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

Updated: Oct 16, 2019
  • Author: Daniel R Ouellette, MD, FCCP; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
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Answer

Anticoagulants

Heparin augments the activity of antithrombin III and prevents the conversion of fibrinogen to fibrin. Full-dose LMWH or full-dose unfractionated IV heparin should be initiated at the first suspicion of DVT or PE.

With proper dosing, several LMWH products have been found safer and more effective than unfractionated heparin both for prophylaxis and for treatment of DVT and PE. Monitoring the aPTT is neither necessary nor useful when giving LMWH, because the drug is most active in a tissue phase and does not exert most of its effects on coagulation factor IIa.

Many different LMWH products are available around the world. Because of pharmacokinetic differences, dosing is highly product specific. Several LMWH products are approved for use in the United States: enoxaparin (Lovenox), dalteparin (Fragmin), and tinzaparin (Innohep). Enoxaparin and tinzaparin are currently approved by the FDA for treatment of DVT. Dalteparin is FDA approved for prophylaxis and has approval for cancer patients. Each of the other agents has been approved by the FDA at a lower dose for prophylaxis, but all appear to be safe and effective at some therapeutic dose in patients with active DVT or PE.

Fractionated LMWH administered subcutaneously is now the preferred choice for initial anticoagulation therapy. Unfractionated IV heparin can be nearly as effective but is more difficult to titrate for therapeutic effect. Warfarin maintenance therapy may be initiated after 1-3 days of effective heparinization.

The weight-adjusted heparin dosing regimens that are appropriate for prophylaxis and treatment of coronary artery thrombosis are too low to be used unmodified in the treatment of active DVT and PE. Coronary artery thrombosis does not result from hypercoagulability but rather from platelet adhesion to ruptured plaque. In contrast, patients with DVT and PE are in the midst of a hypercoagulable crisis, and aggressive countermeasures are essential to reduce mortality and morbidity rates.

Enoxaparin (Lovenox)

Exonaparin was the first low-molecular-weight heparin (LMWH) released in the United States. It was approved by the FDA for both treatment and prophylaxis of DVT and PE. Enoxaparin enhances the inhibition of factor Xa and thrombin by increasing antithrombin III activity. In addition, it preferentially increases the inhibition of factor Xa. LMWH has been used widely in pregnancy, although clinical trials are not yet available to demonstrate that it is as safe as unfractionated heparin. Except in overdoses, checking PT or aPTT has no utility, as aPTT does not correlate with anticoagulant effect of fractionated LMWH. Factor Xa levels can be monitored if concern arises about whether the dose is adequate.

Dalteparin (Fragmin)

Dalteparin is an LMWH with many similarities to enoxaparin but with a different dosing schedule. It is approved for DVT prophylaxis in patients undergoing abdominal surgery. Except in overdoses, checking PT or aPTT has no utility, as aPTT does not correlate with anticoagulant effect of fractionated LMWH. LMWH. Factor Xa levels can be monitored if concern arises about whether the dose is adequate.

Tinzaparin (Innohep)

Tinzaparin is approved for treatment of DVT in hospitalized patients. Enhances inhibition of factor Xa and thrombin by increasing antithrombin III activity. In addition, preferentially increases inhibition of factor Xa.

Heparin (Hep-Lock U/P, Hep-Lock, Hep-Flush-10)

Heparin augments the 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 the reaccumulation of a clot after spontaneous fibrinolysis. When UFH is used, the aPTT should not be checked until 6 hours after the initial heparin bolus, because an extremely high or low value during this time should not provoke any action

Warfarin (Coumadin, Jantoven)

Warfarin (Coumadin) interferes with the hepatic synthesis of vitamin K–dependent coagulation factors. It is used for the prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders. Never administer warfarin to patients with thrombosis until after they have been fully anticoagulated with heparin (the first few days of warfarin therapy produce a hypercoagulable state). Failing to anticoagulate with heparin before starting warfarin causes clot extension and recurrent thromboembolism in approximately 40% of patients, compared with 8% of those who receive full-dose heparin before starting warfarin. Heparin should be continued for the first 5-7 days of oral warfarin therapy, regardless of the PT time, to allow time for depletion of procoagulant vitamin K–dependent proteins.

Tailor the warfarin dose to maintain an INR in the range of 2.5-3.5. The risk of serious bleeding (including hemorrhagic stroke) is approximately constant when the INR is 2.5-4.5 but rises dramatically when the INR is over 5. In the United Kingdom, a higher INR target of 3-4 often is recommended.

Evidence suggests that 6 months of anticoagulation reduces the rate of recurrence to half of the recurrence rate observed when only 6 weeks of anticoagulation is given. Long-term anticoagulation is indicated for patients with an irreversible underlying risk factor and recurrent DVT or recurrent pulmonary embolism.

Procoagulant vitamin K–dependent proteins are responsible for a transient hypercoagulable state when warfarin is first started and stopped. This is the phenomenon that occasionally causes warfarin-induced necrosis of large areas of skin or of distal appendages. Heparin is always used to protect against this hypercoagulability when warfarin is started; when warfarin is stopped, however, the problem resurfaces, causing an abrupt, temporary rise in the rate of recurrent venous thromboembolism.

At least 186 different foods and drugs reportedly interact with warfarin. Clinically significant interactions have been verified for a total of 26 common drugs and foods, including 6 antibiotics and 5 cardiac drugs. Every effort should be made to keep the patient adequately anticoagulated at all times, because procoagulant factors recover first when warfarin therapy is inadequate.

Patients who have difficulty maintaining adequate anticoagulation while taking warfarin may be asked to limit their intake of foods that contain vitamin K.

Foods that have moderate to high amounts of vitamin K include Brussels sprouts, kale, green tea, asparagus, avocado, broccoli, cabbage, cauliflower, collard greens, liver, soybean oil, soybeans, certain beans, mustard greens, peas (black-eyed peas, split peas, chick peas), turnip greens, parsley, green onions, spinach, and lettuce.

Fondaparinux sodium (Arixtra)

Fondaparinux sodium is a synthetic anticoagulant that works by inhibiting factor Xa, a key component involved in blood clotting. 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.


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