International Normalized Ratio Goal Research Articles

Fixed- Versus Variable-Dose Prothrombin Complex Concentrate for the Emergent Reversal of Vitamin K Antagonists: A Systematic Review and Meta-Analysis.

Four-factor prothrombin complex concentrate (4-PCC) is recommended for rapid reversal of vitamin K antagonists (VKAs) such as warfarin, yet optimal dosing remains uncertain. A systematic review was conducted of PubMed, Embase, and Ovid MEDLINE (Wolters Kluwer) databases from January 2000 to August 2023 for clinical studies comparing fixed- vs. variable-dose 4-PCC for emergent VKA reversal with at least one reported clinical outcome. Abstracts and full texts were assessed independently and in duplicate by two reviewers. Data were extracted independently and in duplicate by two reviewers using predefined extraction forms. The analysis comprised three randomized trials and 16 cohort studies comprising a total of 323 participants in randomized trials (161 in fixed dosage and 162 in variable dosage) and 1912 patients in cohort studies (858 in fixed-dose and 1054 in variable dose). Extracranial bleeding was the predominant indication, while intracranial hemorrhage varied. Overall, a fixed-dose regimen may be associated with a lower dose of 4-PCC and results in a reduction in 4-PCC administration time compared with a variable-dose regimen. A fixed-dose regimen also likely results in increased clinical hemostasis. While there is no clear difference between the two regimens in terms of achieving a goal international normalized ratio (INR) less than 2, a fixed-dose regimen is less likely to achieve a goal INR less than 1.5. High certainty evidence indicates that the fixed-dose regimen reduces both mortality and the occurrence of thromboembolic events. Additional subgroup analyses provides exploratory data to guide future studies. A fixed-dose regimen for 4-PCC administration provides benefits over a variable-dose regimen in terms of dose reduction, faster administration time, improved clinical hemostasis, and reduced mortality and thromboembolic events. Further studies are warranted to better refine the optimal fixed-dose regimen.

Evaluation of adjusted international normalized ratio goal in patients with HeartMate 3 left ventricular assist devices.

The HeartMate3 left ventricular assist device (HM3 LVAD) has shown a low incidence of thrombosis, but bleeding risk is as high as 43%. We aim to describe the impact of lower international normalization ratio (INR) goal on clinical outcomes. In February 2019, our tertiary care institution lowered INR goal in HM3 patients from manufacturer recommendations to 1.8-2.2 and retrospectively analyzed the data. Two cohorts were compared: patients with lower INR goal upon implant (De novo) and those with subsequently lowered INR goal (Adjusted). The Adjusted group also served as its own historical control. Both groups continued aspirin 81 milligrams daily per manufacturer recommendations. The primary outcomes were incidences of bleed and thrombosis events within 12 months. Secondary outcomes included survival free of disabling stroke or reoperation to remove or replace the device and Rosendaal time in therapeutic range (TTR) over 12 months. Thirty-one patients were evaluated for inclusion with 26 meeting criteria. Within 12 months, incidence of bleeding events was 25% and 28.6% in the De novo and Adjusted groups, respectively. Incidence of thrombotic events within 12 months was 0% in the De novo group and 7.1% in the Adjusted group. Twelve-month survival free of disabling stroke or reoperation to remove or replace the device was higher over 12 months for patients in the De novo group (91.7% vs. 78.6%). Median 12-month TTR was 36%, which was primarily attributable to subtherapeutic deviations. A lower INR goal may be safe when initiated De novo following implantation of the HM3. This study informs the need for larger prospective studies.

Potential Association of Holidays on Internationalized Normalized Ratio in Warfarin-Users at a Multidisciplinary Clinic.

Warfarin is approved by the United States Food and Drug Administration for numerous clinical indications. The effectiveness of warfarin is highly dependent on the time-in-therapeutic range based on the international normalized ratio (INR) goal, which may be altered by changes in diet, alcohol intake, concomitant drugs, and travel, all of which are prevalent during the holidays. At this time, there are no published studies assessing the impact of holidays on INR in warfarin-users. A retrospective chart review was conducted on all adult patients taking warfarin and managed at a multidisciplinary clinic. Patients were included if they were taking warfarin at home regardless of indication for anticoagulation. The INR pre- and post-holiday was assessed. Of a total of 92 patients, the mean age was 71.5 ± 14.3 years, and most patients were on warfarin with an INR goal of 2 - 3 (89%). There were significant differences in INR before and after Independence Day (2.55 vs. 2.81, P = 0.043) and Columbus Day (2.39 vs. 2.82, P < 0.001). The remaining holidays showed no significant differences in INR before and after each respective holiday. There may be factors related to Independence and Columbus Day that are increasing the level of anticoagulation in warfarin-users. Although the mean post-holiday INR values, in essence, maintained within the typical target of 2 - 3, our study underscores the specialized care that is warranted in higher risk patients to prevent a continued increase in INR and subsequent toxicities. We hope our results would be hypothesis-generating and aid in the development of larger, prospective evaluations to validate the findings of our present study.

3-Factor versus 4-Factor Prothrombin Complex Concentrates for the Reversal of Vitamin K Antagonist-Associated Coagulopathy: A Systematic Review and Meta-analysis

Long-term anticoagulation is used worldwide to prevent or treat thrombotic events. Anticoagulant therapy using vitamin K antagonists (VKAs) is well established; however, anticoagulants carry an increased risk of potentially life-threatening bleeding. In cases of bleeding or need for surgery, patients require careful management, balancing the need for rapid anticoagulant reversal with risk of thromboembolic events. Prothrombin complex concentrates (PCCs) replenish clotting factors and reverse VKA-associated coagulopathy. Two forms of PCC, 3-factor (3F-PCC) and 4-factor (4F-PCC), are available. Using PRISMA methodology, we systematically reviewed whether 4F-PCC is superior to 3F-PCC for the reversal of VKA-associated coagulopathy. Of the 392 articles identified, 48 full texts were reviewed, with 11 articles identified using criteria based on the PICOS format. Data were captured from 1,155 patients: 3F-PCC, n = 651; 4F-PCC, n = 504. ROBINS-I was used to assess bias. Nine studies showed international normalized ratio (INR) normalization to a predefined goal, ranging from ≤1.5 to ≤1.3, following PCC treatment. Meta-analysis of the data showed that 4F-PCC was favorable compared with 3F-PCC overall (odds ratio [OR]: 3.50; 95% confidence interval [CI]: 1.88-6.52, p < 0.0001) and for patients with a goal INR of ≤1.5 or ≤1.3 (OR: 3.45; 95% CI: 1.42-8.39, p = 0.006; OR: 3.25; 95% CI: 1.30-8.13, p = 0.01, respectively). However, heterogeneity was substantial (I 2 = 62%, I 2 = 70%, I 2 = 64%). Neither a significant difference in mortality (OR: 0.72; 95% CI: 0.42-1.24, p = 0.23) nor in thromboembolisms was reported. These data suggest that 4F-PCC is better suited than 3F-PCC for the treatment of patients with VKA-associated coagulopathy, but further work is required for a definitive recommendation.

Concordance of experienced-based maintenance warfarin dosing vs. algorithm-based dosing

IntroductionWarfarin maintenance dosing algorithms improve the time in therapeutic International Normalized Ratio (INR) range (TTR), a surrogate marker for clinical outcomes. Despite demonstrated benefit, many anticoagulation providers utilize experience-based dosing instead. This study assessed rates of concordance between experience-based and algorithm-based warfarin dosing at a single anticoagulation clinic. MethodsWithin University of Utah Health Thrombosis Service, patients on a maintenance dose of warfarin with an INR goal of 2.0–3.0 or 2.5–3.5 and who had INR results during November 2019 were included. Experienced-based approaches for out-of-range INRs were compared to a validated dosing algorithm to determine algorithm concordance rates as well as likelihood that algorithm concordance would return the INR into therapeutic range. ResultsDuring the one-month study period, there were 1120 out-of-range INRs in 770 patients included in this analysis. Providers’ decisions were 50.5% algorithm-concordant for dosing adjustments and 59.2% concordant for follow-up intervals. Algorithm-concordant dosing practices resulted in a significantly higher likelihood of returning the subsequent INR to the target range (odds ratio [OR] 1.33, 95% confidence interval [CI] 1.05–1.68), whereas algorithm-concordant follow-up intervals did not significantly impact return of INR to therapeutic range (OR 0.79, 95% CI 0.62–1.00). Baseline deviation from INR goal was determined to be significantly different between concordant and discordant study groups. Controlling for the deviation magnitude attenuated the significance of dosing concordance rates on return to INR target range (adjusted OR 1.16, 95% CI 0.91–1.48), while impact of follow-up concordance remained not statistically significant (adjusted OR 0.84, 95% CI 0.66–1.07). No provider characteristics were associated with the likelihood of return to INR goal. ConclusionExperience-based dosing was concordant with a validated dosing algorithm only half the time. Algorithm-concordant dosing increased the likelihood of returning the next INR to therapeutic range, though controlling for deviation magnitude attenuated the statistical significance of dosing concordance with return to INR goal rates. These findings support further research regarding implementing strategies that promote the use of a validated dosing algorithm among experienced anticoagulation providers.

Standard Versus Higher Intensity Anticoagulation for Patients With Mechanical Aortic Valve Replacement and Additional Risk Factors for Thromboembolism

Current guidelines recommend targeting an international normalized ratio (INR) of 2.5 to 3.5 for patients with mechanical aortic valve replacement (AVR) and additional risk factors for thromboembolic events. Available literature supporting the higher intensity (INR) goal is lacking. We aimed to evaluate the association of standard and higher intensity anticoagulation on outcomes in this patient population. The Michigan Anticoagulation Quality Improvement Initiative database was used to identify patients with mechanical AVR and at least one additional risk factor. Patients were classified into 2 groups based on INR goal: standard-intensity (INR goal 2.5) or higher-intensity (INR goal 3.0). Cox-proportional hazard model was used to calculate adjusted hazard ratios. One hundred and forty-six patients were identified of whom 110 (75.3%) received standard-intensity anticoagulation and 36 (24.7%) received higher intensity anticoagulation. Standard-intensity patients were older and more likely to be on aspirin. Atrial fibrillation was the most common additional risk factor for inclusion. The primary outcome of thromboembolic events, bleeding, or all-cause death was 13.9 and 19.5/100-person-years in the standard-intensity and higher intensity groups, respectively (adjusted HR 2.58, 95% confidence interval 1.28 to 5.18). Higher-intensity anticoagulation was significantly associated with any bleeding (adjusted HR 2.52, 95% confidence interval 1.27 to 5.00) and there were few thromboembolic events across both groups (5 events total). These results challenge current guideline recommendations for anticoagulation management of mechanical AVR in patients with additional risk factors.

28-Year-Old Man With Recurrent Vertigo, Syncope, and Progressive Memory Impairment

28-Year-Old Man With Recurrent Vertigo, Syncope, and Progressive Memory Impairment

Safety of warfarin therapy in children with coronary aneurysm due to Kawasaki disease

Objective: To investigate the safety of warfarin for Kawasaki disease (KD) with coronary artery aneurysm (CAA) and its prognosis. Methods: Twenty one children with KD complicated with giant CAA, multiple CAA in one coronary artery or thrombosis in coronary artery were enrolled in this prospective study. Warfarin was used to control the goal international normalized ratio (INR) ranging from 2.0 to 3.0. The CAA diameter, number, location and thrombus in coronary artery were recorded at the beginning of treatment, 1, 2, 3, 4 weeks and 2, 3, 6, 12 months after treatment, as well as the influence on INR, electrocaroliogram, creatine kinase-MB (CK-MB), troponin I. Standardized warfarin bleeding risk training and management was implemented. Children were divided into implementation group and non-implementation group according to the status of actual implementation of their parents. The incidence of bleeding events was compared between the two groups. Comparisons between groups were performed using a Rank sum test and a Fisher exact test. Results: In the 21 patients (15 males and 6 females), the age of onset ranged from 2 months to 6 years. There were 4 cases with grade Ⅱ, 7 cases with grade Ⅲ, 7 cases with grade Ⅳ and 3 cases with grade Ⅴ according to the severity of coronary arterial lesions before treatment. The time of clinical detection of thrombus in 10 children with thrombosis ranged from the fourth day to the fourth month. The dose distribution of warfarin was 0.06-0.10 mg/(kg·d), and the INR was 1.80-2.59. Among the 10 cases with thrombus, 8 cases had disappearance of thrombi and 2 cases with grade Ⅴ had thrombus organization to different degree. After treatment, the coronary artery ectasia of the 4 cases with grade Ⅱ all returned to normal. Among the 7 cases with grade Ⅲ, 3 cases of coronary artery aneurysms returned to normal, and 4 cases did not change. Among the 7 cases with grade Ⅳ , 5 cases of coronary artery aneurysms shrank to grade Ⅲ, and 2 cases remained unchanged. Three cases with grade Ⅴ lesions had no changes in aneurysm. Neither new thrombus nor new CAA was detected during the treatment. There was no significant change in electrocardiogram before and after treatment. No statistically significant difference was found regarding the troponin I (0.07 (0-3.01) vs. 0.04 (0-0.29) μg/L, Z=0.932, P>0.05) and CK-MB (20.6 (11.2-58.2) vs. 29.0 (16.7-47.0) U/L, Z=1.906, P>0.05) before and after treatment. The incidence of bleeding events in the implementation group was significantly lower than that in the non-implementation group (2/15 vs. 4/6, Fisher=5.689, P=0.031). Conclusions: The application of goal INR of 2.0-3.0 and adjustment of warfarin dose according to the severity of CAA combined with standardized and strict warfarin bleeding risk training and management, can increase the safety of warfarin therapy in children with KD, improve the prognosis of coronary artery lesions, promote the dissolution of thrombi, prevent new thrombosis, and effectively reduce the incidence of bleeding complication.

Investigating the International Normalized Ratio Thresholds for Complication in Shoulder Arthroplasty

In patients on warfarin anticoagulation therapy, elective shoulder arthroplasty surgeons must carefully balance bleeding and embolic risks. Currently, an international normalized ratio (INR) threshold of 1.5 is supported in the setting of elective surgery. However, no previous study has investigated the optimal preoperative INR target specifically in shoulder arthroplasty. The purpose of this study was to evaluate the association of preoperative INR with rates of transfusion, complication, and readmission/revision surgery in shoulder arthroplasty. Patients who underwent elective shoulder arthroplasty were identified in a national database. The primary outcome of interest was the risk for all-cause complication at 30 days postoperatively. Major and minor complication, revision surgery, and readmission rates were also investigated. From 2006 to 2016, 1,014 procedures were identified who had undergone elective shoulder arthroplasty with a perioperative INR lab result within 24 hours of surgery. In our cohort, 550 patients (54.2%) were women, with an average age of 71.0 ± 9.8 years. After controlling for confounders, patients with a preoperative INR > 1.5 were 18.9 times as likely to have a major complication as those with a preoperative INR ≤ 1.0 (P = 0.003). Patients with an INR of 1.25 < INR ≤ 1.5 did not have a statistically significant risk of minor or major complication in comparison with those with an INR ≤ 1.0 (P = 0.23, P = 0.67). Although recent hip and knee arthroplasty literature has found that an INR < 1.25 may be an optimal preoperative INR goal, our results did not find an increased risk for bleeding and complication with an INR ≤ 1.5 for shoulder arthroplasty. These results support current guidelines recommending a preoperative INR ≤ 1.5 for shoulder arthroplasty.

Gastrointestinal Bleeding Rates in Left Ventricular Assist Device Population Reduced with Octreotide Utilization.

Patients with continuous-flow left ventricular assist devices have a high risk of gastrointestinal bleeding (GIB) and recurrent bleeding. Studies have shown octreotide can reduce the risk of GIB. This retrospective, case-crossover study, evaluated the efficacy of octreotide for the prevention of recurrent GIB in patients with left ventricular assist devices between August 2008 and October 2018. A total of 32 patients received octreotide and were included in the study. Hospital admission for GIB was evaluated before and after the initiation of octreotide. Each case served as his/her own control. Most patients were on a reduced aspirin dose (56.2%) and had a reduced international normalized ratio goal (59.4%) before starting monthly octreotide. The most common dose of long-acting octreotide was 30 mg every 28 days. Overall, octreotide decreased the frequency of GIB (4.3 vs. 0.9 events/year, p < 0.001). Nineteen (59.4%) patients did not have a subsequent gastrointestinal bleed. Of the 13 patients who rebled after initiation of octreotide, the frequency of events decreased by 2.6 bleeds per patient per year (4.8 vs. 2.2; p = 0.043). In high-risk patients who have failed conventional therapy, octreotide can be useful for the prevention of recurrent GIB.

Propensity score adjusted comparison of three-factor versus four-factor prothrombin complex concentrate for emergent warfarin reversal: a retrospective cohort study

BackgroundProthrombin Complex Concentrates (PCC) are prescribed for emergent warfarin reversal (EWR). The comparative effectiveness and safety among PCC products are not fully understood.MethodsPatients in an academic level one trauma center who received PCC3 or PCC4 for EWR were identified. Patient characteristics, PCC dose and time of dose, pre- and post-INR and time of measurement, fresh frozen plasma and vitamin K doses, and patient outcomes were collected. Patients whose pre-PCC International Normalized Ratio (INR) was > 6 h before PCC dose or the pre-post PCC INR was > 12 h were excluded. The primary outcome was achieving an INR ≤ 1.5 post PCC. Secondary outcomes were the change in INR over time, post PCC INR, thromboembolic events (TE), and death during hospital stay. Logistic regression modelled the primary outcome with and without a propensity score adjustment accounting for age, sex, actual body weight, dose, initial INR value, and time between INR measurements. Data are reported as median (IQR) or n (%) with p < 0.05 considered significant.ResultsEighty patients were included (PCC3 = 57, PCC4 = 23). More PCC4 patients achieved goal INR (87.0% vs. 31.6%, odds ratio (OR) = 14.4, 95% CI: 3.80–54.93, p < 0.001). This result remained true after adjusting for possible confounders (AOR = 10.7, 95% CI: 2.17–51.24, p < 0.001). The post-PCC INR was lower in the PCC4 group (1.3 (1.3–1.5) vs. 1.7 (1.5–2.0)). The INR change was greater for PCC4 (2.3 (1.3–3.3) vs. 1.1 (0.6–2.0), p = 0.003). Death during hospital stay (p = 0.52) and TE (p = 1.00) were not significantly different.ConclusionsPCC4 was associated with a higher achievement of goal INR than PCC3. This relationship was observed in the unadjusted and propensity score adjusted results.

Abstract 17422: Transcatheter Mitral Valve Thrombosis: A Case Report and Literature Review

Background: Trans-catheter mitral valve replacement (TMVR) is an exciting alternative therapy for complex patients with mitral valve disease. The experience with TMVR is new and there is a lot yet to discover about their durability, long-term outcomes, and complications including, mitral transcatheter heart valve (THV) thrombosis. Many factors have been speculated to be associated with the increased risk of THV thrombosis. Here, we report a case of mitral THV thrombosis then discuss published data on the subject. Case presentation: A 72-year-old woman who underwent TMVR for severe mitral regurgitation with mitral annular calcification. She was discharged on aspirin and clopidogrel for thromboprophylaxis. She presented after 30 days with symptomatic heart failure. Her transesophageal echocardiogram showed increased mean trans-mitral gradient with severe subvalvular thickening with immobile neo-anterior leaflet. She was subsequently started on a heparin drip with bridge to warfarin with international normalized ratio goal of 2.5 to 3.5. Discussion: Since most patients undergoing TMVR are within a high-risk population, caution should be implemented to minimize complications, valve dysfunction, and failure. We reviewed 42 TMVR papers with total of 1484 patients including 60 with mitral THV thrombosis. We discussed the most common strategies used for mitral THV thromboprophylaxis and treatment. Conclusion: Given current evidence, post-TMVR anticoagulation should be considered for at least 3 months, especially in those without significant bleeding risk. Longer anti-coagulation therapy should be considered for patients with multiple risk factors for thrombus formation. Additionally, systematic active screening with close clinical follow up help promptly identify those with subclinical THV thrombosis or need longer anti-coagulation therapy.

Weight-Based Dosing Versus a Fixed-Dose Regimen of 4-Factor Prothrombin Complex Concentrate in Obese Patients Requiring Vitamin K Antagonist Reversal.

Despite an increase in the use of fixed-dose protocols of 4-factor prothrombin complex concentrate (4F-PCC) for the reversal of vitamin K antagonists (VKAs), there remains a paucity of data in obese patients. In this study, we aimed to compare the proportion of patients attaining international normalized ratio (INR) goals using a weight-based dosing strategy versus a fixed-dose regimen of 4F-PCC. This was a retrospective study conducted in patients 18years of age or older, weighing ≥ 100kg, who received either a weight-based dose or fixed dose of 4F-PCC (2000 units) for the reversal of VKA, and had a documented baseline and post-treatment INR. The primary outcome was the proportion of patients achieving an INR of < 2 for all indications of warfarin reversal, except in patients with intracranial hemorrhage, where the goal was an INR of < 1.5. A total of 44 patients met the inclusion criteria; 25 patients in the weight-based dosing group and 19 patients in the fixed-dose group. The median baseline INR was similar in both groups (weight-based dosing group 3.2 [interquartile range {IQR} 2.8-3.7] vs fixed-dose group 3.0 [IQR 2.7-4.9], p = 1). The median post-treatment INR was significantly lower in the weight-based dosing group compared to the fixed-dose group (1.3 [IQR 1.2-1.5] vs 1.6 [IQR 1.5-1.9], p < 0.01). However, there was no significant difference in the primary outcome between both groups (weight-based dosing strategy 84% vs fixed dose strategy 90%, p =0.68). Our findings suggest that a fixed-dose regimen of 2000 units in obese patients weighing ≥ 100kg is adequate to achieve these INR goals.

Management of Valvular Heart Failure Due To Mechanical Mitral Valve Thrombosis During Pregnancy

Background Mechanical heart valves may pose hemodynamic challenges leading to significant heart failure during pregnancy, especially if thrombosis or stenosis occurs. On the other hand, warfarin can have teratogenic effects, and expectant mothers may try to avoid it during pregnancy. Case A 38-year-old woman with 30-week pregnancy complained of progressive dyspnea on minimal exertion. She had a history of congenital mitral valve abnormality for which had undergone mechanical valve replacement 21 years prior, with subsequent mechanical valve thrombosis after she held her warfarin for several days during a previous pregnancy which was treated successfully with tissue plasminogen activator (tPA). The patient's anticoagulation had been changed to enoxaparin from weeks 7 to 12 to decrease the risk of teratogenesis. Her international normalized ratio (INR) remained therapeutic afterwards, so her mildly elevated mean mitral gradient (MMG) was initially attributed to increased cardiac output of pregnancy. However, as her dyspnea worsened, concerns for thrombosis increased. She underwent transthoracic echocardiography (TTE) which evidenced that her MMG had increased from 12 to 20-22 mmHg over the last 3 months prior to presentation, with no decrease in her right or left ventricular systolic functions. Fluoroscopy and transesophageal echocardiography (TEE) showed no anterior leaflet mobility. She was admitted to the cardiovascular critical care unit where she received tPA infusion for 24 hours with subsequent TTE evaluation. Although the MMG normalized, there was still residual leaflet restriction. Fibrinolytics were continued for a total of 48 hours, and she was bridged to warfarin with heparin (goal partial thromboplastin time [PTT] 2-2.5 of control range). Her INR goal range was increased to 3-4. She underwent cesarean section and tubal ligation at 34 weeks of pregnancy. Neither she nor her baby had complications. Conclusion This case supports the cautious use of fibrinolysis in pregnant patients presenting with progressive heart failure secondary to mechanical valve thrombosis under intensive, multi-disciplinary monitoring by cardiologist and maternofetal medicine specialists.

Anticoagulation following mitral valve repair.

Anticoagulation after mitral valve repair is controversial and guidelines are not well-established. This study evaluated the association between postoperative warfarin use and complications after mitral valve repair, including bleeding and thromboembolic incidents, readmission, and mortality. This retrospective study investigated 1097 patients who underwent elective mitral valve repair between April 2003 and March 2017, and was naïve to atrial fibrillation or prior cardiac surgery. This cohort had no other indication for or against anticoagulation. About 775 patients were placed on warfarin with international normalized ratio goal 2.5 and 322 patients were not anticoagulated. The association between anticoagulation and complications was assessed with univariate comparisons between groups and multiple logistic regression. Postoperative warfarin use was associated with a reduced composite of bleeding and thromboembolic complications (pulmonary embolism, TIA, stroke, pericardial effusion or cardiac tamponade, gastrointestinal bleeding, and reoperation for bleeding) with an odds ratio of 0.29 (95% confidence interval, 0.13-0.64, P = .003). There was no difference in 30-day or 6-month mortality or readmission rate between groups. Long-term survival estimates were superior in the warfarin group (10-year: 92% vs 85%; log-rank P < .001). Our analysis showed that postoperative warfarin use was associated with an overall reduced composite of bleeding and thromboembolic incidents and superior long-term survival. These findings suggest that anticoagulation with warfarin following mitral valve repair may be a safe and effective means for avoiding postoperative complications and that a large prospective randomized clinical trial is warranted.

Evaluation of dosing and safety outcomes of low-dose prophylactic warfarin in children after cardiothoracic surgery.

Prophylactic warfarin with an International Normalized Ratio (INR) goal of 1.5 to 2.0 is one antithrombotic therapy utilized in children after cardiothoracic surgery (CTS); published sources suggest a dose of 0.1 mg/kg per day to achieve this goal. However, few studies have evaluated dosing in this population. The purpose of this study was to evaluate dosing and safety outcomes in children receiving warfarin after CTS. A descriptive, retrospective review was conducted to evaluate warfarin dosing and INR outcomes in patients 18 years of age or younger who underwent CTS and received prophylactic warfarin with an INR goal of 1.5 to 2.0 from January 2014 through December 2018. The primary objective was to determine the median initial warfarin dose. Secondary objectives included identifying the percentage of documented INR values that were outside the therapeutic range, the percentage of patients with therapeutic INRs at discharge, and the 30-day readmission rate. Twenty-six patients were included in the review. The median initial warfarin dosage was 0.07 mg/kg/d (interquartile range [IQR], 0.05-0.10 mg/kg/d). Of the total of 177 INR values collected during the entire study period, 67 (37.9%) were therapeutic, 64 (36.2%) were subtherapeutic, and 46 (26.0%) were supratherapeutic. Eighteen patients (69.2%) had at least 1 supratherapeutic INR at any point during the study period, most frequently on days 2 through 4 of therapy. At discharge, 11 patients (42.3%) had therapeutic INRs. Four patients (15.4%) were readmitted within 30 days, with bleeding documented in 2 patients during their readmission. The majority of patients received an initial warfarin dose less than that specified in published recommendations but still had a supratherapeutic INR at least once during the study period. When initiating warfarin after CTS, a dosage of <0.1 mg/kg per day and frequent monitoring may be needed to achieve an INR goal of 1.5 to 2.0.

Effect of post-operative anticoagulation management in patients who have undergone On-X mechanical heart valve replacement surgery on post-discharge warfarin therapy.

We evaluated the effect of the proportion of time maintained within the target international normalized ratio (INR) postoperatively in hospitalized patients who underwent On-X mechanical heart valve replacement on warfarin therapy after discharge. Inclusion was patients who were ≥18years, received warfarin for a minimum of 10days without any interruptions during hospitalization and followed by the anticoagulation service (ACS) clinic after discharge between June 2006 and June 2016. Patients were excluded if they had incomplete medical records, INR goal changes, known as warfarin resistance, transferred to another facility or expired during the study. The patients were divided into 3 groups according to the proportion of time maintained within therapeutic INR range (TTR) from day 4 to 10 of warfarin initiation (low: <30%, moderate: ≥30% to <70%, and high: ≥70%). The number of days needed to reach target INR for 2 consecutive measurements after discharge and the number of ACS visits was compared among the groups. Among 539 postoperative patients, 273 were included. The baseline demographics were similar among the 3 groups. The mean time needed to reach target INR for 2 consecutive measurements was 68.6±106.1days. The low group required time needed to reach target INR for 2 consecutive measurements of 94.0±140.9days compared with 44.8±57.1days in the high group (P=.007). Additionally, the low group had more ACS visits than the high group (low, 6.6±5.2 vs high, 4.6±3.9; P=.025). Patient compliance affected the time needed to reach target INR for 2 consecutive measurements (compliant, 42.36±58.5days vs non-compliant, 132.0±157.1days, P<.001). The study implicated that high postoperative TTR would reduce the time to require post-discharge target INR and the number of ACS visits.

Assessment of the Impact of Pharmacist-led Transitions of Care Services in a Primary Health Center.

Background: The impact of pharmacist-led transition of care services with collaborative drug therapy management has shown to improve patients' outcomes and decrease health costs. Compelling statistics show higher readmission rates for under-insured patients compared with insured patients at primary health care clinics. Methods: This is a single center, prospective, cohort study designed to examine team-based collaborative drug therapy management and its effect on therapeutic outcomes of under-insured patients with target chronic diseases managed in a primary health center. Targeted chronic diseases included dyslipidemia, diabetes, hypertension, anticoagulation disorders, chronic obstructive pulmonary disease, and heart failure. The primary outcome measures included percentage of time in therapeutic international normalized ratio (INR) and percentage of patients at targeted goals of blood pressure, lipids, and hemoglobin A1c (HbA1c). Secondary outcomes included reduced emergency department visits, number of patient encounters, hospital readmissions within 30 days of discharge, and disease exacerbation rates. Results: Patients were at INR goal 58% of the time compared with 52% at baseline (P = .66). There was a 9% improvement in mean HbA1c in the intervention group when compared with baseline (9.6% vs 10.9%, P = .03). With pharmacist intervention, 73.8% of the patients had their blood pressure at goal compared with 50% at baseline (P = .14). A limited number of patients were readmitted for different reasons, including uncontrolled disease states. Conclusions: The pharmacist-physician collaborative drug therapy management led to improved blood pressure control, average HbA1c, and time in therapeutic INR range. A decrease in health care utilization was also identified.

Effect of Low-Intensity vs Standard-Intensity Warfarin Prophylaxis on Venous Thromboembolism or Death Among Patients Undergoing Hip or Knee Arthroplasty

The optimal international normalized ratio (INR) to prevent venous thromboembolism (VTE) in warfarin-treated patients with recent arthroplasty is unknown. To determine the safety and efficacy of a target INR of 1.8 vs 2.5 for VTE prophylaxis after orthopedic surgery. The randomized Genetic Informatics Trial (GIFT) of Warfarin to Prevent Deep Vein Thrombosis enrolled 1650 patients aged 65 years or older initiating warfarin for elective hip or knee arthroplasty at 6 US medical centers. Enrollment began in April 2011 and follow-up concluded in October 2016. In a 2 × 2 factorial design, participants were randomized to a target INR of 1.8 (n = 823) or 2.5 (n = 827) and to either genotype-guided or clinically guided warfarin dosing. For the first 11 days of therapy, open-label warfarin dosing was guided by a web application. The primary outcome was the composite of VTE (within 60 days) or death (within 30 days). Participants underwent screening duplex ultrasound postoperatively. The hypothesis was that an INR target of 1.8 would be noninferior to an INR target of 2.5, using a noninferiority margin of 3% for the absolute risk of VTE. Secondary end points were bleeding and INR values of 4 or more. Among 1650 patients who were randomized (mean age, 72.1 years; 1049 women [63.6%]; 1502 white [91.0%]), 1597 (96.8%) received at least 1 dose of warfarin and were included in the primary analysis. The rate of the primary composite outcome of VTE or death was 5.1% (41 of 804) in the low-intensity-warfarin group (INR target, 1.8) vs 3.8% (30 of 793) in the standard-treatment-warfarin group (INR target, 2.5), for a difference of 1.3% (1-sided 95% CI, -∞ to 3.05%, P = .06 for noninferiority). Major bleeding occurred in 0.4% of patients in the low-intensity group and 0.9% of patients in the standard-intensity group, for a difference of -0.5% (95% CI, -1.6% to 0.4%). The INR values of 4 or more occurred in 4.5% of patients in the low-intensity group and 12.2% of the standard-intensity group, for a difference of -7.8% (95% CI, -10.5% to -5.1%). Among older patients undergoing hip or knee arthroplasty and receiving warfarin prophylaxis, an international normalized ratio goal of 1.8 compared with 2.5 did not meet the criterion for noninferiority for risk of the composite outcome of VTE or death. However, the trial may have been underpowered to meet this criterion and further research may be warranted. ClinicalTrials.gov Identifier: NCT01006733.

A Review of Warfarin Dosing and Monitoring

The anticoagulant drug warfarin is a vitamin K antagonist, coumarin derivative which inhibits the synthesis of clotting factors II, VII, IX, and X, as well as the naturally occurring endogenous anticoagulant proteins C and S. Warfarin is still considered the mainstay of oral anticoagulant treatment, it is a difficult drug to manage due to its narrow therapeutic index. An inappropriate management of patients can lead to subtherapeutic or supratherapeutic levels, increasing the risk of thromboembolic episodes or hemorrhagic episodes, respectively. Common indications for the use of warfarin include stroke prevention in atrial fibrillation, preventing thrombus formation in patients with heart valves and treatment of venous thromboembolism. When warfarin therapy is initiated for venous thromboembolism, it should be given the first day, along with a heparin product or fondaparinux. The heparin product or fondaparinux should be continued for at least five days and until the patient's international normalized ratio is at least 2.0 for two consecutive days. The international normalized ratio goal and duration of treatment with warfarin vary depending on indication and risk. Warfarin therapy should be stopped five days before major surgery and restarted 12 to 24 hours postoperatively. Bridging with low-molecular-weight heparin or other agents is based on balancing the risk of throm boembolism with the risk of bleeding.Faridpur Med. Coll. J. Jan 2018;13(1): 40-43