cardiovascular disorders
Medications for Deep Venous Thrombosis
Anticoagulants
The anticoagulants (see figureand table) include Low molecular weight heparins (LMWHs) Unfractionatedheparin(UFH) Factor Xainhibitors: oral (eg,rivaroxaban,apixaban,edoxaban) and parenteral (fondaparinux) Directthrombininhibitors: oral (dabigatranetexilate) and parenteral (argatroban,bivalirudin, desirudin) Warfarin Oralfactor Xainhibitors and directthrombininhibitors are sometimes referred to as direct oral anticoagulants (DOACs). However, there are also parenteral agents that inhibit bothfactor Xaandthrombin(unfractionatedheparin), that inhibit mainlyfactor Xa(LMWH), or that inhibit onlyfactor Xa(fondaparinux). These agents can be used both for patients with DVT and those with pulmonary embolism (PE). LMWH = low molecular weightheparin; TF = tissue factor; UFH = unfractionatedheparin. There are several strategies for anticoagulation of patients with DVT: Initial treatment with an injectableheparin(unfractionated or low molecular weight) followed after several days by long-term treatment with an oral drug (warfarin, afactor Xainhibitor, or a directthrombininhibitor) Initial and long-term treatment with a LMWH Initial and long-term treatment with certain oralfactor Xainhibitors (rivaroxabanorapixaban) Dosing regimens for treatment of DVT differ from those used for prevention of thromboembolism in patients with Atrial Fibrillation . , perhaps lower) risk of serious bleeding ( Anticoagulant treatment references ). Their advantages are that they are effective within several hours and thus do not require a period of overlapping treatment withheparin(bridging treatment), althoughedoxabananddabigatranrequire at least 5 days of pretreatment with an injectable anticoagulant. Also, they are given as a fixed dose and thus, unlikewarfarin, do not require ongoing laboratory testing. The main disadvantage is the higher cost compared towarfarinand the high cost of DOAC reversal agents in the case of bleeding or need for an urgent surgery or procedure. varies. Patients with transient risk factors for DVT (eg, immobilization, surgery) can usually stop taking anticoagulants after 3 to 6 months. Patients with idiopathic (or unprovoked) DVT with no known risk factors, or recurrent DVT should take anticoagulants for at least 6 months and, in selected patients, probably for life unless they are at high risk for bleeding complications. Patients with cancer-associated thrombosis should receive at least 3 months of anticoagulation. Treatment is usually longer in patients receiving ongoing cancer therapy and in patients with advanced, metastatic disease. Patients with selected hypercoagulable states (eg, Antiphospholipid Syndrome (APS) or (UFH) for reducing DVT recurrence, thrombus extension, and risk of death due to PE ( Anticoagulant treatment references ). Like UFH, LMWHs catalyze the action of antithrombin (which inhibits coagulation factor proteases), leading to inactivation of coagulation LMWHs are typically given subcutaneously in a standard weight-based dose (eg,enoxaparin1.5 mg/kg subcutaneously once a day or 1 mg/kg subcutaneously every 12 hours ordalteparin200 units/kg subcutaneously once a day). Patients with renal insufficiency may be treated with UFH or with reduced doses of LMWH. Monitoring is not reliable because LMWHs do not significantly prolong the results of global tests of coagulation. Furthermore, they have a predictable dose response, and there is no clear relationship between the anticoagulant effect of LMWH and bleeding. Ifwarfarinis used after initial anticoagulation, treatment with LMWH is continued until full anticoagulation is achieved withwarfarin(typically about 5 days). Transition to the oral agentsrivaroxabanorapixabancan be done at any time with no overlap. Transition toedoxabanordabigatranrequires at least 5 days of LMWH treatment, but no overlap is needed. LMWHs and direct oral anticoagulants are first-line treatment options for patients with cancer-associated DVT ( Anticoagulant treatment references ), including in patients who have a central venous catheter and develop DVT. Complications of LMWHs include Bleeding During Use of Anticoagulants , Unfractionatedheparinmay be used instead of LMWH for patients who are hospitalized and for patients who have renal insufficiency or failure (creatinine clearance 10 to 30 mL/minute, (0.17 to 0.5mL/s/m2) because UFH is not cleared by the kidneys. UFH is given as a bolus and infusion to achieve full anticoagulation (eg, activated partial thromboplastin time [aPTT] 1.5 to 2.5 times that of the reference range). For outpatients, UFH 333 units/kg initial bolus, then 250 units/kg subcutaneously every 12 hours can be substituted for IV UFH to facilitate mobility; the dose does not need adjustment based on aPTT. Ifwarfarinis used after initial anticoagulation, UFH is continued until full anticoagulation has been achieved withwarfarin(about 5 days). Complications of UFH are similar to those of LMWHs, except that Heparin-induced thrombocytopenia , which is rare and may be life-threatening, is more common with UFHs. Long-term use of UFH causes Rivaroxabanandapixabancan be started as monotherapy immediately upon diagnosis or used in transition from an injectableheparinat any time without overlap. Dosing ofrivaroxabanis 15 mg orally twice a day for 3 weeks followed by 20 mg orally once a day for a total of 3 to 6 months.Apixabandosing is 10 mg orally twice a day for 7 days followed by 5 mg orally twice a day for 3 to 6 months. Beforeedoxabanis started, an initial 5 to 7 days of treatment with LMWH or UFH is required. Thenedoxabanis given 60 mg orally once a day. To transition from an injectable anticoagulant, thefactor Xainhibitor is typically started within 6 to 12 hours after the last dose of a twice-daily LMWH regimen and within 12 to 24 hours after a once-daily LMWH regimen. can be used in select patients with cancer-associated venous thromboembolism (VTE) as an alternative to monotherapy with LMWH ( Treatment references ). Fondaparinux, a parenteral selectivefactor Xainhibitor, may be used as an alternative to UFH or LMWH for the initial treatment of DVT or PE. It is given in a fixed dose of 7.5 mg subcutaneously once a day (10 mg for patients>100 kg, 5 mg for patients<50 kg). It has the advantage of fixed dosing and is less likely to cause thrombocytopenia. Dabigatran150 mg orally twice a day is given only after an initial 5 days of treatment with LMWH. It is typically started within 6 to 12 hours after the last dose of a twice-daily LMWH regimen and within 12 to 24 hours after a once-daily regimen. , desirudin) are available but do not have a role in treatment or Prevention of DVT or PE. Warfarinis a treatment option for patients with DVT who are not pregnant. It is also an option for patients with severe renal dysfunction.Warfarinis also a second-line option for patients with cancer-associated VTE. Warfarin5 to 10 mg can be started immediately along withheparinbecause it takes about 5 days to achieve desired therapeutic effect. Older patients and patients with a liver disorder typically require lowerwarfarindoses. Therapeutic goal is an international normalized ratio (INR) of 2.0 to 3.0. INR is monitored weekly for the first 1 to 2 months ofwarfarintreatment and monthly thereafter; the dose is increased or decreased by 0.5 to 3 mg to maintain the INR within this range. Patients takingwarfarinshould be informed of possible drug interactions, including interactions with foods and nonprescription medicinal herbs. causes skin necrosis in patients with inherited Protein C Deficiency or 1.Kearon C, Aki EA, Ornelas J, et al: CHEST Guideline and Expert Panel Report: Antithrombotic therapy for VTE disease.Chest149:315–352, 2016. doi: https://doi.org/10.1016/j.chest.2015.11.026 2.Segal JB, Streiff MB, Hofmann LV, Thornton K, Bass EB: Management of venous thromboembolism: a systematic review for a practice guideline [published correction appears inAnn Intern Med2007 Mar 6;146(5):396. 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