Thrombophilias in Pregnancy Medication

Updated: Jun 14, 2018
  • Author: Edward H Springel, MD, FACOG; Chief Editor: Ronald M Ramus, MD  more...
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Medication

Medication Summary

The decision to provide thromboprophylaxis to patients in pregnancy depends on

any prior personal history of VTE, the presence of high versus low risk thrombophilia, and the setting in which a prior VTE occurred (pregnancy/estrogen-related, idiopathic, or in the setting of non-recurrent risk factors such as fractures, surgery, or immobilization. These factors affect the decision to provide prophylaxis, as well as the timing (antenatal or postpartum only) and intensity of therapy. The goals of pharmacotherapy are to prevent or correct thromboembolic disorders, prevent complications, and reduce morbidity.

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Anticoagulants, Hematologic

Class Summary

Once the diagnosis of VTE is made, therapeutic anticoagulation should be initiated in the absence of contraindications. Anticoagulants prevent recurrent or ongoing thromboembolic occlusion of the vertebrobasilar circulation. In patients with heparin-induced thrombocytopenia, LVAD implantation has been performed successfully, albeit with additional risk, by using alternative anticoagulants.

Heparin

Heparin may be used if thrombocytopenia is not present. 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. It prevents the recurrence of a clot after spontaneous fibrinolysis. Pregnancy category C.

Warfarin (Coumadin, Jantoven)

Warfarin, which is administered orally, is used if long-term anticoagulation is needed. The international normalized ratio (INR) is followed, with a target range of 2-3. A CT scan of the brain must be performed prior to any anticoagulant use to rule out preexisting intracranial hemorrhage. Pregnancy category X.

Enoxaparin (Lovenox)

Enoxaparin is produced by the partial chemical or enzymatic depolymerization of unfractionated heparin (UFH). LMWH differs from UFH by having a higher ratio of antifactor Xa to antifactor IIa.

Enoxaparin 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, preventing clot reaccumulation after spontaneous fibrinolysis.

The advantages of enoxaparin include intermittent dosing and a decreased requirement for monitoring. Heparin anti–factor Xa levels may be obtained if needed to establish adequate dosing. There is no utility in checking activated partial thromboplastin time (aPTT); the drug has a wide therapeutic window, and aPTT does not correlate with the anticoagulant effect. The maximum antifactor Xa and antithrombin activities occur 3-5 hours after administration.

Dalteparin (Fragmin)

LMW heparin with antithrombotic properties; it enhances inhibition of factor Xa and thrombin by antithrombin, with minimal effect on aPTT. Pregnancy category B.

A 2004 study demonstrated that higher doses of Dalteparin may be needed in the pregnant population to achieve therapeutic levels. Although additional studies are needed on other LMWHs, careful attention should be paid to ensure that patients are being adequately treated. Given that all the LMWHs are metabolized by the kidneys, the results of this study could be generalized to Enoxaparin and Tinzaparin.

Tinzaparin

Tinzaparin is an LMW heparin with antithrombotic properties; it enhances inhibition of factor Xa and thrombin by antithrombin, with minimal effect on aPTT. Use with caution in pregnant women due to association with gasping syndrome in premature infants.

Argatroban

Argatroban is a selective thrombin inhibitor that inhibits thrombin formation by binding to the active thrombin site of free and fibrin-bound thrombin. It inhibits thrombin-induced platelet aggregation.

Dabigatran etexilate (Pradaxa)

Dabigatran etexilate is a selective thrombin inhibitor that inhibits thrombin formation by binding to the active thrombin site of free and fibrin-bound thrombin. It inhibits thrombin-induced platelet aggregation. Pregnancy category C

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Bivalirudin (Angiomax)

Bivalirudin inhibits coagulant effects by preventing thrombin-mediated cleavage of fibrinogen to fibrin. Pregnancy category B.

Fondaparinux (Arixtra)

Fondaparinux is a synthetic heparin pentasaccharide that causes an antithrombin lll mediated selective inhibition of factor Xa. This interrupts the blood coagulation cascade, which in turn inhibits thrombin formation and thrombus development. Pregnancy category B

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Rivaroxaban (Xarelto)

Rivaroxaban is a selective and reversible inhibition factor of Xa (FXa) in the intrinsic and extrinsic coagulation pathways. This interrupts the blood coagulation cascade, which in turn inhibits thrombin formation and thrombus development. Pregnancy category C.

Apixaban (Eliquis)

Inhibits platelet activation and fibrin clot formation via direct, selective, and reversible inhibition of free and clot-bound factor Xa. Factor Xa, as part of the prothrombinase complex, catalyzes the conversion of prothrombin to thrombin. Thrombin both activates platelets and catalyzes the conversion of fibrinogen to fibrin. Category B in pregnancy.

Edoxaban (Savaysa)

Selective Xa inhibitor, inhibits free factor Xa and prothrombinase activity and inhibits thrombin-induced platelet aggregation. Pregnancy category C.

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Antiplatelet Agents

Class Summary

These agents can be considered to help prevent future ischemic strokes.

Aspirin (Ecotrin, Ascriptin Maximum Strength, Ascriptin, Bayer Aspirin)

Aspirin's efficacy in preventing stroke relies on the inhibitory effect of aspirin on platelet function. This presumably helps to prevent thrombus formation and propagation.

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