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

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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

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

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

To wait ? To delay ? To dose ? To reverse ?

Elective neurosurgery

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

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

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

Urgent Neurosurgery (outside ICH)

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.

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

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

European Heart Journal 2018; 39: 1330–1393

Intra Cranial Bleeding

Lancet 2014; 383: 955–62

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

Neurocrit Care. 2018

Neurocrit Care. 2018

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. 24.2 mL, respectively; p = 0.04

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: 2309-2316.

Stroke. 2018 ;49: 2309-2316.

Stroke. 2018 ;49: 2309-2316.

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

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

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

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

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)