ThromboPhonia E02, Re-starting Anti-Coagulation After Intracranial Hemorrhage

Objective 1: Summarize the most recent guidelines regarding when to re-start anti-coagulation after ICH (ASA, DVT-P, Xa inhibitors, warfarin)

ASA

• 2-4 weeks
• 2 weeks for mechanical valve, 4 weeks for atrial fibrillation

DVT Prophylaxis

• Intermittent pneumatic compression stockings for first 48 hours, then safe to resume DVT prophylaxis

Warfarin

• 2-4 weeks
• 2 weeks for mechanical valve, 4 weeks for atrial fibrillation

DOACs

• No evidence for restarting DOACs after ICH
• Guideline states that it seems reasonable to assume that the risks and benefits of resuming DOAC therapy will be largely similar to those associated with resuming warfarin therapy because these agents have shown similar if not superior efficacy and safety to warfarin in clinical trials^​1​
• Caveat: REALIGN trial showed use of dabigatran in patients with mechanical heart valves was associated with increased rates of thromboembolic and bleeding complications as compared with warfarin^​2​

Objective 2: What factors need to be taken into consideration when making this decision?

High risk features for thromboembolism with mechanical valve

• History of atrial fibrillation
• History of previous VTE
• LV dysfunction
• Hypercoagulable state

Risk of recurrence of ICH

• Deep hemorrhage, good BP control 1-2% risk
• Lobar hemorrhage with cerebral amyloid angiopathy (CAA) features risk 5-10% / year

Indication for anticoagulation

Mechanical valve vs. Atrial fibrillation

Objective 3: Interpret the evidence behind the guidelines

• The evidence for anticoagulation resumption after ICH is derived from observational studies and is subject to the confounding and bias inherent in this type of research

• Two studies published in 2010 reached very different conclusion regarding the timing of anticoagulation resumption after ICH
  • Hawryluk et al performed a systematic review and concluded that a 72-hour cutoff for anticoagulation resumption seemed to separate recurrent ICH from thromboembolic complications, and therefore resuming anticoagulation about 72 hours after initial presentation should be considered^​3​
    • It should be noted that others suggest that >70% of patients with acute ICH develop at least some hematoma expansion within 24 hours
  • In contrast, Majeed et al concluded that post-ICH warfarin resumption should be delayed at least a month and may be optimal between week 10 and week 30^​4​

• Yung et al found that resuming anticoagulation during the index ICH admission was protective for mortality (30-day odds ratio of 0.49) whereas intraventricular hemorrhages, ICH associated with more severe categorization scores, and INRs>3.0 at ICH presentation all predicted increased mortality risk^​5​

• Poli et al found useful factors that may help identify patients at higher risk of recurrent ICH:
  • Male sex, hypertension, previous ischemic stroke, prosthetic heart valve, renal failure, cancer, and ICH classified as spontaneous^​6​

• Kurumatsu et al investigated the association between resuming anticoagulation and incidence of hemorrhagic and ischemic complications after VKA-related ICH in 719 patients surviving to discharge from 19 German tertiary care centers; the median time to VKA resumption was 31 days^​7​
  • Mortality was significantly lower after anticoagulation resumption in the subgroup of patients with atrial fibrillation^​7​

Objective 4: Describe instances where one would consider re-starting anti-coagulation earlier/later

Subdural hematoma: 4 weeks for ASA; 8 weeks for anti-coagulation (ask your local Neurosurgeon as their opinion varies on this)

Objective 5: Develop an approach to re-starting anti-coagulation after ICH including which agent to use and why

Step 1: Stratify risk of thromboembolism

High risk features in mechanical valve

• History of Atrial Fibrillation
• History of previous VTE
• LV dysfunction
• Hypercoagulable state

Low risk if no features

High risk if any features

Atrial fibrillation

• CHADS2 Score
• Prior history of stroke

Step 2: Stratify risk of ICH Recurrence

• Deep hemorrhage, good BP control 1-2% risk
• Lobar hemorrhage with cerebral amyloid angiopathy (CAA) features risk 5-10% / year

Step 3: Decision making warfarin vs. ASA?

Any high-risk features (step 1) + any ICH location – restart warfarin 2 weeks

No high-risk features (step 1) + lobar hemorrhage /CAA features – restart ASA 2 weeks

Step 4: Is it safe to restart?

Repeat CT head to ensure hematoma stable

SBP below 150 at minimum, goal of SBP below 130 long-term

Objective 6: How would you approach this scenario?

Step 1: Stratify risk of thromboembolism

No high-risk features (history of atrial fibrillation, history of previous VTE, LV dysfunction, hypercoagulable state); therefore, low risk from thromboembolism perspective.

This patient has aortic valve which is lower risk than mitral valve.

Step 2: Stratify risk of ICH Recurrence

Lobar hemorrhage with features of cerebral amyloid angiopathy seen on neuroimaging, therefore higher risk of ICH recurrence.

Step 3: Decision making warfarin vs. asa ?

This patient was on ASA and warfarin dual therapy prior to ICH. There is little evidence regarding restarting dual therapy after ICH. Given that this patient has an aortic valve replacement which has lower risk of thromboembolic complications than mitral valve and is at high risk of ICH recurrence, we can consider switching to ASA monotherapy, starting 2 weeks after ICH.

Step 4: Is it safe to restart?

Yes, repeat CT head showed stable ICH and BP well controlled.

Objective 7: What do guidelines suggest?

• 2 studies, Kuramatsu and Witt, found similar rates of thromboembolic complications in patients not resuming anticoagulation and those who were taking antiplatelet therapy, both of which were higher than patients resuming anticoagulation^​6,8​. This questions the practice of switching patients to antiplatelet therapy.

Guideline Summary

• Although additional information is needed regarding the optimal timing of anticoagulation resumption, available evidence indicates that waiting 14 days may best balance the risk of recurrent bleeding, thromboembolism, and mortality after GI bleeding^​1​
• When to resume anticoagulation after ICH is less clear, with evidence ranging from 72 hours to 30 weeks^​1​
• See table below for individual factors for and against restarting anticoagulation after intracranial hemorrhage^​1​

Objective 8: Would scenario change depending on type of valve? What if the indication was AF, not mechanical valve?

The scenario would change depending on the type of valve. If it was a mechanical mitral valve, warfarin is only option for anticoagulation. The recommendation would be to start warfarin 2 weeks after ICH, however some providers would restart within 1 week. A mechanical aortic valve has lower risk of thromboembolic complications and therefore can use ASA initially instead of warfarin.

If indication for anticoagulation is atrial fibrillation, it can be restarted later. Higher CHADS2 score and prior history of stroke support restarting anticoagulation after major bleeding. The absence of other stroke risk factors in atrial fibrillation would support not restarting anticoagulation^​1​.

Objective 9: Does the type of bleeding matter? (lobar versus deep ICH)

Yes! Higher risk of recurrence for lobar hemorrhages especially with features of cerebral amyloid angiopathy when compared to deep hemorrhage with good BP control.