Paradoxical Embolism Medication

Pharmacologic treatment of paradoxical embolism (PDE) is based on anticoagulation to prevent clot propagation. Anticoagulants, including heparin and low-molecular-weight heparins (LMWHs) such as enoxaparin and tinzaparin, are used for acute cases. The direct thrombin inhibitor lepirudin is used in patients with heparin-induced thrombocytopenia (HIT). The dosages of all of these medications are adjusted in patients with compromised renal states. Warfarin is used for long-term anticoagulation over a period of months.

Thrombolytics are used commonly to lyse a clot in patients with acute arterial occlusion, preventing permanent damage such as occurs in ischemic stroke, pulmonary embolism (PE), and arterial occlusion. Dosages for thrombolytics vary, depending on the site involved.

Class Summary

Anticoagulants are used for the treatment of thromboembolic disorders.

Heparin

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

Enoxaparin (Lovenox)

Enoxaparin 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.

Desirudin (Iprivask)

Desirudin is a highly selective thrombin inhibitor. It inhibits fibrin formation, activation of coagulation factors, and thrombin-induced platelet aggregation. This results in prolongation of the activated partial thromboplastin time.

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. Tailor the dose to keep the international normalized ratio (INR) in the range of 2-3 with an overlap of 3-5 days of a therapeutic activated partial thromboplastin time (aPTT) using the heparin regimen previously described.

Lepirudin (Refludan)

Lepirudin, a recombinant hirudin derived from yeast cells, is a highly specific direct thrombin inhibitor. It is indicated for anticoagulation in HIT and associated thromboembolic disease. Its action is independent of antithrombin III. Lepirudin blocks the thrombogenic activity of thrombin. It affects all thrombin-dependent coagulation assays (eg, aPTT values increase in a dose-dependent manner). Adjust the dose on the basis of aPTT ratios (target, 1.5-2.5 times normal) determined every 4 hours and then daily.

Class Summary

Thrombolytic agents are used to restore circulation through a previously occluded vessel by bringing about rapid and complete removal of a pathologic intraluminal thrombus or embolus that has not been dissolved by the endogenous fibrinolytic system.

Alteplase (Activase)

Alteplase is a tissue plasminogen activator (tPA) used in the management of acute myocardial infarction (AMI), acute ischemic stroke (AIS), and pulmonary embolism (PE). Its safety and efficacy with concomitant administration of heparin or aspirin during the first 24 hours after symptom onset have not been investigated.

Streptokinase (Streptase)

Acts with plasminogen to convert plasminogen to plasmin. Plasmin degrades fibrin clots, fibrinogen, and other plasma proteins. Increase in fibrinolytic activity that degrades fibrinogen levels for 24-36 h takes place with IV infusion of streptokinase.

Reteplase (Retavase)

Reteplase is a recombinant tPA that forms plasmin after facilitating cleavage of endogenous plasminogen. In clinical trials, it has been shown to be comparable with tPA in achieving patency at 90 minutes. Heparin and aspirin are usually given concomitantly and afterwards.

Tenecteplase (TNKase)

Tenecteplase is a modified version of alteplase that is made by substituting 3 amino acids. It has a longer half-life than alteplase and thus can be given as a single bolus infused over 5 seconds (as opposed to the 90 minutes required for alteplase). It appears to cause less non–intracranial bleeding than alteplase but carries a comparable risk of intracranial bleeding and stroke.

Base the dose on the patient's weight. Initiate treatment as soon as possible after the onset of AMI symptoms. Because tenecteplase contains no antibacterial preservatives, it must be reconstituted immediately before use.

Class Summary

Antiplatelet agents inhibit platelet aggregation and reduce thrombotic stroke in transient ischemia of the brain.

Clopidogrel (Plavix)

Clopidogrel selectively inhibits adenosine diphosphate (ADP) binding to platelet receptors and subsequent ADP-mediated activation of the glycoprotein (GP) IIb/IIIa complex, thereby inhibiting platelet aggregation.

Ticlopidine

Ticlopidine is second-line antiplatelet therapy for patients in whom aspirin is not tolerated or is ineffective.

Dipyridamole 200 mg/aspirin 25 mg (Aggrenox)

Dipyridamole-aspirin is a combination antiplatelet agent that takes advantage of the additive antiplatelet effects of the 2 drugs. Dipyridamole acts via the adenosine-platelet A2-receptor system, whereas aspirin inhibits platelet aggregation by causing irreversible inhibition of cyclooxygenase system, thereby reducing generation of thromboxane A2, a powerful enhancer of platelet aggregation and vasoconstriction.