Diagnosis of ITP Remains a Challenge for Clinicians

Ronald S. Go, MD

Idiopathic thrombocytopenic purpura (ITP) is a disorder that can present as bruising or mucosal bleeding, but is usually diagnosed through a process of elimination, explained Ronald S. Go, MD.

Currently, there are several effective treatments for ITP, such as frontline prednisone, followed by splenectomy or rituximab (Rituxan). The addition of bone marrow stimulants, such as romiplostim (Nplate) and eltrombopag (Promacta), can be beneficial for patients who do not respond to the primary therapies.

These treatments have made a significant impact on the treatment of patients with the disorder, but Go said that the biggest unmet need is in the diagnostic stage. As there are no established tests, clinicians must rule out other possibilities before settling on ITP, which creates room for misdiagnosing.

OncLive: Could you begin by discussing the presentation of ITP?

In an interview with OncLive, Go, an associate professor of medicine at Mayo Clinic, discussed the current treatment strategies of patients with ITP, as well as the process that some physicians use to determine whether a patient is suffering from the disorder.Go: The presentation is isolated thrombocytopenia. Of course, patients do not generally come to doctors because they know their platelet counts are low. Mucosal bleeding symptoms and bruising are the initial presentations of ITP. Patients will then have a complete blood count done to look for isolated thrombocytopenia. If there are other cytopenias, anemia, or leukopenia, then we have to look for other possible causes of bicytopenia or pancytopenia. Most often, ITP is [characterized] by low platelets.

What is the current treatment for these patients?

We then look at the history to make sure there is nothing else causing the low platelets, such as medications, comorbidities like liver disease, or conditions associated with hypersplenism, all of which can cause thrombocytopenia. The first question is, “Who needs treatment?” Generally speaking, it is for those who have platelet counts below 30,000, according to the ASH guidelines. Unless your patient is above 30,000 and is actively bleeding or has symptoms, then we do not treat—we watch. As far as treatment is concerned, most of the time the first-line of treatment is prednisone if there is no contraindication. That works for about 80% of the patients. The platelets will improve, and then we taper them over a couple of weeks. In some patients, that may be the end of it, but in some patients there may be a relapse.

What other kinds of agents are used?

We sometimes use intravenous immunoglobulin (IVIG) if somebody is actively bleeding. IVIG works about two-thirds of the time, but it is temporary and only works for a few days. Dexamethasone can be used as a steroid in the first-line treatment of patients with ITP.Once the prednisone is used and either the patient does not respond or relapses, the usual second-line treatment is either splenectomy or rituximab. Splenectomy has the best track record in terms of long-term remission; roughly about two-thirds of patients will respond to it. That may be the last treatment for many patients, meaning that it is either curative or it keeps the platelets above 30,000, even though it may not be normal. Rituximab is more frequently used before splenectomy, because it is a nonsurgical treatment. The idea with using rituximab is that it removes the CD20-positive B cells and the antibody-producing cells.

Then, there is a class of drugs that we call the thrombopoietin receptor agonists. They have the ability to stimulate the thrombopoietin receptor, and so the megakaryocytes make more platelets. These drugs are very active, too; about 80% of the time, they work in patients who are refractory to steroids or have at least 1 line of therapy. It works in most cases. The only downside of that treatment is that it does not modify the disease.

What is the biggest challenge or unmet need that you would like to see addressed in the management of ITP?

The treatments that I mentioned earlier—prednisone, splenectomy, and rituximab—either remove or treat the source of antibody production, or remove the place where antibody and platelet complex are destroyed. Thrombopoietin receptor agonists make the patients create more platelets, but at the same time, platelets are still being destroyed. It does not change the natural history of the disease. That is the downside, and you have to use it indefinitely. It is very effective, I must say.There is an unmet need in terms of the diagnosis. There is no single test; it is not like diabetes where there is a blood glucose level, fasting, or hemoglobin A1c. Even in hemolytic anemia, there are tests that can show that is happening. ITP is a diagnosis of exclusion; we do not have a test to look at the breakdown of platelet destruction. We are inferring that the platelet is being destroyed, but we do not actually have a gold standard test to say, "this is ITP." We exclude everything else, then we can say it.

That is probably the main challenge. That is in part why some patients respond to certain ITP treatments, because it is likely that a good proportion of these patients have ITP. They don't really have immune-mediated destruction—we just put them into this basket diagnosis of ITP because they do not meet the criteria of thrombocytopenia.

What would be your advice to community physicians who may have to manage a patient with ITP?

Not everybody responds to the 6 or 7 treatments that we have available. For refractory patients, more treatments are more than welcome. We still need to continue to look for drugs in these patients. I must say, with the advent of romiplostim and eltrombopag, and other oral platelet-stimulating agents, a fraction of patients who do not respond to anything is becoming uncommon. Just like any other disease, there is [an unmet] need for the patients who do not respond.The main thing to keep in mind is that you have to make sure there are no other causes for the thrombocytopenia. Just exclude the other causes as best as possible. The other thing is that not all ITP needs treatment.

As far as treatment is concerned, there are many options—even experts do not necessarily have the same pattern or sequence of treatment beyond the first- or second-line setting. It is based on the individual physician, as there are no comparative data after the first-line setting.

The other thing that is important to make sure of is that there are no other cytopenias like anemia or neutropenia [present] in addition to the thrombocytopenia, because there are certain bone marrow disorders that may present as severe thrombocytopenia. However, the other cell lines are not very affected. There may be a mild anemia or leukopenia, but in the presence of other cell lines, one has to look for other causes or diagnoses than ITP.