Understanding the Pathophysiology of ITP

Video

Ivy Altomare, MD: Thank you for joining us for this OncLive® Peer Exchange® program on adult idiopathic thrombocytopenia purpura (ITP). I’m Dr. Ivy Altomare, an associate professor of medicine at Duke University Medical Center. Joining me for this discussion is Dr. Terry Gernsheimer, professor of medicine within the division of hematology at the University of Washington School of Medicine, and director of medical transfusion service, and medical director of transfusion services at Seattle Cancer Care Alliance/Fred Hutchinson Cancer Research Center; and Dr. Keith McCrae, director of benign hematology at the Taussig Cancer Institute, and professor of molecular medicine at The Cleveland Clinic Lerner College of Medicine.

Immune thrombocytopenia is frequently encountered in clinical practice. In this OncLive® Peer Exchange® panel discussion, we will be discussing the nuances of diagnosing and managing adult ITP, when to initiate therapy, and how to manage refractory disease. We’ll provide a practical perspective on current treatment options, as well as look at future developments in the field. Thank you for joining us. Let’s begin.

Let’s start by talking about the pathophysiology of ITP. Dr. Gernsheimer?

Terry Gernsheimer, MD: For many, many years, we thought that the whole problem with ITP was that antibodies were produced for an unknown reason against a person’s own platelets and that it was completely a destructive process, that these antibodies caused platelet destruction and optimization by monocytes, particularly macrophages in the spleen. But more recently, in the last probably 10 to 20 years, we’ve realized that there is not only a shortened platelet survival, but also a decrease in platelet production. Some of that is due to abnormal apoptosis in the bone marrow by megakaryocytes, probably by the affected antibodies as well. Also, some of it is because we don’t see an increase in thrombopoietin levels. The reason for this is not completely clear.

Then, we’re also realizing that T cells play a role in ITP. They may be directly cytotoxic to platelets. They may also be directly cytotoxic to megakaryocytes. So, this is a lot more complicated than we originally thought.

Ivy Altomare, MD: And I would imagine that it’s not one mechanism in one patient. You have patients that are more dependent on lack of Tregs (regulatory T cells), and you have other patients that have a higher antibody burden. Do we have any way to determine that?

Terry Gernsheimer, MD: At this point, we really don’t. Antibody measurements against platelets and ITP are really not what we wished they would be. They’re certainly not at the level of the Coombs test, where you could make the diagnosis of autoimmune hemolytic anemia. The significance of antiplatelet antibody, and also the positivity is not always there. And so, we really have to be thinking that we have to look at this in other ways, to determine whether or not we’ve got an issue.

Ivy Altomare, MD: We’ll be talking about the management of adult ITP, but we know that it occurs in children as well. Fortunately, the pediatric version is more self-limited. Dr. McCrae, what are the key differences between adult and pediatric ITP?

Keith R. McCrae, MD: The major difference is the self-limited nature, mostly of pediatric ITP. About 75% of children who develop ITP will achieve a complete remission within the next 6 to 9 months. This is often likely even without any therapy. It is not exactly clear why that is. In ITP, in children as opposed to adults, it’s more commonly clearly associated with a preceding viral infection. I think the interesting thing is, we use the terms “children” and “adults.” When does a child become an adult, in terms of ITP? It’s not age 18. It’s probably somewhere around age 12 to 13, or maybe even a little bit younger. So, when we talk about classical childhood ITP, we think more of children 7 years of age or less.

Transcript Edited for Clarity

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