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Anticoagulation and VTE

Warfarin

Vitamin K antagonist – reduces production of Vitamin K dependent clotting factors (2, 7, 9 and 10) in the liver, and protein C and protein S.

Takes time to deplete current factors before therapeutically anticoagulated.

Pros – reversible, can be monitored, OK in renal failure, cheap

Cons – needs to be monitored, drug interactions +, takes time to work and may have initial prothrombotic period

 

Reversal of warfarin:

  • Vitamin K 1 – 10 mg oral or IV (5 mg typical dose); takes 6 – 8 hours
  • Prothrombinex – rapidly replaces clotting factors, useful in urgent settings; also give vitamin K for medium term effect
  • FFP – useful if prothrombinex unavailable or contra-indicated

 

DOACs / NOACs

Apixaban and rivaroxaban directly inhibit factor Xa

Dabigatran directly inhibits thrombin

Pros – do not require monitoring, become therapeutic quickly within a few hours

Cons – become therapeutic quickly, may be dependent on renal function, difficult to reverse

 

Reversal of DOACs:

  • Multidisciplinary management with haematology, cardiology, anaesthetist, ICU
  • Stop and withhold the drug
  • Check renal function – may affect washout period – and check coags/Xa levels/ROTEM if available
  • Control bleeding if able – surgically or via IR
  • Maintain hydration and replace with blood products as appropriate
  • Activated charcoal an option if drug was taken within 2 hours (except for rivaroxaban)
  • Dabigatran has a monoclonal antibody for reversal
    • Idarucizumab
    • Dabigatran can also be dialysed off
  • Apixaban and rivaroxaban are protein bound and so can’t be dialysed off, and have no reversal agents available currently
  • Prothrombinex can be used, and tranexamic acid

 

Aspirin

Irreversibly inhibits COX-1, which blocks thromboxane A2 synthesis and prevents platelet aggregation

Continuing aspirin might increase risk of bleeding but not severity or need for intervention

 

Clopidogrel

Binds to and blocks ADP receptors on platelets

 

Ticagrelor

Inhibits P2Y12 receptors, which are a subset of ADP receptors

Recommendations for dual antiplatelets after coronary stents:

  • Drug eluting stents higher risk and often need DAPT for up to 12 months
  • Bare metal stents lower risk
    • Minimum 4 weeks
    • Defer elective surgery for minimum 6 weeks but preferably 3 months
  • ?May be reversed with platelet transfusion

 

Heparin

Acts via antithrombin III to inactivate thrombin, factor Xa and others

Pros – short acting, reversible, independent of renal function, safe in breastfeeding and pregnancy

Cons – injection, intensive monitoring needed with variable levels, risk of HITS

Reversal of heparin:

  • Protamine

 

HITS (heparin induced thrombocytopaenia syndrome):

  • Fall in platelet count > 50 % within 2 weeks of exposure to heparin
  • Immune mediated – antibodies against heparin form which then activate platelets, causing the activation of platelets, resulting in consumption of platelets and increased clot risk
  • 1 – 3 % of patients may be susceptible
  • Management
    • Stop all heparin exposure
    • Manage with another parenteral anticoagulant (e.g. bivalirudin, fondaparinux) until platelets normalise

 

Clexane (low molecular weight heparin)

Also acts on antithrombin III with more predictable onset and more focussed action against factor Xa

Pros – no monitoring required, long half life vs. heparin (OD cf. BD), can be monitored with Xa levels if needed

Cons – injectable, dependent on renal function, less reversible than heparin, dependent on ideal body weight

Protamine reverses 60 – 75 %

 

 

Assessing peri-operative risk (patients on thinners)

Need to weigh up risks of bleeding vs underlying risks of clotting or complications.

Multidisciplinary management – discussion with peri-operative medicine, cardiology, haematology, anaesthetists etc.

What is the risk of bleeding specific to the procedure and the patient?

What is the risk of clots specific to the patient?

 

If there is high risk of thromboembolic complications – (AF with CHADSVASc > 4, mechanical mitral valve, recent VTE <  3 months, thrombophilia) – bridge anticoagulation with heparin/clexane

If intermediate risk – consider bridging for low bleeding risk procedures

If low risk – should be ok to withhold.

 

How long to wash out anticoagulation:

Rivaroxaban – 48 hours, or 72 hours if eGFR < 30                                        (5 days if cirrhosis)

Apixaban – 48 hours, or 72 hours if eGFR < 50                                        (5 days if cirrhosis)

Dabigatran – 72 hours, or 4 days if eGFR < 50, or 5 days if eGFR < 30

Warfarin – Stop 5 days prior, check INR day prior or day of surgery

Heparin infusion – 6 hours prior (no bolus on recommencing)

Clexane -Last treatment dose 24 hours prior, last prophylactic dose 12 hours prior

Clopidogrel or ticagrelor – 5 days minimum

 

Restarting anticoagulation:

  • 50 % of major bleeds occur between theatre and the next morning
  • 90 % of major bleeds occur in first four days
  • Risk of VTE is constant for the first four weeks post-operatively
  • EAU guidelines suggest restarting when bleeding is no longer a serious risk – typically four days post surgery

 

Risk assessment for VTE:

 

Risk factors:

  • Age > 75 years
  • Personal history VTE
  • Family history VTE
  • BMI > 35
  • Surgical patients with major abdominal or pelvic surgery for cancer
  • Critically ill patients
  • Isolated lower limb immobilisation
  • Venous compression
  • IBD
  • Central lines
  • Trauma
  • Pregnancy
  • “Cancer”

 

 

Contra-indications for mechanical prophylaxis:

  • Severe peripheral arterial disease / ulcers
  • Recent skin graft
  • Peripheral arterial bypass surgery
  • Severe leg oedema or pulmonary oedema from heart failure
  • Allergy
  • Other local skin issues
  • Patients admitted for stroke (can have SCDs)
  • Severe peripheral neuropathy (can have SCDs)

 

Contra-indications for chemical prophylaxis:

  • Already anticoagulated
  • Major bleeding
  • Thrombocytopaenia (platelets < 50)
  • Recent bleeding
  • Uncontrolled hypertension > 230 mmHg

For all patients:

  • Assess risk of VTE based on risk factors
  • Assess risk of bleeding
  • Conduct a risk assessment and document same
  • Usually manage with prophylactic clexane or heparin plus TEDS whilst in hospital

 

Indications for extended prophylaxis up to 4 weeks (EAU guidelines)

  • Radical cystectomy
  • RALP + LND, if intermediate-high risk for VTE
  • Open radical prostatectomy
  • Open nephrectomies
  • Lap partial/nephrectomy, if high risk
  • RPLND
  • High risk patients only for other procedures – e.g. PCNL, open prolapse surgery