venous%20thromboembolism%20-%20prevention
VENOUS THROMBOEMBOLISM - PREVENTION
Venous thromboembolism is comprised of pulmonary embolism and deep venous thrombosis and is associated with significant morbidity and mortality.
Decision on which type of prophylaxis must be individualized for each patient.
All patients admitted for major trauma, surgery or acute medical illness should be assessed for risk of venous thromboembolism and bleeding before starting prophylaxis for venous thromboembolism.
Early mobilization and leg exercises for any patient recently immobilized is recommended. Immobilized patients should also be adequately hydrated.
Intermittent pneumatic compression devices periodically compress calf &/or thighs and stimulate fibrinolysis. It has been shown to be effective in prophylaxis of asymptomatic deep venous thrombosis in surgical patients.
Graduated compression stockings may be used for deep venous thrombosis prophylaxis in surgical patients with no contraindication for use.

Principles of Therapy

Prophylaxis Decisions

  • Decision on which type of prophylaxis must be decided individually for each patient
  • Routine VTE prophylaxis is not recommended for low-risk patients unless risk status changes

Considerations

  • Clinical judgment
  • Review of literature for group recommendations
  • Patient’s unique risks for thrombosis
  • Patient’s renal function
  • Potential for adverse effects
  • Local availability of products

Contraindications to Anticoagulant Prophylaxis

  • Active bleeding, history of or high risk of bleeding [eg hemophilia, thrombocytopenia, gastrointestinal bleeding]
  • Severe hepatic disease
  • Currently on anticoagulation treatment
  • Other factors (eg high risk of falls, on palliative treatment)

Pharmacotherapy

Anticoagulants

Low-Dose Unfractionated Heparin (LDUH)

  • Inhibits clotting of blood through enhancement of antithrombin III activity; antithrombin III inactivates thrombin (factor IIa), factor Xa, factor IXa, factor XIIa and factor XIa
    • Unfractionated Heparin (UFH) also inhibits the activation of factors V and VIII by thrombin
  • In surgical patients and medical patients, subcutaneous (SC) LDUH has been shown to significantly reduce the incidence of asymptomatic DVT, symptomatic DVT and PE, fatal PE and total mortality
    • The use of LDUH has been shown to result in an increase in major bleeding but there is no increase in fatal bleeding
  • Monitoring of the anticoagulant effect is not required when SC LDUH is used
  • To detect Heparin-induced thrombocytopenia (HIT), which occurs in 2-3% of patients receiving LDUH, baseline platelet count should be obtained and regularly monitored

Low-Molecular-Weight Heparin (LMWH)

  • Similar to Heparin, these compounds enhance the action of antithrombin III but they have a higher ratio of anti-factor Xa to anti-IIa activity than Heparin
    • Produce a more predictable anticoagulant response than Heparin
    • They have less effect on platelet activity
  • It has been shown that SC LMWH is as effective as LDUH in surgical and medical patients in decreasing the incidence of asymptomatic DVT, symptomatic DVT and PE, fatal PE and total mortality
    • Risk of bleeding is similar to LDUH
  • Monitoring of the anticoagulant effect is not required
  • HIT is less common with LMWH, occurring in <1% of patients, but baseline platelet count should still be obtained and monitored

Antithrombin III

  • A human plasma- derived protein which acts to inhibit thrombin and other activated clotting factors (eg factors IX, X, XI, XII)
  • Cofactor through which heparin exerts its effects
  • Genetic and acquired insufficiency of antithrombin III is associated with susceptibility to thromboembolic disorders
  • Goal of therapy is to restore plasma-antithrombin III to normal level
  • Dose and duration of treatment should be individualized based on patient’s pretreatment condition and presence of active coagulation

Factor Xa Inhibitors

  • Eg Apixaban, Edoxaban, Fondaparinux, Rivaroxaban

Apixaban

  • A direct and competitive factor Xa inhibitor that does not require antithrombin III for antithrombotic activity
  • Indicated for the prevention of VTE in patients undergoing hip or knee placement surgery

Edoxaban

  • Prophylactic option against stroke and systemic embolism in patients with non-valvular atrial fibrillation
  • Requires initial therapy with parenteral anticoagulants prior to starting therapy
  • Should only be used in patients with high creatinine clearance (>95 mL/minute)
  • There are ongoing studies proving the efficacy of Edoxaban as prophylaxis against VTE after total knee or hip replacement and hip fracture surgery
    • Several studies have shown that the efficacy of Edoxaban for VTE prevention after surgery was comparable to Enoxaparin and Warfarin

Fondaparinux

  • Used for prophylaxis of VTE in patients undergoing hip fracture, hip replacement surgery or knee replacement surgery
  • Specifically inhibits factor Xa, which results in effective inhibition of thrombin generation
  • Studies have shown that in patients undergoing major orthopedic surgery, factor Xa inhibitor was more effective than LMWH in preventing VTE 
    • Risk of clinically relevant bleeding is similar to LMWH
  • Monitoring of the anticoagulant effect is not required
  • Moderate thrombocytopenia has occurred and platelet count should be monitored

Rivaroxaban

  • Recommended prophylactic agent for VTE following elective total hip or knee replacement
  • Also used for the prevention of systemic embolism in patients with non-valvular atrial fibrillation
  • Increased risk of stroke was noted upon discontinuation of Rivaroxaban in clinical trials of patients with atrial fibrillation
    • Consider adding alternative anticoagulant when Rivaroxaban is discontinued for reasons other than bleeding
  • Spinal or epidural hematomas, including subsequent paralysis, may occur with neuraxial anesthesia (epidural or spinal anesthesia) or spinal puncture, in patients who are anticoagulated

Warfarin

  • Vitamin K antagonist (VKA)
  • May be appropriate when used for long-term prophylaxis in patients who are immobilized by illness, trauma or surgery
  • Inhibits the synthesis of the vitamin K-dependent coagulant proteins (factors II, VII, IX, and X) and inhibits at least 2 vitamin K-dependent anticoagulant factors (proteins C and S)
  • Effective in preventing asymptomatic DVT but use is limited by necessary international normalised ratio (INR) monitoring, bleeding risk and delay in onset of action

Direct Thrombin Inhibitors

  • Eg Argatroban, Bivalirudin, Dabigatran, Hirudin

Argatroban

  • Competitive inhibitor of thrombin and forms a reversible complex with thrombin
  • For prevention and treatment of HIT-associated thrombosis and for anticoagulation during percutaneous coronary interventions when Heparin is contraindicated due to history of HIT

Bivalirudin

  • An analog of Hirudin
  • Anticoagulant used with aspirin in patients undergoing percutaneous coronary interventions including those with or at risk of HIT

Dabigatran

  • Used for prophylaxis of VTE in patients who will undergo elective orthopedic surgery
  • Also has use in preventing stroke and systemic embolization in patients with nonvalvular atrial fibrillation
  • Investigation of postmarketing reports of serious bleeding rates is ongoing
  • Patients with atrial fibrillation are advised against discontinuing Dabigatran without talking to their physicians because bleeding risks do not outweigh the stroke prevention benefits of Dabigatran

Hirudin

  • Inhibits thrombin and forms an irreversible complex with thrombin
  • 2 recombinant forms
    • Desirudin - used for postop thromboprophylaxis in patients undergoing hip arthroplasty in Europe
    • Lepirudin - used for treatment of thrombosis complicating HIT in North America 
  • Effective in preventing asymptomatic DVT but use is limited by necessary INR monitoring, bleeding risk and delay in onset of action

Antiplatelets

Aspirin

  • May be considered for the prevention of recurrent VTE in patients with unprovoked proximal DVT or PE who discontinued anticoagulant therapy
  • Prophylactic efficacy is inferior to LMWH and anticoagulants
  • Not to be used as an alternative therapy if patient has no contraindications and is willing to undergo treatment with anticoagulants

Non-Pharmacological Therapy

General Measures for Prophylaxis of Venous Thromboembolism (VTE)

Mobilization

  • Early mobilization and leg exercises for any patient recently immobilized is recommended
  • Immobility increases risk of DVT by approximately 10x
  • Early and frequent ambulation may be recommended in patients undergoing the following procedures:
    • Vascular surgery without additional thromboembolic risk factors
    • Transurethral or other low-risk urological procedures
    • Laparoscopic procedure

Hydration

  • Immobilized patients should be adequately hydrated
  • Hemoconcentration can reduce blood flow especially in the deep veins of immobile patients

Pre-Operative/Operative Measures

  • Patient should be advised to defer antiplatelet agent intake prior to elective hip/knee arthroplasty
  • Neuraxial anesthesia is preferred for patients at risk for VTE undergoing elective hip/knee arthroplasty

Mechanical Measures

  • Less efficacious than pharmacologic thromboprophylaxis in decreasing the risk of DVT 
    • Not as intensively studied as pharmacologic prophylaxis
    • No established standards for size, pressure or physiologic standards
  • Acceptable alternative in patients in whom risk of bleeding outweighs the benefits of pharmacotherapeutic DVT prophylaxis
  • May be used in combination with anticoagulant prophylaxis to improve efficacy
    • Although its use may reduce or delay administration of anticoagulant thromboprophylaxis
  • Emphasis must be made toward proper use of and optimal compliance with the mechanical device
  • Increase mean blood flow velocity in the leg veins and reduce venous stasis
  • Contraindications: Patients at risk of ischemic skin necrosis

Inferior Vena Cava (IVC) Filters

  • May be considered in patients with severe PE who have received anticoagulant therapy, and those with contraindications to anticoagulants
  • Benefits should be weighed against potential complications when to be used in patients with progressive or recurrent VTE despite anticoagulant therapy
  • The American College of Chest Physicians is against the use of IVC filters in patients with acute PE who were previously treated with anticoagulants

Intermittent Pneumatic Compression (IPC) Devices

  • Periodically compress calf and/or thighs and stimulate fibrinolysis
  • Have been shown to be effective in prophylaxis of asymptomatic DVT in surgical patients
    • When combined with LDUH reduces the risk of symptomatic PE in cardiac surgery patients
    • Have been shown to be more effective than graduated compression stockings (GCS) in high-risk patients in combination with anticoagulants or when anticoagulants are contraindicated
  • Many times IPC devices are applied immediately prior to surgery and are replaced by GCS after surgery because IPC devices may cause discomfort in the conscious patient
  • Complications: Compartment syndrome, skin ulceration and common peroneal nerve palsy

Graduated Compression Stockings (GCS)

  • May be used for DVT prophylaxis in surgical patients with no contraindication for use of GCS
    • Although little evidence supports the efficacy of GCS in preventing VTE 
  • May be used in chronic DVT patients to improve leg pain and swelling more rapidly
    • Routine use in patients with acute DVT with symptoms of post-thrombotic syndrome is not recommended
  • Compress the lower leg veins in a graded fashion reducing venous distension and increasing venous return to the deep venous system
  • Correct size and alignment is needed
    • It is important to measure the patient correctly and to use the correct size
    • Pressure of 16-20 mmHg at the ankle in the supine position with graduated compression to the knee or above
    • Assure that toe hole is aligned under toe
    • Check fitting daily for change in leg circumference
    • Do not fold down
    • Remove daily for ≤30 minutes
  • Contraindications: Massive leg edema, pulmonary edema, severe peripheral arterial disease, anatomic leg deformity, dermatitis, recent skin graft (within 6 months), loss of skin integrity
  • Complications: Compartment syndrome, skin ulceration and common peroneal nerve palsy
  • Latest guideline from American College of Chest Physicians recommends against the use of GCS and instead, suggests use of IPC device in patients for whom Heparin is contraindicated

Venous Foot Pumps (VFP)

  • Deliver external compression to the venous system of the foot increasing venous return thus reducing venous stasis in the lower extremity
  • For orthopedic surgery patients who are unable to bear own weight

Electrical Stimulation

  • Device that stimulates the intrinsic foot muscles to contract and consequently compress the plantar venous plexus
  • Designed to increase the venous blood flow velocity out of the leg to reduce the incidence of VTE after surgery
  • May be effective in reducing venous stasis and edema
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