1. Neurosurgery and DOACs
P Albaladejo, MD, PhD
Department of Anesthesia and Critical Care
Grenoble-Alpes University Hospital
France
Disclosures: Bayer Healthcare, Boehringer Ingelheim, BMS-Pfizer, Sanofi, Daiichi Sankyo, LFB, CSL Behring, Octapharma, BBraun, Sandoz, Portola

2. Toolbox

3. 33% renal (active) 33% renal (inactive) 33% hepatic
DOACs
Elimination
½ life
Tmax
Dabigatran anti-IIa
14-17h
0.5 à 2 h
80% renal 20% hepatic
Rivaroxaban
anti-Xa
7-13h
2-4h
33% renal (active) 33% renal (inactive) 33% hepatic
Apixaban anti-Xa
8-15h
3-4h
25% renal 75% hepatic
Edoxaban anti-Xa
10-14h
1.5h
35% renal
PRADAXA
XARELTO
ELIQUIS
LIXIANA

4. DOACs Age Weight Creatinin Cockcroft Comedications Scheme Indication
Last intake
Age
Weight
Creatinin
Cockcroft
Comedications

5. DOACs and coagulation assays
European Heart Journal 2018; 39: 1330–1393

6. To wait ?
To delay ?
To dose ?
To reverse ?

7. Elective neurosurgery

8. DOACs in elective surgery
European Heart Journal 2018; 39: 1330–1393

9. Anaesth Crit Care Pain Med. 2017; 36: 73-76
Low hemorrhagic risk
High hemorrhagic risk
Before the
procedure
No DOA the evening before and the morning of the procedure
rivaroxaban
apixaban
edoxaban
Cockcroft
≥ 30 ml/mn
Last DOA on D-3
dabigatran
≥ 50 ml/mn
Last DOA on D-4
30-49 ml/mn
Last DOA on D-5
No bridging
No dosage
After the procedure
Resumption at the usual time but at least 6h after the procedure
« Prophylactic » dose of anticoagulant
At least 6 hours after the procedure if venous thromboprophylaxis is indicated
« Therapeutic » dose of anticoagulant
as soon as the hemostasis allows it
(between 24 and 72 hours)
Anaesth Crit Care Pain Med. 2017; 36: 73-76

10. Add 2 days, no bridging, dose if necessary
Low hemorrhagic risk
High hemorrhagic risk
Before the
procedure
No DOA the evening before and the morning of the procedure
rivaroxaban
apixaban
edoxaban
Cockcroft
≥ 30 ml/mn
Last DOA on D-3
dabigatran
≥ 50 ml/mn
Last DOA on D-4
30-49 ml/mn
Last DOA on D-5
No bridging
No dosage
After the procedure
Resumption at the usual time but at least 6h after the procedure
« Prophylactic » dose of anticoagulant
At least 6 hours after the procedure if venous thromboprophylaxis is indicated
« Therapeutic » dose of anticoagulant
as soon as the hemostasis allows it
(between 24 and 72 hours)
Add 2 days, no bridging, dose if necessary
For neurosurgery (or Spinal/Epidural)
Anaesth Crit Care Pain Med. 2017; 36: 73-76

11. Urgent Neurosurgery (outside ICH)

12. Res Pract Thromb Haemost. 2017;1:296–300.
“…..a patient who underwent urgent neurosurgery for acute onset paraplegia due to a spontaneous subdural spinal hematoma less than 5 hours after she had taken rivaroxaban.
Sagittal T2, sagittal T1, axial T2 at the level of T12 hyper intense nodule, suggestive for recent bleeding (white arrows)
Res Pract Thromb Haemost. 2017;1:296–300.

13. Res Pract Thromb Haemost. 2017;1:296–300.

14. Anaesth Crit Care Pain Med. 2018; 37: 391-399

15. European Heart Journal 2018; 39: 1330–1393

16. Intra Cranial Bleeding

17. Lancet 2014; 383: 955–62

18. A total of 128 patients with preadmission DOAC (n = 65) or VKA (n = 63) intake were compared.
Neurocrit Care. 2018

19. Neurocrit Care. 2018

20. Neurocrit Care. 2018

21. 18 patients in the DOAC group and 71 in the warfarin group
modified Rankin Scale
Cerebrovasc Dis Extra. 2017; 7: 62-71
6.2 vs mL, respectively; p = 0.04

22. Prospective 12-month observational study in 15 tertiary stroke centers in the US, Europe, and Asia.
premorbid modified Rankin Scale score of <2 with acute nontraumatic anticoagulant-related
Stroke. 2018; 49:

23. Stroke. 2018 ;49:

24. Stroke. 2018 ;49:

25. Out of 400 consecutive patients with ICH, 15 patients were
DOAC-ICH and 24 patients were warfarin-ICH
Journal of Stroke and Cerebrovascular Diseases 2018

26. Anaesth Crit Care Pain Med. 2018; 37: 391-399

27. Recommendations for Direct Thrombin Inhibitor Reversal
We recommend administering idarucizumab to patients with intracranial hemorrhage associated with dabigatran ……
We suggest administering aPCC (50 units/kg) or 4-factor PCC (50 units/kg) to patients with intracranial hemorrhage associated with direct thrombin inhibitors if idarucizumab is not available …….
In patients with dabigatran-associated intracranial hemorrhage and renal insufficiency or dabigatran overdose, we suggest hemodialysis if idarucizumab is not available.
We recommend against administration of rFVIIa or FFP in direct thrombin inhibitor-related intracranial hemorrhage.
Neurocrit Care 2016; 24: 6–46

28. Recommendations for Oral Direct Factor Xa Inhibitors Reversal
We suggest administering a 4-factor PCC (50 U/kg) or activated PCC (50 U/kg) …..
Neurocrit Care 2016; 24: 6–46

29. DOACs widely used (with some complex combination)
Type, dose, indication, Cockcroft, comedication (antiplatelet agent)
High bleeding risk of the procedure
No bridging, dosage (help hemato) for elective surgery
Preop interruption: standard protocols + dosage or + 2 days
Delay ± dose ± reverse (antidotes, PCCs) for urgent procedures
Protocols and aids (referent)