Anticoagulant

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Anticoagulants are "agents that prevent blood clotting".^[1] They interfere with coagulation and may be used to prevent embolism and thrombosis.

Anticoagulation is dangerous due to drug toxicity and should be managed in a systematic manner.^[2]

Vitamin K antagonists[edit]

Warfarin[edit]

For more information, see: warfarin.

Warfarin is a commonly used oral anticoagulant that interferes with the Vitamin K dependent coagulation co-factors.

Indirect thrombin inhibitors[edit]

Heparins[edit]

Heparins bind to and activate the enzyme inhibitor antithrombin III. The activated antithrombin III then inactivates thrombin, factor Xa, and components of coagulation.

Unfractionated heparin[edit]

Details of the usage of heparin are available in clinical practice guidelines by the American College of Chest Physicians^[3]:

• Non-weight based heparin dose adjustment
• Weight-based heparin dose adjustment

Heparin dose may also be adjusted by using an anti-Xa assay to measure heparin function, which is related to heparin levels. The goal heparin level is 0.3 to 0.7 U/mL for unfractionated heparin but a higher level for low molecular weight heparin.^[4][5][6]

Low molecular weight heparin[edit]

For more information, see: Low molecular weight heparin.

The last dose of low molecular weight heparin prior to coronary artery bypass surgery should occur 24 hours before the procedure in order to prevent high residual anti-Xa levels.^[7]

Direct thrombin inhibitors (antithrombins)[edit]

Direct thrombin inhibitors (antithrombins) bind directly to thrombin^[8] and are used for heparin-induced thrombocytopenia and during percutaneous coronary interventions.^[9]

• Argatroban is for treating heparin-induced thrombocytopenia (HIT)
• Bivalirudin is a recombinant protein
• Dabigatran is given orally and may be as effective as warfarin and with less bleeding but increased dyspepsia for the treatment of embolism and thrombosis.^[10] However, dabigatran my increase acute coronary syndrome.^[11]
• Desirudin
• Hirudin is a recombinant protein for treating heparin-induced thrombocytopenia (HIT)
• Lepirudin
• Ximelagatran is a recombinant protein that is an oral direct thrombin inhibitor

Low molecular weight heparins may provide better anticoagulation for prophylaxis of deep venous thrombosis among orthopedic patients than direct thrombin inhibitors because the latter may increase bleeding complications.^[12] However, if anticoagulation is started before surgery, direct thrombin inhibitors may be more effective.

Factor Xa inhibitors[edit]

• Apixaban is taken orally and can prevent can prevent embolism and thrombosis during perioperative care according to randomized controlled trials of knee^[13] and hip^[14] surgery. May also reduce embolism better than warfarin in atrial fibrillation. Hepatic metabolism.
• Fondaparinux can prevent embolism and thrombosis during perioperative care according to randomized controlled trials of hip fracture surgery^[15].
• Idraparinux is a synthetic derivative of heparin that has a long half life that allows once-weekly dosage. A randomized controlled trial compared idraparinux to warfarin and found that idraparinux is equivalent for deep venous thrombosis but is inferior for pulmonary embolism.^[16]
  • Idrabiotaparinux is idraparinux with biotin added to allow rapid reversal of anticoagulation with avidin. Idrabiotaparinux may be more effective than warfarin for pulmonary embolism.^[17]
• Rivaroxaban can be given orally. It can prevent embolism and thrombosis during perioperative care according to randomized controlled trials of two weeks of therapy after knee arthoplasty^[18] or 5 weeks of therapy after hip arthroplasty.^[19][20]

Warfarin combined with heparin[edit]

Warfarin combined with heparin did not benefit survivors of acute myocardial infarction in a randomized controlled trial.^[21]

Warfarin combined with heparin reduced events, but increased bleeding, among survivors of acute myocardial infarction in a randomized controlled trial.^[22]

Adverse effects[edit]

Risk factors[edit]

Various risk factors, such as history of chronic obstructive pulmonary disease, prior gastrointestinal hemorrhage and anemia, have been identified.^[23]

Bleeding is more likely when more than one antithrombotic is used.^[24][25]

Accidental falls may not increase rate of major bleeding.^[26]

Prediction[edit]

In atrial fibrillation, the risk of bleeding can be estimated with the HAS-BLED clinical prediction rule.^[27]

In acute acute coronary syndrome, the risk of bleeding with heparin can be estimated with a clinical prediction rule (http://www.crusadebleedingscore.org/). Additional clinical prediction rules are available.^[28]

Prevention[edit]

Proton pump inhibitors may reduce the risk of gastrointestinal hemorrhage among patients undergoing anticoagulation.^[29]

Treatment[edit]

"Prothrombin complex concentrate immediately and completely reverses the anticoagulant effect of rivaroxaban in healthy subjects but has no influence on the anticoagulant action of dabigatran at the PCC dose used in this study" according to a randomized controlled trial. ^[30]

References[edit]

See also[edit]

• Coagulation
• Embolism and thrombosis

External links[edit]

• The Ninth ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence-Based Guidelines 2012
• The Eighth ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence-Based Guidelines