International Normalized Ratio Levels Research Articles

Circulation: Cardiovascular Interventions Editors’ Picks

<i>Circulation: Cardiovascular Interventions</i> Editors’ Picks

Stuck Mechanical Tricuspid Valve Prosthesis

A 44-year–old woman underwent mitral valve and tricuspid valve (TV) replacement 6 years earlier using an ATS bileaflet tilting disc prostheses (ATS Medical Inc., Minneapolis, MN) for combined valvular stenosis and regurgitation because of rheumatic heart disease. On a routine clinic visit, the patient reported progressive fatigue and pedal edema over the previous few weeks. On physical examination, she was hemodynamically stable with evidence of elevated jugular venous pressure, hepatomegaly, and 3-mm pitting ankle and leg edema. Cardiac auscultation revealed closing and opening mechanical clicks; however, mitral and tricuspid clicks could not be distinguished. A grade 2/6 holodiastolic rumble and a grade 2/6 systolic murmur were audible at the left lower sternal border. An ECG showed atrial fibrillation with a ventricular rate at 75 beats per minute. Baseline laboratory investigations showed an international normalized ratio level of 1.8 with white cell count of 4960/mm3, erythrocyte sedimentation rate of 9 mm/h, and C-reactive protein level of 4 mg/L. Blood cultures were negative. A transthoracic echocardiogram showed both mechanical tricuspid discs stuck in a fully open position throughout the cardiac cycle (Figure 1A and 1B and …

Risk of Intracranial Hemorrhage among Patients with Acute Ischemic Stroke Receiving Warfarin and Treated with Intravenous Tissue Plasminogen Activator: Xian Y, Liang L, Smith EE, et al. JAMA 2012;307:2600–8.

The authors of this retrospective observational study analyzed national data from the American Heart Association “Get with the Guidelines–Stroke Registry” to determine the safety of tissue plasminogen activator (tPA) administration for acute ischemic stroke in patients on prior warfarin therapy with an international normalized ratio (INR) of 1.7 or lower. The main outcome measure studied was symptomatic intracranial hemorrhage (sICH), with secondary outcome measures of systemic hemorrhage, any tPA complication, or in-hospital mortality. Of 23,437 total patients receiving tPA in the Registry, a total of 1802 (7.7%) patients were on warfarin before admission. Compared to their non-warfarin peers, these patients tended to have more comorbidities, and after adjustment for these characteristics the authors found no difference in primary or secondary outcomes between the two groups. Furthermore, the authors found no correlation between INR level (at or below 1.7) and sICH risk among patients on warfarin receiving tPA. The authors concluded that there is sufficient evidence to back American Heart Association guidelines that allow for the use of tPA for acute ischemic stroke in warfarin-treated patients with an INR≤1.7.

Preprocedural Therapeutic International Normalized Ratio Influence on Bleeding Complications in Atrial Fibrillation Ablation With Continued Anticoagulation With Warfarin

Safety of atrial fibrillation (AF) ablation in conditions of periprocedural therapeutic international normalized ratio (INR) in combination with heparin is still uncertain, and little is known about the pre-procedural therapeutic INR influence on bleeding complications (BC) in this method. The subjects were 150 consecutive patients who underwent catheter ablation for AF with therapeutic INR. The patients were classified into 2 groups, BC (Group BC) and no BC (Group No BC), by whether they did or did not have BC, respectively. Differences in various parameters, including pre- and post-procedural prothrombin time-INR and activated partial thromboplastin time (APTT), were compared between the 2 groups. None of the patients experienced stroke or transient ischemic attack. In the 22 patients (15%) who had BC (Group BC), 3 patients had major and 19 patients had minor BC. There were no significant differences between the 2 groups in pre-procedural INR, APTT, and amount of heparin administered during the procedure. However, post-procedural INR and APTT were significantly prolonged in Group BC (2.5 ± 0.5 vs. 2.2 ± 0.5, P=0.016, 65 ± 45 vs. 44 ± 11, P<0.0001 respectively). Multivariable analysis showed that post-procedural APTT was the only independent bleeding risk factor (P=0.022). AF ablation with peri-procedural therapeutic INR in combination with heparin seems to be safe. Presence or absence of BC are not related to the pre-procedural INR level, but to post-procedural APTT.

Clinical and prognostic significance of coagulation assays in melanoma

The activation of coagulation and fibrinolysis is frequently found among cancer patients. Such tumors are considered to be associated with a higher risk of invasion, metastases, and eventually worse outcome. The aim of this study is to explore the clinical and prognostic value of blood coagulation tests for melanoma patients. Pretreatment blood coagulation tests including prothrombin time (PT), activated partial thromboplastin time (APTT), prothrombin activity (PTA), international normalized ratio (INR), D-dimer (DD), fibrinogen (F) levels, and platelet (PLT) counts were carried out. This prospective study included 61 melanoma patients [stage I-II (n=10), stage III (n=14), stage IV (n=37), M1c (n=26) disease], and 50 healthy controls. It included 34 (56%) men, median age 53 years, range 16-88 years. Over half of the patients (54%) were in the metastatic stage and most of them (70%) had M1c. The plasma level of pretreatment blood coagulation tests including DD, F, APTT, INR levels, and PLT counts showed a statistically significant difference between the patient and the control group (P<0.001 for all, but P=0.049 for INR). The levels of INR, DD, F, and PLT counts were higher and APTT was lower in the melanoma group, whereas the PT and PTA levels did not show any significant difference. There was a significant association between PT, PTA, INR, and PLT levels and the age of the patient. Patients with node metastasis in M0 disease had higher levels of PTA and PLT counts (P=0.002 and 0.048, respectively) and lower levels of PT and INR (P=0.056 and 0.046, respectively). The M1c patients tended to have higher plasma F levels (437 vs. 297 mg/dl, P=0.055) than M1a and M1b patients. The 1-year survival rate for all patients was 70%. In association with distant metastasis, advanced metastatic stage (M1c), elevated lactate dehydrogenase, and erythrocyte sedimentation rate, only elevated plasma F levels had a significantly adverse effect on survival among the coagulation parameters (P=0.031). The 1-year survival rates for patients with high and normal F levels were 58 and 88%, respectively. In conclusion, changes in the coagulation-fibrinolytic system are often present in melanoma and elevation in the plasma F level is associated with decreased survival.

24 Correction of INR and Coagulation Factor Levels in a Randomized Clinical Trial of Four-Factor Prothrombin Complex Concentrate (PCC-4) Versus Plasma for Urgent Vitamin K Antagonist Reversal

Study Objectives: Rapid anticoagulant reversal is essential for subjects on vitamin K antagonists (VKA) that present with acute, major bleeding. The International Normalized Ratio (INR), factor (F) levels (FII, FVII, FIX, and FX) and protein (P) C and PS were assessed pre- and post-administration of PCC-4 or plasma in subjects taking VKAs presenting with major bleeding. Methods: Subjects (aged ≥ 18 years) requiring urgent VKA reversal for acute, major bleeding were randomized (1:1) to receive PCC-4 (containing FII, FVII, FIX, FX, PC and PS; Beriplex P/N, CSL Behring) (N = 98) or plasma (N = 104) in this prospective, randomized phase IIIb trial. Dose was based on baseline INR and subject's weight. Consequently, PCC-4 (reconstituted to 25 IU of FIX/mL) was stratified by baseline INR (2 - <4; 4-6; > 6) into 3 different doses (as randomized): 25 (n = 47), 35 (n = 24), and 50 (n = 27) IU of FIX/kg, respectively. The corresponding plasma doses were: 10 (n = 53), 12 (n = 20) and 15 (n = 31) mL/kg. Per protocol, vitamin K was also administered by slow IV infusion. INR and factor levels (FII, FVII, FIX, FX, PC, PS) were measured pre-infusion (baseline) and up to 24 h after the start of the infusion. Results: No significant differences were detected between groups in the mean baseline INR (Table) . However, at 0.5 h after the start of the infusion, the mean INR in the PCC-4 group was significantly lower than the plasma group for each dose. The INR reversal was most pronounced in the baseline INR > 6 group; the mean INR in the PCC-4 group reduced from 10.6 to 1.5 within 0.5 h of the start of infusion versus INR 10.9 to 3.7 in the plasma group. The difference between groups was still evident at 1 h at all doses, although INR was similar by 24 h post-infusion. Median factor levels at baseline were <50% in both groups with no differences between PCC-4 and plasma groups at any dose (p > 0.05). Factor levels were higher than baseline at 0.5 h after the start of the infusion for both groups (p<0.05); for each PCC-4 dose at 0.5 h, factor levels were > 50% (except for FVII at INR 4-6 and > 6 [≥ 45%] and PS at INR 4-6 [> 48%]), whereas levels were <50% for all plasma doses (except for INR 2 - <4 for FIX [58%] and PC [53%]). Each factor level at 0.5 h was significantly higher after PCC-4 than plasma for each dose (p<0.05). Factor levels were also higher than baseline at 24 h for each dose in both groups (p<0.05).Tabled 1 Conclusion: Marked INR corrections and factor level increases were observed within 0.5 h of the start of PCC-4 infusion, irrespective of dose; these improvements were not observed until much later in the plasma group (> 3 h; data not shown). After 24 h, INRs and factor levels were similar between treatment groups. Therefore, whilst both products achieved INR reversal by 24 h, PCC-4 was more successful in the first hour.

Seizure as the first presentation of diabetes mellitus

Seizure as the first presentation of diabetes mellitus

Administration of tramadol or ibuprofen increases the INR level in patients on warfarin

Case report Anticoagulation with the vitamin-K antagonist warfarin is widely used in cardiology to reduce the risk of thromboembolism in cardiac arrhythmias such as atrial fibrillation. The target international normalized ratio (INR) level should often be kept in the interval of 2.0-3.0, in order to diminish the risk of thromboembolism and decrease the risk of adverse effects such as hemorrhage. Monitoring of the INR is necessary [1]. A 74-year-old man was admitted to hospital with recurrence of atrial fibrillation. The patient had been suffering from paroxysmal atrial fibrillation for 5 years and was treated with warfarin. At the time of admission, the patient presented with the feeling of irregular heart rhythm, palpitations, shortness of breath, mild chest pain and with an ECG showing atrial fibrillation. The patient was biochemically screened. This included renal function parameters, electrolytes and thyroid-stimulating hormone. Because of chest pain, troponin Tand CK-MB were included. We found no bleeding of either the skin or the mucosa by physical examination. Finally, INR status was evaluated. The initial blood sample showed an increased INR of 5.8, otherwise the biochemical analysis was normal. Due to the increased INR, the warfarin treatment was immediately paused. We treated the atrial fibrillation of the patient successfully with direct current cardioversion. During the hospitalization, the patient’s preceding INRvalues and his medication was reviewed. We found that the elevation in INR-value was coincident with the prescription of tramadol, which was prescribed due to pain in the back. The patient’s INR-values were monitored on a regular basis. The patient was on 50 mg tramadol three times a day, for four days. He stopped the treatment due to reduced pain in the back. At this time, the INR was 5.3. The previous records of the INR showed that the patient had had steady INR-values in the interval 2.1–2.6 for more than 9 months. After the discontinuation of tramadol, the patient was treated with ibuprofen starting the next day. The dose was 400 mg three times a day until being hospitalized. During this approxmately one month period, the patient’s INR was measured on three occasions, the values being 4.4, 3.9 and 5.7. (Fig. 1). No other drugs were prescribed and no changes in the medication took place during this time. The patient received no potential inhibitors of cytochrome P450 2D6. We checked the Danish Prescription Database to confirm the data. The patient denies any use of over-the-counter drugs during this period. The pause with warfarin treatment and the discontinuation of NSAID treatment normalized the INR values within two days, and the patient was discharged in a good state of health, with sinus rhythm and with a nearly normalized INR value. The patient continued anticoagulation with the same dosage of warfarin as before admission, with periodic INR monitoring at his general practitioner. Reports of interaction between tramadol and warfarin are sparse. The PubMed database contains only a few reports regarding tramadol and warfarin interaction, while the interaction between the NSAID and warfarin is better elucidated. The NSAIDs inhibit platelet aggregation reversibley; the evidence is not substantial for ibuprofen itself, but for all inhibitors of the cyclooxygenase as a class, it is well documented [2–4]. The demonstrated interaction may indicate a pharmacokinetic interaction between warfarin and ibuprofen, leading to inhibition of the metabolism of warfarin. Both warfarin and ibuprofen are metabolized by cytochrome

Effects of CYP4F2 Gene Polymorphisms on Warfarin Clearance and Sensitivity in Korean Patients With Mechanical Cardiac Valves

Recently, a single nucleotide polymorphism of CYP4F2 (rs2108622) was reported to have a significant relationship with the stable warfarin dose. However, the underlying mechanism of CYP4F2 effects on the stable warfarin dose has not been studied. This study aimed to examine the effects of cytochrome P450 (CYP) 4F2 gene on warfarin clearance and sensitivity in Korean patients with mechanical heart valves. One hundred ninety-one patients with mechanical heart valves who were on anticoagulation therapy with warfarin and maintained international normalized ratio levels of 2-3 for 3 consecutive times were followed up, retrospectively. Warfarin enantiomer concentrations were determined by a validated high-performance liquid chromatography method. Genotypes of vitamin K epoxide reductase complex subunit 1, CYP2C9, CYP2C19, CYP4F2, human microsomal epoxide hydroxylase, calumenin, and γ-glutamyl carboxylase were determined. From multiple linear regression models, vitamin K epoxide reductase complex subunit 1, CYP2C9, CYP4F2, and age were found to have significant effects on warfarin stable dose. The stable warfarin daily doses of patients with the CC, CT, and TT genotypes in the CYP4F2 gene were 5.34 ± 2.04, 5.33 ± 1.64, and 6.55 ± 2.12 mg, respectively. The higher dose requirements in patients with TT alleles in CYP4F2 were attributable to a low warfarin sensitivity (international normalized ratio/warfarin plasma concentration); the warfarin sensitivity in CC, CT, and TT genotypes was 2.1 ± 1.2, 1.0 ± 0.4, and 0.8 ± 0.6, respectively. The similarity between the dose requirements of patients with CT and CC alleles was explained through the combined result of warfarin sensitivity and clearance outcomes. Apparent plasma (S)- and (R)-warfarin clearances were found to be 37.7% and 34.1% lower in CT genotype patients than in CC genotype patients, respectively. The dose variability in CYP4F2 genotypes was attributable to both warfarin clearance and sensitivity differences.

Survival of patients with portal vein thrombosis: analysis based on disease onset.

To identify prevalent causes and determine survival rates of patients with portal vein thrombosis (PVT) in the Western Saudi Arabia. Retrospective chart review of patients diagnosed with chronic liver disease and portal vein thrombosis in two major cities in Western Saudi Arabia during the period 2000-2009. Among 1349 patients screened, 109 patients met the inclusion criteria, 67 patients had acute PVT and 42 patients had chronic PVT. The relative risk of developing PVT is higher in males in whom acute PVT is 1.32 vs. 0.68 in females (95% CI: 090-1.94). Mean survival age of acute and chronic PVT (Kaplan-Meier) is 5.61 years (95% CI: 4.52-6.70). Univariate and multivariate regression analysis identified several variables in which international normalized ratio (INR) level on presentation was found to be a significant variable in survival. Mean survival for acute or chronic PVT is about five years. The first determination of INR level is a useful predictor of survival.

An audit into the prescribing practices of warfarin in a paediatric setting

ObjectiveEvaluate if clinicians at Birmingham Children's Hospital (BCH) are adhering to the warfarin NPSA (National Patient Safety Alert) and to investigate if warfarin has been prescribed and administered correctly according...

Abstract 10: Intracranial Hemorrhage Risks among Warfarin Treated Acute Ischemic Stroke Patients Receiving Thrombolytic Therapy

Background While intravenous thrombolytic therapy (tPA) improves the outcomes of ischemic stroke, treatment of those receiving warfarin raises concerns regarding symptomatic intracranial hemorrhage (ICH). While guidelines suggest excluding patients with an international normalized ratio (INR) &gt;1.7, little is known about the use and safety of tPA in warfarin-treated patients in clinical practice. Methods Data from 23,437 ischemic stroke patients treated with tPA with an INR ≤1.7 in 1,203 Get With The Guidelines-Stroke hospitals between April 2009 and June 2011. Multivariable logistic regression analysis was performed to evaluate the association of preadmission warfarin use on ICH risk while adjusting for potential confounders. Results Overall 1,802 (7.7%) were taking warfarin prior to admission. Warfarin treated patients were older (median 77 vs. 71 years, p&lt;0.001) and had more comorbid illness and greater stroke severity (median National Institutes of Health Stroke Scale 14 vs. 11, p&lt;0.001). Crude rates of ICH were higher in those taking warfarin 5.7% vs. 4.7% (unadjusted OR 1.22, 95% CI 0.99-1.51). However, after risk adjustment, ICH risks were similar (adjusted OR 1.01, 95% CI 0.82-1.25). These findings were consistent across several sensitivity analyses (Table). There were no significant differences between warfarin and non-warfarin users for serious systemic hemorrhage (0.9% vs. 0.9%; adjusted OR 0.78; 95% CI 0.48-1.24), any tPA complications (10.6% vs. 8.4%; adjusted OR 1.09; 95% CI 0.93-1.29), and in-hospital mortality (11.4% vs. 7.9%; adjusted OR 0.94; 95% CI 0.79-1.13). Among those receiving warfarin, a trend toward higher crude ICH rates was observed among those with higher baseline INR levels (Cochran-Mantel-Haenszel trend test, p=0.03). After adjustment for risk factors, higher INR levels had a marginally significant association with ICH risk (adjusted OR 1.10, 95% CI 1.00-1.20, p=0.06 for each 0.1 units increase in INR). Conclusion This represents the largest clinical experience of the safety of thrombolysis in warfarin treated patients who meets clinical guideline eligibility criteria. Use of intravenous tPA among warfarin-treated stroke patients (INR ≤1.7) was not associated with increased ICH risk compared to non-warfarin treated patients in routine clinical practice. These data provide empirical support of current AHA/ASA guideline recommendations.

Quality Improvement in an Anticoagulation Clinic

We sought to improve patient outcomes and efficiency in our anticoagulation clinic through development of a new protocol for managing heart valve patients with subtherapeutic international normalized ratio (INR) tests. The new protocol standardized use of 1 anticoagulation agent while warfarin was retitrated, timelines for INR retesting, and target INR levels depending on the type of valve implanted. The new protocol provided significant improvements in patient care; however, outcomes for clinic operating efficiency were mixed.

A Bjork-Shiley Valve 40 Years in Action

The Bjork–Shiley mechanical heart valve (Shiley Corp, Irvine, CA) was one of the earliest tilting disc valve prosthesis used for the replacement of diseased cardiac valves. This valve was implanted in a large number of patients in the 1970s and early 1980s. A change in the valve design in the early 1980s led to a high rate of fracture and disc escape and a high patient mortality. As a result, the manufacturer of this valve stopped the production of the valve. We recently treated a patient with a Bjork–Shiley mitral valve prosthesis implanted more than 40 years ago. An 83-year-old man with cardiomyopathy, permanent atrial fibrillation, and a biventricular pacemaker with threatened skin erosion of the pacemaker pocket underwent revision of the pacemaker pocket with transfer of the pacemaker generator to a sub-pectoral position. He had undergone a mitral valve replacement with a Bjork– Shiley tilting disc valve in 1970 (Fig 1). In preparation for surgery, an intravenous heparin infusion was started and warfarin was withheld until international normalized ratio level reached 2. The Bjork–Shiley tilting disc valve was a low profile mechanical valve with a Delrin disc held in a tantalum housing by two metal struts. The valve was introduced in clinical practice in 1969 [1]. The initial Delrin disc was subsequently replaced with a pyrolytic carbon disc. This valve provided significant advantage over the bulky Starr–Edwards cage ball valve with a lower transvalvular gradient [2]. A change in the design of the valve led to a high failure rate of this valve and its disappearance from

Admission International Normalized Ratio Levels, Early Treatment Strategies, and Major Bleeding Risk Among Non–ST-Segment–Elevation Myocardial Infarction Patients on Home Warfarin Therapy

Background— Non–ST-segment–elevation myocardial infarction patients on home warfarin pose treatment concerns because of their potential increased risk of bleeding. Expert opinion from the American College of Cardiology/American Heart Association guidelines suggest holding anticoagulants and initiating antiplatelet therapy among therapeutically anticoagulated non–ST-segment–elevation myocardial infarction patients. Yet, little is known about contemporary treatment patterns and bleeding risks in this population. Methods and Results— We stratified 5787 non–ST-segment–elevation myocardial infarction patients on home warfarin therapy using data from the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With the Guidelines by admission international normalized ratio (INR) levels: subtherapeutic (INR &lt;2), therapeutic (INR, 2–3), and supratherapeutic (INR &gt;3). Multivariable logistic generalized estimating equations models were constructed to examine the associations between admission INR level, early antithrombotic treatment and invasive therapy, and risk of in-hospital major bleeding. Among these patients, 46%, 35%, and 19% had subtherapeutic, therapeutic, and supratherapeutic admission INR levels, respectively. Risk of major bleeding was higher among patients with therapeutic (15%; adjusted odds ratio, 1.25; 95% confidence interval [CI], 1.03–1.50) and supratherapeutic (22%; odds ratio, 1.60; 95% CI, 1.30–1.97) anticoagulation compared with the subtherapeutic group (12%). Among patients with admission INR ≥2, 45% were treated with early (within 24 hours) heparin, 35% with early clopidogrel, 14% with early glycoprotein IIb/IIIa inhibitor, and 36% with early invasive strategy. Early antithrombotic treatment was associated with increased bleeding risk (odds ratio, 1.40 [95% CI, 1.14–1.72] for heparin; 1.50 [95% CI, 1.22–1.84] for clopidogrel; and 1.82 [95% CI, 1.43–2.32] for glycoprotein IIb/IIIa inhibitor); however, an early invasive strategy was not (odds ratio, 1.09; 95% CI, 0.86–1.37). No significant interactions were observed between INR level and use of each early treatment in its association with bleeding. Conclusions— National patterns of early antithrombotic treatment for non–ST-segment–elevation myocardial infarction patients on home warfarin diverge from expert opinion provided by current practice guidelines. Early antithrombotic treatment was associated with increased bleeding risk regardless of admission INR level.

Circulation : Clinical Summaries

<i>Circulation</i> : Clinical Summaries

Thrombolytic therapy for ischaemic stroke in patients using warfarin: a systematic review and meta-analysis

BackgroundIt is uncertain whether thrombolytic therapy is safe in patients with acute ischaemic stroke who are treated with warfarin and have a subtherapeutic international normalised ratio (INR) at stroke onset.MethodsThe...

Incidence of thromboembolic complications in patients with atrial fibrillation or mechanical heart valves with a subtherapeutic international normalized ratio: A prospective multicenter cohort study

Subtherapeutic international normalized ratio (INR) is frequently encountered in clinical practice, and patients with high-risk atrial fibrillation (AF) and with mechanical heart valve (MHV) with inadequate anticoagulation may be exposed to an increased risk of thromboembolic events (TE). However, there are no prospective data evaluating this risk. Consecutive patients with a history of stable anticoagulation, but with a subtherapeutic INR, were prospectively included. Data on use and dose of low-molecular weight heparin (LMWH) bridging therapy were collected. The incidence of objectively confirmed TE and of major bleeding events within 90 days after the index INR was assessed. Five hundred and one patients with INR value 0.5-1 INR units below the lower limit of the patient-specific target INR were included in the study (280 with MHV and 221 with AF and CHADS2 score ≥3). LMWH was prescribed for 64 patients (12.8%). During follow-up, seven patients had a TE (1.40%; 95% confidence interval 0.68, 2.86%; 5.58 events for 100 patients year). All the events occurred within 14 days after the index INR. When we consider only patients who did not receive bridging therapy, the incidence of TE was 1.14% (5 of 437 patients; 95% confidence interval 0.49, 2.64%; 4.58 events for 100 patients year). There were no major bleeding events. The risk of TE in this population was not negligible. Given the frequent observation of subtherapeutic INR levels when monitoring vitamin K antagonists, this finding warrants additional investigation to improve the management of these patients.

Interpretation of Point-of-care INR Results in Patients Treated with Dabigatran

BackgroundPoint-of-care devices for measurement of the international normalized ratio (INR) are commonly used to monitor therapy and maintain therapeutic levels of anticoagulation in patients treated with vitamin K antagonists. Dabigatran, a new oral, reversible direct thrombin inhibitor approved for stroke prevention in patients with atrial fibrillation does not require routine coagulation monitoring. However, case reports have identified falsely elevated point-of-care INR levels in patients treated with dabigatran using one of these devices (Hemochron). This in vitro study was designed to verify this issue. MethodsWe compared INR levels in whole blood and plasma using a Hemochron Jr. Signature+ point-of-care device (International Technidyne Corporation, Edison, NJ) with routine laboratory monitoring, using blood from healthy volunteers that was spiked with increasing concentrations of dabigatran. ResultsProthrombin time and INR levels were increased about 2- to 4-fold with the point-of-care device compared with laboratory measures across the plasma dabigatran concentration range 50-1400 ng/mL. At plasma concentrations of dabigatran likely to be observed in patients, at a dose of 150 mg twice daily (60-275 ng/mL), whole blood point-of-care INR values increased from 1.7 to 4.0, versus 1.1 to 1.5 measured with the laboratory coagulometer. Similar differences in prothrombin time were observed in plasma samples. ConclusionsINR levels in patients taking dabigatran are substantially higher using a Hemochron Jr. point-of-care device compared with laboratory values. We discourage the use of these devices specifically, as well as the use of the INR in general, for measuring the anticoagulant effect of dabigatran.

Trends in Oral Anticoagulation Therapy Among Korean Patients With Atrial Fibrillation: The KORean Atrial Fibrillation Investigation

Background and ObjectivesAnticoagulation with vitamin K antagonists (VKAs) such as warfarin provides effective stroke prophylaxis in patients with atrial fibrillation (AF). We conducted a large multicenter survey of Korean patients with AF to determine trends in VKA use.Subjects and MethodsEligible patients were adults with AF that had been prescribed VKAs. Medical records from a total of 5616 patients {mean age 63.6±12.2 years, male 3150 (56.1%)} in 27 hospitals from Jan. 2001 to Oct. 2007 were reviewed.ResultsThe mean international normalized ratio (INR) was 2.04±0.64, and mean dosage of VKA was 3.66±1.50 mg. Individuals in their sixties (1852 patients) accounted for about one third of patients studied. As patients grew older, INR increased and VKA dosage decreased. The dosage of VKA in male patients was larger than that in females for all ages. A total of 2146 (42.4%) patients had an INR of 2-3, and less than 40% patients in their sixties had an INR within optimal range. The dosage of oral anticoagulant for optimal INR level was 3.71 mg.ConclusionIn this study, less than half of the Korean patients with AF on VKA reached the therapeutic range of INR. Mean dosage of VKA was 3.66±1.50 mg, and the dosage of oral anticoagulant for optimal INR level was 3.71 mg, which decreased with age.