INRs within therapeutic ranges for patients receiving oral anticoagulation. An overall tendency for underdosing is observed. Improvement is necessary, given the high morbidity and mortality associated with insufficient anticoagulation in rehabilitation inpatients.

Warfarin responses in total joint and hip fracture patients

Warfarin is considered as a narrow therapeutic drug—an agent for which small changes in dosage can lead to significant changes in response. The precision of warfarin treatment is especially relevant in an acute-care setting. In this study, we examined the effect of various risk factors on warfarin response in the early postoperative period after total joint arthroplasty and hip fracture fixation. A total of 260 patients placed on warfarin for thrombosis prophylaxis were retrospectively studied. Risk factors for warfarin sensitivity include age 80 years or older and hip fracture fixation. Patients aged 80 years or older who had hip fracture fixation were 4.7 times more likely to experience an international normalized ratio (INR) at or greater than 4.0 than other patients (therapeutic target range of INR, 1.8–2.2). The largest subtherapeutic risk group in this study were men weighing 180 lb or more. They were 5.7 times less likely to achieve an INR of 1.6 than the other patients. Factors such as body weight, age, and gender should be considered when ordering warfarin therapy. Current hospital warfarin sliding scales should be reviewed for their efficacy to ensure that the target outcome is achieved.

Low dose oral anticoagulation therapy in Chinese children with congenital heart disease.

This study aims to evaluate the efficacy of a low dose warfarin regimen for Chinese children requiring anticoagulation therapy and its safety when monitored on an outpatient basis. Current recommendations are based on extrapolations from the adult experience and a high target international normalised ratio (INR) is adopted amongst the Western countries. This is a 10-year retrospective study from January 1986 to June 1996. Effectiveness of warfarin therapy was monitored by the prothrombin time, standardised and expressed as the INR. A target INR of 1.5-2.5 was adopted for children with cardiac diseases requiring anticoagulation therapy for primary and secondary prophylaxis against thromboembolism. From the clinical records, demographic data, induction warfarin dosage, changes of dosages and related events on follow-up, frequency of outpatient visits, complications and serial INR results were reviewed. Thirty-five patients (23 boys, 12 girls) were included with a mean age at initiation of warfarin therapy of 8.4+/-5.8 years. Amongst these, 66% (n = 23) were after isolated valvar replacement, 28% (n = 10) after Fontan operation with or without valvar replacement and 6% (n = 2) after deep vein thrombosis. Regression estimate of the induction dose was 0.05-0.13 mg x kg(-1) in order to achieve the target INR range after 2 days of warfarin therapy. The daily maintenance warfarin dose was correlated with the bodyweight [dose (mg x day(-1))= 0.04 x bodyweight (kg) + 0.87, r = 0.63, P<0.0001]. Young children required significantly higher daily warfarin maintenance dose when adjusted for bodyweight [dose (mg x kg day(-1)) = antilog(10)¿-0.02 x age (years)- 0.80¿, r = -0.74, P<0.0001]. The mean maintenance warfarin dosage was significantly lower in patients after the Fontan operation, with or without valvar replacement, in the absence of apparent liver dysfunction. The total period of followup was 159 patient-years. No serious bleeding complications or embolic phenomena were documented. One patient died of thrombosis of the mitral valve prosthesis. The overall incidence of thrombosis was 0.6 per 100 patient-years. A low dose warfarin regimen to maintain a target INR of 1.5-2.5 provides adequate protection in Chinese children against thromboembolism whilst allowing safe outpatient monitoring of the anticoagulation status.

Monitoring “Mini-Intensity” Anticoagulation With Warfarin: Comparison of the Prothrombin Time Using a Sensitive Thromboplastin With Prothrombin Fragment F1+2 Levels

Treatment with warfarin using a target International Normalized Ratio (INR) range of 1.7 to 2.5 is efficacious for many clinical indications, but the minimal intensity of anticoagulation required for antithrombotic protection has yet to be determined. 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). Plasma measurements of F1+2, a marker of factor Xa action on prothrombin in vivo, were also obtained to determine the suppressive effect of warfarin on hemostatic system activity. Overall, 20 of 21 patients with a history of cerebrovascular events (mean age, 61 years) could be reliably regulated with warfarin in the target INR range. F1+2 levels were significantly suppressed from baseline in all patients, with a mean reduction of 49% (range, 28% to 78%). We found a significant relationship between the extent of suppression of prothrombin activation levels and the baseline measurements. A mean reduction of 65% was observed for those patients with baseline F1+2 greater than or equal to 1.5 nmol/L, but only 38% for baseline F1+2 less than or equal to 0.5 nmol/L. Overall, 68% of plasma samples obtained during stable anticoagulation were within the target INR range. PTs were also determined on all plasma samples with two thromboplastins of lower sensitivity (C+, ISI = 2.09; and automated simplastin, ISI = 2.10). Only 47% and 35% of PT determinations, respectively, were within the target range with these reagents. We conclude that prothrombin activation can be significantly suppressed in vivo with use of warfarin in an INR range of 1.3 to 1.6. This level of anticoagulation can be reliably achieved by monitoring PTs with a thromboplastin of high sensitivity.

Monitoring "mini-intensity" anticoagulation with warfarin: comparison of the prothrombin time using a sensitive thromboplastin with prothrombin fragment F1+2 levels

Treatment with warfarin using a target International Normalized Ratio (INR) range of 1.7 to 2.5 is efficacious for many clinical indications, but the minimal intensity of anticoagulation required for antithrombotic protection has yet to be determined. 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). Plasma measurements of F1+2, a marker of factor Xa action on prothrombin in vivo, were also obtained to determine the suppressive effect of warfarin on hemostatic system activity. Overall, 20 of 21 patients with a history of cerebrovascular events (mean age, 61 years) could be reliably regulated with warfarin in the target INR range. F1+2 levels were significantly suppressed from baseline in all patients, with a mean reduction of 49% (range, 28% to 78%). We found a significant relationship between the extent of suppression of prothrombin activation levels and the baseline measurements. A mean reduction of 65% was observed for those patients with baseline F1+2 greater than or equal to 1.5 nmol/L, but only 38% for baseline F1+2 less than or equal to 0.5 nmol/L. Overall, 68% of plasma samples obtained during stable anticoagulation were within the target INR range. PTs were also determined on all plasma samples with two thromboplastins of lower sensitivity (C+, ISI = 2.09; and automated simplastin, ISI = 2.10). Only 47% and 35% of PT determinations, respectively, were within the target range with these reagents. We conclude that prothrombin activation can be significantly suppressed in vivo with use of warfarin in an INR range of 1.3 to 1.6. This level of anticoagulation can be reliably achieved by monitoring PTs with a thromboplastin of high sensitivity.