PDSA’s exhibit booth at the 2022 ASH meeting in New Orleans.
(left-right: Melissa Hilsabeck, Peter Pruitt, Ken Kruse, Caroline Kruse, Jennifer DiRaimo, and Barbara Pruitt)
This year’s 64th American Society of Hematology (ASH) Annual Meeting and Exposition was held as a hybrid in-person and virtual event in New Orleans, LA, December 10-13, 2022. The meeting attracted more than 25,000 thousand clinicians, researchers, and health-care stakeholders, including the team from PDSA, to share ground-breaking research in the field of hematology. In this edition of the e-news, we report on two abstracts presented at the ASH meeting, showcasing new insights into immune thrombocytopenia (ITP).
In this study, researchers assessed whether children with ITP had small undetected bleeds in the brain, similar to common skin bleeds such as petechiae and purpura. Small bleeds in the brain, also called cerebral microbleeds (CMBs), have been described and identified in 43% of adults with ITP, but have never been investigated in children with a low platelet count. CMBs can only be detected using specialized technology called susceptibility weighted magnetic resonance imaging (SW-MRI).
Using SW-MRI, 38 children with ITP were recruited from the Imperial College Healthcare NHS Trust ITP Centre, in the United Kingdom. Participants with ITP were between the ages of 8-17 years and had a recorded platelet count under 30,000/µL (at least once). Clinical symptoms and bleeding experiences were collected on all participants through surveys and other assessment tools and compared to 20 age-matched healthy controls (siblings without ITP). Of the 38 children recruited, 66% had chronic ITP and 78% had received treatment for their ITP in the past.
Five of the 38 participants were found to have a CMB. No CMBs were seen in the healthy controls. All of the CMBs were found in children who had chronic ITP and had experienced more serious bleeding identified as scoring a higher value on the bleeding scale tools. None of the children with ITP with low bleeding scores were found to have CMBs.
SW-MRI may be useful in determining the safety of the current approach to the management of childhood ITP based on bleeding symptoms. The CMBs were not linked to cognitive impairment, fatigue, or a reduced quality of life in this study. However, more work in this area is underway.
Comments from PDSA Medical Advisors
Current national ITP guidelines recommend active observation of children with newly diagnosed ITP in the setting of no or mild bleeding symptoms regardless of the platelet count. From prior pediatric ITP studies, we know that the platelet count does not fully predict current or future clinical bleeding; we think of a very low platelet count as necessary but not sufficient for bleeding. Medical treatment, often effective in the short term, may not impact future clinical bleeding or increase the likelihood of ITP remission. Where prior studies examined outward clinical bleeding symptoms, this important study utilized brain imaging to examine the presence of microscopic brain bleeds in children with ITP who had low platelet counts. The findings of this small study are reassuring in that those children with low bleeding scores, who most likely would have been closely observed according to current treatment guidelines, had normal brain imaging. This provides safety data suggesting that clinical bleeding scores are helpful in guiding pediatric ITP treatment. On the flip side, some children with high bleeding scores had microscopic brain bleeds despite receiving multiple ITP-directed treatments; this could be an incentive to continue developing better treatments. Further study of the impact of the MRI findings in both children and adults is needed.
This study investigated whether patients over the age of 60 years with a low platelet count had a higher risk for a diagnosis of a blood cancer compared to individuals in this same age group with a normal platelet count. To accomplish this, provincial health administrative records were analyzed in Ontario, Canada. Participants were included if their physician reported completing a consultation for thrombocytopenia, and they had a platelet count less than 100,000 within six months of the recorded consultation date. Participants were excluded if the records revealed they had other low blood counts, a history of cancer or liver disease, or a known inherited bleeding disorder as well as several other criteria.
Medical records were available for 4,390 participants with a low platelet count and for 17,556 matched adults without a low platelet count between January 2009 – December 2019. Overall, 8.6% of participants over 60 with a low platelet count were diagnosed with a blood cancer over a four-year follow-up period, compared to 1.2% who were over 60 and did not have a low platelet count. These findings did not change when age, gender, severity, or duration of thrombocytopenia were factored into the analysis. The most common hematological cancer was myelodysplastic syndrome (MDS), and over half of the identified blood cancers required immediate treatment. Bone marrow biopsy was successful in identifying the majority of blood cancers diagnosed.
Overall, this population-based study suggests that bone marrow biopsies can be useful in detecting underlying blood cancers among patients with thrombocytopenia over the age of 60 years.
Comments from PDSA Medical Advisors
This study utilizes an administrative database to report the diagnostic outcomes of adults over the age of 60 years with thrombocytopenia (a low platelet count). Although ITP is a diagnostic possibility in individuals of any age with a platelet count equal to (or less than) 100,000, the disorder remains a diagnosis of exclusion and other causes for a low platelet count must be considered. The types of diagnostic evaluation required in patients with thrombocytopenia may vary based on patient-specific factors, such as age, underlying conditions, and medications, as well as provider preferences. In this administrative database focused on thrombocytopenic adults over the age of 60 years, some patients had a diagnostic bone marrow evaluation within the first year after consultation for thrombocytopenia and others had this evaluation in subsequent years. In 31% of cases, MDS was identified with other blood cancer cases being lymphoma or leukemia.
The authors suggest that a bone marrow evaluation should be considered as part of the diagnostic evaluation for thrombocytopenia in adults >60 years. A bone marrow biopsy at initial diagnosis is not standard management of all cases. In this regard, it was disappointing that the clinical features evaluated did not discriminate ITP from blood cancer. It is important to realize that in this study the authors excluded approximately three times as many patients who were not only thrombocytopenic but who also had other abnormalities in their white blood count or their hemoglobin. While these cases were excluded, the authors did not have clinical information on other findings such as abnormalities on physical examination. ITP remained by far the most common diagnosis in these patients, but this would not have been the situation in over 90% of these cases if the other abnormalities had been included. There are still many questions that remain, and the authors are working to answer as many as possible.