PERIOPERATIVE ANTICOAGULANT TREATMENT IN BRAIN SURGERY
Authors: Papacocea Toma 
Published: November 2024

In clinical practice, neurosurgeons are often faced with problems raised by the anticoagulant therapy of patients with cerebral pathologies. They are routinely asked to decide between the risk of postoperative ICH and the benefit of therapeutic AC in high-risk situations and without strong guidelines. There are many controversial situations in which the neurosurgeon can be put in a dilemma regarding the best therapeutic attitude towards anticoagulation.

The first question related to the anticoagulant treatment that the neurosurgeon asks before a brain intervention is: how
long before the operation should the chronic anticoagulant therapy be stopped, under safe conditions? Another problem that neurosurgeons often face is that of postoperative anticoagulant treatment. One of the questions they frequently ask themselves is: how quickly can the anticoagulant treatment be introduced/resumed after brain surgery?

In this presentation we will try to answer these important questions. For this, we will study patients with cerebral pathology who are on anticoagulation for various health issues (VTE, afib,
hearth valves etc.). First of all, we have to assess the thrombosis risk for each patient. And we have:

Low risk patients

Moderate risk patients

High risk patients

Very high-risk patients

1. VTE with target INR 2.0-3.0 unless:

§ VTE in prior 3 months = high risk

§Associated with malignancy = moderate risk

2. Non-valvular AF with target INR 2.0-3.0 unless:

§ Previous stroke or TIA = high risk

1. VTE provoked by malignancy

1. VTE in prior 6-12 weeks

2. Aortic caged ball/disc heart valves

3. AF with previous stroke / TIA

4. Valvular heart disease

5. Any indication with target INR 3.0-4.0

1. VTE in prior 6 weeks

2. Metallic mitral valves

In balance with the thrombotic risk, there is the postoperative haemorrhagic risk. In this matter, we must emphasize that any brain surgery is considered high bleeding risk intervention!

Regarding the pre-operative management of patients with anticoagulant treatment, we have some clear guidelines.

Therefore, for low-risk patients, we have to:

Stop VKA 5 days before surgery to allow INR to normalise;
Check INR 1 day prior (ideally) or the morning of the procedure (urgently);
If on DOAC’s stop 2 days before surgery.

N.B: Safe INR is <1,4 for brain surgery
For moderate and high risk patients, we must:

Stop VKA 5 days before surgery to allow INR to normalise;
Start prophylactic dose of LMWH 3 days pre-operatively (start at 08.00h);
Check INR 1 day prior (ideally) or the morning of the procedure (urgently);
On day of procedure omit LMWH dose at 08.00h;
If on DOAC’s bridging with LMWH is not mandatory.

The use of LMWH between the time of stopping the VKA and the operation is called bridging therapy, and the goal is that the patient is not left completely non-anticoagulated.

For very high-risk patients, the attitude is:

VTE in prior 6 weeks: ideally avoid surgery. Consider use of temporary inferior vena cava (IVC) filter. Then manage as per high risk.
Metallic mitral valves. LMWH is not recommended in metallic valves; UFH may be preferable.

Then manage as per high risk.

But what about anticoagulation after craniotomy? This is a more controversial issue than the previous and we should keep in mind that, in operated neurosurgical patients, the consequences of either haemorrhage or thromboembolism can be devastating. We have 2 indications of postoperative anticoagulation:
- VTE prophylaxis;
- resuming preoperative anticoagulation.

For the first situation, a study regarding VTE prophylaxis was published in 2021 (1) and its conclusion is that initiating anticoagulant prophylaxis with subcutaneous enoxaparin sodium 40 mg once per day within 72 h of surgery can be done safely while reducing the risk of developing lower extremity DVT.
What about therapeutic doses of anticoagulants in operated patients? When can we start them? Few studies to date have attempted to determine the optimal time to resume anticoagulation after craniotomy. As a result, the decision of when to restart anticoagulation remains largely subjective and highly variable between surgeons.

A Brazilian study from 2020 (2) showed that:
- Postop. VTE was statistically associated with a delay in starting therapeutic AC of more than two days.
- ICH was not statistically associated with AC started after the 2nd postop. day, which may encourage the strategy of early AC treatment.
- The frequency of bleeding complication was statistically significant higher in patients treated with warfarin(13.8 % vs. 0% in NOAC group).

A very recent study published this year (3) has an interesting conclusion: therapeutic AC in postoperative craniotomy patients from postoperative days 2 to 10 did not result in any major complications.

Another recent study (4) draws the following conclusions:
- The risk of postoperative hemorrhage is most significant within the first 24 hours after intervention, and anticoagulation must be avoided during this time period.
- From postop day 2, the use of low doses of LMWH is recommended in patients at high risk of DVT.
- AC can be safely resumed starting with postop.

At the end of this presentation, we can draw some conclusions that could serve as future guidelines for postoperative anticoagulant treatment:

- From postop day 2, low doses of LMWH can be used in patients at risk of DVT.
- In patients with high thrombotic risk LMWH in prophylactic dose is started 8-12 hours postoperatively.
- If low bleeding risk, VKA can be resumed in postoperative day 2 together with LMWH until desired INR is reached.
- Full anticoagulation can be safely restored 7 days postoperatively even in high bleeding risk patients.
- DOAC’s can be resumed 24 hr post-operatively at normal dose. If patient has high VTE risk consider prophylactic dose of LMWH on evening of surgery.

References
Robert G. Briggs, Yueh-Hsin Lin, Nicholas B. Dadario, Isabella M. Young, Andrew K. Conner, Wenjai Xu, Onur Tanglay, Sihyong J. Kim, R. Dineth Fonseka, Phillip A. Bonney, Arpan R. Chakraborty, Cameron E. Nix, Lyke R. Flecher, Jacky T. Yeung, Charles Teo, Michael E. Sughrue. Optimal timing of post-operative enoxaparin after neurosurgery: A single institution experience. Clin Neurol Neurosurg 2021 Aug. 207: 106792.
Jose Orlando de Melo Junior, Marcia Aparecida Lodi Campos Melo, Luiz Antonio da Silva Lavradas Junior, Plinio Gabriel Ferreira Lopes, Ingra Ianne Luiz Ornelas, Paula Lacerda de Barros, Paulo Jose da Mata Pereira, Paulo Niemeyer Filho. Therapeutic anticoagulation for venous thromboembolism after recent brain surgery: Evaluating the risk of intracranial haemorrhage. Clin Neurol Neurosurg. 2020 Oct 197: 106202.
John M. Wilson, Kierany B. Shelvin, Sarah E. Lawhon, George A. Crabill, Ellery A. Hayden. Safety and timing of early therapeutic anticoagulation therapy after craniotomy. Surg Neurol Int. 2024; 15: 31.
Vikram A. Mehta, Timothy Y. Wang, Eric W. Sankey, Elizabeth P. Howell, C. Rory Goodwin, Jerrold H. Levy, Allan H. Friedman. Restarting Therapeutic Anticoagulation After Elective Craniotomy for Patients with Chronic Atrial Fibrillation: A Review of the Literature. World Neurosurg. 2020 May 137: 130-136.