Practice Pearl 4: Challenges in Treatments and Final Thoughts


Experts discuss the challenges in the management of hemophilia and provide some final thoughts.


  • Practice Pearl 4: Calculating Doses for Individualized Treatment
  • Practice Pearl 4: Dosing Complications and Various Dosage Vials

Luigi Brunetti, PharmD, MPH: That brings us to challenges. We have a new paradigm in how we’re going to manage our patients with hemophilia. But what are some of the challenges, perhaps Dr. Sidonia, that you have as a provider?

Robert F. Sidonio, Jr, MD: Everything has changed with Hemlibra [emicizumab], and we obviously have the inhibitor patients, it’s changed their lives tremendously. And I think that’s when we really realized that the strategies that we had—for example, doing bypassing agent prophylaxis—just didn’t work that well. We thought that they were OK, but for some reason, I don’t know why, we thought that they had to give 20 doses of a bypassing agent to treat a bleed. That obviously nowadays would not be considered. And so it’s such a dramatic improvement for them.

And then for the noninhibitor patient, it gives them another option of managing their hemophilia. The big question that comes up is about how active in sports they can be with Hemlibra because it now provides a study mimic of factor VIII, so it isn’t factor VIII. And is that enough to protect, and do you need those peaks of factor VIII that we were giving before their baseball game, does that matter?

We’ve seen some of this issue, but for the most part we have had some patients who are doing pretty well. One of the guys that we talk to tells me he exercises every day. I don’t know how he has time to exercise every day, but that’s what he does. And he talks about how he doesn’t have to use factor VIII before those sessions anymore, and he does CrossFit and all these other things. And he participates in other sports and he says he doesn’t have to do that anymore, which is great.

The other big issue that we’re reaching, and these are all good problems to have because we have options, is do we start that newborn child on Hemlibra for prophylaxis? Certainly, there are not a lot of data to support that yet. It has the label. We know that they may need a little bit more of that. But we know in relatively young children regarding the bleeding risks, they just need a small amount of protection, to protect against those life-threatening bleeds.

And so, I’m plugging my clinical trial, but we really want to collect these data. I know in Europe they’re collecting it as well. It’s really important to collect these data because we want to give this to the community such that they feel comfortable making a decision about that. And when they ask me how many patients have started on prophylaxis in the first 6 months of life, that’s still a relatively small number. There are a few papers that have some experiences, which are helpful for us and guiding us. Those are the big challenges that we’re confronting. Again, these are good problems to have, and that tells us that we need to continue to do the research and collect these data uniformly, because we need this for our patient discussions.

Luigi Brunetti, PharmD, MPH: Sure. And from the pharmacist’s perspective or pharmacy perspective, what are some of the challenges, maybe with a specific focus on preparation differences, of course, and dosing?

Giles Slocum, PharmD: Right. This is a novel product for pharmacy. Hemophilia as a whole is a foreign topic for a lot of pharmacists. Even from that end, there’s going to be an education piece with this new product, a newish product at this time. The dosing we’re getting at can be a little bit complicated. The 2 different types of concentrations could be a little bit confusing. Considering our volume for the administration component is also something that we need to be aware of.

All of this is easily fixable with good quality education that can be provided. I would say another concern that we potentially have is, what do we do with these breakthrough bleeds that come in with these patients on emicizumab? We have a knee-jerk reaction when we read severe hemophilia A with inhibitors. And are we going to our aPCC [activated prothrombin complex concentrate]? Something we’re doing at our institution is in the allergy bar, putting in aPCC as an allergy, with more information about it and the risks and the max dose that we would see. We are trying to circumvent all of these things with education, best practice alerts that would potentially pop up when patients come in to our center. Those are a couple of the challenges on the pharmacy end that we need to be aware of.

Robert F. Sidonio, Jr, MD: There’s a laboratory component that I don’t think I mentioned as well. You can’t use the traditional 1-stage factor VIII assay, so if somebody has started emicizumab, even if they started it last week, their factor VIII is going to measure as greater than 200 to 300 IU dL-1. So we try to put some warnings in our system, and sometimes that’s challenging because it may warn them in the emergency department, but once they get to inpatient care, then maybe the trainees don’t notice those warnings. We’ve had that challenge if somebody has to be on factor VIII, if they have to be on a continuous infusion, you have to have the chromogenic assay specifically with bovine components. It doesn’t react to emicizumab. And so you can measure factor VIII.

It’s really important that your center is ready for this, that the family understands these challenges, so they don’t get frustrated. Again, this is going to be the way it is I think with nonfactor products. You’re going to continue to see where we have challenges in measuring that, and we have to be prepared for that. Thankfully those bleeding events are relatively rare, and we just have to be prepared and tell our oncology colleagues and those who aren’t as well trained in hemophilia so they understand those things, because they may only encounter a few of these patients in their practice.

Luigi Brunetti, PharmD, MPH: To put the dosing challenges with emicizumab into perspective, using different vial sizes is not something new to emicizumab, right?

Robert F. Sidonio, Jr, MD: Sure, correct.

Luigi Brunetti, PharmD, MPH: Many pharmacists are involved in being the product stewards for factor VIII because a lot of the vials have a different amount of factor in them because of variability between lots.

Robert F. Sidonio, Jr, MD: Correct.

Luigi Brunetti, PharmD, MPH: So, it’s something similar between the 2. To me more of the nuance is for pharmacists to recognize the drawing up and educating patients on how to appropriately do that to avoid dosing errors. I think that would be pretty important.

Robert F. Sidonio, Jr, MD: Well, you have to remember that these patients were on factor VIII before, and this month they may get these vials and maybe those aren’t available, and they get smaller vials this month. And so they’ve certainly dealt with multiple changes in their vial sizes, and actually they’ll get fewer of those changes because it’s not going to change much for an adult, their dosing regimen, unless they change their frequency.

Luigi Brunetti, PharmD, MPH: Thank you both for all of your answers and shedding some light on such an important topic. It’s been extremely informative, and before we end the discussion, I’d like to get some final thoughts from each of the panelists.

Robert F. Sidonio, Jr, MD: This is the golden age of hemophilia I think now. They used to talk about this in the 1970s, and certainly before the 1980s, about the golden age, but this certainly is it. And patients have so many options including the most recent option with Hemlibra. It’s great for them to have these different options. It always comes with additional challenges that we have to accept, but it further cements the role of the Hemophilia Treatment Center [HTC], the pharmacist, and the entire team of educating the patients that we simply can’t just write a prescription, and everyone is going to do fine. So our role is going to be ongoing about education, making sure they understand these new products. And in the next few years we’ll be talking about a new product, I’m sure, and so it’s really important for us to educate people about these new products and be there for the patients.

Giles Slocum, PharmD: To echo what you’re saying, these new products, they’re continually going to be coming out. And so, this is an exciting option on the table for us. It does come with the complications listed, showing that importance of an HTC and the interdisciplinary conversation that needs to be taking place where we include the patient for these decisions.

Luigi Brunetti, PharmD, MPH: Thank you all for your contributions to this discussion, and on behalf of our panel, we thank you for joining us and we hope you found this Practice Pearls discussion to be useful and informative.

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