Oral Anticoagulants in Treatment of Deep Venous Thrombosis

Abstract

DVT is a clinical manifestation of VTE, It results from imbalance between hemostatic mechanisms (vascular wall, platelets and coagulations factors) and the fibinolytic system. So pathogenesis of DVT according to Virchow's triad referes to blood stasis, hypercoagulability and endothelium injury. Trauma and the major orthopedic surgery are strong risk factors of DVT and from the moderate risk factors; pregnancy, hypercoagulability, previous history of DVT and the use of oral contraceptives pills. Also the increased age, bed rest and metabolic syndrome are weak risk factors of DVT.

Anticoagulants are the treatment of DVT, warfarin is the standard drug of choice, but the delayed onset requires bridging with heparin or LMWH for approximately 1 week to provide an immediate antithrombotic effect and to reduce the risk of thrombus growth or embolization. HIT, increased risk of osteoporosis and requirement of close monitoring of heparin with the variability in dose-response, the narrow therapeutic index and the numerous drug and dietary interactions associated with VKA have led clinicians, patients and investigators to search for alternative agents. New orally administered anticoagulants, direct thrombin inhibitor (Dabigatran) and direct FXa inhibitors (Rivaroxaban, Apixaban and Edoxaban), are used to replace the current agents. They are characterized by rapid onset, direct and specific mode of action, don,t require monitoring and low potential for drug and food interactions. Clinical studies in thromboembolism indicate superior or at least non-inferior efficacy compared with enoxaparin and VKA at comparable safety outcomes. Also surgery can be done within 24-48 hours from the stopping of the new oral anticoagulants.

The limitations of the new substances may arise from gastrointestinal bleeding as no specific antidotes, no available monitoring with high cost and sometimes require dose adjustment in cases of renal impairment and old age. Management of bleeding at first by withdrawal of the anticoagulant, with dabigatran gastric lavage and activated charcoal decrease it,s absorption soon after ingestion, also hemodialysis is considered in extreme cases. With rivaroxiban over dose, PCC can reverse its anticoagulant effect.