10.7 Anticoagulants + Bridging

Question 1

You are asked to anaesthetise an 84-year-old patient with a fractured
neck of femur, who is normally on warfarin, and has an INR of 3.5.

What are your main concerns regarding perioperative anticoagulation?

Answer 1

• Indication for warfarin:
  AF? heart valve? recurrent thromboembolic disease?
• Correct of coagulopathy prior to surgery –
  consider prothrombin complex concentrate, fresh frozen plasma, vitamin K
• Not emergent surgery although should avoid prolonged delay
• May permit neuraxial anaesthesia techniques
• Bridging therapy will depend on indication for warfarin and patient assessment
• Other fall-related complications, especially head injury, should be excluded

Question 2

What is warfarin?

How does it work?

Answer 2

• Synthetic coumarin derivative
• Antagonises vitamin K metabolism to deplete active vitamin K,
  inhibiting the vitamin K-dependent synthesis of
  clotting factors II, VII, IX, and X

Question 3

What is unfractionated heparin?

How does it work?

Answer 3

• A mixture of sulphated glycosaminoglycans of
  variable lengths and molecular weights
  (3,000 to 30,000 Daltons)
• Activates antithrombin III (AT) to inhibit clotting factors IIa, IXa, Xa, XIa, and XIIa

Question 4

What is the difference between unfractionated and fractionated heparin?

Why would you choose one over the other?

Answer 4

• Fractionated or low-molecular-weight heparin (LMWH)
  is a mixture of heparin salts with
  an average molecular weight of less than 8,000 Daltons
• AT activated by LMWH selectively inhibits factor XIa

Question 5

Advantages of LMWH

Answer 5

• For prophylactic doses,
  less frequent subcutaneous dosing
• For treatment doses,
  no requirement for continuous intravenous infusion
  and regular APTT monitoring
• Lower risk of heparin-induced thrombocytopaenia (HIT)

Question 6

Advantages of heparin

Answer 6

• As an intravenous infusion, therapeutic levels can be rapidly attained
• Ability to monitor effect using APTT
• Rapid elimination once infusion stopped
• May be reversed with protamine (less effective for LMWHs)

Question 7

What other drugs for thromboprophylaxis are available?

Answer 7

• Fondaparinux—synthetic analogue of the pentasaccaride fragment of heparin
• Danaparoid—heparinoid
• Lepirudin—direct thrombin inhibitor
• Dabigatran—direct thrombin inhibitor
• Rivaroxaban—direct factor Xa inhibitor

Question 8

How will you reverse the effect of warfarin?

Answer 8

Target INR for regional anaesthesia is 1.5, but higher INR might be acceptable for GA and surgery.

• Stop warfarin.
  The effect of warfarin will reverse over a period of 2 to 4 days.
• Vitamin K is a specific antidote for warfarin.
  Oral or intravenous administration of vitamin K can be expected to reverse warfarin
  –4 to 6 hours after administration.

° oral vitamin K is the treatment of choice unless very rapid reversal of
anticoagulation is required.
For most patients, 1–2 mg of oral vitamin K is sufficient,
but if the INR is particularly high, 5 mg orally may be required.

° A sustained response is achieved with intravenous vitamin K 5–10 mg.
Initial effect may appear in 2 to 4 hours,
and multiple doses may be needed.

• Prothrombin Complex Concentrate (PCC) (e.g. Octaplex/Beriplex) is
  derived from virally irradiated human plasma,
  thus reducing the risk of viral transmission,
  and contains the clotting factors II, VII, IX, and X. PCCs
  provide immediate reversal of warfarin,
  but the effect will begin to wear off after 6–12 hours.

Earlier PCCs were associated with a significant thrombotic risk due to the
presence of phospholipids and activated clotting factor VII, as well as protein
C & S, but the newer products carry a very low risk.