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      News & Perspective Drugs & Diseases CME & Education Academy Video Decision Point
      Drugs & Diseases > Emergency Medicine

      Deep Venous Thrombosis (DVT) Medication

      Updated: Jun 05, 2019
      • Author: Kaushal (Kevin) Patel, MD; Chief Editor: Barry E Brenner, MD, PhD, FACEP  more...
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      Medication

      Medication Summary

      The goals of pharmacotherapy for deep venous thrombosis (DVT) are to reduce morbidity, to prevent the postthrombotic syndrome (PTS), and to prevent pulmonary embolism (PE), all with minimal adverse effects and cost. The main agent classes include anticoagulants and thrombolytics. [169]

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      Anticoagulants

      Class Summary

      These agents prevent recurrent or ongoing thrombolytic occlusion of the vertebrobasilar circulation.

      Rivaroxaban (Xarelto)

      Rivaroxaban is a direct oral anticoagulant (DOAC) that works as a factor Xa inhibitor which blocks platelet activation by selectively blocking the active site of factor Xa without requiring a cofactor (eg, antithrombin III) for activity. It is indicated for a variety of treatment and prophylaxis VTE indications including the following:

      Risk reduction of stroke and systemic embolism in nonvalvular atrial fibrillation

      Treatment of DVT and PE

      Reduction in risk of recurrent DVT and/or PE

      DVT prophylaxis following hip or knee replacement surgery

      VTE prophylaxis in acutely ill medical patients who have restricted mobility without high risk of bleeding

      Risk reduction of major cardiovascular events in setting of CAD (off-label use) or PAD 

      Acute symptomatic superficial vein thrombosis (off-label use)

      Heparin-induced thrombocytopenia (off-label use)

      Apixaban (Eliquis)

      Apixaban is a direct oral anticoagulant (DOAC) that works as a factor Xa inhibitor which blocks platelet activation by selectively and reversibly blocking the active site of factor Xa without requiring a cofactor (eg, antithrombin III) for activity. It inhibits free and clot-bound factor Xa, and prothrombinase activity; no direct effect on platelet aggregation, but indirectly inhibits platelet aggregation induced by thrombin. It is indicated in the following:

      DVT prophylaxis following hip or knee replacement surgery

      Risk reduction of stroke and systemic embolism in nonvalvular atrial fibrillation

      Treatment of DVT and PE

      Reduction in risk of recurrent DVT and/or PE

      Heparin-induced thrombocytopenia (off-label use)

      Dabigatran (Pradaxa)

      Dabigatran is a direct oral anticoagulant (DOAC) that works as a direct thrombin inhibitor. It blocks free and clot-bound thrombin and thrombin-induced platelet aggregation. It is indicated for the following:

      Risk reduction of stroke and systemic embolism in nonvalvular atrial fibrillation

      Treatment of DVT and PE

      DVT prophylaxis following hip or knee replacement surgery

      Edoxaban (Savaysa)

      Edoxaban is a direct oral anticoagulant (DOAC) that works as a factor Xa inhibitor indicated to reduce the risk of stroke and systemic embolism associated with nonvalvular atrial fibrillation (NVAF) as well as treatment for treatment of DVT and PE

      Betrixaban (Bevyxxa)

      Betrixaban is a direct oral anticoagulant (DOAC) that works as a factor Xa inhibitor  indicated for extended prophylaxis of venous thromboembolism (VTE) in adults hospitalized for acute medical illness who are at risk for thromboembolic complications owing to moderate or severe restricted mobility and other risk factors that may cause VTE.

      Fondaparinux sodium (Arixtra)

      Fondaparinux sodium is a synthetic anticoagulant that works by inhibiting factor Xa. It provides a highly predictable response and has a bioavailability of 100%. The drug has a rapid onset of action and a half-life of 14-16 hours, allowing for sustained antithrombotic activity over a 24-hour period. Fondaparinux sodium does not affect prothrombin time or activated partial thromboplastin time, nor does it affect platelet function or aggregation. Indications of its use include the following:

      Treatment for Acute Coronary Syndrome (off-label use)

      Treatment or prophylaxis for VTE such as DVT and PE 

      Acute symptomatic superficial vein thrombosis (off-label use)

      Heparin-induced thrombocytopenia (off-label use)

      Heparin

      Heparin augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin. It does not actively lyse but is able to inhibit further thrombogenesis. Heparin prevents reaccumulation of a clot after a spontaneous fibrinolysis.

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      Low Molecular Weight Heparins

      Class Summary

      Low-molecular-weight-heparin (LMWH) is prepared by selectively treating unfractionated heparin (UFH) to isolate the low molecular weight (<9000 Da) fragments. Its activity is measured in units of factor X inactivation, and monitoring of the activated partial thromboplastin time (aPTT) is not required. The dose is weight adjusted. Enoxaparin (Lovenox), dalteparin (Fragmin), and tinzaparin (Innohep) have received US Food and Drug Administration (FDA) approval for the treatment of deep venous thrombosis (DVT) in the United States. Enoxaparin is approved for inpatient and outpatient treatment of DVT.

      Dalteparin (Fragmin)

      Dalteparin enhances inhibition of factor Xa and thrombin by increasing antithrombin III activity. In addition, it preferentially increases inhibition of factor Xa. Except in overdoses, no utility exists in checking prothrombin time (PT) or activated partial thromboplastin time (aPTT) because aPTT does not correlate with anticoagulant effect of fractionated low-molecular-weight heparin (LMWH). The average duration of treatment is 7-14 days.

      Enoxaparin (Lovenox)

      Enoxaparin is a low-molecular-weight (LMWH) used in treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE) as well as DVT prophylaxis. It enhances inhibition of factor Xa and thrombin by increasing antithrombin III activity. It slightly affects thrombin and clotting time, and it preferentially increases inhibition of factor Xa. The average duration of treatment is 7-14 days.

      Tinzaparin (Innohep)

      Tinzaparin enhances inhibition of factor Xa and thrombin by increasing antithrombin III activity. In addition, it preferentially increases inhibition of factor Xa. The average duration of treatment is 7-14 days.

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      Vitamin K Antagonists

      Class Summary

      Coumarins are a class of oral anticoagulant drugs that act as antagonists to vitamin K. Its mechanism of action interferes with the interaction between vitamin K and coagulation factors II, VII, IX, and X where vitamin K acts as a cofactor. Coumarins produce their anticoagulant effect by inhibiting the carboxylation necessary for biologic activity.

      Warfarin (Coumadin)

      Warfarin interferes with hepatic synthesis of vitamin K–dependent coagulation factors. It is used for prophylaxis and treatment of venous thrombosis, pulmonary embolism (PE), and thromboembolic disorders. The dose must be individualized and adjusted to maintain an international normalized ratio (INR) of 2-3. The use of warfarin is also indicated in the use treatment and/or prevention of other thromboembolic disease processes, such as left ventricular thrombus in setting of myocardial infarction, stress (takotsubo) cardiomyopathy, and stroke or transient ischemic attack. It is also considered for anticoagulation in the setting of atrial fibrillation or flutter, mechanical aortic or mitral valve replacement, idiopathic or inherited pulmonary hypertension, heparin-induced thrombocytopenia, and after total hip or knee arthroplasty and hip fracture surgery. 

      The use of warfarin requires bridging with short-acting anticoagulants, such as heparin or LMWH, to attain the therapeutic INR range so as to avoid warfarin-induced skin necrosis. This is due to the initial preferential inhibition of protein C and Factor VII over factors II, VII, IX, and X which leads to a hypercoagulable state causing necrosis. The use of short-acting anticoagulants will counter this paradoxical activation of the coagulation cascade and act as a “bridge” to attain warfarin's blood-thinning effects.

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      Thrombolytics

      Class Summary

      These agents are used to dissolve a pathologic intraluminal thrombus or embolus that has not been dissolved by the endogenous fibrinolytic system. Also used for the prevention of recurrent thrombus formation and rapid restoration of hemodynamic disturbances.

      Tenecteplase (TNKase)

      Tenecteplase is a modified version of alteplase (tPA) made by substituting 3 amino acids of alteplase. It has a longer half-life and, thus, can be given as a single bolus over 5 seconds infusion instead of 90 minutes with alteplase. It appears to cause less non-intracranial bleeding but has similar risk of intracranial bleeding and stroke as alteplase. The dose should be weight based. Treatment should be initiated as soon as possible after onset of acute myocardial infarction symptoms. Because tenecteplase contains no antibacterial preservatives, it must be reconstituted immediately before use.

      Alteplase, tPA (Activase)

      Alteplase is a thrombolytic agent used for deep venous thrombosis (DVT) or pulmonary embolism (PE). It is a tissue plasminogen activator (tPA) produced by recombinant DNA and considered in the management of acute myocardial infarction, acute ischemic stroke, and submassive to massive PE. The safety and efficacy of this regimen with coadministration of heparin and aspirin during the first 24 hours after symptom onset have not been investigated.

      Reteplase (Retavase)

      Reteplase is a tissue plasminogen activator (tPA) produced by recombinant DNA and used in the management of acute myocardial infarction, acute ischemic stroke, and pulmonary embolism (PE). Heparin and aspirin are usually given concomitantly and after reteplase.

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