Medication Summary
The goals of pharmacotherapy for inferior vena caval thrombosis (IVCT) and deep vein 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.
Anticoagulants
Class Summary
Heparin or warfarin may be used to prevent the propagation of thrombi. Therapy is usually converted to oral anticoagulation with warfarin, but the time course of warfarin therapy is somewhat empiric.
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.
Dalteparin (Fragmin)
Dalteparin is a low molecular weight heparin that enhances inhibition of factor Xa and thrombin by increasing antithrombin III activity. In addition, it preferentially increases the inhibition of factor Xa.
Enoxaparin (Lovenox)
Enoxaparin is a low molecular weight heparin that is produced by partial chemical or enzymatic depolymerization of unfractionated heparin (UFH). It binds to antithrombin III, enhancing its therapeutic effect. The heparin-antithrombin III complex binds to and inactivates activated factor X (Xa) and factor II (thrombin). It does not actively lyse but is able to inhibit further thrombogenesis. It prevents reaccumulation of clots after spontaneous fibrinolysis.
Tinzaparin (Innohep)
Tinzaparin is a low molecular weight heparin that enhances inhibition of factor Xa and thrombin by increasing antithrombin III activity. In addition, it preferentially increases the inhibition of factor Xa.
Vitamin K Antagonists
Class Summary
Coumarins are a class of oral anticoagulant drugs that act as antagonists to vitamin K. The mechanism of action is to interfere with the interaction between vitamin K and coagulation factors II, VII, IX, and X. Vitamin K acts as a cofactor at these levels. Coumarins produce their anticoagulant effect by inhibiting the carboxylation necessary for biologic activity.
Warfarin (Coumadin, Jantoven)
Warfarin interferes with hepatic synthesis of vitamin K–dependent coagulation factors. It is used for prophylaxis and treatment of venous thrombosis, PE, and thromboembolic disorders. Warfarin may be used to prevent the propagation of thrombi.
Thrombolytics
Class Summary
Most thrombolytic agents have been reported in the treatment of IVCT. The relative merits of thrombolytic therapy must be weighed against the risks of hemorrhagic complications.
Thrombolytic agents are used to dissolve a pathologic intraluminal thrombus or embolus that has not been dissolved by the endogenous fibrinolytic system. They are also used for the prevention of recurrent thrombus formation and rapid restoration of hemodynamic disturbances. Urokinase, tissue-type plasminogen activator (tPA), and streptokinase have all been used. Typically, delivery is catheter directed with or without a pulse spray. Patients require concurrent heparin therapy; however, tPA protocols do not use concurrent heparin because of the risk of bleeding complications. This therapy may play the greatest role as part of combination therapy with endovascular interventions.
Urokinase
Urokinase is a direct plasminogen activator isolated from human fetal kidney cells grown in culture. It acts on endogenous fibrinolytic system and converts plasminogen to enzyme plasmin. Plasmin degrades fibrin clots, fibrinogen, and other plasma proteins. Urokinase is nonantigenic but more expensive than streptokinase, which limits its use. When used for purely local fibrinolysis, it is administered as local infusion directly into area of thrombus and with no bolus. The dose must be adjusted to achieve clot lysis or patency of the affected vessel.
Streptokinase (Streptase)
Streptokinase acts with plasminogen to convert plasminogen to plasmin. Plasmin degrades fibrin clots as well as fibrinogen and other plasma proteins. An increase in fibrinolytic activity that degrades fibrinogen levels for 24-36 hours takes place with intravenous (IV) infusion of streptokinase.
Alteplase (Activase, Cathflo Activase)
Alteplase is a tPA used in the management of acute myocardial infarction, acute ischemic stroke, and PE. Safety and efficacy with concomitant administration of heparin or aspirin during the first 24 hours after symptom onset have not been investigated.
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Virchow triad/venous thromboembolism (VTE) risk factors.
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Photo showing dilated superficial abdominal veins (upper quadrant), with bruising and thrombosed large abdominal veins (lower quadrant).
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Abdominal CT scan shows absent inferior vena cava with thrombosis of very prominent collateral veins in the abdominal wall, corresponding to right side of abdomen as seen in earlier photo.
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Veins of abdomen and thorax. Unless stated otherwise, lithograph plate is from Gray's Anatomy (online edition of the 20th US edition of Gray's Anatomy of the Human Body, originally published in 1918).
