Which medications in the drug class Anticoagulant Agents are used in the treatment of Protein C Deficiency?

Updated: Jan 04, 2019
  • Author: Shamudheen Rafiyath, MD; Chief Editor: Perumal Thiagarajan, MD  more...
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Answer

Anticoagulant Agents

Anticoagulation is the mainstay of therapy for the treatment and prevention of venous thromboembolism (VTE) in patients with protein C deficiency.

Heparin

Primarily used during the treatment of an acute thrombotic event or before initiating oral anticoagulant therapy.

Heparin mediates anticoagulant effects by augmenting the effect of the anticoagulant protein antithrombin.

Higher doses are needed in infants and children due to their low antithrombin levels.

Enoxaparin (Lovenox)

Produced by partial chemical or enzymatic depolymerization of unfractionated heparin (UFH). Binds to antithrombin, enhancing its therapeutic effect. The heparin-antithrombin complex binds to and inactivates activated factor X (Xa) and factor II (thrombin).

Does not actively lyse but is able to inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis.

Advantages include intermittent dosing and decreased requirement for monitoring. Heparin anti–factor Xa levels may be obtained if needed to establish adequate dosing.

LMWH differs from UFH by having a higher ratio of antifactor Xa to antifactor IIa compared with UFH.

Prevents DVT, which may lead to pulmonary embolism in patients undergoing surgery who are at risk for thromboembolic complications. Used for prevention in hip replacement surgery (during and following hospitalization), knee replacement surgery, or abdominal surgery in those at risk of thromboembolic complications, or in nonsurgical patients at risk of thromboembolic complications secondary to severely restricted mobility during acute illness.

Used to treat DVT or PE in conjunction with warfarin for inpatient treatment of acute DVT with or without PE or for outpatient treatment of acute DVT without PE.

No utility in checking aPTT (drug has wide therapeutic window and aPTT does not correlate with anticoagulant effect).

May be used during the treatment of an acute thrombotic event, before initiating PO anticoagulant therapy, or SC as an outpatient medication.

Dalteparin (Fragmin)

Enhances inhibition of factor Xa and thrombin by increasing antithrombin activity. In addition, preferentially increases inhibition of factor Xa.

Except in overdoses, no utility exists in checking PT or aPTT because aPTT does not correlate with anticoagulant effect of fractionated LMWH.

Average duration of treatment is 7-14 d.

Fondaparinux (Arixtra)

Synthetic anticoagulant, which works by inhibiting factor Xa, a key component involved in blood clotting. Provides highly predictable response. Bioavailability is 100%, has a rapid onset of action, and a half-life of 14-16 h, allowing for sustained antithrombotic activity over 24-h period. Does not affect prothrombin time or activated partial thromboplastin time, nor does it affect platelet function or aggregation.

Prevents DVT, which may lead to pulmonary embolism, in patients undergoing orthopedic surgery who are at risk for thromboembolic complications.

Warfarin (Coumadin)

Acts by preventing proper functional synthesis of the vitamin K–dependent procoagulant proteins prothrombin; factors VII, IX, and X; and anticoagulant proteins C and S.

Tailor dose to maintain an INR in the range of 2 to 3.

Rivaroxaban (Xarelto)

Rivaroxaban is an oral factor Xa inhibitor that inhibits coagulation by selectively blocking the active site of factor Xa without requiring a cofactor (eg, antithrombin III) for activity. It is indicated for treatment of DVT or PE, and to reduce risk of recurrent DVT and PE following initial treatment. It is also indicated for prophylaxis of DVT in patients undergoing knee or hip replacement surgery.

Dabigatran (Pradaxa)

Dabigatran is an oral anticoagulant agent that inhibits thrombus development through direct, competitive inhibition of thrombin (thrombin enables fibrinogen conversion to fibrin during the coagulation cascade). It inhibits free and clot-bound thrombin and thrombin-induced platelet aggregation. It is indicated for the treatment of DVT or PE in patients who have been treated with a parenteral anticoagulant for 5 to 10 days. It is also used to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and prophylaxis of  DVT and PE in patients who have undergone total hip arthroplasty.

Apixaban (Eliquis)

Apixaban is an oral anticoagulant that inhibits platelet activation and fibrin clot formation via direct, selective and reversible inhibition of free and clot-bound factor Xa (FXa). FXa, as part of the prothrombinase complex consisting also of factor Va, calcium ions, and phospholipid, catalyzes the conversion of prothrombin to thrombin. Thrombin both activates platelets and catalyzes the conversion of fibrinogen to fibrin. It is indicated for the treatment of DVT and PE, to reduce the risk of recurrent DVT following initial therapy. It is also indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, and for prophylaxis of DVT and PE in patients who have undergone hip or knee replacement surgery.

Edoxaban (Savaysa)

 Edoxaban, a selective factor Xa inhibitor, inhibits free factor Xa and prothrombinase activity and inhibits thrombin-induced platelet aggregation. Inhibition of factor Xa in the coagulation cascade reduces thrombin generation and thrombus formation. It is indicated for the treatment of DVT and PE, to reduce the risk of recurrent DVT following initial therapy. It is also indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.

 


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