Monitoring Oral Anticoagulant Therapy

Abstract

Since 1984, when I was matriculated as a medical student, I have taken an interest in all the three major areas, but my main occupation in the past 12 years has been with the quantitative epistemological discipline of statistics, which deals with the collection, analysis, interpretation, and presentation of numerical data. The formal foundation for theoretical statistics is mathematical statistics, in which I took a master's degree (MSc) in 1995.Concurrently, in the past nine years, and especially since 1995, when I was first employed at the Department of Biostatistics, I have been occupied with biostatistics, which focuses on the development and use of statistical methods to solve problems and to answer questions that arise in human biology and medicine. My experience has been within various scientific disciplines including different medical specialties, and in every case I have found that knowledge of the subject matter of the particular area is an important prerequisite in order to be able to communicate with the specialist.A remarkable feature of many of the scientific problems I have encountered as a biostatistician is their similarity! It is striking, and fascinating, how different scientific areas have encountered the same epistemological challenges and how they independently have invented almost the same (good or bad) strategies for dealing with the analysis and interpretation of data. Another striking feature is the difference in language and traditions, which hinders the different areas in communicating their epistemological problems and discoveries to each other. With this in mind I consider it the principal goal of biostatistics to 1) collect epistemological and cognitive problems and solutions from different subject matter areas of research; 2) distill the problems and solutions through the language of mathematical statistics; 3) present, analyze and discuss the problems and solutions in a general setting within the mathematical-statistical scientific community; and 4) translate possible solutions to the problems to the language and traditions of the particular subject matter disciplines.A major challenge as a biostatistician is the translation of solutions and suggestions from very general terms to terms which are recognized by the subject matter specialist. I hope that this dissertation will be judged on the scientific usefulness of its applications of general statistical methodology, rather than on its exact compliance with the language and traditions of the subject matter disciplines, which it involves.

Predicting the warfarin maintenance dose in elderly inpatients at treatment initiation: accuracy of dosing algorithms incorporating or not VKORC1/CYP2C9 genotypes

“…Furthermore, some protocols that use a first fixed loading dose of 10 mg are unsuitable for elderly patients in whom they carry a risk of severe overanticoagulation. Moreover, in the high-range INR values obtained with these protocols (> 4.5), INR measurement lacks accuracy, which hampers dosage prediction [27]. One limitation of our study is the lack of patient follow-up beyond the achievement of the maintenance dose.…”

“…A fixed 4-mg dose used for 3 days has been shown to be safe, avoiding marked over-or under-anticoagulation [19,20], and to produce INR 3 values in the 1.5-4.5 range in most patients. In this range, INR measurement accuracy and precision are optimal, which facilitates dose prediction [27]. In very different settings, clinical warfarin dosing algorithms incorporating INR values obtained in the first week successfully predicted the warfarin maintenance dose, and some of them demonstrated a good safety profile [8,[13][14][15][28][29][30].…”

The Coagulopathy of Chronic Liver Disease

“…Moreover, they do not require regular laboratory monitoring to adjust the dosage, whereas vitamin K antagonists require monitoring with the use of the INR, the validity of which has been questioned in patients with chronic liver disease. 57 Other potential advantages of these new drugs over low-molecularweight heparin are their oral route of administration and their mechanism of action, which is independent of antithrombin (low in these patients). However, specially designed clinical trials are needed because patients with chronic liver disease are usually excluded from the randomized clinical trials of these drugs.…”

Hypercoagulability in cirrhosis: causes and consequences

“…Monitoring anticoagulation in cirrhosis Conventional INR is unreliable in cirrhosis [112] and the anti‐FXa activity measured in non‐anticoagulated patients is negatively correlated with the severity of liver disease and positively with antithrombin levels [111]. Therefore, monitoring VKA and LMWH in patients with cirrhosis remains a challenge.…”