Which medications in the drug class Thrombolytics are used in the treatment of Pulmonary Embolism (PE)?

Updated: Jun 06, 2019
  • Author: Daniel R Ouellette, MD, FCCP; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
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Answer

Thrombolytics

Thrombolysis is indicated for hemodynamically unstable patients with pulmonary embolism. Thrombolysis dramatically improves acute cor pulmonale. Thrombolytic therapy has replaced surgical embolectomy as the treatment for hemodynamically unstable patients with massive pulmonary embolism.

Fibrinolytic regimens currently in common use for pulmonary embolism include two forms of recombinant tPA, alteplase and reteplase. Alteplase usually is given as a front-loaded infusion over 90 or 120 minutes. Reteplase is a new-generation thrombolytic with a longer half-life; it is given as a single bolus or as 2 boluses administered 30 minutes apart.

The faster-acting agents reteplase and alteplase are preferred for patients with pulmonary embolism, because the condition of patients with pulmonary embolism can deteriorate extremely rapidly.

Many comparative clinical studies have shown that administration of a 2-hour infusion of alteplase is more effective (and more rapidly effective) than urokinase or streptokinase (both discontinued by the FDA) over a 12-hour period. One prospective, randomized study comparing reteplase and alteplase found that total pulmonary resistance (along with pulmonary artery pressure and cardiac index) improved significantly after just one half hour in the reteplase group as compared with 2 hours in the alteplase group. Fibrinolytic agents do not seem to differ significantly with respect to safety or overall efficacy.

Empiric thrombolysis may be indicated in selected hemodynamically unstable patients, particularly when the clinical likelihood of pulmonary embolism is overwhelming and the patient's condition is deteriorating. The overall risk of severe complications from thrombolysis is low and the potential benefit in a deteriorating patient with pulmonary embolism is high. Empiric therapy especially is indicated when a patient is compromised so severely that he or she will not survive long enough to obtain a confirmatory study. Empiric thrombolysis should be reserved, however, for cases that truly meet these definitions, as many other clinical entities (including aortic dissection) may masquerade as pulmonary embolism, yet may not benefit from thrombolysis in any way.

Newborns may be relatively resistant to thrombolytics because of their lack of fibrinogen activity.

Reteplase (Retavase)

Reteplase is a second-generation recombinant tissue plasminogen activator (recombinant tPA) that forms plasmin after facilitating cleavage of endogenous plasminogen. In clinical trials, reteplase has been shown to be comparable to the recombinant tPA alteplase in achieving TIMI, 2 or 3 patency, at 90 minutes. Reteplase is given as a single bolus or as 2 boluses administered 30 minutes apart.

As a fibrinolytic agent, reteplase seems to work faster than its forerunner, alteplase, and may be more effective in patients with larger clot burdens. It has also been reported to be more effective than other agents in lysis of older clots. Two major differences help to explain these improvements. Because reteplase does not bind fibrin as tightly as does alteplase, this allows reteplase drug to diffuse more freely through the clot. Another advantage seems to be that reteplase does not compete with plasminogen for fibrin-binding sites, allowing plasminogen at the site of the clot to be transformed into clot-dissolving plasmin.

The FDA has not approved reteplase for administration to patients with pulmonary embolism. Studies of the drug's use for pulmonary embolism have employed the same dose approved by the FDA for coronary artery fibrinolysis.

Alteplase (Activase, Cathflo Activase)

Alteplase, a recombinant tPA, is used in the management of acute myocardial infarction (AMI), acute ischemic stroke, and pulmonary embolism. Alteplase is most often used to treat patients with pulmonary embolism in the ED. It is usually given as a front-loaded infusion over 90-120 minutes. It is FDA approved for this indication. Most ED personnel are familiar with alteplase's use, because it is widely employed in the treatment of patients with AMI. An accelerated 90-minute regimen is widely used, and most believe it is safer and more effective than the approved 2-hour infusion. An accelerated-regimen dose is based on patient weight.

Heparin therapy should be instituted or reinstituted near the end of or immediately following infusion, when the aPTT or thrombin time returns to twice normal or less.


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