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FAQs: Treatment of ITP
FAQs: Clinical Considerations in the Treatment of ITP

Released: October 10, 2022

Expiration: October 09, 2023

Catherine M. Broome
Catherine M. Broome, MD
David J. Kuter
David J. Kuter, MD, DPhil
Cindy Neunert
Cindy Neunert, MD, MSCS
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Key Takeaways

  • In individuals with immune thrombocytopenia (ITP), the SARS-CoV-2 virus and the COVID-19 vaccines may cause a reduction in platelet counts.
  • A one‑size‑fits‑all treatment approach should not be used in the management of patients with ITP following initial therapy; rather, treatment should be tailored and personalized after discussions with the patient.
  • The TPO-RAs avatrombopag, eltrombopag, and romiplostim are all effective in ITP, but patient preference, dosing schedule, and route of administration are considerations that need to be weighed before treatment selection.

In this commentary adapted from a discussion among David J. Kuter, MD, DPhil; Catherine M. Broome, MD; and Cindy Neunert, MD, MSCS, the experts address important clinical questions about the optimal management of patients with immune thrombocytopenia (ITP).

Does the SARS‑CoV-2 virus and/or the COVID‑19 vaccines cause bleeding and/or affect platelet counts in individuals with ITP?

Catherine M. Broome, MD:
For individuals with ITP, COVID‑19 infection can be concerning because the virus and the vaccines can affect platelet counts in some patients. The virus and/or the vaccines can trigger a relapse in individuals with ITP or an immune response in those with or without any history of ITP. At my institution, we are very cognizant of frequently monitoring our patients with ITP after vaccination as well as during and after COVID-19 infections. We take this proactive approach to be able to react rapidly to any decrease in the platelet counts. 

David J. Kuter, MD, DPhil:
In a prospective study of a cohort of 2.53 million vaccinated adults in Scotland, there was no positive correlation between increasing incidence of ITP or thrombosis and vaccination among the 0.82 million who received mRNA-based vaccine (BNT162b2). By contrast, there was a small increased risk of thrombosis and ITP among the 1.71 million who received the adenovirus-based vaccine (ChAdOx1). In patients known to have ITP, the primary concern is that there is a 3% to 5% chance that patients will experience a drop in their platelet counts (usually short lived) after vaccination. 

Why is splenectomy unpopular in otherwise healthy children and young adolescents with ITP compared with adult patients?

Cindy Neunert, MD, MSCS:
Since there are no reliable predictors of response to splenectomy, there will be patients who will not respond to splenectomy. Therefore, part of the challenge is in the inability to predict an individual’s response to splenectomy, particularly when considering the associated lifelong complications and long-term lifestyle adjustments in a rather young group of patients. The risks associated with splenectomy are lifelong, and this can seem even more important in a younger population. Many pediatric healthcare professionals (HCPs) have to consider and discuss these issues with our younger patients with ITP. Shared decision-making about patients’ treatment goal is important as it may make patients feel more comfortable about undergoing splenectomy as a potential treatment option, particularly if it meets all their goals. It is not that splenectomy is never an option, but rather guidelines suggest delaying the procedure for a year and engaging in shared decision-making to ensure that splenectomy is the approach that is most aligned with patient values and preferences. Of note, splenectomy still remains the treatment of choice for emergency life-threatening bleeding events in both adults and children.  

In what specific line of therapy is fostamatinib an appropriate treatment, and in which group of patients would you consider using fostamatinib?

Catherine M. Broome, MD:
Considering all the available treatment options, the data show that patients tend to respond better to fostamatinib in the second line as opposed to the third or later lines of therapy. With this information in hand, treatment should be selected after a detailed discussion with the patient about the potential adverse events, mechanism of action, and all concerns that the patient may have about the class effects of all potential treatments. It is apparent that rituximab has become a less viable option in the COVID-19 era, especially with the blunting of responses to vaccines known to be associated with rituximab. It is unclear if there is a perfect patient or group of patients for whom fostamatinib is most appropriate. A particular challenge that we have as we move forward in the field is understanding which group of patients respond best to specific treatments. Improved knowledge of this would substantially help in the optimal selection and sequencing of treatments for our patients with ITP.

I believe that there are various subtypes of ITP. I do not think that ITP is one disease, and so, we cannot use a one‑size‑fits‑all approach in the treatment of all our patients. Some patients will respond better to SYK inhibitors, and some will respond better to BTK inhibitors. For some patients, complement activation is the primary factor contributing to platelet destruction in the disease, whereas for others, desialylation is the prominent feature in the disease. The disease driver needs to be better understood upfront before the best treatment approach can be selected. Until then, there is no right or wrong second-line treatment because of the dearth of strong evidence to guide individualized treatment selection and sequencing. 

Is there a role for thrombosis prophylaxis in patients with ITP and a risk for thrombosis?

David J. Kuter, MD, DPhil:
Thrombotic disorders such as deep vein thrombosis or pulmonary embolism may occur for a variety of reasons in patients with or without a history of ITP. A low platelet count in a patient presenting with thrombosis may be the initial sign of ITP or other diseases associated with increased platelet turnover. Since ITP is known as a prothrombotic disorder, the risk of developing arterial and/or venous thrombotic events is higher in patients with ITP compared with those without. To date, IV immunoglobulin is the only treatment for which we have solid data in terms of increasing the risk for thrombosis. I would not automatically recommend that patients who are receiving treatment for ITP be placed on a blood thinner unless they are experiencing blood clots. At present, thrombosis prophylaxis for patients with ITP is not necessary.

Catherine M. Broome, MD:
I agree with Dr. Kuter. Unless a patient is undergoing a procedure such as splenectomy for which the patient requires 10 days of postoperative anticoagulation, I would not recommend the use of prophylactic anticoagulation.

David J. Kuter, MD, DPhil:
There is an increased risk of thrombosis in patients with ITP who have undergone a splenectomy vs those who have not. So, the real question that is still in need of supporting evidence is should we place all our patients with ITP who have successfully undergone splenectomy on an anticoagulant? 

What is your preferred thrombopoietin receptor agonist (TPO‑RA): avatrombopag, eltrombopag, or romiplostim?

Catherine M. Broome, MD:
I always discuss the benefits and the risks associated with the TPO-RAs avatrombopag, eltrombopag, and romiplostim with all my patients with ITP while considering patients’ preferences before making a shared treatment decision. Hence, I have used all 3 agents. Even though my personal favorite is romiplostim because I find it to be reliable, I have mostly used avatrombopag and eltrombopag in patients who prefer orally available treatments rather than subcutaneous injections.

Cindy Neunert, MD, MSCS:
It can be challenging to make a choice among the 3 TPO-RAs. I predominantly treat pediatric patients with ITP in my clinical practice. Eltrombopag is associated with dietary restrictions, including taking the medication 2 hours before or 4 hours after the intake of calcium-rich foods or mineral supplements. Also, right now for younger children, the oral liquid requires mixing of oral packets. Therefore, in my practice, I find that romiplostim is often favored by parents because it is not associated with any of these dietary restrictions and does not require in-home mixing.

In addition, the dosing schedule also plays a major role in the patient’s preference. Romiplostim is administered subcutaneously once weekly, whereas avatrombopag and eltrombopag are taken orally once daily. Among my patients who are primarily children or teenagers, it can be very challenging to get them to comply with taking a medication daily whereas romiplostim gives them the flexibility of a once-weekly dosing regimen. On the other hand, romiplostim requires an injection which for many patients requires a weekly visit to the physician’s office for administration. The choice of TPO-RA also depends on the treating center and its capabilities. We have had success with the insurance companies approving in-home treatment administrations, which alleviates the burden of having to travel to the clinic to receive subcutaneously injected medications. However, for older adolescents and adult patients who prefer oral medications rather than injections, avatrombopag is preferred as it does not have the dietary restrictions and hepatotoxicity associated with eltrombopag. 

David J. Kuter, MD, DPhil:
In the outpatient setting, insurance coverage certainly affects which TPO-RA is administered. HCPs who do not recommend TPO-RAs often do not have a clear understanding of how to appropriately dose these agents. For instance, a dose reduction in one week followed by a dose increase in the next week based solely on the platelet counts will most certainly result in unexpected complications. When treating a patient with a TPO-RA, it is important that the HCP is careful not to dose modify too frequently. As a matter of fact, HCPs who treat patients with chronic ITP tend to check platelet counts on a weekly or every-other-week basis. I would advocate that once a patient is on a stable dosing regimen, blood counts need to be less frequent and when this approach is followed, the patient tends to fare well on the stable dose. Tests performed on a patient over months will show that blood counts fluctuate within a wide range. The goal of treatment is to keep patients within that identified wide range. In summary, I think that HCPs need continuing education on how to optimally use these agents in clinical practice.

Your Thoughts?
What challenges do you experience in your practice when it comes to recommending TPO-RAs in the management of your patients with ITP? Answer the polling question and join the conversation in the discussion box below.

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