Warfarin Dosing Nomogram Research Articles

Implications of an inpatient warfarin dosing nomogram on safety outcomes post-discharge.

Many hospitals have implemented warfarin dosing nomograms to improve patient safety. To our knowledge, no study has assessed the impact inpatient warfarin initiation has in both medical and surgical patients, on safety outcomes post discharge. To evaluate the impact of a suggested institutional nomogram for the initiation of warfarin, the primary endpoint was the incidence of bleeding throughout follow up. Secondary endpoints included the composite of INR changes ≥0.5/day and INR >4. Patients were followed for a period of 2weeks post-discharge. The composite endpoint was evaluated for an effect on reaching therapeutic INR, time to reach therapeutic INR, and bleeding events throughout follow up. A single center retrospective study comparing the safety of adherence vs. non-adherence to a warfarin nomogram. A total of 206 patients were included, 73 patients in the nomogram adherence vs. 133 in the nonadherence arm. There was no difference in the proportion of patients who bled throughout the follow up period, adherence 9.6% vs. nonadherence to the nomogram 13.5%, p = 0.407. There was however a statistical difference in the mean total number of bleeding events, 0.096 (7/73) in the adherence vs. 0.158 (21/133) in the non-adherence arm, p = 0.022. There was also no difference in the composite endpoint, 19.2% in the adherence vs. 28.6% in the non-adherence arm p = 0.180. A positive correlation between the inpatient composite and risk of bleeding throughout follow up was noted. The findings of this study support adherence to the nomogram as opposed to non-adherence.

Assessment of Dosing and Patient Factors on the Efficacy of Warfarin Following Total Joint Replacement.

The purpose of this study was to determine the percentage of patients discharged with a subtherapeutic INR <1.8 using our institutions inpatient warfarin dosing nomogram following total joint arthroplasty (TJA). We examined predisposing risk factors for a subtherapeutic discharge (INR <1.8), including increased body weight, age, gender, end stage renal disease (ESRD), smoking, and peri-operative transfusion.Chart review identified 249 patients for study inclusion. Logistic regression (LR) was used to identify associated risk factors for a subtherapeutic INR (<1.8) on day of discharge.The majority of patients (58.6%, 146 of 249) following TJA surgery were found to have a subtherapeutic INR level (INR<1.8) at discharge (mean length of stay 2.6 days). Multivariate LR analysis found that weight greater than 180 lbs. (OR 2.08, CI 1.09, 3.98, P=0.027) was found to increase the odds of a subtherapeutic INR on day of discharge. Our results were not significant for weight 20% beyond ideal body weight, age (>65y), gender, peri-operative transfusion, smoking, ESRD or autoimmune disease.A patient’s body weight influences response to warfarin following TJA. An inpatient warfarin dosing nomogram that takes into account a patient’s weight should be used to reduce the risk of subtherapeutic INR levels in obese TJA patients.

Factors influencing warfarin response in hospitalized patients

The objective of this study was to investigate the influence of simultaneous factors that potentially keep patients far from achieving target INR range at discharge in hospitalized patients. Prospective cross-sectional observational study conducted at the Cardiology Department and Intensive Care Unit (ICU) of the Assiut University Hospitals. One-hundred and twenty patients were enrolled in the study from July 2013 to January 2014. Outcome measures were discharge INRs, bleeding and thromboembolic episodes. Bivariate analysis and multinomial logistic regression were conducted to determine independent risk factors that can keep patients outside target INR range.Patients who were newly initiated warfarin on hospital admission were given low initiation dose (2.8mg±0.9). They were more likely to have INR values below 1.5 during hospital stay, 13 (27.7%) patients compared with 9 (12.3%) previously treated patients, respectively (p=.034). We found that the best predictors of achieving below target INR range relative to within target INR range were; shorter hospital stay periods (OR, 0.82 for every day increase [95% CI, 0.72–0.94]), being a male patient (OR, 2.86 [95% CI, 1.05–7.69]), concurrent infection (OR, 0.21 [95% CI, 0.07–0.59]) and new initiation of warfarin therapy on hospital admission (OR, 3.73 [95% CI, 1.28–10.9]).Gender, new initiation of warfarin therapy on hospital admission, shorter hospital stay periods and concurrent infection can have a significant effect on discharge INRs. Initiation of warfarin without giving loading doses increases the risk of having INRs below 1.5 during hospital stay and increases the likelihood of a patient to be discharged with INR below target range. Following warfarin dosing nomograms and careful monitoring of the effect of various factors on warfarin response should be greatly considered.

Genetics-Based Pediatric Warfarin Dosage Regimen Derived Using Pharmacometric Bridging

Warfarin dosage regimens using CYP2C9 and VKORC1 polymorphisms have been extensively studied in adults and is included in US Food and Drug Administration-approved warfarin labeling. However, no dosage algorithm is available for pediatric patients. To derive a genetics-based pediatric dosge regimen for warfarin, including starting dose and titration scheme. A model-based approach was developed based on a previously validated warfarin dosage model in adults, with subsequent comparison to pediatric data from pediatric warfarin dose, genotyping, and international normalized ratio (INR) results. The adult model was based on a previously established model from the CROWN (CReating an Optimal Warfarin dosing Nomogram) trial. Pediatric warfarin data were obtained from a study conducted at the Children's Hospital of Los Angeles with 26 subjects. Variant alleles of CYP2C9 (rs1799853 or *2, and rs1057910 or *3) and the VKORC1 single nucleotide polymorphism (SNP) rs9923231 (-1639 G>A) were assessed, where the rs numbers are reference SNP identification tags assigned by the National Center for Biotechnology Information. A pediatric warfarin model was derived using the previously validated model and clinical pharmacology considerations. The model was validated, and clinical trial simulation and stochastic modeling were used to optimize pediatric dosage and titration. The final dosage regimen was optimized based on simulations targeting a high (≥60%) proportion of INRs within the therapeutic range by week 2 of warfarin therapy while minimizing INRs >3.5 or <2. The proposed pediatric warfarin dosage scheme based on individual CYP2C9 (alleles *1,*2,*3) and VKORC1 rs9923231 (-1639 G>A) genotypes may offer improved dosage compared to current treatment strategies, especially in patients with variant CYP2C9 and VKORC1 alleles. This pilot study provides the foundation for a larger prospective evaluation of genetics-based warfarin dosage in pediatric patients.

Application of a genomics‐guided warfarin dosing nomogram for hospitalized patients

Adverse drug reactions (ADRs) due to warfarin are an important cause of emergency department visits, and also occur frequently among hospitalized patients. We now know common genetic variations in CYP2C9‐mediated metabolism of warfarin, as well as its target VKORC1, account for much of the dosing variation. Accordingly, we hypothesized that application of a pharmacogenomics‐guided warfarin dosing algorithm that our group developed, known as WRAPID, may be clinically useful in guiding warfarin initiation and dosing for hospitalized patients. We initiated a personalized medicine‐based inpatient consult service with a goal of providing WRAPID‐based warfarin dosing recommendations. We now have data on a series of patients who were initiated on warfarin as inpatients who subsequently developed a supratherapeutic international normalized ratio (INR). When assessed by our service, most were shown to possess genotypes associated with marked sensitivity to warfarin, including one patient with the rare CYP2C9 *3/*3 genotype, as well as several with CYP2C9 *2/*2 and/or VKORC1‐1639 A/A genotype. Based on our WRAPID‐guided dosing, warfarin dose was accurately predicted to be as low as 0.5 mg. Accordingly, we believe genomics‐guided warfarin dosing is useful for identifying hospitalized patients at risk for ADRs, thereby reducing length of stay and preventing readmissions. Funding: AMOSO Drug Innovation Fund.

A Safe, Effective, and Easy to Use Warfarin Initiation Dosing Nomogram for Post–Joint Arthroplasty Patients

Venous thromboembolism (VTE) is a complication after joint arthroplasty, and pharmacologic prophylaxis is recommended to reduce this risk. Warfarin is often used, but initial dosing and management can be difficult. We studied a single-center prospective cohort of consecutive (n = 351) post–joint arthroplasty/revision patients who were initiated on warfarin using a new initiation nomogram and then discharged to home with home health services. The mean time to an international normalized ratio (INR) of 2.0 or higher was 5 days, with a mean INR of 2.1 on the fifth postoperative day. Two patients (0.6%) had an INR higher than 5 in the first 10 days of therapy. Adverse events were uncommon: 4 patients (1.14%) had VTE, 1 had major bleeding episode, and 6 patients (1.7%) had minor bleeding. A specific warfarin dosing nomogram managed by an anticoagulation service and used in joint arthroplasty/revision patients who are discharged to home with home health services leads to effective anticoagulation with few associated adverse events.

The Effectiveness of Warfarin Dosing from a Nomogram Compared with House Staff Dosing

The purpose of this study is to address the safety and efficacy of a warfarin dosing nomogram. Patients undergoing hip or knee arthroplasty were randomized to warfarin dosed by nomogram (n = 106) or by house staff (n = 110) during their hospital stay. The average daily dose of warfarin was 4.14 mg for the nomogram group and 4.18 mg for the house staff group. On postoperative day 4, the average international normalized ratio was 1.55 in the nomogram group compared with 1.59 in the house staff group. On postoperative day 4, 19.1% of the patients in the nomogram group had a therapeutic international normalized ratio, compared with 14.7% in the house staff group. There were no differences in bleeding or thrombotic complications in the 2 groups. This nomogram appears to be both safe and effective.

Retrospective Analysis of the Effect of Argatroban and Coumadin on INR Values in Heparin Induced Thrombocytopenia.

Background: Patients who develop Heparin-induced thrombocytopenia(HIT) are at an increased risk for thrombosis. They may require long term anticoagulant therapy and are often stepped down from either argatroba, lepirudinn or danaparoid to oral warfarin therapy. Step down of anticoagulation therapy is complicated by falsely elevated PT/INR which can cause difficultly in assessing the appropriate time to discontinue Argatroban therapy. Patients may be increased risk of bleeding due to receiving combined therapy. Previous studies analyzing this effect of combined therapy were observed in healthy individuals. The experience at this institution is complicated utilization of abnormally low rates of argatroban to achieve therapeutic aPTT levels.Method: This is a retrospective chart review study analyzing the trends of INRs with argatroban and warfarin concomitant therapy. All patients during the period of January 2002 to December 2005 receiving argatroban were identified from pharmacy records. Only patients with argatroban and warfarin stepdown therapy were considered for this analysis. The only exclusion criteria was documented end stage liver failure. ANOVA analysis was deemed appropriate and SPSS program was utilized. Direct thrombin Inhibitor (DTI) levels was utilized for argatroban monitoring starting in 2005. The primary endpoint was to determine the effect Argatroban has on INR by analyzing the INR with concomitant argatroban and coumadin therapy, argatroban alone and evaluating the true INR with coumadin alone. The secondary endpoint was to observe any adverse effects and complications from concomitant therapy mainly bleeding and mortality.Results: The primary endpoints are displayed in table 1. Ninety-three percent of patients required a maintenance argartroban rate of less than 1.0 mcg/kg/min with 68 % requiring less than 0.5 mcg/kg/min. There was a stronger correlation when argatroban rates were less than 0.25 mcg/kg/min and the associated twofold increase previously noted in other trials with combined therapy was not observed. The secondary endpoints are shown in table 2. Less than 50% of the patients in both major and minor bleeding episodes and 33% of mortality had documented INRs > 4.0.Conclusions: The argatroban rates documented in this study are 50–75% less than 2–4 mcg/kg/min usually reported in literature. In addition, the conversion from aPTT to DTI monitoring resulted in a greater than 60% reduction in argatroban rates. However the correlation was also stronger at these lower rates. Although there was not a high percentage of bleeds with INR's greater than 4.0, the relationship between DTI and INR suggest that a lower combined INR could be targeted for therapeutic efficacy. A warfarin dosing nomogram based on these finding will be developed and tested. Information regarding ISI was not available at the time of this abstract.Primary EndpointsArgatroban Rate(mcg/kg/min)NINR on warfarin aloneINR on warfarin and argatrobanANOVA< 0.05133.17 ± 1.374.01 ± 2.900.7340.06–0.25323.68 ± 1.064.19 ± 1.170.7040.26–0.5142.71 ± 1.123.38 ± 1.690.220.5–1.0133.10 ±0.795.00 ± 0.540.54>1.062.74 ± 1.475.13 ± 3.690.162Secondary Endpoints -Complicationsn (%)outcomes with INR > 4.0 on both agentsTotal Bleeding11 (13%)5 (45%)Major7 (8%)3 (43%)Minor4 (5%)2 (50%)High requiring PRBC with no bleeding*5 (6%)5 (100%)Mortality15 (17%)5 (33%)* all INRs >5.5

Warfarin Initiation and the Potential Role of Genomic-Guided Dosing

Warfarin Initiation and the Potential Role of Genomic-Guided Dosing

Comparison of a Frail-Friendly Nomogram with Physician-Adjusted Warfarin Dosage for Prophylaxis after Orthopaedic Surgery on a Geriatric Rehabilitation Unit

ABSTRACTWarfarin dosing for thromboprophylaxis in post-operative patients is time-consuming. Warfarin-dosing nomograms can be used in post-operative arthroplasty patients, but warfarin requirements are lower in frail older people. We modified an existing post-arthroplasty nomogram to a frail-friendly version and evaluated its performance in a frail elderly post-orthopaedic surgery on a geriatric rehabilitation ward to determine if it would improve quality indicators for oral anticoagulation. On a geriatric rehabilitation unit, post-operative orthopaedic patients were assigned to either physician-adjusted warfarin dosing or the nursing-administered nomogram. The proportion of days within target INR values was significantly higher in the nomogram group (77%, 95% CI 74% to 81%) compared to the physician-adjusted group (53%, 95% CI 46% to 60%), with no major bleeding or thromboembolic complications. The number of warfarin-related telephone calls to physicians was significantly reduced by tenfold. Use of a frail-friendly nomogram improved quality and efficiency of patient care on a geriatric rehabilitation unit.

Oral anticoagulant initiation: rationale for the use of warfarin dosing nomograms.

Oral anticoagulants prevent thrombosis however they are associated with bleeding. The risk of both bleeding and thrombosis is increased when the International Normalized Ratio (INR) is outside the desired therapeutic range. Hence, oral anticoagulants should be administered with the intention of maximizing the "time within the therapeutic range." The frequency of INR values outside this range can be decreased by (1) warfarin initiation algorithms that guide initial therapy and (2) use of computerized systems to guide chronic warfarin therapy. This article reviews these techniques.