Clinical versus fixed warfarin dosing and the impact on quality of anticoagulation (The ClinFix trial).

Different dosing strategies exist to initiate warfarin, most commonly fixed warfarin dosing (FWD), clinical warfarin dosing (CWD), and genetic-guided warfarin dosing (GWD). Landmark trials have shown GWD to be superior when compared to FWD in the EU-PACT trial or CWD in the GIFT trial. COAG trial did not show differences between GWD and CWD. We aim to compare the anticoagulation quality outcomes of CWD and FWD. This is a prospective cohort study with a retrospective comparator. Recruited subjects in the CWD (prospective) arm were initiated on warfarin according to the clinical dosing component of the algorithm published in www.warfarindosing.org. The primary efficacy outcome was the percentage time in the therapeutic range (PTTR) from day 3 to 6 till day 28 to 35. The study enrolled 122 and 123 patients in the CWD and FWD, respectively. The PTTR did not differ statistically between CWD and FWD (62.2 ± 26.2% vs. 58 ± 25.4%, p = 0.2). There was also no difference between both arms in the percentage of visits with extreme subtherapeutic international normalized ratio (INR) (<1.5; 15 ± 18.3% vs. 16.8 ± 19.1%, p = 0.44) or extreme supratherapeutic INR (>4; 7.7 ± 14.7% vs. 7.5 ± 12.4%, p = 0.92). We conclude that CWD did not improve the anticoagulation quality parameters compared to the FWD method.

Brain Metastasis With a Solitary Lesion Secondary to Knee Joint Ewing Sarcoma: A Case Report.

Brain metastasis from Ewing sarcoma is rare and can present with various symptoms. We present a 21-year-old female who underwent surgery for Ewing sarcoma of the knee joint and, after six months, was reported with complaints of headache and vomiting. Considering recommended investigations, metastatic Ewing sarcoma of the brain was diagnosed, and a treatment protocol, such as a combination of surgery, chemotherapy, and radiation, was given. Our observation shows this is the first case reported with a solitary metastatic brain lesion associated with Ewing sarcoma.

Genetic and Non-Genetic Factors Impact on INR Normalization in Preprocedural Warfarin Management.

BACKGROUND: Annually, 10% of warfarin patients will likely need to stop warfarin prior to elective surgery to achieve a baseline international normalization ratio (INR) level (INR ≤ 1.2) at the time of the procedure. This study explores the influence of genetic and non-genetic factors on INR normalization in the Arab (major part of Near Eastern) population in preprocedural warfarin management. METHODS: An observational prospective cohort study was designed to recruit Arab patients taking warfarin and scheduled for an elective procedure. Two INR readings were recorded. DNA extraction and genotyping of variants in CYP2C9*2, CYP2C9*3, CYP4F2*3, VKORC1*2, and FII (rs5896) and FVII (rs3093229) genes using real-time polymerase chain reaction were performed. RESULTS: Data from 116 patients were included in the analysis. CYP2C9 and VKORC1 genetic variants carriers required lower maintenance dose compared to non-carriers. The analysis showed that ciprofloxacin, antiplatelet medications, and INR index (INR at visit 1) are the only factors associated with the INR decline rate. Also, the proportion of CYP2C9*3 carriers with normal INR (≤1.2) on the day of surgery was significantly lower than those with wild-type genotype (28% vs 60%, p=0.013). In addition, heparin bridging, INR target, and Sudanese nationality are significant predictors of INR normalization (≤1.2) on the day of the procedure. CONCLUSION: Despite the confirmed effect of genetic factors on warfarin maintenance dose, the study was not able to find a significant effect of any genetic factor on the rate of INR normalization possibly due to the small sample size. Index INR and interacting medications showed to be significant predictors of INR decline rate.

Bridging vs Non-Bridging with Warfarin Peri-Procedural Management: Cost and Cost-Effectiveness Analyses.

The warfarin peri-procedural management in Qatar is predominantly based on bridging (63%), compared to non-bridging. This study sought to perform a first-time cost analysis of current warfarin peri-procedural management practices, including a cost-effectiveness analysis (CEA) of predominant bridging vs predominant non-bridging practices. From the hospital perspective, a one-year decision-analytic model followed the cost and success consequences of the peri-procedural warfarin in a hypothetical cohort of 10,000 atrial fibrillation patients. Success was defined as survival with no adverse events. Outcome measures were the cost and success consequences of the 63% bridging (vs not-bridging) practice in the study setting, ie, Hamad Medical Corporation, Qatar, and the incremental cost-effectiveness ratio (ICER, cost/success) of the warfarin therapy when predominantly bridging based vs when predominantly non-bridging based. The model was based on Monte Carlo simulation, and sensitivity analyses were performed to confirm the robustness of the study conclusions. As per 63% bridging practices, the mean overall cost of peri-procedural warfarin management per patient was USD 3,260 (QAR 11,900), associated with an overall success rate of 0.752. Based on the CEA, predominant bridging was dominant (lower cost, higher effect) over the predominant non-bridging practice in 62.2% of simulated cases, with a cost-saving of up to USD 2,001 (QAR 7,303) at an average of USD 272 (QAR 993) and was cost-effective in 36.9% of cases. Being between cost-saving and cost-effective, compared to predominant non-bridging practices, the predominant use of bridging with warfarin seems to be a favorable strategy in atrial fibrillation patients.

Anticoagulation clinic drive-up service during COVID-19 pandemic in Qatar.

Coronavirus Disease 2019 (COVID-19) is a pandemic affecting many countries worldwide. Given the increasing incidence especially in elderly and individuals with comorbid conditions, it is advised by health authorities to stay home if possible, maintain social distancing and stay away from those who are sick or could be infected. Patients with comorbidities especially cardiovascular disease are at higher risk of getting infected with COVID-19 and have worse prognosis. Among efforts to safely manage warfarin patients during this pandemic, we introduced a hospital drive-up anticoagulation testing service. This service can reduce the risk of exposure of anticoagulation patients to COVID-19 by reducing the contact time with the different personnel at the hospital and by maintaining those patients at a safe distance from others.

The effect of genetic and nongenetic factors on warfarin dose variability in Qatari population.

The objective of this study is to estimate the prevalence of VKORC1, CYP2C9, and CYP4F2 genetic variants and their contribution to warfarin dose variability in Qataris. One hundred and fifty warfarin-treated Qatari patients on a stable dose and with a therapeutic INR for at least three consecutive clinic visits were recruited. Saliva samples were collected using Oragene DNA self-collection kit, followed by DNA purification and genotyping via TaqMan Real-Time-PCR assay. The population was stratified into derivation and validation cohorts for the dosing model. The minor allele frequency (MAF) of VKORC1 (-1639G>A) was A (0.47), while the MAF's for the CYP2C9*2 and *3 and CYP4F2*3 were T (0.12), C (0.04) and T (0.43), respectively. Carriers of at least one CYP2C9 decreased function allele (*2 or *3) required lower median (IQR) warfarin doses compared to noncarriers [24.5 (14.5) mg/week vs. 35 (21) mg/week, p < 0.001]. Similarly, carriers of each additional copy of (A) variant in VKORC1 (-1639G>A) led to reduction in warfarin dose requirement compared to noncarriers [21(7.5) vs. 31.5(18.7) vs. 43.7(15), p < 0.0001]. CYP4F2*3 polymorphism on the other hand was not associated with warfarin dose. Multivariate analysis on the derivation cohort (n = 104) showed that a dosing model consisting of hypertension (HTN), heart failure (HF), VKORC1 (-1639G>A), CYP2C9*2 & *3, and smoking could explain 39.2% of warfarin dose variability in Qataris (P < 0.001). In the validation cohort (n = 45), correlation between predicted and actual warfarin doses was moderate (Spearman's rho correlation coefficient = 0.711, p < 0.001). This study concluded that VKORC1 (-1639G>A), CYP2C9*2 & *3 are the most significant predictors of warfarin dose along with HTN, HF and smoking.

Evaluation of pharmacist-based compared to doctor-based anticoagulation management in Qatar.

RATIONALE, AIMS AND OBJECTIVES: For over 60 years, warfarin has been the mainstay anticoagulant used in the outpatient setting for the prevention and treatment of a wide variety of thromboembolic clinical conditions. Guidelines recommend that health care providers managing oral anticoagulation therapy should do so in a systematic and coordinated fashion. Studies have shown that, when compared to traditional doctor-based anticoagulation management, pharmacist-managed anticoagulation services can improve patient outcomes. The first pharmacist-based anticoagulation clinic in Qatar was launched in 2013 at Alwakra Hospital. The primary objective of this research was to evaluate the impact of pharmacist versus doctor-based anticoagulation management on the percentage time under therapeutic INR (International Normalized Ratio; TTR), INR within therapeutic range and the extreme out of range INRs. METHOD: A retrospective cohort study was designed to compare the anticoagulation control of pharmacist-based warfarin clinic to the usual doctor-care. RESULTS: Data from 278 patients taking warfarin (78 managed at pharmacist and 200 at doctor-based clinic) were evaluated. Subjects followed at the pharmacist-based clinic had a superior TTR compared to those managed at the doctor-based clinic (81.8% vs. 69.8%, P < 0.001). Additionally, the percentage of visits within therapeutic range were significantly higher in the pharmacist's group compared to doctor's group (76.5% vs. 71.2%, P = 0.011). At the same time, percentage of visits with extreme subtherapeutic INR was reduced in the pharmacist-managed clinic (5.17% vs. 7.05%, P = 0.007) CONCLUSIONS: Our study indicates that pharmacist-based anticoagulation has better INR control when compared to the traditional anticoagulation management. Pharmacist-managed anticoagulation clinics should be considered and supported for warfarin management.

Rifampin-warfarin interaction in a mitral valve replacement patient receiving rifampin for infective endocarditis: a case report.

INTRODUCTION: Warfarin therapy is associated with many drug interactions that may cause a significant alteration in its anticoagulant effect. Rifampin is a widely used antimicrobial that has major interactions with several medications including warfarin due to its strong P-glycoprotein and liver enzyme inducer activity especially on CYP2C9, CYP3A4, CYP1A2 and CYP2C19. PRESENTATION: We report a case of a 34-year-old Srilankan female chronically treated with warfarin for her mitral valve replacement. The patient developed infective endocarditis and was started on a 6-week treatment with rifampin along with other antibiotics. Warfarin dose was increased from 52.5 to 210 mg/week over the course of the rifampin therapy, however, the INR remained subtherapeutic throughout the whole period and reached 2.4 by the end of rifampin therapy. DISCUSSION AND EVALUATION: Anticoagulation management was challenging in the period following the end of rifampin therapy as well, and multiple dose adjustments starting with an increase and followed by reduction were required till she was stable on an 80 mg/week warfarin dose 5 weeks post-rifampin therapy. CONCLUSION: Our findings suggest the importance of close monitoring of warfarin therapy during and after the use of rifampin to minimize the risks of under and over-anticoagulation and improve the safety and efficacy of warfarin therapy.