Antithrombotics & Surgery

Content by Dr Mark Crowther.

THIS GUIDELINE IS NOT TO BE USED FOR THE FOLLOWING PATIENTS

1. PATIENTS WITHIN 6 WEEKS OF A VENOUS THROMBOSIS – DISCUSS WITH HAEMATOLOGY
2. PATIENTS WITH A PROSTHETIC HEART VALVE – DISCUSS WITH CARDIOLOGY
3. PATIENTS WITHIN 1 YEAR OF CORONARY ARTERY STENTING – DISCUSS WITH CARDIOLOGY

General Notes

1. Stopping any anticoagulant or antiplatelet agent will increase the patients risk of thrombosis and a risk/balance assessment should be made and discussed with the patient
2. Liaison with Blood Bank is crucial, especially where platelet transfusions are required as they keep limited stock, procedures may need to be delayed until platelets are sourced
3. Reversal of anticoagulation is only one aspect of the management of bleeding – remember local control, optimisation of pH, temperature, platelet count and haemoglobin, and if necessary the Major Haemorrhage Protocol.
4. Tranexamic acid should not be given if DIC is suspected or haematuria
5. Remember to restart antiplatelets/anticoagulants when bleeding risk past and consider bridging with prophylactic low molecular weight heparin
6. See end of document for specific advice for neuroaxonal anaesthesia and lumbar punctures
7. This Guideline is based on the:
   1.  British Society of Haematology Guidelines on ‘Peri‐operative management of anticoagulation and antiplatelet therapy’ and ‘Guideline on the management of bleeding in patients on antithrombotic agents’,
   2.  the NHS Scotland consensus statement on ‘Consensus Statement for Management of Anticoagulants and Antiplatelet drugs in Patients with Hip Fracture’
   3. Association of Anaesthetists of Great Britain & Ireland The Obstetric Anaesthetists’ Association Regional Anaesthesia UK Guideline ‘Regional anaesthesia and patients with abnormalities of coagulation’

Aspirin

1. Onset of action <1 hour (3-4 hours enteric coated)
2. Length of effect after discontinuation 5–7 days
3. Routine surgery – for most surgery no need to stop (including neuroaxonal anaesthesia), for surgery with very high bleeding risk stop 7 days before
4. Urgent surgery – for most surgery no action required, for surgery with very high bleeding risk consider stopping aspirin, give 1g iv tranexamic acid prior to surgery and 1-2 units of platelets if excessive bleeding

Clopidogrel

1. Onset of action 2 hours
2. Length of effect after discontinuation 5–7 days (has effect on transfused platelets as well for 12 hours after last dose)
3. Routine surgery – stop 7 days before
4. Urgent non-orthopaedic surgery –
   1. Stop clopidogrel
   2. Neuroaxonal anaesthesia contraindicated for 7 days after last dose
   3. Low bleeding risk surgery can proceed as normal and consider tranexamic acid if bleeding
   4. High bleeding risk surgery should be delayed as long as possible after last dose of clopidogrel. Give 1g iv tranexamic acid prior to surgery. If excessive bleeding and last dose clopidogrel >12 hours previously give 2 unit platelet transfusion
5. Urgent orthopaedic surgery
   1. Stop clopidogrel
   2. Neuroaxonal anaesthesia contraindicated for 7 days after last dose
   3. Low bleeding risk surgery can proceed as normal and consider tranexamic acid if bleeding
   4. High bleeding risk surgery (platelets<100, intramedullary nail, pathological fracture, periprosthetic fracture) delay until 24 hours after last dose of clopidogrel. Consider 1g iv tranexamic acid and 2 unit platelet transfusion if excessive bleeding.

Clopidogrel and Aspirin (Dual Antiplatelet Therapy)

1. Onset of action < 1 hour
2. Length of effect after discontinuation 5–7 days
3. Routine surgery – stop clopidogrel 7 days before but continue aspirin throughout unless very high risk of bleeding then stop 7 days before, neuroaxonal anaesthesia safe while on aspirin
4. Urgent non-orthopaedic surgery –
   1. Stop clopidogrel
   2. Neuroaxonal anaesthesia contraindicated for 7 days after last dose of clopidogrel
   3. Stop aspirin if high bleeding risk
   4. Low bleeding risk surgery can proceed as normal and consider 1g iv tranexamic acid if bleeding
   5. High bleeding risk surgery should be delayed as long as possible after last dose of clopidogrel. Give 1g iv tranexamic acid prior to surgery. If excessive bleeding and last dose clopidogrel >12 hours previously give 2 unit platelet transfusion
5. Urgent orthopaedic surgery
   1. Stop Clopidogrel
   2. Neuroaxonal anaesthesia contraindicated for 7 days after last dose of clopidogrel
   3. Delay surgery until 24 hours after last dose of Clopidogrel. Consider tranexamic acid and 2 unit platelet transfusion if excessive bleeding.

Dipyridamole

1. Limited information available for this drug
2. Onset of action < 1 hour
3. Length of effect after discontinuation 24 hours
4. Routine surgery – stop 24 hours before
5. Urgent non-orthopaedic surgery –
   1. Stop dipyridamole
   2. Neuroaxonal anaesthesia contraindicated for 24 hours after last dose
   3. Low bleeding risk surgery can proceed as normal and consider 1g iv tranexamic acid if bleeding
   4. High bleeding risk surgery should be delayed as long as possible after last dose of dipyridamole. Give 1g iv tranexamic acid prior to surgery. If excessive bleeding give 2 unit platelet transfusion.
6. Urgent orthopaedic surgery
   1. Stop dipyridamole
   2. Neuroaxonal anaesthesia contraindicated for 24 hours after last dose
   3. Low bleeding risk surgery can proceed as normal and consider tranexamic acid if bleeding
   4. High bleeding risk surgery (platelets<100, intramedullary nail, pathological fracture, periprosthetic fracture) delay until 24 hours after last dose of dipyridamole. Consider tranexamic acid and 2 unit platelet transfusion if excessive bleeding.

Dipyridamole/Aspirin (Dual Antiplatelet Therapy)

1. Limited information available for this drug combination
2. Onset of action < 1 hour
3. Length of effect after discontinuation 5-7 days
4. Routine surgery – stop dipyridamole 24 hours before but continue aspirin throughout unless very high risk of bleeding then stop 7 days before, neuroaxonal anaesthesia safe while on aspirin
5. Urgent non-orthopaedic surgery –
   1. Stop dipyridamole
   2. Stop aspirin if high bleeding risk
   3. Low bleeding risk surgery can proceed as normal and consider 1g iv tranexamic acid if bleeding
   4. High bleeding risk surgery should be delayed as long as possible after last dose of dipyridamole. Give 1g iv tranexamic acid prior to surgery. If excessive bleeding give 2 unit platelet transfusion.
   5. Neuroaxonal anaesthesia contraindicated for 24 hours after last dose
6. Urgent orthopaedic surgery
   1. Stop dipyridamole
   2. Neuroaxonal anaesthesia contraindicated for 24 hours after last dose
   3. Delay until 24 hours after last dose of dipyridamole. Consider tranexamic acid and 2 unit platelet transfusion if excessive bleeding.

Prasugrel

1. Limited information available for this drug
2. Onset of action 1 hour
3. Length of effect after discontinuation 5-7 days
4. Routine surgery as per clopidogrel
5. Urgent surgery as per clopidogrel

Ticagrelor

1. Limited information available for this drug
2. Onset of action 1 hour
3. Length of effect after discontinuation 3-5 days
4. Routine surgery as per clopidogrel
5. Urgent surgery as per clopidogrel
6. Bleeding as per clopidogrel

Alteplase, Tenecteplase, Reteplase, Streptokinase, Urokinase

1. Onset of action minutes
2. Length of effect after discontinuation 48 hours
3. Routine surgery delay for >48 hours
4. Urgent surgery if cannot be delayed for 48 hours after administration:
   1. Stop infusion of fibrinolytic drugs and other antithrombotic drugs
   2. Administer FFP 12 ml/kg
   3. Administer iv tranexamic acid 1 g tds
   4. Check fibrinogen – if there is depletion of fibrinogen, administer cryoprecipitate or fibrinogen concentrate
   5. Discuss with Haematology

Warfarin and Other Vitamin K Antagonists

THIS GUIDELINE DOES NOT INCLUDE THE FOLLOWING PATIENTS:

• PATIENTS WITHIN 6 WEEKS OF A VENOUS THROMBOSIS – DISCUSS WITH HAEMATOLOGY
• PATIENTS WITH A PROSTHETIC HEART VALVE – DISCUSS WITH CARDIOLOGY

1. Onset of action 24 hours
2. Length of effect after discontinuation 5 days
3. Monitored using INR
4. Routine surgery where reversal is required
   1. Pre-op
      1. Stop warfarin 5 days before surgery
      2. Check INR afternoon before surgery, if INR>1.4 give 1mg oral vitamin K and repeat INR prior to surgery
   2. Post-op
      1. Commence prophylactic low molecular weight heparin when haemostasis is secure
      2. Recommence warfarin at normal dose when eating
      3. Continue low molecular weight heparin until INR therapeutic for 2 days
5. Urgent surgery where reversal is required
   1. Pre-op
      1. Give 10mg iv vitamin K
      2. If surgery is required in less than 6 hours give Beriplex (discuss with Haematology and be aware Beriplex carries a 20% risk of unwanted thrombosis)
      3. Recheck INR prior to surgery and discuss with Haematology if >1.4
   2. Post-op
      1. Commence prophylactic low molecular weight heparin when haemostasis is secure
      2. Recommence warfarin at normal dose when eating
      3. Continue low molecular weight heparin until INR therapeutic for 2 days

Apixaban

1. Onset of action 2-4 hours
2. Length of effect after discontinuation 12-24 hours assuming GFR>30ml/min
3. Monitored using apixaban levels
4. Routine surgery if full reversal required:
   1. If GFR>30 stop 48 hours before
   2. If GFR<30 stop 72 hours before
   3. If minor procedure/low bleeding risk can just miss dose prior to surgery.  Post-op consider prophylactic low molecular weight heparin when haemostasis is secure then restarting apixaban when eating and >12 hours from last dose of low molecular weight heparin
5. Urgent surgery where reversal is required
   1. If last dose taken in previous 4 hours consider activated charcoal
   2. If last dose taken in previous 12 hours:
      1. Assume therapeutic anticoagulation
      2. Delay surgery as long as possible
      3. If surgery cannot be delayed give 1g iv tranexamic acid and proceed. Give Beriplex (discuss with Haematology) if significant bleeding.
   3. If last dose taken >12 hours previously – Check apixaban level if:
      1. <25ng/ml unlikely to be significant anticoagulant activity and can proceed as normal.
      2. >25ng/ml repeat every 3 hours and when <25ng/ml can proceed as normal. If surgery cannot be delayed give 1g iv tranexamic acid and proceed. Give Beriplex (discuss with Haematology) if significant bleeding.
   4. Consider prophylactic low molecular weight heparin when haemostasis is secure then restarting apixaban when eating and >12 hours from last dose of low molecular weight heparin

Edoxaban

1. Onset of action 2-4 hours
2. Length of effect after discontinuation 12-24 hours assuming GFR>30ml/min
3. Monitored using edoxaban levels
4. Routine surgery if full reversal required:
   1. If GFR>30 stop 48 hours before
   2. If GFR<30 stop 72 hours before
   3. If minor procedure/low bleeding risk can just miss dose prior to surgery.
5. Post-op consider prophylactic low molecular weight heparin when haemostasis is secure then restarting edoxaban when eating and >12 hours from last dose of low molecular weight heparin
6. Urgent surgery where reversal is required
   1. If last dose taken in previous 24 hours:
      1. Assume therapeutic anticoagulation
      2. Delay surgery as long as possible
      3. If surgery cannot be delayed give 1g iv tranexamic acid and proceed. Give Beriplex (discuss with Haematology) if significant bleeding.
   2. If last dose taken >24 hours previously – Check edoxaban level if:
      1. <25ng/ml unlikely to be significant anticoagulant activity and can proceed as normal.
      2. >25ng/ml repeat every 3 hours and when <25ng/ml can proceed as normal. If surgery cannot be delayed give 1g iv tranexamic acid and proceed. Give Beriplex (discuss with Haematology) if significant bleeding.
   3. Consider prophylactic low molecular weight heparin when haemostasis is secure then restarting edoxaban when eating and >12 hours from last dose of low molecular weight heparin

Rivaroxaban

1. Onset of action 2-4 hours
2. Length of effect after discontinuation 12-24 hours assuming GFR>30ml/min
3. Monitored using rivaroxaban levels
4. Routine surgery if full reversal required:
   1. If GFR>30 stop 48 hours before
   2. If GFR<30 stop 72 hours before
   3. If minor procedure/low bleeding risk can just miss dose prior to surgery.  Post-op consider prophylactic low molecular weight heparin when haemostasis is secure then restarting rivaroxaban when eating and >12 hours from last dose of low molecular weight heparin
5. Urgent surgery where reversal is required
   1. If last dose taken in previous 24 hours:
      1. Assume therapeutic anticoagulation
      2. Delay surgery as long as possible
      3. If surgery cannot be delayed give 1g iv tranexamic acid and proceed. Give Beriplex (discuss with Haematology) if significant bleeding.
   2. If last dose taken >24 hours previously – Check rivaroxaban level if:
      1. <25ng/ml unlikely to be significant anticoagulant activity and can proceed as normal.
      2. >25ng/ml repeat every 3 hours and when <25ng/ml can proceed as normal. If surgery cannot be delayed give 1g iv tranexamic acid and proceed. Give Beriplex (discuss with Haematology) if significant bleeding.
   3. Consider prophylactic low molecular weight heparin when haemostasis is secure then restarting rivaroxaban when eating and >12 hours from last dose of low molecular weight heparin

Dabigatran

1. Onset of action 3 hours
2. Length of effect after discontinuation 12-24 hours assuming GFR60ml/min
3. Monitored using dabigatran levels
4. Routine surgery if full reversal required stop:
   1. 48 hours if GFR>60mls/min
   2. 72 hours if GFR 50-80
   3. 96 hours if GFR 30-50
5. If minor procedure/low bleeding risk can just miss dose prior to surgery. Consider prophylactic low molecular weight heparin when haemostasis is secure then restarting dabigatran when eating and >12 hours from last dose of low molecular weight heparin
6. Urgent surgery where reversal is required
   1. If last dose taken in previous 24 hours:
      1. Consider activated charcoal if last dose < 4 hours
      2. Assume therapeutic anticoagulation
      3.  Delay surgery as long as possible
      4.  If surgery cannot be delayed give 5g iv idarucizumab (discuss with Haematology) then proceed
   2.  If last dose taken >24 hours previously – Check dabigatran level if:
      1. <25ng/ml unlikely to be significant anticoagulant activity and can proceed as normal.
      2. >25ng/ml give 5g iv idarucizumab (discuss with Haematology) then proceed
   3. Consider prophylactic low molecular weight heparin when haemostasis is secure then restarting dabigatran when eating and >12 hours from last dose of low molecular weight heparin

Unfractionated Intravenous Heparin

1. Onset of action – minutes
2. Length of effect after discontinuation – 1 – 2 hours
3. Monitored using APTTr
4. Routine surgery stop 2 hours prior to surgery, check APTTr prior to surgery and if normal proceed.
5. Urgent surgery if:
   1. can wait 2 hours treat as routine surgery
   2. if cannot wait 2 hours stop infusion and give iv protamine (1mg per 80-100 units UFH administered in the previous two hours; max 50mg and no faster than 5mg/min) then recheck APTTr

Low Molecular Weight Heparin (LMWH)

1. Onset of action – 2 hours
2. Length of effect after discontinuation – prophylactic dose 12 hours, treatment dose 24 hours assuming GFR>30ml/min
3. Monitored using anti-Xa assay
4. Routine surgery stop treatment dose 24 hours prior or prophylactic dose 12 hours prior
5. Urgent surgery
   1. if can wait treat as routine surgery
   2. if cannot wait and last dose of LMWH within therapeutic window:
      1. check anti-Xa level if <0.1U/ml unlikely to be significant anticoagulation present
      2. < 8 hours – give 1mg iv protamine per 100 anti-Xa units of LMWH at an infusion rate of 5mg/min with maximum dose of 50mg
      3. >8 hours – give 0.5mg iv protamine per 100 anti-Xa units of LMWH at an infusion rate of 5mg/min with maximum dose of 50mg
      5. give 1g iv tranexamic acid prior to surgery
      6. consider further doses of protamine if further bleeding
      7. consider 90micrograms/kg recombinant FVIIa (NovoSeven) if life-threatening haemorrhage (discuss with Haematology)

Fondaparinux

1. Onset of action – 2 hours
2. Length of effect after discontinuation – prophylactic dose 12 hours, treatment dose 24 hours
3. Monitored using anti-Xa assay
4. Routine surgery stop treatment dose 48 hours prior or prophylactic dose 24 hours prior
5. Urgent surgery
   1. if can wait treat as routine surgery
   2. if cannot wait give 1g iv tranexamic acid
   3. check anti-Xa level if <0.1U/ml unlikely to be significant anticoagulation present
   4. consider 90micrograms/kg recombinant FVIIa (NovoSeven) if life-threatening haemorrhage (discuss with Haematology)