Initial anticoagulation

initial and long term anticoagulation (first 3-6 months)

Initial phase of treatment, which include intensified anticoagulants is followed by long term anticoagulants for 3-6 months in majority of patients (1)

• the goal is to rapidly extinguish thrombin and fibrin clot generation
• multiple therapeutic options are available
  • conventional treatment involves parenteral heparin bridging to vitamin K antagonists (VKAs)
    • LMWH is usually preferred due to disadvantages of intravenous unfractionated heparin
      • inter-individual dose requirements that make close laboratory therapeutic monitoring a necessity
      • 8-10-fold higher risk for heparin-induced thrombocytopenia (HIT) than LMWH
        
        
    • UFH may be preferable in
      • patients with high bleeding risk
      • special patient populations e.g.
        • morbidly obese (BMI >= 40 kg/M2) and underweight patients (weight < 50 kg)
        • patients with severe renal impairment or unstable renal function (creatinine clearance <30 mL/min)
          
          
    • fondaparinux can also be employed as a parenteral agent for hospitalized patients in whom transition to a vitamin K antagonist (VKA) is anticipated
      
      
    • vitamin K antagonist (VKA) therapy can begin as soon as therapeutic levels of UFH/LMWH are achieved
      • parenteral therapy with UFH or LMWH should continue for at least 5 days of overlap and until an INR of 2 or more is achieved for 24 h
        
        
  • direct oral anticoagulants (DOACs)/ novel non-anti-vitamin K antagonist anticoagulants (NOACs)
    • have recently emerged as a treatment option for DVT
      • dabigatran and edoxaban therapy must include initial 7- 9 days treatment with a parenteral agent prior to beginning these agents.
      • apixaban and rivaroxaban can be used as a 'single drug approach' (without initial parenteral therapy)
    • is the preferred first-line anticoagulant therapy in non-cancer patients with proximal DVT
    • disadvantages include
      • longer elimination half-lives (7- 15 h) than UFH or LMWH
      • could accumulate in patients with suboptimal renal (estimated creatinine clearance <30 mL/min) or hepatic function
        
        
• thrombolytic therapy
  • can be used in patients with acute extensive proximal lower extremity DVT or patients with proximal DVT that fails to respond to initial anticoagulation
    
    
• vena cava filter
  • used when anticoagulation is absolutely contraindicated in patients with newly diagnosed proximal DVT
    • retrievable filter should be removed rapidly as soon as contraindications are resolved and anticoagulation can be started (2,3)
      
      

NICE suggest (4):

• measure baseline full blood count, renal and hepatic function, PT and APTT but start anticoagulation before results available. Review and if necessary act on results within 24 hours
• offer anticoagulation for at least 3 months. Take into account contraindications, comorbidities and the person’s preferences
• after 3 months (3 to 6 months for active cancer) assess and discuss the benefits and risks of continuing, stopping or changing the anticoagulant with the person. See long-term anticoagulation for secondary prevention(linked item)

Anticagulatant considerations considered in terms of:

• No renal impairment, active cancer, antiphospholipid syndrome or haemodynamic instability
  • offer apixaban or rivaroxaban
  • if neither suitable, offer one of:
    • LMWH for at least 5 days followed by dabigatran or edoxaban
    • LMWH and a VKA for at least 5 days, or until INR at least 2.0 on 2 consecutive readings, then a VKA alone
      
      
• Renal impairment (CrCl estimated using the Cockcroft and Gault formula; see the BNF)
  
  • CrCl 15 to 50 ml/min, offer one of:
    • apixaban
    • rivaroxaban
    • LMWH for at least 5 days then
      • edoxaban or
      • dabigatran if CrCl >= 30 ml/min
    • LMWH or UFH and a VKA for at least 5 days, or until INR at least 2.0 on 2 consecutive readings, then a VKA alone
      
      
  • CrCl < 15 ml/min, offer one of:
    • LMWH
    • UFH
    • LMWH or UFH and a VKA for at least 5 days, or until INR at least 2.0 on 2 consecutive readings, then a VKA alone
  • Note cautions and requirements for dose adjustments and monitoring in SPCs. Follow local protocols, or specialist or MDT advice
• Active cancer (receiving antimitotic treatment, diagnosed in past 6 months, recurrent, metastatic or inoperable
  
  • Consider a DOAC
  • if a DOAC is not suitable, consider one of:
    • LMWH
    • LMWH and a VKA for at least 5 days or until INR at least 2.0 on 2 consecutive readings, then a VKA alone
  • Offer anticoagulation for 3 to 6 months. Take into account tumour site, drug interactions including cancer drugs, and bleeding risk
• Antiphospholipid syndrome (triple positive, established diagnosis)
  • Offer LMWH and a VKA for at least 5 days or until INR at least 2.0 on 2 consecutive readings, then a VKA alone

Reference:

• (1) Wang K-L, Chu P-H, Lee C-H, et al. Management of Venous Thromboembolisms: Part I. The Consensus for Deep Vein Thrombosis . Acta Cardiologica Sinica. 2016;32(1):1-22
• (2) Mazzolai L et al. Diagnosis and management of acute deep vein thrombosis: a joint consensus document from the European society of cardiology working groups of aorta and peripheral circulation and pulmonary circulation and right ventricular function. Eur Heart J. 2017 Feb 17.
• (3) Streiff MB et al. Guidance for the treatment of deep vein thrombosis and pulmonary embolism. J Thromb Thrombolysis. 2016;41(1):32-67.
• (4) National Institute for Health and Care Excellence (NICE) 2020. Venous thromboembolic diseases: diagnosis, management and thrombophilia testing