In this article perioperative anticoagulation refers to balancing the risk of bleeding and the risk of a blood clot in patients taking anticoagulants who undergo elective surgery.

Management will depend on:

  • The medication prescribed to prevent thrombosis;
  • The risk of thrombosis; and
  • The risk of bleeding from the surgery.

Warfarin

Warfarin is often regarded as the most challenging antithrombotic agent to manage perioperatively, primarily due to its long half-life. The Australasian Society of Thrombosis and Haemostasis released a consensus statement on the subject, which gives some guidance in management. The first aspect in need of consideration is the risk of bleeding from surgery. If the risk is low (e.g. minor dental surgery or minor dermatological procedures), warfarin can be continued without disruption.

If the risk of bleeding from surgery is high, warfarin therapy will need to be interrupted, and the risk of thrombosis, while the patient is not taking warfarin, needs to be considered. After cessation of warfarin, it takes a significant amount of time for the INR (International Normalised Ratio – a measure of how long it takes the blood to clot) to fall to a level at which it is acceptable to perform surgery. During this time the INR is not in the therapeutic range, putting the patient at an increased risk of thrombosis.

The patient may require ‘bridging therapy’ with a shorter acting anticoagulant in the days before surgery which can be stopped suddenly to cover the patient during this period. This shorter acting anticoagulant may also be required in the days after surgery until the patient’s INR returns to a therapeutic level. There is much disagreement among health professionals regarding which patients should receive bridging therapy. This decision is generally based on the patient’s baseline risk of thrombosis.

If the patient has a low baseline risk of thrombosis, stopping warfarin 3-5 days before surgery will usually be sufficient time for the INR to fall low enough for surgery to be performed, and in these circumstances anticoagulant therapy during this time is generally not required. However, if the patient has a high risk of thrombosis, bridging is recommended. A shorter acting agent should be started 2-3 days before surgery, or when the INR is no longer therapeutic.

The agents of choice are unfractionated heparin, or low molecular weight heparin (e.g. enoxaparin). Heparin should be stopped 4-6 hours before surgery, while enoxaparin should be stopped 12-24 hours before surgery. Patients will also need thromboprophylaxis after surgery as per usual practice. The decision of which patients are classed as ‘low’ or ‘high’ baseline risk of thrombosis and therefore which patients should receive bridging therapy, is at the discretion of each physician, and varies markedly between prescribers.

Further information on the perioperative management of warfarin can be found on the Medical Journal of Australia website under “Warfarin reversal: consensus guidelines, on behalf of the Australasian Society of Thrombosis and Haemostasis”.

Newer Oral Anticoagulants

This issue will occur less frequently with the introduction of the newer anticoagulants rivaroxaban (Xarelto®) and dabigatran (Pradaxa®), which are now sometimes used where warfarin was once the only option. Both these agents have a much shorter half-life than warfarin, which makes perioperative management easier. However, as they are new, there is limited data on the subject.

Dabigatran has a half-life of approximately 12-17 hours. In patients with normal renal function, the product information suggests dabigatran should be stopped at least 24 hours before standard invasive procedures. However, in cases where the patient is likely to be at a higher risk of bleeding (e.g. major surgery), or when there is delayed clearance due to renal impairment, stopping dabigatran up to 2-4 days before surgery should be considered.

Rivaroxaban has a half-life of approximately 5-13 hours, with younger patients generally having a shorter half-life (5-9 hours) and the elderly longer (11-13 hours). The product information suggests that rivaroxaban should be stopped at least 24 hours prior to surgery if possible.

However individual patient factors should be taken into account and the benefit or risk assessment may indicate rivaroxaban should be stopped even earlier, particularly where the patient is at very high risk of bleeding, or in major surgery where complete haemostasis is required.

Most people taking dabigatran and rivaroxaban will not require bridging therapy before surgery. The expert opinion is that provided the patient is of normal renal function and low bleeding risk these anticoagulants can be safely stopped for surgery for up to 48 hours. A minority of patients with special circumstances (e.g. renal impairment), may require bridging before surgery. After surgery however, bridging is not required as both dabigatran and rivaroxaban have an immediate onset of action, and can be given at the time when heparin would normally be given.

For patients on warfarin, the INR is commonly used before surgery to check that warfarin has been cleared from the body. However, the INR result does not have an established correlation to the anticoagulative ability, or lack thereof, of either rivaroxaban or dabigatran. Therefore INR should not be used to determine a patient’s bleeding risk, and hence suitability for surgery, if the patient has been taking either of those newer medications.

Another factor to consider is the reversibility of anticoagulation. The effect of warfarin can be reversed using vitamin K, however there is currently no product available which can reverse the pharmacodynamic effect of either rivaroxaban or dabigatran. Prothrombin complex concentrate (ProthrombinexTM-HT), recombinant blood factor VII (NovoSeven® RT) and fresh frozen plasma have been used for immediate symptomatic management of clinically significant bleeding.

However, while non-clinical experimental studies have shown that prothrombin complex concentrate and factor VII reduce the anticoagulation effect of rivaroxaban and dabigatran, there is currently no data to confirm this effect in patients.

Conclusion

If interruption of anticoagulant therapy is required for surgery, this should always be done in conjunction with the medical practitioner who instigated the therapy. There are limited guidelines for the management of perioperative anticoagulation regarding warfarin and the newer drugs, dabigatran and rivaroxaban. If warfarin is stopped for surgery, bridging therapy with a short acting anticoagulant may be required.

While the newer drugs have shorter half-lives compared to warfarin, management is complicated by the lack of evidence regarding how long before surgery they should be ceased, and also inability to reverse their anticoagulant effect.

References:

  1. Baker R, Coughlin P, Salem H, Gallus A, Harper P, Wood E. Warfarin reversal: consensus guidelines, on behalf of the Australasian Society of Thrombosis and Haemostasis. Med J Aust 2004; 181 (9): 492-497.
  2. Pradaxa (dabigatran) Australian approved product information. North Ryde: Boehringer Ingelheim Pty Ltd. Approved 24 November 2008, amended 18 April 2012.
  3. Xarelto (rivaroxaban) Australian approved product information. Pymble: Bayer Australia Ltd. Approved 24 November 2008, amended 3 April 2012.
  4. National Prescribing Service. Good Anticoagulant Practice. NPS Medicinewise 2013; February.
  5. Perioperative and periprocedural management of patients taking antithrombotic therapy. [revised 2012 Feb] In: eTG complete [Internet]. Melbourne: Therapeutic Guidelines limited; 2013 March. Available from http://www.online.tg.org.au/complete/tablet/tgc/cvg6/3533.htm?rhsearch=Perioperative. Accessed 18 March 2013.

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