Anticoagulants

Because of the narrow therapeutic index of warfarin and unfractionated heparin (UFH), monitoring their anticoagulant effects is required. On the other hand, lowmolecular- weight heparin (LMWH) and fibrinolytic agents need to be monitored only under certain circumstances. Although newer anticoagulants will not require routine monitoring for dose titration, a means to determine their systemic effects and individual (patient-specific) response to administration will likely have roles in clinical practice. The prothrombin time is used to monitor vitamin K antagonist therapy. This test is sensitive to the plasma concentrations (activity) of clotting factors II (prothrombin), V, VII, and X. Vitamin K antagonists affect the vitamin K–dependent factors II, VII, IX, and X, as well as proteins C, S, and Z. Thus, the prothrombin time does not reflect the effect of vitamin K antagonists on some factors (IX and proteins C, S, and Z) and is sensitive to others (factor V) (not directly influenced by treatment). The prothrombin time is not an ideal test for monitoring vitamin K antagonists; however, its simplicity and widespread availability have established its place in clinical practice. By convention, prothrombin times are now reported as international normalized ratios (INRs). This is the ratio of the patient’s prothrombin time to a control prothrombin time, raised to a power—the international sensitivity index (ISI). The latter reflects the calibration of the thromboplastin used for the prothrombin time testing to an internationally agreed upon standard. In many laboratories the reagent currently used is a recombinant thromboplastin, which has an ISI of 1.0 There are several cautions related to interpreting the results of prothrombin time tests that are worth monitoring. Since the test is sensitive to the level of factor V in the plasma, improper sample storage or delayed testing may cause loss of factor V (activity) and yield prothrombin time values above the expected range. High concentrations of heparin may also prolong the prothrombin time; this usually occurs when the sample is obtained within a few minutes of administering a bolus dose. Direct thrombin inhibitors, such as hirudin, bivalirudin, argatroban, and ximelagatran, may also prolong the prothrombin time to a variable degree.