Laboratory Monitoring of Oral Vitamin K Anticoagulation

Abstract

Vitamin K antagonists (VKA) have been used for many years as effective anticoagulant therapy. The laboratory plays a crucial role in measuring the prothrombin time (PT) and calculating the international normalized ratio (INR). Each component of the calculation has the potential to increase error in the final result. This article discusses the laboratory aspects of monitoring VKA including sample requirements, PT, determination of the INR, point of care (POC) testing, external quality assurance/proficiency testing, and reversal strategies for VKA therapy. The implementation of the PT/INR reporting standard was a significant improvement in laboratory medicine. However, further room for improvement exists in the management of PT/INR testing, to clarify the role of POC testing and continue the harmonization process to ensure reliability and reproducibility of INR results.

Applied Nanotechnologies in Anticoagulant Therapy: From Anticoagulants to Coagulation Test Performance of Drug Delivery Systems

“…The PT assay is a straightforward test that evaluates the extrinsic and common pathway factors of coagulation. It is defined as the time in seconds for plasma to clot after the addition of calcium and the thromboplastin reagent, which uses an extrinsic activator pathway (Figure 2) [66]. Commercial thromboplastin reagents have different sources, methods of preparation by their different manufacturers, and, consequently, varying sensitivities to coagulation factors, resulting in uncertainty in PT results [13].…”

“…In addition, there are various coagulation analyzers available from several manufacturers. The influence of these two factors is responsible for the variability in PT results among laboratories [66]. To bypass the variability and standardize the PT results, in 1983, the World Health Organization (WHO) introduced the INR concept.…”

“…The ISI reflects the ability of thromboplastin to reduce the vitamin-K-dependent factor in comparison with a standard thromboplastin defined by the WHO [13]. While the INR approach has reduced the variability of patients' interlaboratory results, on the other hand, the determination of ISI has generated a source of variability depending on the reagent/instrument utilized in the laboratory and the source of plasma used to generate MNPT [66].…”

“…VKAs interfere with three of the five factors of the extrinsic pathway. Thus, the PT/INR is the most sensitive technique for monitoring the VKA levels, as well as, possible fluctuations in VKA levels due to several interactions presented by these drugs [66]. Despite the fact that INR has brought an important means of standardization for interlaboratory results, the need for improvements in the technique to ensure more reliable results still exists.…”

“…VKAs interfere with three of the five factors of the extrinsic pathway. Thus, the PT/INR is the most sensitive technique for monitoring the VKA levels, as well as, possible fluctuations in VKA levels due to several interactions presented by these drugs [66].…”