Genetic and non-genetic factors were shown to affect warfarin dosing; however, their effect may vary from one population to the other. No previous studies were conducted on the Qatari population to elucidate these factors. Research question: What is the prevalence of VKORC1, CYP2C9, and CYP4F2 genetic variants in Qataris? and what is their contribution to warfarin dose variability? Study design: An observational cross-sectional study Methods: Hundred and fifty warfarin-treated Qatari patients on a stable dose and a therapeutic INR for at least 3 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. Results: The minor allele frequency (MAF) of VKORC1 (-1639G>A) was A 0.46, 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 loss of function CYP2C9 allele (*2 or *3) required significantly lower warfarin doses iv compared to non-carriers (24 mg/week vs. 34.1 mg/week, p<0.001). VKORC1 (-1639G>A) and CYP4F2*3 polymorphisms on the other hand were not associated with warfarin dose. Multivariate analysis on the derivation cohort showed that congestive heart failure (CHF) (P=0.002), and CYP2C9*2 & *3 (P<0.001) were associated with lower warfarin dose while smoking (P=0.003) was associated with higher warfarin dose. These factors explained 24.1% of warfarin dose variability in Qatari patients. CYP2C9*2 & *3 variants accounted for 11.8% of warfarin dose variability. In the validation cohort, correlation between predicted and actual warfarin doses was moderate (Spearman's rho correlation coefficient= 0.41, p=0.005). Conclusion: This study showed that CYP2C9*2 & *3 are the most significant predictors of warfarin dose along with CHF and smoking. Dose reduction should be considered in patients with CHF and those carrying at least one of the CYP2C9*2 & *3 alleles. While dose increase should be considered in smokers. v DEDICATION To my loving family vi ACKNOWLEDGMENTS The completion of this thesis would not have been possible without the kind support and assistance of so many individuals whose names may not all be enumerated. All their efforts and contributions are highly and sincerely appreciated and acknowledged. At foremost, I want to thank GOD for giving me all the strength and good health to complete this work. I would like to extend my gratitude to my family; mom, dad, Aya & Tala, who never seemed to cease their support and reassurance even with distance keeping us apart. My beloved husband, Ammar who always believed in me and stood by my side every step of the way, my son Farouk for always being my source of joy and inspiration. I would like to extend my special thanks and gratitude to my supervisor Dr. Hazem F. Elewa for never being hesitant to share his knowledge and expertise with me, for always supporting and fostering my achievements, and always promoting me to stand out.

Hamad General Hospital Anticoagulation Clinic is one of the largest collaborative-practice clinics of its type in Qatar. The patients being followed at this clinic are typically complex and vulnerable. During the coronavirus disease 2019 pandemic, measures were implemented at the clinic to minimize the exposure of patients and healthcare providers to the acute respiratory syndrome coronavirus-2 and to promote social distancing. These measures included extending INR-recall period, transitioning to direct oral anticoagulant drugs whenever feasible, home visits to elderly and immunocompromised patients for INR testing, establishing an anticoagulation hotline, and relocation of warfarin dispensing from the main pharmacy to the anticoagulation clinic. In addition, the clinic shifted its multidisciplinary team meetings onto an online platform using Microsoft Teams. Telehealth consultations were extensively utilized to closely follow up with the patients and ensure that anticoagulation efficacy and safety remained optimal. The aim of this paper is to share our experience and describe the measures adopted by the clinic as part of the Hamad Medical Corporation response to the emerging situation.

Low SAMe-TT2R2 score of <2 was validated as a predictor of optimum anticoagulation control, reflected by mean time in therapeutic range (TTR) above 65% to 70%, among warfarin-treated atrial fibrillation patients. This study aimed to validate the ability of SAMe-TT2R2 score and its individual components in predicting anticoagulation control (mean TTR and clinical events) among a cohort of venous thromboembolism (VTE) patients in Qatar. A total of 295 patients were retrospectively evaluated. There was a trend toward statistical significance in mean TTR between low (<2) and high (≥ 2) SAMe-TT2R2 score groups ( P = .05), a difference that was not sustained when a cutoff of 3 was used (ie, a score of 3 or more). Patients with poor INR control (TTR <70%) were numerically less likely to have SAMe-TT2R2 score of <2 compared with those with good INR control, though the difference was not statistically significant (16.7% vs 83.3%, respectively, P = .4). No thromboembolic events were reported, and no association was found between the score and risk of bleeding. Non-Caucasian origin was the only significant predictor of good anticoagulation in the studied cohort. In conclusion, SAMe-TT2R2 score could not predict quality of anticoagulation control in a cohort of VTE patients treated with warfarin in Qatar. Contribution of other clinical factors and whether a different scoring may yield better prediction of anticoagulation control remains to be tested.