Laboratory and Point of Care Monitoring of Vitamin K Antagonist Treatment

Vitamin K antagonist (VKA) therapy is given to patients either after a thrombosis or prophylactically to prevent a thrombotic event. VKAs block the action of vitamin K reductase which converts inactive forms of Factors II, FVII, FIX, FX, protein C, S and Z to their functional enzyme zymogens. In this way the levels of functional clotting factors in the circulation are reduced and thus the potential of the blood to clot is lowered. VKA therapy requires careful monitoring as pharmacological responses vary significantly between individuals; too much anticoagulation can increase bleeding risks, but too little increases the risk of a new or extended thrombosis. The effects of VKA therapy are monitored using the International Normalised Ratio (INR). This is a standardised test based on the prothrombin time (PT), developed in the 1980s to allow comparability between all different methods and reagents. This then means that a patient can be tested anywhere in the world and the same INR results would be obtained. The INR tests can be performed in a laboratory setting but also since the late 1990s as a Point of Care test (POCt). Although this test has been standardised, there is still potential to see differences between methods in particular samples or in certain patient conditions. An understanding of the factors affecting this straightforward test, and constant quality control, is required to ensure results are valid and reliable, and patient treatment is optimised. Comparability between different test systems for INR monitoring is greatest in over-anticoagulated patients, and strategies for treatment of these patients, for example, with reversal agents such as Vitamin K either orally or by injection need to be in place.