Anticoagulants: A Review of the Pharmacology, Dosing, and Complications

Abstract

Anticoagulants remain the primary strategy for the prevention and treatment of thrombosis. Unfractionated heparin, low molecular weight heparin, fondaparinux, and warfarin have been studied and employed extensively with direct thrombin inhibitors typically reserved for patients with complications or those requiring intervention. Novel oral anticoagulants have emerged from clinical development and are expected to replace older agents with their ease of use and more favorable pharmacodynamic profiles. Hemorrhage is the main concerning adverse event with all anticoagulants. With their ubiquitous use, it becomes important for clinicians to have a sound understanding of anticoagulant pharmacology, dosing, and toxicity.

Keywords: Anticoagulants; Apixaban; Coagulation; Dabigatran; Direct thrombin inhibitors; Low molecular weight heparins; Rivaroxaban; Thrombosis; Unfractionated heparin; Warfarin.

Fig. 1

The coagulation cascade is comprised of the intrinsic (contact activation) pathway and the extrinsic (tissue factor) pathway. Each pathway generates a series of reactions in which inactive circulating enzymes and their co-factors are activated. These activated factors then catalyze the next reactions in the cascade. Thrombin plays a pivotal role by triggering the conversion of soluble fibrinogen to insoluble fibrin monomers, which serve as the foundation for thrombus formation. Thrombin also activates factors VIII, V, and XIII. Factor XIII generates the covalent bonds that link fibrin strands ensuring structural integrity. Anticoagulants, either through their interaction with Antithrombin (AT) or through a direct inhibition of thrombin, interrupt these enzymatic reactions