Unfractionated heparin (UFH), which has been available commercially for over half a century, has been the most widely used agent for quickly suppressing thrombosis. When given intravenously, UFH quickly binds to and activates antithrombin, which then inhibits several activated factors in the clotting cascade. For decades, UFH was invaluable for treating arterial and venous thrombosis, and no alternative was available. The short half-life of UFH and the fact that its action could be reversed readily with protamine made it an almost ideal antithrombotic agent. However, variable pharmacokinetics, together with problems of inaccuracy and unreliability of the activated partial thromboplastin time, have made it difficult to use this drug optimally. In addition, side effects such as osteoporosis, heparin-induced thrombocytopenia (HIT), and delayed HIT have led to increased concerns about the use of UFH in view of the advantages offered by newer agents. Fractionating heparin into low-molecular-weight heparins that still retain the pentasaccharide active site provided a way to achieve the same type of therapeutic effect with more predictable dosing and fewer adverse effects. Similarly, a pentasaccharide has been synthesized and marketed as fondaparinux. Although these advances have improved our therapeutic options, continued advances on the horizon raise the question of whether the use of UFH will soon be abandoned.
Unfractionated heparin (UFH) has been in clinical use for more than half a century. Despite its undoubted contribution to the treatment and prevention of thrombosis, heparin is significantly limited by its variable biochemical composition and unpredictable pharmacokinetics. The situation is compounded by the fact that methods for monitoring heparin do not necessarily reflect its therapeutic effect. The activated partial thromboplastin time (aPTT) is a method for monitoring heparin therapy that is simple, cheap, and readily available. However, it is also poorly standardized and is affected by numerous factors-both analytic and preanalytic-that are unrelated to the heparin effect. Establishing an appropriate therapeutic range for the aPTT is challenging for smaller clinical laboratories, and the antifactor Xa method of measuring heparin levels is not widely available. The College of American Pathologists published consensus guidelines in an effort to improve the laboratory monitoring of UFH therapy. However, it seems unlikely that the laboratory problems associated with monitoring UFH will be resolved. Unfractionated heparin is highly antigenic and carries a significant risk of heparin-induced thrombocytopenia (HIT). Even in the absence of thrombocytopenia or thrombosis, the presence of heparin-associated antibodies may predict adverse clinical outcomes and strengthen the rationale for the ultimate replacement of UFH. Fortunately, alternatives to UFH, such as low-molecular-weight heparins, direct thrombin inhibitors, and more specific factor Xa inhibitors, are becoming available for clinical use. The pharmacokinetics of these agents are more predictable and rely much less on laboratory monitoring. Nonheparin agents also eliminate the risk of HIT. The emergence of these newer anticoagulants makes the continued use of UFH increasingly difficult to justify.
Weight-adjusted nomograms have been a significant advance in the use of unfractionated heparin (UFH). Clinical trials have demonstrated the ability of weight-adjusted nomograms to achieve a therapeutic activated partial thromboplastin time (aPTT) more rapidly than with standard UFH dosing. Despite this advantage, a significant number of patients have subtherapeutic and supratherapeutic aPTTs. Real-world experiences also corroborate the inability to keep UFH therapeutic with the use of nomograms. Despite the limitations of UFH nomograms, they have been used in several different types of venous and arterial thrombosis treatment settings. Unfortunately, these nomograms are not all consistent and require a considerable amount of time for training health care professionals on their use in order to limit the potential for medication errors. Although UFH nomograms have provided advancement over standard UFH dosing, their limitations still generate the desire for a more predictable anticoagulant.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.