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Diagnosing Idiopathic Thrombocytopenia Purpura

Panelists:Ivy Altomare, MD, Duke University Medical Center; Terry Gernsheimer, MD, Fred Hutchingson Cancer Research Center; Keith R McCrae, MD, The Cleveland Clinic
Published: Wednesday, Jan 17, 2018



Transcript: 

Ivy Altomare, MD: Dr. Gernsheimer, you mentioned the youth of antiplatelet antibodies. How do we diagnose idiopathic thrombocytopenia purpura? What are the useful techniques? What is not helpful?

Terry Gernsheimer, MD: The major thing to understand is that it is, to a large extent, a diagnosis of exclusion. We’re no longer doing bone marrows on most of the patients for whom we suspect ITP in. Truly, the only way to make a diagnosis is to see if someone is responding to the therapy of which you would expect them to respond to. If someone doesn’t respond to corticosteroids, or if someone doesn’t respond to IVIg, you really have to start to question the diagnosis. That might be a time to go back and do a bone marrow.

Ivy Altomare, MD: It does make it difficult, though. The response rate to those agents is high, but it’s not 100%.

Terry Gernsheimer, MD: It is not 100%. That’s the point where you would go back, rethink this, and look, again, for other disorders. And at that point, you may perhaps do a bone marrow and say, “Are there indeed increased, or at least normal numbers of megakaryocytes in the bone marrow?”

Ivy Altomare, MD: The normal or increased numbers of megakaryocytes. Is there anything other than that, on the bone marrow, that could help, histologically?

Terry Gernsheimer, MD: Well, you want to make sure there’s no other abnormalities with other cell lines, assuming that the patient hasn’t been treated. We do flow cytometry to make sure that there is not some lymphoid malignancy which might be associated with ITP, meaning that this is a secondary ITP. We frequently do flow cytometry to make sure that there’s not a myelodysplastic syndrome underlying the thrombocytopenia. So, that’s where the bone marrow becomes helpful.

Ivy Altomare, MD: Yes. Can you mention, again, the utility or lack thereof of antiplatelet antibody testing?

Terry Gernsheimer, MD: Yes. When I was a resident, my mentor said to me, “The relationship between platelet antibodies and reality are that there is no real relationship between the two.”
There are a few places that do relatively good testing. But again, I can’t remember the last time I did antiplatelet antibodies to make the diagnosis of ITP.

Ivy Altomare, MD: Do you have anything to add, Dr. McCrae, about the diagnosis?

Keith R. McCrae, MD: No. I would agree with that. I tell people that the best diagnostic test for ITP is a response to standard therapy, as you mentioned. And when they don’t respond, then you have to really think about, could this be an inherited, congenital thrombocytopenia that hasn’t been discovered? We don’t see this as much on the adult side. It’s more common with children. But I agree with everything Dr. Gernsheimer said.

Terry Gernsheimer, MD: One of the things that always strikes me is that it’s great when we have somebody who needs to be treated.

Ivy Altomare, MD: It is more difficult to do this in real practice than it seems, you know? Diagnosis of exclusion is so hard.

Terry Gernsheimer, MD: Right. It’s very, very hard. If you have somebody who has a low platelet count, but not a low enough platelet count to be treated, and all of the other counts are normal, are you dealing with some dropout of megakaryocytes for some other reason? Do they have a myelodysplastic syndrome? At some point, it becomes a watch and wait scenario with some patients. You just have to wait and see. Do they drop? Do they develop some other abnormality in other cell lines? So those are the tougher patients, I think, the ones who don’t meet therapy to make the diagnosis.

Ivy Altomare, MD: Right.

Keith R. McCrae, MD: One thing I would add is that we didn’t mention drug-induced thrombocytopenia, which some people would consider as a form of secondary ITP. People ask, “What drugs can cause thrombocytopenia?” I say, “What drugs can’t?” We clearly have ones that more commonly do so, things like Bactrim (sulfamethoxazole and trimethoprim), heparin, or vancomycin, or things like that. But really, it’s very important to go over every patient’s medication very closely, and also to ask them if they’re taking any herbal supplements or things like that. I’ve had a couple of patients in whom I think those were implicated in their thrombocytopenia.

Ivy Altomare, MD: Yes. One of the things that I see in clinical practice is testing of H. pylori, quite often. Dr. Gernsheimer, can you comment on that? Do you find that it’s useful? And if you find H. pylori and treat the H. pylori, and you suspect ITP, what will it remit? What happens?

Terry Gernsheimer, MD: This has been a very interesting story, as this has unfolded. H. pylori infection was initially looked at because it was seen in certain lymphomas. Then, people were looking for it in lupus. The Italian group went to some of their refractory patients and looked for H. pylori infection. I want to make it very clear that we’re talking about infection, not previous exposure. Many of us have H. pylori antibodies. Many of us have been exposed. So, they then eradicated H. pylori and found that half of the patients that they treated actually went into remission. I remember when this was presented. They actually brought the room to our feet. They really did.

So, of course, everybody then started looking. The study was repeated in New York. There were no responses. The study was then repeated in Japan. There were lots of responses. Since then, I generally will look for a H. pylori infection either by a breast test or by a stool antigen test. You’re looking for active infection, not just doing an antibody, which tells you the patient has, at some point, been exposed. I think it’s so easy to treat. I’ve had a few responders who I believe probably responded. I think it’s so easy to treat that and you don’t really need an H. pylori infection to make you happy. So, we frequently will treat these patients. We’ll look, we’ll treat, and if we get lucky, maybe we’ll see a response.

Ivy Altomare, MD: But you haven’t seen a 50% response rate?

Terry Gernsheimer, MD: Oh, no way. No.

Transcript Edited for Clarity 

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Transcript: 

Ivy Altomare, MD: Dr. Gernsheimer, you mentioned the youth of antiplatelet antibodies. How do we diagnose idiopathic thrombocytopenia purpura? What are the useful techniques? What is not helpful?

Terry Gernsheimer, MD: The major thing to understand is that it is, to a large extent, a diagnosis of exclusion. We’re no longer doing bone marrows on most of the patients for whom we suspect ITP in. Truly, the only way to make a diagnosis is to see if someone is responding to the therapy of which you would expect them to respond to. If someone doesn’t respond to corticosteroids, or if someone doesn’t respond to IVIg, you really have to start to question the diagnosis. That might be a time to go back and do a bone marrow.

Ivy Altomare, MD: It does make it difficult, though. The response rate to those agents is high, but it’s not 100%.

Terry Gernsheimer, MD: It is not 100%. That’s the point where you would go back, rethink this, and look, again, for other disorders. And at that point, you may perhaps do a bone marrow and say, “Are there indeed increased, or at least normal numbers of megakaryocytes in the bone marrow?”

Ivy Altomare, MD: The normal or increased numbers of megakaryocytes. Is there anything other than that, on the bone marrow, that could help, histologically?

Terry Gernsheimer, MD: Well, you want to make sure there’s no other abnormalities with other cell lines, assuming that the patient hasn’t been treated. We do flow cytometry to make sure that there is not some lymphoid malignancy which might be associated with ITP, meaning that this is a secondary ITP. We frequently do flow cytometry to make sure that there’s not a myelodysplastic syndrome underlying the thrombocytopenia. So, that’s where the bone marrow becomes helpful.

Ivy Altomare, MD: Yes. Can you mention, again, the utility or lack thereof of antiplatelet antibody testing?

Terry Gernsheimer, MD: Yes. When I was a resident, my mentor said to me, “The relationship between platelet antibodies and reality are that there is no real relationship between the two.”
There are a few places that do relatively good testing. But again, I can’t remember the last time I did antiplatelet antibodies to make the diagnosis of ITP.

Ivy Altomare, MD: Do you have anything to add, Dr. McCrae, about the diagnosis?

Keith R. McCrae, MD: No. I would agree with that. I tell people that the best diagnostic test for ITP is a response to standard therapy, as you mentioned. And when they don’t respond, then you have to really think about, could this be an inherited, congenital thrombocytopenia that hasn’t been discovered? We don’t see this as much on the adult side. It’s more common with children. But I agree with everything Dr. Gernsheimer said.

Terry Gernsheimer, MD: One of the things that always strikes me is that it’s great when we have somebody who needs to be treated.

Ivy Altomare, MD: It is more difficult to do this in real practice than it seems, you know? Diagnosis of exclusion is so hard.

Terry Gernsheimer, MD: Right. It’s very, very hard. If you have somebody who has a low platelet count, but not a low enough platelet count to be treated, and all of the other counts are normal, are you dealing with some dropout of megakaryocytes for some other reason? Do they have a myelodysplastic syndrome? At some point, it becomes a watch and wait scenario with some patients. You just have to wait and see. Do they drop? Do they develop some other abnormality in other cell lines? So those are the tougher patients, I think, the ones who don’t meet therapy to make the diagnosis.

Ivy Altomare, MD: Right.

Keith R. McCrae, MD: One thing I would add is that we didn’t mention drug-induced thrombocytopenia, which some people would consider as a form of secondary ITP. People ask, “What drugs can cause thrombocytopenia?” I say, “What drugs can’t?” We clearly have ones that more commonly do so, things like Bactrim (sulfamethoxazole and trimethoprim), heparin, or vancomycin, or things like that. But really, it’s very important to go over every patient’s medication very closely, and also to ask them if they’re taking any herbal supplements or things like that. I’ve had a couple of patients in whom I think those were implicated in their thrombocytopenia.

Ivy Altomare, MD: Yes. One of the things that I see in clinical practice is testing of H. pylori, quite often. Dr. Gernsheimer, can you comment on that? Do you find that it’s useful? And if you find H. pylori and treat the H. pylori, and you suspect ITP, what will it remit? What happens?

Terry Gernsheimer, MD: This has been a very interesting story, as this has unfolded. H. pylori infection was initially looked at because it was seen in certain lymphomas. Then, people were looking for it in lupus. The Italian group went to some of their refractory patients and looked for H. pylori infection. I want to make it very clear that we’re talking about infection, not previous exposure. Many of us have H. pylori antibodies. Many of us have been exposed. So, they then eradicated H. pylori and found that half of the patients that they treated actually went into remission. I remember when this was presented. They actually brought the room to our feet. They really did.

So, of course, everybody then started looking. The study was repeated in New York. There were no responses. The study was then repeated in Japan. There were lots of responses. Since then, I generally will look for a H. pylori infection either by a breast test or by a stool antigen test. You’re looking for active infection, not just doing an antibody, which tells you the patient has, at some point, been exposed. I think it’s so easy to treat. I’ve had a few responders who I believe probably responded. I think it’s so easy to treat that and you don’t really need an H. pylori infection to make you happy. So, we frequently will treat these patients. We’ll look, we’ll treat, and if we get lucky, maybe we’ll see a response.

Ivy Altomare, MD: But you haven’t seen a 50% response rate?

Terry Gernsheimer, MD: Oh, no way. No.

Transcript Edited for Clarity 
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