1. ‫بسم ا الرحمن الرحيم‬
‫1‬

2. • .
Should anticoagulation be resumed after cerebral
hemorrhage?
An everyday story
Moataz Fatthy MSc
2

3. 3

4. AGENDA…
• Rationale
• Risk factor
• Risk Stratification
• Complications
• Management
4

5. 5

6. • The most feared and the most deadly
complication of oral anticoagulant therapy
• Anticoagulant therapy during and after
anticoagulation-associated ICH.
6

7. • Unfortunately, little evidence from clinical trials on
which to base the decision.
• Nevertheless, the potential benefit of resuming
anticoagulation outweighs the considerable risk.
7

8. Please pick your poison
(Franklin michota , MD)
8

9. • narrow therapeutic window
• vary considerably in dose-
response from patient to
patient
• subject to significant
interactions with other drugs
and with foods.
• monitored with laboratory
testing
• good patient compliance
• patient education is
essential.
9

10. • Warfarin has a striking effect on the
incidence and outcomes of ICH.
• While the overall incidence of ICH
in the general population is
approximately 25 per 100,000
person-years
• The incidence in patients on warfarin
is exponentially higher, at 2 to 3 per
100 per year, and appears to be
increasing.
10

11. • In addition, once ICH occurs, the
risk of death is up to twice as high in
those on warfarin
• The bulk of this effect is likely due
to a higher risk of ongoing bleeding
after the event.
11

12. 12

13. 13

14. Risk factors for intracerebral hemorrhage
during warfarin anticoagulation
Firmly established risk
factors Possible risk factors
• Advancing age (especially • Concomitant use of aspirin
>75 years) • Cerebral amyloid angiopathy
• Hypertension (especially • Asian or Mexican-American
ethnicity
systolic blood pressure >160
• Tobacco smoking
mmHg)
• Heavy alcohol consumption
• History of cerebrovascular • Leukoaraiosis detected by brain
disease CT/MRI
• Intensity of anticoagulation • Microbleeds by T2*-weighted
MRI
14

15. 15

16. • A population-based study has
reported a four-fold increase in the
incidence of warfarin-associated ICH
during the 1990s due to the
increasing use of warfarin in elderly
patients
• Antiplatelet therapy with
aspirin increases ICH risk by about
40 percent
16

17. • Dual antiplatelet therapy with
aspirin plus clopidogrel increases the
risk of ICH twofold compared with
aspirin
• Combining adjusted-dose
warfarin with aspirin appears to
double the ICH risk compared with
similar intensities of warfarin
anticoagulation without aspirin.
17

18. 18

19. Suggested patient risk stratification for arterial
or venous thromboembolism
19

20. INDICATION FOR VITAMIN K ANTAGONIST
MECHANICAL HEART ATRIAL VENOUS
VALVE FIBRILLATION THROMBOEMBOLISM
Recent event (within 3
Any mitral valve prosthesis CHADS2 score ≥ 5 months(
Older prosthetic aortic Recent stroke or transient Severe thrombophilia (low
valve ischemic attack (within 3 protein C, protein S, or
High risk
Recent stroke or transient months( antithrombin level;
ischemic attack (within 6 Rheumatic valvular heart antiphospholipid antibody
( months disease syndrome; multiple
( abnormalities
Venous thromboembolic
Bileaflet aortic valve event in the past 3 to 12
prosthesis and one of the months
following: Nonsevere thrombophilic
Atrial fibrillation CHADS2 score 3 or 4 conditions (eg,
Prior stroke or transient heterozygous factor II
Moderate risk Prior stroke or transient
ischemic attack mutation(
Hypertension ischemic attack Recurrent venous
Diabetes thromboembolism
Congestive heart failure Active cancer (treated
Age over 75 within 6 months, or
( palliative treatment
Bileaflet aortic valve CHADS2 score ≤ 2 and no Single venous
prosthesis without atrial thromboembolic event >
Low risk prior stroke or transient
fibrillation, and with no 12 months ago and no
ischemic attack 20
other stroke risk factors other risk factors

21. INDICATION FOR VITAMIN K ANTAGONIST
MECHANICAL HEART ATRIAL VENOUS
VALVE FIBRILLATION THROMBOEMBOLISM
Recent event (within 3
Any mitral valve prosthesis CHADS2 score ≥ 5 months(
Older prosthetic aortic Recent stroke or transient Severe thrombophilia (low
valve ischemic attack (within 3 protein C, protein S, or
High risk
Recent stroke or transient months( antithrombin level;
ischemic attack (within 6 Rheumatic valvular heart antiphospholipid antibody
( months disease syndrome; multiple
( abnormalities
21

22. INDICATION FOR VITAMIN K ANTAGONIST
MECHANICAL HEART ATRIAL VENOUS
VALVE FIBRILLATION THROMBOEMBOLISM
Venous thromboembolic
Bileaflet aortic valve event in the past 3 to 12
prosthesis and one of the months
following: Nonsevere thrombophilic
Atrial fibrillation CHADS2 score 3 or 4 conditions (eg,
Prior stroke or transient heterozygous factor II
Moderate risk Prior stroke or transient
ischemic attack mutation(
Hypertension ischemic attack Recurrent venous
Diabetes thromboembolism
Congestive heart failure Active cancer (treated
Age over 75 within 6 months, or
( palliative treatment
22

23. INDICATION FOR VITAMIN K ANTAGONIST
MECHANICAL HEART ATRIAL VENOUS
VALVE FIBRILLATION THROMBOEMBOLISM
Bileaflet aortic valve CHADS2 score ≤ 2 and no Single venous
prosthesis without atrial thromboembolic event >
Low risk prior stroke or transient
fibrillation, and with no 12 months ago and no
ischemic attack 23
other stroke risk factors other risk factors

24. 24

25. Extracranial bleeding leads Intracranial bleeding such as
to death or disability in only ICH leads to death or
3% of cases disability 76% of cases
25

26. Higher risk of expansion
26

27. • Unfortunately, continued bleeding is common after
ICH.
• In patients In warfarin-associated ICH, up to 50% of
patients who present within 3 hours of symptom onset,
25% of hematomas expand more than 30% over the
first hour, and another 12% expand this amount over
the next 24 to 48 hours or may be longer.
• Over 70% of patients presenting acutely develop at
least some amount of expansion within 24 hours.
27

28. Higher risk of expansion
• A large hematoma volume on presentation
• Early presentation, especially within 3 hours (??undergo
computed tomography (CT( while still bleeding(
• Higher INR is a significant predictor, not just of higher risk, but
also of a more delayed expansion.
• Certain radiographic findings indicate higher risk. One is the
“spot sign,” ie, contrast extravasation after contrast-enhanced
CT.
• Apparently, the more spots present, and the denser the contrast,
the greater the risk “spot-sign score”
28

29. The “spot sign” (arrow), contrast extravasation after contrast-enhanced computed
tomography, is associated with a high risk of hematoma expansion.
GOLDSTEIN J N , GREENBERG S M Cleveland Clinic
Journal of Medicine 2010;77:791-799

30. 30

31. In the acute phase.. In the chronic phase..
? ?
31

32. In the acute phase.. In the chronic phase..
• how does the risk of further • how does the risk of
bleeding (hematoma recurrent hemorrhage
expansion) compare with compare with the excess
the short-term risk of risk of thromboembolism if
thromboembolism? the patient does not resume
anticoagulation therapy?
32

33. • Anticoagulant reversal should be the
Acute phase primary consideration in the first 24
management hours
Heparin or LMWH is recommended
72 hours after ICH is diagnosed
Not underweight (< 50 kg),
Normal renal function (creatinine clearance > 30
mL/minute/1.73 m2)
Normal platelet function.
Does not have coagulopathy.
warfarin-related ICH has concomitant DVTor PE (ie, < 4
weeks old), then caval interruption therapy would be
indicated.
33

34. • Anticoagulant reversal should be the
Acute phase primary consideration in the first 24
management hours
Lines of reversal
Vitamin K 5 to 10 mg intravenously
Prothrombin complex concentrates 10 to 50 U/kg
Recombinant factor VIIa 40 to 80 μg/kg
Fresh frozen plasma 10 to 50 U/kg.
34

35. There are few relevant guidelines for the reversal of
anticoagulation in patients with AAICH, and expert opinion
on this subject differs
• PCC, recombinant factor
VIIa, or fresh frozen
plasma given with
intravenous vitamin
K were advocated in the
2008 American College
of Chest Physicians
Guidelines for patients
with life-threatening
bleeding such as
intracranial hemorrhage 35

36. There are few relevant guidelines for the reversal of
anticoagulation in patients with AAICH, and expert opinion
on this subject differs
• Replacement of the vitamin
K-dependent factors to
correct the INR and the
administration of intravenous
vitamin K. PCCs were
considered a reasonable
alternative to FFP.
Recombinant factor VIIa was
not routinely recommended
as a sole agent for reversal
36

37. • Other guidelines have • PCC preparations are not
suggested using various readily available in
combinations of vitamin emergency departments
K, FFP, PCC, and at most United States
recombinant factor VIIa hospitals; their use is
often restricted to
hematology specialists,
reducing their immediate
availability.
37

38. Chronic phase
management
Evaluations of patients for their risk of thrombosis in light of their
original indication for oral anticoagulant therapy.
The risk of ICH is related to the intensity of anticoagulation, a lower
target international normalized ratio may be the best compromise,
depending on the patient.
Alternatively, antiplatelet therapy alone may offer some benefit with less
risk of ICH
38

39. Whether and when to resume anticoagulation ?
• Old Dilemma
• A new trend
39

40. Old Dilemma
• ICH in patients with atrial fibrillation, the risk of
thromboembolism would need to exceed 7% per year to justify
restarting anticoagulation after deep ICH,and no risk level was
high enough to justify restarting anticoagulation after lobar ICH.
• The American Heart Association comments that for nonvalvular
atrial fibrillation, long-term anticoagulation should be avoided
after spontaneous lobar ICH, but that antiplatelet agents may be
considered.
• The decision to restart anticoagulation may also be a function of
whether the underlying risk factor is a temporary or long term
one . 40

41. Old Dilemma
Clearly, the risk is high on the first day, but small after the
first few days.
• A history of embolic stroke
with atrial fibrillation,
should be restarted on
warfarin after 10 to 14 days,
depending on the risk of
thromboembolism and ICH
recurrence.
41

42. Old Dilemma
• The American College of
Chest Physicians
recommends starting
prophylactic-dose
heparin the day after an
ICH, with no clear
guidance on restarting
warfarin.
42

43. Old Dilemma
• The American Heart
Association suggests
that, in patients with a
very high risk of
thromboembolism for
whom restarting warfarin
is considered, warfarin
may be restarted 7 to 10
days after ICH onset.
43

44. A new trend
• The decision to resume • Patients determined to be
anticoagulation after at high risk of
anticoagulant-associated thrombosis and low risk
intracranial hemorrhage of rebleeding are the best
should be based on the candidates for resuming
risk of rebleeding vs the anticoagulation.
risk of thrombosis.
44

45. INDICATION FOR VITAMIN K ANTAGONIST
MECHANICAL HEART ATRIAL VENOUS
VALVE FIBRILLATION THROMBOEMBOLISM
Recent event (within 3
Any mitral valve prosthesis CHADS2 score ≥ 5 months(
Older prosthetic aortic Recent stroke or transient Severe thrombophilia (low
valve ischemic attack (within 3 protein C, protein S, or
High risk
Recent stroke or transient months( antithrombin level;
ischemic attack (within 6 Rheumatic valvular heart antiphospholipid antibody
( months disease syndrome; multiple
( abnormalities
Venous thromboembolic
Bileaflet aortic valve event in the past 3 to 12
prosthesis and one of the months
following: Nonsevere thrombophilic
Atrial fibrillation CHADS2 score 3 or 4 conditions (eg,
Prior stroke or transient heterozygous factor II
Moderate risk Prior stroke or transient
ischemic attack mutation(
Hypertension ischemic attack Recurrent venous
Diabetes thromboembolism
Congestive heart failure Active cancer (treated
Age over 75 within 6 months, or
( palliative treatment
Bileaflet aortic valve CHADS2 score ≤ 2 and no Single venous
prosthesis without atrial thromboembolic event >
Low risk prior stroke or transient
fibrillation, and with no 12 months ago and no
ischemic attack 45
other stroke risk factors other risk factors

46. Suggested risk stratification for recurrent intracranial hemorrhage
Cerebral amyloid angiopathy or lobar
intracranial hemorrhage
High risk
Microbleeds on magnetic resonance
imaging
Hypertensive vasculopathy or deep
intracranial hemorrhage with any of the
: following
Normal international normalized ratio at the
Moderate risk time the hemorrhage is diagnosed
Patient not compliant with the dosing and
monitoring of vitamin K antagonist therapy
Patient not compliant with antihypertensive
therapy
Hypertensive vasculopathy or deep
Low risk intracranial hemorrhage in a compliant
patient
46

47. Suggested risk stratification for recurrent intracranial hemorrhage
Cerebral amyloid angiopathy or lobar
intracranial hemorrhage
High risk
Microbleeds on magnetic resonance
imaging
47

48. Suggested risk stratification for recurrent intracranial hemorrhage
Hypertensive vasculopathy or deep
intracranial hemorrhage with any of the
: following
Normal international normalized ratio at the
Moderate risk time the hemorrhage is diagnosed
Patient not compliant with the dosing and
monitoring of vitamin K antagonist therapy
Patient not compliant with antihypertensive
therapy
48

49. Suggested risk stratification for recurrent intracranial hemorrhage
Hypertensive vasculopathy or deep
Low risk intracranial hemorrhage in a compliant
patient
49

50. RISK OF ICH RISK OF THROMBOEMBOLISM
High Moderate Low
High Do not resume Do not resume Do not resume
Individualized Individualized
Moderate Do not resume
approach approach
Low Resume Resume Do not resume
50

51. How to avoid …
• Good control of warfarin intensity and limiting the use
of aspirin, will reduce the risk of ICH.
• Blood pressure control is especially important for
avoiding ICH. The use of warfarin in elderly patients
should go hand in hand with aggressive blood pressure
management.
• If patients on long-term warfarin have a history of falls,
risk factor screening/intervention program for reducing
the risk of falls may be of value. 51

52. Take home message
• Pick up your poison
• ICH is the nightmare
• Acute management includes anticoagulant reversal and
should be the primary consideration in the first 24
hours
• Patients determined to be at high risk of thrombosis
and low risk of rebleeding are the best candidates for
resuming anticoagulation.
• Consider INR control ,BP control, patients with
recurrent falls and other anticoagulation methods with
higher compliance 52

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