1. Difficult situations in anticoagulation after stroke
George Ntaios
University of Thessaly, Larissa/Greece

2. Disclosures
Scholarships: European Stroke Organization; Hellenic Society of Atherosclerosis.
Honoraria: Medtronic; Quintiles; Boehringer-Ingelheim.
Speaker fees/Advisory Boards: Sanofi; Boehringer-Ingelheim; Galenica; Elpen; Bayer; Winmedica; BMS/Pfizer; Amgen
Research support: European Union (Horizon 2020); BMS/Pfizer (ERISTA)
Most relevant disclosure

3. AF on VKA (INR:1.9) Very good recovery
Clinical case vignette: an 80-year-old patient with a
history of hypertension, diabetes mellitus, congestive
heart failure, and atrial fibrillation on acenocoumarol
presents with a right putaminal hemorrhage. International
normalized ratio at admission is 1.9 and brain
computed tomography (CT) reveals extensive leukoaraiosis.
The patient has a good recovery with a modified
Rankin scale score of 2 at discharge. Would you restart
anticoagulation?

4. Restart OAC after AF/OAC-related ICH
Nielsen et al. Circulation 2015

5. Restart OAC after AF/OAC-related ICH
Nielsen et al. Circulation 2015

6. Restart OAC after AF/OAC-related ICH
!?!?!?!!
Nielsen et al. Circulation 2015

7. We need to individualize

8. Bleeding vs. thromboembolic risk

9. Prognostic scores?
HAS-BLED
CHA2DS2-VASC2
CHADS2

10. Estimate bleeding risk in AF: HAS-BLED
HAS-BLED Risk Criteria
Score
Hypertension
1 point
Abnormal renal/liver tests
1-2 point
Stroke
Bleeding
Labile INR
2 points
Elderly
1 points
Drugs or alcohol
1-2 points
Risk of major bleeding depends on patient factors (HAS-BLED – border registry).

11. Estimate embolic risk in AF: CHA2DS2VASc
CHA2DS2Vasc Risk Criteria
Score
Congestive heart failure
1 point
Hypertension
Age >75 years
2 point
Diabetes mellitus
Stroke/ transient ischemic attack
2 points
Vascular disease
Age 65-74
Female sex 1
Estimate thromboembolic risk in AF if not anticoagulated  chads, chadsvasc scores, show them. But they were not validated in the perioperative period

12. Well, sorry…. CHA2DS2Vasc Risk Criteria CHADS2 Risk Criteria
HAS-BLED Risk Criteria
Congestive heart failure
Labile INR
Hypertension
Diabetes mellitus
Bleeding
Stroke/ transient ischemic attack
Stroke
Vascular disease
Abnormal renal/liver tests
Age >75 years
Elderly
Age 65-74
Drugs or alcohol
Female sex
Estimate thromboembolic risk in AF if not anticoagulated  chads, chadsvasc scores, show them. But they were not validated in the perioperative period

13. Cerebral microbleeds

14. Cerebral microbleeds & ICH risk
Charidimou et al. Stroke 2013

15. Cerebral microbleeds & ischemic stroke risk
Charidimou et al. Stroke 2013

16. If you anticoagulate, choose a low-dose NOAC
Ruff et al. Lancet 2013

17. Anticoagulation after AF-stroke: how soon (or late?)
So, let us discuss about few of them using some patient examples…
This was the CT angiograpjy of an AF patient who was not anticoagulated. As you see, there is…..

18. The 1-3-6-12 rule TIA  1 day Small infarct  3 days
Moderate infarct 6 days
Large infarct  12 days
Now, there are two points which we could keep in mind to make our life easier and the life of our patients safer. Recently the EHRA provided an expert-opinion rule, i.e. the rule, which means that ….. But we need to keep in mind that this is not supported yet by high quality data.

19. NOACs could be the answer?
The second point is that perhaps in these cases, a NOAC, rather than a vitamin K antagonist, is the best choice that you could make. Why? Because as we all know, the NOACs are so much safer than antivitamin-Ks, and this high safety profile is exactly what you need in the acute phase where the bleeding risk of the patients is higher. And perhaps, among all NOACs, you would like to choose dabigatran, because as we know, it is associated with the lowest risk for hemorrhagic stroke in secondary stroke prevention, which is close to 80% compared to warfarin!
Ruff et al. Lancet 2013

20. The ALESSA score Age Ischemic index LESion >1.5 cm  1 point
≥80 years  2 points
70-79 years  1 point
Ischemic index LESion >1.5 cm  1 point
Severe Atrial enlargement  1 point
The second point is that perhaps in these cases, a NOAC, rather than a vitamin K antagonist, is the best choice that you could make. Why? Because as we all know, the NOACs are so much safer than antivitamin-Ks, and this high safety profile is exactly what you need in the acute phase where the bleeding risk of the patients is higher. And perhaps, among all NOACs, you would like to choose dabigatran, because as we know, it is associated with the lowest risk for hemorrhagic stroke in secondary stroke prevention, which is close to 80% compared to warfarin!
Paciaroni, in preparation

21. The ALESSA score
The second point is that perhaps in these cases, a NOAC, rather than a vitamin K antagonist, is the best choice that you could make. Why? Because as we all know, the NOACs are so much safer than antivitamin-Ks, and this high safety profile is exactly what you need in the acute phase where the bleeding risk of the patients is higher. And perhaps, among all NOACs, you would like to choose dabigatran, because as we know, it is associated with the lowest risk for hemorrhagic stroke in secondary stroke prevention, which is close to 80% compared to warfarin!
Paciaroni, in preparation

22. SHORT CASE REPORT - Kouklis

23. Bridging VKA with LMWH
Explain bridging
Rio-Antirio bridge

24. “ Do not bridge !!!! ” https://bridge.dcri.duke.edu/
ALSO: PERIOP-2 in Canada (
Douketis. N Engl J Med 2015

25. “ Do not bridge !!!! ” https://bridge.dcri.duke.edu/
ALSO: PERIOP-2 in Canada (
Douketis. N Engl J Med 2015

26. Pre-operative discontinuations of NOACs
Sumary slide – Heidbuchel
Heidbuchel. European Heart Journal 2013

27. Sumary slide – Heidbuchel
Heidbuchel. European Heart Journal 2013

28. Ischemic stroke in anticoagulated patient
So, let us discuss about few of them using some patient examples…
This was the CT angiograpjy of an AF patient who was not anticoagulated. As you see, there is…..

29. Acute endovascular treatment - thrombectomy
Andexanet produced near complete normalization of all coagulation parameters measured within 2 minutes of completion of infusion.
Vanacker, Stroke 2016

30. INR >1.5 Ischemic stroke in VKA-treated patient
So, let us discuss about few of them using some patient examples…
This was the CT angiograpjy of an AF patient who was not anticoagulated. As you see, there is…..

31. Ischemic stroke in dabigatran-treated patients
So, let us discuss about few of them using some patient examples…
This was the CT angiograpjy of an AF patient who was not anticoagulated. As you see, there is…..

32. Idarucizumab: a reversal agent for dabigatran
Thrombin
Dabigatran
Idarucizumab

33. Idarucizumab: a reversal agent for dabigatran

34. Time after end of infusion (hours)
Idarucizumab: a reversal agent for dabigatran 70 65 60 55
dTT (s) 50 45 40 35 30 –2 2 4 6 8 10 12 24 36 48 60 72
Time after end of infusion (hours)

35. Arterial occlusion accessible by mechanical thrombectomy in CTA ?No
Arterial occlusion accessible by mechanical thrombectomy in CTA ?
Yes
Within 4.5 hours after onset ?
Last intake of Dabigatran not known
Yes
Within 6 hours after onset?
aPTT/dTT/TT prolonged
Last intake of Dabigatran <24 hours
Yes No
Yes No
Yes No
Idarucizumab
No attempt for recanalization
Mechanical
thrombectomy
IV rt-PA

36. Ischemic stroke in dabigatran-treated patients

37. Ischemic stroke under Xa inhibitors
So, let us discuss about few of them using some patient examples…
This was the CT angiograpjy of an AF patient who was not anticoagulated. As you see, there is…..

38. Andexanet: an antidote for Xa inhibitors

39. Ciraparantag: an antidote for … all
Andexanet produced near complete normalization of all coagulation parameters measured within 2 minutes of completion of infusion.
Ansell et al. NEJM2014

40. Arterial occlusion accessible by mechanical thrombectomy in CTA ?No
Arterial occlusion accessible by mechanical thrombectomy in CTA ?
Yes
Within 4.5 hours after onset ?
Last intake of Xa inhibitors not known
Yes
Within 6 hours after onset?
Anti-Xa assays prolonged
Last intake of Xa inhibitors <24-48 hours
Yes No
Yes No
Yes No
Andexanet alpha / ciraparantag
No attempt for recanalization
Mechanical
thrombectomy
IV rt-PA

41. Take-home messages Restart anticoagulants after ICH?
How soon OAC after IS?
Do not bridge!
Ischemic stroke in anticoagulated patient?