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This section details the mechanisms of actions and guideline recommendations of anticoagulation in patients with VTE
Anticoagulant drugs are designed to modulate the coagulation cascade by inhibiting the conversion of fibrinogen to fibrin and preventing the subsequent formation of a thrombus. A number of orally available and parenteral (i.e. infused or injected) drugs are available for the prevention of VTE.
Anticoagulants and their targets. VKAs inhibit the synthesis of Factors II, VII, IX and X. The heparins inhibit Factor Xa and thrombin indirectly through antithrombin, and fondaparinux indirectly inhibits Factor Xa alone via antithrombin. Rivaroxaban, apixaban and edoxaban directly inhibit Factor Xa and dabigatran directly inhibits thrombin
For more information on these anticoagulants, including dosing recommendations, please refer to our ‘Which anticoagulant?’ table here.
The 2012 American College of Chest Physicians (ACCP) guidelines for the prevention of VTE in patients undergoing surgery or hospitalized for other medical conditions are summarized below.22,23
|ACCP recommendation for anticoagulant prophylaxis [grade of recommendation]||Duration of anticoagulation [grade of recommendation]|
|Major orthopaedic surgery – high VTE risk24|
|Elective hip or knee replacement||Low-dose UFH, LMWH, fondaparinux (parenteral); adjusted-dose VKA, aspirin, apixaban, dabigatran or rivaroxaban (oral) [1B]; IPCD [1C]||10–14 days [1B] and up to 35 days [2B]|
|Hip fracture surgery||Low-dose UFH, LMWH, fondaparinux (parenteral); adjusted-dose VKA, aspirin (oral) [1B]; IPCD [1C]||10–14 days [1B] and up to 35 days [2B]|
|Surgery associated with high VTE risk||Low-dose UFH or LMWH [1B]||No specific recommendations|
|Abdominal or pelvic surgery for cancer and high VTE risk||LMWH [1B]||4 weeks [1B]|
|Other surgery associated with moderate VTE risk||Low-dose UFH or LMWH [2B]||No specific recommendations|
|Surgery associated with low VTE risk||No pharmacological prophylaxis [2C]||–|
|Hospitalized medical patients22|
|High VTE risk||Low-dose UFH, LMWH or fondaparinux [1B]||Duration of immobilization or acute hospital stay [2B]|
|Low VTE risk||No pharmacological or mechanical prophylaxis [1B]||–|
N/A, not applicable
Risks and benefits of anticoagulant prophylaxis
The benefits of thromboprophylaxis after major orthopaedic surgery have been shown to outweigh the risks of bleeding, regardless of the therapy used, resulting in clear guideline recommendations for thromboprophylaxis.24
Although data regarding thromboprophylaxis after hip fracture surgery are limited, LMWHs, low-dose UFH, adjusted-dose VKA, fondaparinux, aspirin and intermittent pneumatic compression devices (IPCD) appear to have positive efficacy and safety profiles and are recommended.24 In the real-world XAMOS study, rivaroxaban was shown to be similarly efficacious and as safe as enoxaparin as thromboprophylaxis after hip/femur or below-knee fracture surgery.25
Patient characteristics that are associated with an increased risk of bleeding with anticoagulant use include:26
Validated risk scores have been developed to help identify which hospitalized acutely medically ill patients at increased risk of VTE may benefit from anticoagulant prophylaxis.27,28
Scoring algorithms to assess the risk of bleeding may also help physicians to decide whether a patient should receive thromboprophylaxis.
|Bleeding risk factor||Points|
|Active gastroduodenal ulcer||4.5|
|Bleeding during the 3 months before admission||4|
|Platelet count <50 × 109 cells/l||4|
|Advanced age, ≥85 years vs <40 years||3.5|
|Severe renal failure, eGFR <30 ml/min/m2 vs ≥60 ml/min/m2||2.5|
|Hepatic failure (INR >1.5)||2.5|
|Intensive care unit/coronary care unit||2.5|
|Central venous catheter||2.5|
|Cancer at the time of hospital admission||2|
|Age, 40–84 years vs <40 years||2|
|Moderate renal impairment, eGFR 30–59 ml/min/m2 vs ≥60 ml/min/m2||1|
eGFR, estimated glomerular filtration rate
The risk of bleeding increased exponentially in patients with a risk score of ≥7.0 points. In the cases where bleeding contributed to death, the mean score was 8.6. Both major bleeding and any bleeding were uncommon in patients with a bleeding risk score of <7.0.26
Among other potential adverse events, HIT can be associated with the use of heparins in up to 5% of patients after cardiac or orthopaedic surgery.29 HIT usually occurs in the first weeks of therapy; therefore, platelet counts should be monitored in patients receiving heparins for more than a few days.
The optimal duration of thromboprophylaxis is an important consideration when balancing the benefits and risks of therapy: