Perioperative management of anticoagulant drugs in the surgical patient

Introduction

Anticoagulation in patients undergoing surgical procedures is challenging.

Interrupting anticoagulation for a procedure increases the risk of thromboembolism.

Surgery has associated bleeding risks that are increased by the anticoagulants administered for thromboembolism prevention.

First of all, we are going to explain the coagulation cascade in a simple way.

Damaged blood vessel:

Injury to vessel lining triggers the release of clotting factors.

This step changes the prothrombin into thrombin.  

Formation of platelet plug:

Vasoconstriction limits blood flow and platelets form a sticky plug.

With the presence of thrombin, the fibrinogen changes into fibrin.  

Development of clot:

Fibrin strands adhere to the plug to the form an insoluble clot.

Exists a lot of blood thinners that works in this cascade of coagulation.

Like Warfarin, Direct thrombin inhibitor, Factor Xa inhibitors, etc.

In the case of the Warfarin:

• Inhibits the vitamin K-dependent clotting factors II, VII, IX and X, as well as the t iregulatory factors protein C, protein S, and protein Z
• It takes several days until the anticoagulant effect is reduced and then reestablished perioperatively.

It is used in these pathologies.

This is how the warfarin affects blood clotting.

Warfarin reduces the body’s ability to make vitamin K, which interferes with protein creation.

Lower levels of clotting protein makes blood cells less likely to clot.

The newer direct oral anticoagulants:

• Direct thrombin inhibitor Dabigatran.
• Factor Xa inhibitors Rivaroxaban, Apixaban, Edoxaban.
• Have shorter half-lives, easier to discontinue and resume rapidly.
• But the direct factor Xa inhibitors lack an approved drug-specific antidote.

This raises concerns about treatment of bleeding and management of patients who require an urgent surgery.

This figure shows the Factors Xa inhibitors: Apixaban and Rivaroxaban and the direct thrombin inhibitors in the factor II : Dabigatran.

Comparison of Warfarin vs Heparin

ESTIMATING THROMBOEMBOLIC AND HEMORRHAGIC RISK?

Annual risk thromboembolic and hemorrhagic.

Very high thrombotic risk:

Patients with a risk of more than 10 %, with a mitral valve prosthesis, recent stroke , atrial fibrillation, and recent VTE.

High bleeding risk procedure:

BleedMAP

This is the stratification of perioperative hemorrhagic risk, based on four predictive factors:

• History of bleeding from patient
• Be a carrier of mechanical mitral valve
• Have an active neoplasm
• Low platelet count

BleedMAP => Hemorrhage

HAS – Bleeding score

Score ≥3 was the most predictive variable for bleeding

DOACs suspension prior to surgery:

• INR less than 1.5 at the time of surgery.
• Time that has been estimated depends on the drug, standing in 5 days in the case of warfarin and being enough 2-3 days in the case of acenocoumarol.
• Interval may be shortened in those associated cases at lower hemorrhagic risk, in which it can be allowed an INR 1.5-1.8.

If the INR is >1.5, administer a low dose oral vitamin K (1 to 2 mg) to hasten normalization of the PT/INR.

Restarting the drug after surgery:

• After 24 hours after surgery if it has been possible to start oral tolerance, the same dose that the patient was receiving preoperatively.
• If warfarin is withheld for 5 days before surgery and is restarted soon, patients would have a subtherapeutic INR for approx 8 days (4 days before and 4 days after surgery).

For patients at very high or high thromboembolic risk, or cases where it is not possible to start oral tolerance, bridging may be appropriate.

Use of bridging PREoperatively:

• Reserve bridging for individuals considered at very high or high risk of thromboembolism.
• Recent stroke, mechanical heart valve, CHA2DS2-VASc score of 7 or 8.
• In these cases, the bridging agent (therapeutic subcutaneous dose of LMW heparin) is started three days before surgery.

Therapeutic dosing 

• For individuals with a potential arterial thromboembolic source (atrial fibrillation, mechanical heart valve) or VTE within the preceding month. 
• Typical regimens include enoxaparin, 1 mg/kg subcutaneously twice daily.

Intermediate dosing 

• Individuals with atrial fibrillation or VTE within the preceding month when bridging is needed but concerns about bleeding are greater. 
• Typical regimens include enoxaparin, 40 mg twice daily.

Prophylactic dosing 

• Is not used for bridging in patients with AF,  there is no evidence that prophylactic dose heparin prevents stroke in this setting. 
• This dose level may be reasonable in patients who have had a VTE event between within the preceding 3 to 12 months.
• Typical prophylactic regimens include enoxaparin, 40 mg once daily.

Timing

We discontinue LMW heparin 24 hours before the planned surgery or procedure.

If a twice-daily LMW heparin regimen is given, the evening dose the night before surgery is omitted.

If a once-daily regimen is given, one-half of the total daily dose is given on the morning of the day before surgery.

Use of bridging POSToperatively:

• After warfarin is restarted in the postoperative setting, it takes 5 to 10 days to attain a full anticoagulant effect as measured by an INR above 2.0. 
• Individuals with high or very high risk of thromboembolism needs a heparin bridging agent during this period.
• Resumption of bridging:

Until there is adequate hemostasis clinical assessment of the wound site, drainage fluid amount, expected postoperative bleeding and correct hemoglobin levels.

This assessment will vary depending on the surgery type and individual patient considerations.

Low bleeding risk

Minor procedures associated with a low bleeding risk in which bridging is used, therapeutic-dose of LMW heparin can usually be resumed 24 hours after the procedure.

Major bleeding risk

Major surgery or those with a high bleeding risk procedure, the therapeutic dose of LMW heparin should be delayed for 48 to 72 hours after hemostasis has been secured.

Resumed

Warfarin is generally resumed on the same postoperative day as the heparin. 

Heparin can be discontinued when the INR reaches the therapeutic range (2,0) for individuals at moderate thromboembolism risk.

Perioperative management of the oral direct thrombin inhibitors and factor Xa inhibitors

Rapid offset and onset of Dabigatran/Ribaroxaban activity obviates the need for bridging anticoagulation

Dabigatran, Ribaroxaban and Apixaban:

High risk Resumen 48 to 72 hours after surgery.

Low risk Resumen 24 hours after surgery.

Urgent invasive procedure with Warfarin?

Time to reversal:

• Discontinuing warfarin: 5-14 days.
• Vitamin K: 6 to 24 hours to correct the INR.
• Fresh frozen plasma: 12 to 36 hours for complete reversal.
• Prothombin complex:15 min after 10 min to 1 hour infusion.
• Recombinant factor VIIa: 15 min after bolus infusion.

Urgent invasive procedure with Dabigatran/Ribaroxaban?

Take-home messages: 

• If the patient bleeds from the procedure, their anticoagulant may need to be discontinued for a longer period, resulting in a longer period of increased thromboembolic risk. 
• A balance between reducing the risk of thromboembolism and preventing excessive bleeding must be reached for each patient.
• Resumption of bridging anticoagulation too early, especially the use of therapeutic dose heparin within 24 hours after surgery, is associated with a two- to fourfold increased risk for major bleeding compared with no bridging or prophylactic dose heparin.