Recent advances in the management of venous thromboembolism

Abstract

Venous thromboembolism (VTE) is a spectrum of diseases that includes deep vein thrombosis (DVT) and pulmonary embolism (PE). Anticoagulant treatment is the mainstay of therapy for VTE. Unfractionated heparin (UFH) or low molecular weight heparin (LMWH) followed by vitamin K antagonists have been the treatment of choice for most patients with VTE, with the aim to prevent thrombus extension or embolization and recurrent VTE. Fondaparinux, a selective, indirect, parenteral factor Xa inhibitor, is now also approved for the initial treatment of VTE and represents an important alternative to UFH or LMWH. Secondary prevention of VTE with vitamin K antagonists is usually prescribed for a minimum of three months, with the duration of treatment based on the presence or absence of major identifiable risk factors for the index event. Patients with permanent risk factors or patients with recurrent DVT or PE require life long secondary prevention. Over the last years, new oral anticoagulant agents have been developed and are now undergoing extensive clinical evaluation in several settings, including the treatment of VTE. New oral anticoagulants include selective, direct thrombin inhibitors, such as dabigatran etexilate, and selective, direct factor Xa inhibitos, such as rivaroxaban, apixaban or edoxaban. All these drugs are admistered at fixed daily doses and do not require laboratory monitoring. The positive results of the first completed clinical trials suggest that a new era in the management of VTE is about to begin.

Keywords: Anticoagulants; Deep vein thrombosis; Pulmonary embolism; Treatment.

Fig. 1

Mechanism of action of antithrombotic agents in the coagulation pathways. Direct factor Xa (FXa) inhibitors (e.g. Rivaroxaban, Apixaban) are able to inhibit in a selective and reversible manner the active site of both free and prothrombinase-bound FXa. Dabigatran etexilate is an univalent direct thrombin inhibitor that binds exclusively to the active site of thrombin (FIIa) to inactivate fibrin-bound thrombin. Binding with antithrombin (AT) respectively, the unfractionated heparin (UFH) inhibits factors XIa, IXa, Xa, and IIa, where as the low-moleculareight heparin (LMWH) inhibits FXa and FIIa. Fondaparinux is a synthetic pentasaccharide that inhibits FXa only indirectly by binding to AT with high affinity.