VTE Prevention in Surgical Patients

Challenges in selecting optimal therapy

Therapies employed to prevent venous thromboembolism (VTE) in surgical patients vary in efficacy, ease of use, and risk of bleeding.^{3, 55} The standard of care, as reflected in current guidelines, is to use low-molecular-weight heparin (LMWH), fondaparinux, or a vitamin K antagonists (VKA) for thromboprophylaxis after surgery for hip or knee replacement and hip fracture. For abdominal surgery, where the risk of VTE is generally lower than in major orthopaedic surgery, low-dose unfractionated heparin (LDUH) or LMWH can be used. Because of the convenience of less-frequent dosing, LMWH has generally replaced LDUH. Mechanical devices are an appropriate option in patients at high risk of bleeding complications and can be used as an adjunct to anticoagulation in other surgical patients.³

Greater efficacy may be associated with increased bleeding risks

Clinical trials and meta-analyses comparing agents have generally shown LMWH and fondaparinux to be roughly equivalent and VKAs to be less effective for thromboprophylaxis in major orthopaedic surgery. For abdominal surgery, the balance of evidence indicates that LDUH is as effective as LMWH. It is important to note that with currently available treatment options, regimens associated with higher efficacy are often also associated with increased bleeding risks.³

A number of studies have focused on the timing of perioperative anticoagulation. The goal is to balance prevention of postoperative bleeding against the risk of early deep-vein thrombosis (DVT).⁵⁵ Temporal patterns of prophylactic treatment employed in an effort to achieve this goal vary from region to region.

Warfarin: challenges in the outpatient setting

In North America, warfarin is the most common agent used for thromboprophylaxis in patients undergoing hip arthroplasty. Outpatient use of warfarin, however, requires extensive monitoring and dose adjustments, which may account for why European orthopaedists have abandoned its use in favour of the more effective LMWH. The delayed onset of action of warfarin may prevent excessive bleeding perioperatively, but it also increases the risk of early thrombosis.³

Genetic testing can help clinicians determine the optimal warfarin dose for each patient. In a study involving over 1000 patients, dosing based on genetic test results was significantly closer to the required stable therapeutic dose than those derived from a clinical algorithm or a fixed-dose approach.²¹⁵

Duration of prophylaxis: an important aspect of care

The duration of anticoagulation needed to prevent DVT after hospital discharge is an important aspect of care. Accumulating evidence indicates that the risk of VTE after many different types of surgery — including ambulatory surgery — is greater and lasts for longer than previously realised.²⁷⁰

Current guidelines recommend extending prophylaxis for 10 days after knee arthroplasty and for four to six weeks after hip arthroplasty and hip fracture surgery. Extending prophylaxis for four weeks is also recommended for patients after abdominal cancer surgery.^{3, 60, 62} However, in practice, many patients may not receive this duration of treatment.¹¹⁸ The EXCLAIM (EXtended CLinical prophylaxis in Acutely Ill Medical patients) study, involving almost 6000 acutely ill medical patients with recent reduced mobility, demonstrated that extending prophylaxis to 5 weeks in selected groups of medically ill patients was more effective than 10 days of treatment to reduce the risk VTE.²⁰⁷ However, this extended duration of anticoagulant treatment was associated with an increased rate of major bleeding events.²⁰⁷

One reason for the poor uptake of VTE prophylaxis is the inconvenience of parenteral anticoagulants on a long-term basis. Therefore, the introduction of newer oral anticoagulants such as rivaroxaban, dabigatran etexilate and apixaban has the potential to facilitate long-term VTE prophylaxis.^{89, 201}

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Article references

3 - 1. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6)(suppl):381S-453S.
55 - Kakkar AK. Prevention of venous thromboembolism in general surgery.In: Colman RW, Marder VJ, Clowes AW, George JN, Goldhaber SZ, eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 5th ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2006:1361-1367.
215 - Klein TE, Altman RB, Eriksson N, et al; International Warfarin Pharmacogenetics Consortium. Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med. 2009;360(8):753-764.
270 - Sweetland S, Green J, Liu B, et al; Million Women Study collaborators. Duration and magnitude of the postoperative risk of venous thromboembolism in middle aged women: prospective cohort study. BMJ. 2009;339:b4583.
60 - Nicolaides AN, Fareed J, Kakkar AK, et al. Prevention and treatment of venous thromboembolism. International Consensus Statement (guidelines according to scientific evidence). Int Angiol. 2006;25(2):101-161.
62 - Lyman GH, Khorana AA, Falanga A, et al; American Society of Clinical Oncology. American Society of Clinical Oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. J Clin Oncol. 2007;25(34):5490-5505.
118 - Anderson FA Jr, Hirsh J, White K, Fitzgerald RH Jr; Hip and Knee Registry Investigators. Temporal trends in prevention of venous thromboembolism following primary total hip or knee arthroplasty 1996-2001: findings from the Hip and Knee Registry. Chest.2003;124(6)(suppl):349S-356S.
207 - Hull, RD, Schellong, SM, Tapson, VF, et al; EXCLAIM (Extended Prophylaxis for Venous ThromboEmbolism in Acutely Ill Medical Patients With Prolonged Immobilization) Study. Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recently reduced mobility: a randomized trial. Ann Intern Med. 2010;153(1):8-18.
89 - Haas S. New oral Xa and IIa inhibitors: updates on clinical trial results. J Thromb Thrombolysis. 2008;25(1):52-60.
201 - Haas S. New anticoagulants - towards the development of an "ideal" anticoagulant. Vasa. 2009;38(1):13-29.

Fondaparinux: An indirect Factor Xa inhibitor comprising a synthetic pentasaccharide sequence matching the part of the heparin molecule that binds to antithrombin. It is administered by subcutaneous injection.
Heparin: An anticoagulant that exerts its activity by binding to antithrombin and greatly increasing its activity. The principal coagulation factors inhibited by heparin are Factors IIa and Xa. It is administered by intravenous or subcutaneous injection.
Thromboprophylaxis: The use of medication or medical devices to prevent the formation of blood clots.
Vitamin K antagonists: Vitamin K antagonists block the regeneration of the reduced form of vitamin K.
Venous thromboembolism: A condition in which a blood clot (thrombus) forms in a vein, which in some cases then breaks free and enters the circulation as an embolus, finally lodging in and completely obstructing a blood vessel, e.g., in lungs causing a PE. The term encompasses both DVT and PE.
Low-molecular-weight heparin: An anticoagulant derived from unfractionated heparin (UFH), containing only the low-molecular-weight molecules of heparin. It binds to antithrombin, greatly increasing its activity. It inhibits coagulation Factor Xa and, to a lesser extent, Factor IIa. LMWHs are administered by subcutaneous injection.
Warfarin: A vitamin K antagonist. Most commonly used oral anticoagulant in chronic prevention or treatment of VTE.
Prophylaxis: The prevention of a disease or pathological condition.
Dabigatran: The active form of the prodrug dabigatran etexilate, an oral direct thrombin inhibitor.
Parenteral: Not through the alimentary canal but rather by injection through another route.
Rivaroxaban: Oral, direct Factor Xa inhibitor.