New Anticoagulants for the Prevention and Treatment of Venous Thromboembolism

Abstract

Anticoagulant drugs, like vitamin K antagonists and heparin, have been the mainstay for the treatment and prevention of venous thromboembolic disease for many years. Although effective if appropriately used, traditional anticoagulants have several limitations such as unpredictable pharmacologic and pharmacokinetic responses and various adverse effects including serious bleeding complications. New oral anticoagulants have recently emerged as an alternative because of their rapid onset/offset of action, predictable linear dose-response relationships and fewer drug interactions. However, they are still associated with problems such as bleeding, lack of reversal agents and standard laboratory monitoring. In an attempt to overcome these drawbacks, key steps of the hemostatic pathway are investigated as targets for anticoagulation. Here we reviewed the traditional and new anticoagulants with respect to their targets in the coagulation cascade, along with their therapeutic advantages and disadvantages. In addition, investigational anticoagulant drugs currently in the development stages were introduced.

Inherited thrombophilia and anticoagulant therapy for women with reproductive failure

“…Other than factor Xa inhibition, catalysis of AT‐mediated inactivation of FIIa is processed by formation of a ternary heparin‐antithrombin‐thrombin complex. This complex requires chains at least 18 saccharide units long, like most UFH 80 …”

“…Low‐molecular‐weight heparins is a mixture of polymers with molecular weights that vary from 1000 to 10 000 Da, with a mean molecular weight between 4000 and 5000 Da, approximately one third the size of UFH 85 . Variety of commercial LMWHs are available (Table ) 80 . Fifty to 75% of LMWHs are composed of less than 18 saccharides and it has less binding properties than UFH due to its reduced size.…”

Recent advances in the discovery and development of factor XI/XIa inhibitors

“…24 Although the safety profiles of newer oral active site inhibitors of thrombin and FXa are better than heparins, coumarins, and hirudins, the limited availability of standardized assays for measuring these drugs in biological fluids, their short halflives, their relatively high cost, and potential contraindications in patients with severe renal dysfunction represent serious challenges for their therapeutic use. 29,30 All three FXa inhibitors are CYP3A4 and P-glycoprotein substrates that carry potential drug-drug interaction issues. 31 Moreover, more studies are required to determine their use in specific patient populations including pregnant women 32,33 and cancer patients.…”

Cell Type‐Specific Mechanisms in the Pathogenesis of Ischemic Stroke: The Role of Apoptosis Signal‐Regulating Kinase 1

“…Platelet-induced thrombosis is associated with platelet adhesion, activation, and aggregation [ 27 ]. Normally, homeostasis is maintained by coagulation, fibrinolysis, and platelet function [ 28 ]. When homeostasis breaks down, platelets are involved in thrombus formation through a complex process [ 27 ].…”