Treatment Overview

Treatment Overview

Treatment

Prophylaxis (pharmacological)

Prophylaxis of thrombus formation is the preferred treatment strategy in patients at risk of developing thromboembolitic disease.



Aspirin reduces the incidence of venous thromboembolism (VTE) by approximately 25% in high-risk patients, but is associated with an increased risk of bleeding.¹



• SIGN guidelines indicate that aspirin is not recommended as the sole pharmacological agent for VTE prophylaxis in medical patients. Instead, when the assessment of risk favours the use of thromboprophylaxis, unfractionated heparin (UFH), low molecular-weight heparin (LMWH) or fondaparinux should be administered²
  • pharmacological thromboprophylaxis for VTE with UFH/LMWH/fondaparinux is not recommended routinely in acute stroke patients as the reduction in VTE is negated by the increased risk of bleeding³  
     
• LMWH is reported to be more effective than UFH irrespective of severity, but with higher bleeding.⁴ 


Prophylaxis (mechanical)³

Mechanical methods of prophylaxis may include:


• graduated compression stockings
• intermittent pneumatic compression (leggings inflated by a pneumatic pump)
• venous foot pump (simulation of normal walking to increase venous flow from the leg).
   

Few trials have investigated these methods; however, they do not increase the risk of bleeding and so may be preferred in patients for whom increased bleeding would present excessive/unacceptable risk. Mechanical methods are contraindicated in patients at risk of ischemic skin necrosis, e.g. those with critical limb ischemia or severe peripheral neuropathy.²


Medical treatment

Among patients with existing thrombus formation, anticoagulant and thrombolytic therapy options are available:⁵ 


• Anticoagulant therapy prevents further clot deposition, allowing natural fibrinolytic mechanisms to lyse the existing clot.
• Thrombolytic therapy dissolves recent clots promptly by activating a plasma proenzyme, plasminogen, to its active form, plasmin. Plasmin degrades fibrin to soluble peptides.


Anticoagulation 


• Heparin is the first line of therapy. It is administered by bolus dosing (80 mg/kg), followed by a continuous infusion (18 mg/kg/h).⁶
• After successful anticoagulation, a short course of heparin is often followed by a longer course of oral anticoagulant, such as warfarin sodium.
• It has been shown that LMWH, which is a fractionated heparin, is as effective as unfractionated heparin in treating deep venous thrombosis.⁴
• New oral treatments, such as dabigatran and rivaroxaban, are becoming available. They directly inhibit thrombin and Factor Xa, respectively. These treatments are being used following hip and knee surgery^.2
  

Thrombolysis


Streptokinase, urokinase and recombinant tissue-type plasminogen activator (rt-PA) are frequently prescribed for thrombolytic use in patients with thromboembolic diseases. The indication for thrombolytic treatment, as set out by the American College of Chest physicians, is massive embolism with hemodynamic instability in patients who do not seem prone to bleeding.⁷



Absolute contraindications to thrombolysis include:

• active or recent internal bleeding
• recent surgery
• streptococcal infection
• hemorrhagic disease

Surgery

Surgical interventions for venous thromboembolic disorders include thrombectomy/embolectomy and venous interruption.

• Today, surgical thrombectomy is reserved for patients with contraindications to pharmacological thrombolysis or for those in whom other modalities have failed.⁸
• Vena caval filters to protect against fatal PE are often used when anticoagulation therapy is contraindicated, has resulted in complications, or has failed to protect from embolic events
• the vena caval filter is designed to trap potentially lethal emboli, while maintaining vena caval function.⁷
   

References

1. Watson HG, Chee YL. Aspirin and other antiplatelet drugs in the prevention of venous thromboembolism. Blood Rev. 2008;22(2):107–116.
2. Scottish Intercollegiate Guidelines Network guidelines on prevention and management of venous thromboembolism. 2010.Accessed 25 May 2011.
3. Sandercock PA, Counsell C, Kamal AK. Anticoagulants for acute ischaemic stroke. Cochrane Database of Systematic Reviews. 2008;8:(4):CD000024.
4. Sherman DG, Albers GW, Bladin C, et al. The efficacy and safety of enoxaparin versus unfractionated heparin for the prevention of venous thromboembolism after acute ischaemic stroke (PREVAIL Study): an open-label randomised comparison. Lancet. 2007;369(9570):1347–1355.
5. Bauer KA. New anticoagulants. Curr Opin Hematol. 2008;15(5):509–515.
6. Wolfson AB. Harwood-Nuss’ Clinical Practice of Emergency Medicine. Lippincott Williams & Wilkins, 2009.
7. Hyers TM, Agnelli G, Hull RD, et al. Antithrombotic Therapy for Venous Thromboembolic Disease. Chest. 2001;119(1) suppl 176S-193S.
8. Augustinos P, Ouriel K. Invasive approaches to treatment of venous thromboembolism. Circulation. 2004;110(9, Suppl 1):I27–I34.