Title

Pre-analytical variations affecting INR measurement for dose tailoring of anticoagulants.

Abstract

Although warfarin (WRN) has been used as oral anticoagulant therapy for over 60 years, it remains a challenge to use in clinical practice since several factors may complicate WRN response which expressed is in international normalized ratio (INR). Numerous patient related variations may affect the adequacy of the assay interpretation which may lead to into poor clinical management. This study aims investigating the impact of age, sex, hemoglobin, packed cell volume (PCV), and albumin levels as well as patient adherence and drug-drug interactions (DDI) on coagulation monitoring results. INR was recorded in patients under WRN maintenance therapy (n=96). Hemoglobin, PCV and albumin levels were recorded. Patient adherence to WRN regimen was analytically assessed using an LC-MS/MS method. In the study group, 45% achieved the target INR (2 – 3.5). Anemia was more prevalent among uncontrolled patients where 38% suffered severe anemia (5 male and 15 female). Abnormal PCV was observed in 47% of uncontrolled patients (7 male and 18 female). There was a significant difference in age, hemoglobin, and PCV and albumin level between patients who achieved optimum INR and those who did not. Moreover, good relationship was obtained between WRN concentration and INR (R2=0.622) by excluding samples showing DDI (n=16), abnormal albumin (n=9) or steroid (n=6) abnormalities. Analytical assessment revealed lack of adherence to WRN dose. In addition, unsupervised drug consumption or missing prescribed doses was observed in at least 5% of the cases. In conclusion, based on the poor correlation of INR with plasma WRN in these cases, albumin level, hemoglobin, and PCV abnormalities along with DDI are all important factors to consider during clinical monitoring of WRN response. It also highlights the significance of monitoring plasma WRN to assess adherence to scheduled doses. These findings may help to identify the patients who will require closer monitoring for optimizing the outcomes of WRN therapy.

Department

Chemistry Department

Degree Name

MS in Chemistry

Graduation Date

2-1-2019

Online Submission Date

July 2018

First Advisor

Azzazy, Hassan

Committee Member 1

Talima, Hatem

Committee Member 2

Elkady, Ehab

Document Type

Master's Thesis

Extent

98 p.

Rights

The author retains all rights with regard to copyright. The author certifies that written permission from the owner(s) of third-party copyrighted matter included in the thesis, dissertation, paper, or record of study has been obtained. The author further certifies that IRB approval has been obtained for this thesis, or that IRB approval is not necessary for this thesis. Insofar as this thesis, dissertation, paper, or record of study is an educational record as defined in the Family Educational Rights and Privacy Act (FERPA) (20 USC 1232g), the author has granted consent to disclosure of it to anyone who requests a copy.

IRB

Approval has been obtained for this item

Comments

First, I would like to express my sincere gratitude to my advisor Dr. Hassan Azzazy professor of chemistry and Leader of Novel diagnostics & Therapeutic Research group for the continuous support of my master’s study and research, for his patience, motivation, enthusiasm, and immense knowledge. His guidance helped me in all the time of research and writing of this thesis. Moreover, I would like to thank Dr. Faten Farouk who has always been more than happy to answer my questions and help me in the statistical analysis and analytical method development. I would like thank my colleagues especially Ahmed Omaia for his useful remarks. Financial support for the graduate study and international conference from the American University in Cairo is gratefully acknowledged. This work was supported by grants from the University Grants. Last but not the least, my greatest gratitude goes to my family for their love, support carried me to this point and I am eternally grateful for them.

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