In this issue of the e-news
PDSA Medical Advisor Nichola Cooper, MD, and PDSA President and CEO Caroline Kruse were authors on a published article in Medicina that focused on limitations within existing ITP therapies and the value of individualized management strategies to improve the overall quality of life of patients with ITP. The article highlighted the importance for health care providers to have open communication with their ITP patients so they can assess how living with ITP is impacting them, and to use this information to help guide treatment options. As a response to that article, Caroline Kruse was interviewed by Medpage Today, and this interview was published in May 2021. The interview documented the importance of patient-reported outcomes and the need to incorporate the patient voice into treatment decisions. Both the interview and the Medicina article echoed the importance of tailoring treatment plans to the individual based on their needs and the risk for serious bleeding, response to a particular treatment, risk of adverse effects, and the outcome of the patient’s most bothersome symptoms. Emphasis was placed on moving away from treating all ITP patients in the same manner, and individualizing management plans.
Cyclic thrombocytopenia (CTP) is a very rare condition that is often misdiagnosed as immune thrombocytopenia (ITP). In CTP, platelet counts can drop very low (below 5,000 µL) for several days before rapidly increasing back into and sometimes above the normal range. The severity of the thrombocytopenia and duration of these periods of low counts vary among individuals with CTP. CTP is more common in adult women and is overall challenging to treat for 2 reasons: 1) most individuals with CTP appear to respond well to therapy but it is actually just the cycling and 2) most individuals with CTP fail to respond well to therapy. CTP may be more common among individuals with a thyroid condition. Similar to ITP, CTP is heterogeneous (different for everyone) and the underlying cause is not well understood. The diagnosis CTP should be entertained in ITP patients who do not respond well to approved ITP therapies that should sustain their counts, have only mild bleeding symptoms despite a low platelet count, and experience extreme platelet count fluctuations that cycle from low to normal range within 14-36 days on average. While the usual time interval is around 3 weeks, a critical feature is that individual patients tend to be consistent. Spontaneous remission has been reported but is unpredictable. Most ITP therapies are ineffective in preventing platelet counts from plummeting in CTP. One strategy that may be successful in some patients is a trial of cyclosporin and/or danazol.
Comments from PDSA’s Medical Advisors:
The diagnosis of CTP can be overlooked for years. Patients present when their count is low, receive treatment, and their count goes up nicely; attributing the count increase as a response to the administered treatment when in actuality it is just their platelet count fluctuation. Then it appears as if the treatment effect has worn off when the count falls 2-4 weeks later without explanation. The sequence can repeat with a series of typical treatments effective in ITP until the intrinsic cycling becomes obvious. Some patients have undergone splenectomy for difficult ITP without success. Recognizing the fluctuations in platelet count (and sometimes symptoms) are the key to suspecting the diagnosis, which is documented by confirming periodic consistent fluctuations. Treatment is difficult but it is important to help avoid intensive, toxic, and often unsuccessful approaches to treating the patient as if they have severe, refractory ITP. At this time the best management strategy remains unknown; trying danazol and/or cyclosporin would be reasonable.
Of note, cycling can be created in many ITP patients who do NOT have cyclic thrombocytopenia by using thrombopoietic agents incorrectly. This would typically be in the package insert is followed too closely. The patient receives one week worth of treatment with any of romiplostim/nplate (1 shot) or eltrombopag/promacta or avatrombopag/doptelet daily and the count goes too high. Instead of reducing the dose one level, the TPO agent is held. The count falls very low a week later and the TPO agent is administered usually not at a reduced dose.
While ITP can be diagnosed at any age, it is not frequently diagnosed in infants. As a result, there is little information available on how infants respond to second-line therapies, including eltrombopag (Promacta®/Revolade®), a thrombopoietin receptor agonist (TPO-RA). This is also because eltrombopag is currently only available for children over the age of twelve months. This study reviews the experience of two infants with ITP who receiving eltrombopag (off-label) for treatment, after first-line therapies failed to produce an improvement in their platelet count and symptoms.
An infant female was diagnosed with ITP at 3 months of age after developing some petechia (skin bleeding) and a platelet count less than 15,000µL. She did not respond to IVIG and corticosteroids and had a normal bone marrow biopsy. Three months after her diagnosis (when she was 6 months of age), the infant began received eltrombopag and her clinical symptoms improved. After 11 months of using eltrombopag, her platelet count was in a normal range, and she did not experience any side effects from the eltrombopag.
An infant boy was diagnosed with ITP at 5 months of age after presenting with a platelet count of 3,000µL and developing widespread petechia and a broken blood vessel in his eye, in addition to a nosebleed. IVIG and steroids were not successful in improving his platelet count or clinical symptoms. His bone marrow biopsy was normal. He was treated with eltrombopag and five weeks later his platelet count significantly improved. By nine months of age, his platelet count was normal and clinical symptoms improved.
Overall, this study highlights two successful examples of infants with ITP treated with eltrombopag off-label which successfully improving their platelet count and clinical symptoms.
Comments from PDSA’s Medical Advisors:
ITP in very young infants has been reported to be more difficult and refractory than ITP developing in older children and toddlers. It also has been associated with an increased chance of having an underlying genetic immunodeficiency which might explain this in certain cases. Finally in addition to eltrombopag not being approved in children less than the age of 1 year there are other issues to consider in its use. First, there is not a good liquid formulation suitable for infants. Second, infants often consume milk or formula-based products relatively frequently during the day e.g., every 2-4 hours. This makes it difficult respect the need to keep eltrombopag ingestion removed from ingestion of divalent cations. Finally, since eltrombopag is a chelator, it will not only chelate calcium but also iron. In very young children, iron deficiency can contribute to developmental issues separate from any consideration of anemia. Having said all of this, this article illustrates that nonetheless eltrombopag may be a useful second line treatment when first line treatments are unsuccessful and additional treatment is needed.