What is the role of heparins in deep venous thrombosis (DVT) prophylaxis for patients undergoing orthopedic surgery for patients undergoing orthopedic surgery?

Updated: Jul 25, 2019
  • Author: David A Forsh, MD; Chief Editor: Vinod K Panchbhavi, MD, FACS  more...
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Answer

Answer

Standard unfractionated heparin (UFH) is recognized as an acceptable anticoagulant modality and has been used for this purpose in various forms since its discovery by McLean in 1916. UFH acts in conjunction with a circulating plasma cofactor, antithrombin (AT) III and, in its presence, catalyzes the inactivation of factors IIa, Xa, IXa, and XIIa.

By inactivating thrombin, heparin not only prevents fibrin formation but also inhibits thrombin-induced activation of factor V and factor VIII. Of these, factors IIa and Xa are most sensitive. Therefore, heparin has anticoagulant and antithrombotic properties.

Heparin is a heterogeneous mixture of molecules that contain a range of molecular weights of 3-30 kd, with an average of approximately 15 kd. Only one third of the heparin molecules have an active binding site for ATIII, and this fraction is responsible for most of the anticoagulant activity.

Heparin is effective when given by intravenous (IV) or subcutaneous (SC) administration but is inactivated in the GI tract. This agent has a rapid onset of action, its half-life is brief in comparison to warfarin, and it binds to platelets, endothelial cells, and macrophages in vivo. Therapeutic levels of heparin are measured by the activated partial thromboplastin time (aPTT). Because of the rapid clearance of heparin from the bloodstream, therapeutic levels (aPTT of 1.2-1.5 × control) are more likely achieved with continuous IV infusion.

Postoperative DVT prophylaxis with UFH is usually achieved by administering a bolus of 5000 U every 8 hours. This low-dose heparin regimen results in a 60-70% reduction of DVT and PE in low-risk or moderate-risk patients. However, this method is not as effective in patients who are at high risk for development of DVT or PE. In these patients, adjusted-dose heparin with aPTT monitoring is preferred to maintain the desired anticoagulant level. Studies have demonstrated a high hemorrhagic complication rate of 8-15% when this method is used for postoperative DVT prophylaxis.

Heparin overdosage is reversible with protamine sulfate, which itself is an anticoagulant. Each milligram of protamine sulfate can neutralize approximately 100 U of heparin activity. This agent must be administered very slowly by IV infusion over a 10-minute period in doses not to exceed 50 mg. Because heparin is rapidly cleared from the circulation, the amount of protamine required decreases rapidly as the time from initial heparin administration increases. The final dosage required is titrated according to coagulation studies.


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