Finally, warfarin and heparin have narrow therapeutic window with high inter- and intra-patient variability thus, the use of either drug needs careful laboratory monitoring and dose adjustment to ensure proper antithrombotic protection while minimizing the bleeding risk.
2 Warfarin offers the convenience of oral administration but its antithrombotic effect takes hold only during the following three to five days and is subject to interaction with a host of foods and other drugs, 3 often making anticoagulant control hard to obtain. UFH and LMWHs, for example, must be given parenterally, which limits their usage in the outpatient setting and causes a rare but potentially fatal complication of heparin-induced thrombocytopenia. 1Ĭurrently available anticoagulants have several drawbacks. Since their introduction into clinical practice in the late 1980s, low-molecular-weight heparins (LMWHs) have replaced UFH for many indications however, UHF remains the drug of choice in selected patient groups due to its short half-life, its higher safety among patients with renal failure, and the fact that its anticoagulant effects are typically reversible with protamine sulfate.
For decades, two main classes of anticoagulants have been widely used by cardiologists: orally administered vitamin K antagonists (VKAs), in particular warfarin, or parenterally administered unfractionated heparin (UFH). Anticoagulants are frequently prescribed for patients with a variety of cardiovascular diseases to prevent thrombosis, to treat present thrombosis, or to reduce the recurrence of thromboembolic events after a first episode of thrombosis. Thrombin, factor IIa (FIIa), is produced from prothrombin by the action of activated factor X (FXa). The final effect of the coagulation cascade is to produce thrombin, which acts on fibrinogen to generate the fibrin clot. Further research should be focused on improving the standardization and calibration of these assays. Marked interlaboratory variability still exists for PT, INR, and PTT tests. Herein, we review recent data on the monitoring of conventional anticoagulant agents. Recently College of American Pathologists recommend that individual laboratories establish their own therapeutic range by using aPTT values calibrated against accepted therapeutic unfractionated heparin (UFH) levels calibrated against accepted therapeutic UFH levels performing anti-Xa test (which is the most accurate assay for monitoring UFH therapy). In contrast to marked progress in the standardization of PT reagents for INR reporting, no standardization system has been globally adopted for standardization of PTT reagents. However, INRs are reproducible between laboratories for only those patients who are stably anticoagulated with vitamin K antagonists (VKAs) (i.e., at least 6 weeks of VKA therapy), and are not reliable or reproducible between laboratories for patients for whom VKA therapy has recently been started or any other clinical conditions associated with a prolonged PT such as liver disease, disseminated intravascular coagulation, and congenital factor deficiencies. The international normalized ratio (INR) was introduced to “normalize” all PT reagents to a World Health Organization (WHO) reference thromboplastin preparation standard, such that a PT measured anywhere in the world would result in an INR value similar to that which would have been achieved had the WHO reference thromboplastin been utilized. The PT stands alone as the single coagulation test that has undergone the most extensive attempt at assay standardization. Results for a single specimen tested in different laboratories are variable this is mostly attributable to the specific reagents and to a much lesser degree to the instrument used. These two tests depend highly on the combination of reagent and instrument utilized. The prothrombin time (PT) and the activated partial thromboplastin time (aPTT) are laboratory tests commonly used to monitor warfarin and heparin, respectively. Warfarin and heparin have narrow therapeutic window with high inter- and intra-patient variability, thereby the use of either drug needs careful laboratory monitoring and dose adjustment to ensure proper antithrombotic protection while minimizing the bleeding risk.
For the moment, cardiologists and other clinicians also require to master currently available drugs, realizing the mechanism of action, side effects, and laboratory monitoring to measure their anticoagulant effects. Clinicians should be aware of new developments to familiarize themselves with pharmacokinetic and pharmacodynamic characteristics of new anticoagulant agents to appropriately and safely use them.
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