Back Back
FAQs on Management of Antiplatelet Bleeding
Expert Answers to Your Questions About Managing Antiplatelet Therapy and Bleeding 

Released: February 19, 2025

Expiration: February 18, 2026

Deepak L. Bhatt
Deepak L. Bhatt, MD, MPH, MBA, FACC, FAHA, FESC, MSCAI
Activity Information

Activity

Progress
1
Course Completed
Continue
Key Takeaways
  • The bleeding potential with dual antiplatelet therapy is not very different from the bleeding potential with an anticoagulant such as warfarin, even though healthcare professionals may think that anticoagulants are associated with increased bleeding.
  • Although platelet transfusions may be an effective strategy to reverse bleeding in patients treated with prasugrel and clopidogrel, it has limited efficacy at reversing bleeding with ticagrelor because of the reversible binding of ticagrelor.

The use of ADP receptor antagonists (or P2Y12 inhibitors) is expanding because of the demonstrated clinical efficacy seen in patients with acute coronary syndrome (ACS), stroke, and other cardiovascular conditions, while platelet transfusions continue to be the mainstay for reducing bleeding risk in patients receiving antiplatelet therapy that requires urgent or emergent surgery. Ticagrelor, a potent and reversible ADP receptor antagonist, will likely see additional expanded use given its recent label expansions; however, bleeding remains a significant consideration. Platelet transfusions are less effective at reversing bleeding with ticagrelor compared with clopidogrel or prasugrel. Investigational agents designed to specifically reverse ticagrelor are in late-stage development and may address a critical gap in care for patients being treated with ticagrelor who require antiplatelet reversal, especially among those in need of an urgent or emergent coronary artery bypass graft (CABG) surgery.

The commentary below dives more deeply into topics and questions posed by a live audience of healthcare professionals (HCPs) during a symposium on antiplatelet reversal in cardiothoracic surgery, including evidence-based strategies for using ADP receptor antagonists and current antiplatelet reversal options for managing patients requiring surgery and/or bleeding while being treated with antiplatelet therapy. This symposium was held in Los Angeles, California, in January 2025. 

What is the recommended dual antiplatelet therapy (DAPT) for patients with atrial fibrillation (AFib) who undergo CABG surgery? If AFib stops after ablation, what therapy should patients be prescribed?
In general, DAPT is not part of AFib management, including when patients undergo CABG surgery. This was studied in the randomized phase III ACTIVE W trial, which found that the efficacy of warfarin among patients with great international normalized ratio (INR) control was superior to the efficacy of aspirin plus clopidogrel in the AFib setting. Warfarin also significantly lowered the total bleeding risk vs aspirin plus clopidogrel. This is why the bleeding potential with DAPT is not very different from the bleeding potential with an anticoagulant like warfarin, even though HCPs may think anticoagulants are associated with increased bleeding. This is even more true with the use of non–vitamin K antagonist oral anticoagulants or direct oral anticoagulants (DOACs), because these agents have been shown to have significantly less intracranial hemorrhage bleeding risk vs warfarin in randomized clinical trials.

In patients with AFib, HCPs should prescribe a DOAC at the appropriate dose. HCPs can make dosing adjustments based on patients’ renal health or weight in accordance with the relevant labeling. Furthermore, these patients should not routinely be receiving concomitant antiplatelet therapy. In patients with coexisting coronary artery disease (CAD), HCPs should still prescribe an anticoagulant. The clinical trials that have looked at this have not found a significant benefit with adding antiplatelet therapy to an anticoagulant in patients with AFib and stable CAD. Instead, this combination has the potential to increase the bleeding risk. Therefore, HCPs should prescribe an anticoagulant alone at the appropriate dose for this patient population.

If patients with AFib have just received a stent in the past week, their care becomes more complex. I recommend that HCPs discharge their patient after the procedure with the patient receiving an anticoagulant plus a single antiplatelet agent (typically an ADP receptor antagonist). For example, a common regimen used is apixaban plus clopidogrel. For the question regarding treatment choice when patients’ AFib stops after ablation, the risk of a stroke persists for at least a few months because the left atrium is often still stunned. For example, when patients undergo ablation, HCPs will continue treatment with an anticoagulant for a period of time, often indefinitely, or until they are sure patients do not have AFib in the outpatient setting.

Are there any practical protocols for managing emergent CABG surgery with DAPT and decreasing bleeding postoperatively?
HCPs should be particularly careful when patients are receiving DAPT, or any antithrombotic treatment, and need surgery. One practical consideration is the timing of the surgery—can it wait? If the surgery is for a patient with high-risk ACS, then it usually cannot wait. If a patient has stable CAD, then sometimes the surgery can wait. In the United States, it is not common practice to discharge patients who present with ACS and bring them back later for CABG surgery; in other parts of the world, this sometimes happens.

If a patient presents with troponin-positive ACS and the decision is to perform CABG surgery for management, the patient may have received prior antiplatelet therapy or was administered antiplatelet therapy in the emergency department. In either case, for the surgeon, it can be an issue when treating somebody receiving DAPT. In such cases, it is really a matter of weighing all factors, including the potential ischemic risk, cost, and length of hospital stay, to determine the best care for each patient.

What factors must HCPs consider when selecting which ADP receptor to use for patients?
The potential availability of bentracimab is one factor that I think will push the use of ticagrelor in the future. And once a generic option is available for ticagrelor, it is likely going to be used much more. If bentracimab receives FDA approval, ticagrelor could become the preferred ADP receptor antagonist instead of clopidogrel.

Although there are good data supporting the use of prasugrel, its use in practice is limited because of its black box warning about intracranial hemorrhage among patients with prior cerebrovascular disease. Now, HCPs practicing in an office often know whether a patient has a history of cerebrovascular disease, but that is not always easy to determine. in urgent or emergent settings. If a patient has a known history of stroke and/or related deficits, then HCPs should not use prasugrel. Of note, it can be even more difficult to determine a history of transient ischemic attack (TIA) because patients do not always know what a TIA is. Both clopidogrel and ticagrelor have several indications whereas prasugrel has fewer approved indications. Therefore, I suspect the use of ticagrelor will increase if a reversal option becomes available.

What would you do when a patient is experiencing intracranial hemorrhage but bentracimab is not readily available?
For a patient treated with ticagrelor, if bentracimab were FDA approved and available, then I would use it. However, while bentracimab is not yet approved or available, for patients treated with ticagrelor as well as patients treated with clopidogrel or prasugrel, HCPs should consult their local neurologist and neurosurgeon. I certainly would hold any DAPT or anticoagulation for at least 1 week, even if a patient has AFib. Determining when to resume these therapies is a matter of debate. Some data indicate that it depends on the size of the intracranial hemorrhage and the degree of disability that has occurred. Although some guidance is available, a local neurosurgeon and neurologist should be consulted to help with that determination.

It is not clear that platelet transfusions offer help in this situation. But if aspirin, prasugrel, or clopidogrel had been used, I would give the patient platelet transfusions. If a DOAC had been used, I would give the patient one of the specific reversal agents despite their cost and need for a hematologist’s approval in many institutions. Of note, there are data suggesting that the use of reversal agents in the context of DOACs may not improve clinical outcomes, but that is hard to apply to this scenario. If someone is herniating, it is a very real likelihood that nothing is going to make a difference, but HCPs should still want to give patients a chance at recovery. It can be incredibly difficult in patients with intracranial hemorrhage to achieve a beneficial clinical outcome with a particular therapy. So, despite the recent controversy in DOAC reversal, I would use a reversal agent if a patient treated with a DOAC presents with intracranial hemorrhage.

What are your thoughts on the finding that thrombotic effects were not related to bentracimab administration despite occurring within 1 day after infusion in the REVERSE-IT trial?
This is tricky because of the lack of randomization in the phase III REVERSE-IT trial. During this study, investigators told us that if an agent is available, they want to just use it. Thus, there was no placebo comparator. Investigators determined that these thrombotic events were unrelated because experienced adjudicators independently conducted a thorough assessment. So, short of randomization, using independent adjudicators is the only way to determine this.

Of note, there will be an increase in thrombotic events among patients receiving a reversal agent, regardless of administering bentracimab or a DOAC-specific reversal agent. This is because HCPs are, in many cases, discontinuing the antithrombotic agent. Therefore, whatever protective effect it had, it will not be there once removed. Thrombotic events will also increase without any reversal agent because patients are not receiving protection from the antithrombotic agent. That is why registry studies of aspirin have shown an increase in thrombotic events when aspirin is stopped. This is not because of a platelet rebound, but rather because aspirin was the agent preventing ischemic and thrombotic events. Furthermore, surgery is an incredibly thrombotic milieu. Therefore, it gets tricky sometimes when thrombotic events occur. In the REVERSE-IT trial, we had an independent and greatly experienced group that adjudicated these events as not being related to bentracimab.

Your Thoughts
How often do you manage bleeding while a patient is receiving antiplatelet therapy in your practice? You can get involved in the discussion by answering the poll question and posting a comment below.

Continue

Poll

1.

How often do you have to manage bleeding while a patient is receiving antiplatelet therapy?

Submit