Analysis of Children with Secondary ITP an Observational Study of Children of the Parc-ITP Registry of the Intercontinental Cooperative ITP Study Group (ICIS)

Background: Immune thrombocytopenia (ITP) is an autoimmune disorder of variable origin that results in bleeding and decreased platelet count. Primary ITP in children is a diagnosis of exclusion, but following practice guidelines only medical history, clinical examination, complete blood count and blood smear analysis are mandatory for diagnosis. Secondary ITP can be difficult to be diagnosed at initial presentation and is frequently identified during the course of the disease. Little is known about children with secondary ITP after a diagnosis of primary ITP. We are describing such patients within a 2 year observation period.

Methods and Materials: Data for this study were extracted from the Pediatric and Adult Registry on Chronic ITP (PARC-ITP), an international multi-center registry designed to collect data prospectively in children and adults with newly diagnosed primary ITP. Children aged 3 months to 16 years with a corrected diagnosis of secondary ITP within 24 months after having been diagnosed with primary ITP were included in this analysis. We excluded 37 patients with an undefined diagnosis of secondary ITP, i.e. all patients without a clear statement of the cause of secondary ITP. A correction of diagnosis was reported at 6, 12 or 24 months of follow-up (FU) investigations. Clinical and laboratory data were analyzed with descriptive statistics.

Results: A total of 3581 evaluable children with the initial diagnosis of primary ITP were recorded in the PARC-ITP database between 2004 and 2017. Secondary ITP was reported in 99 patients within 24 months FU, 60 were females (60%) with a mean age of 7.13 years (SD 5.2). Diagnosis of secondary ITP was reported with the first FU dataset (6 months after initial diagnosis) in 66 patients. Infectious and autoimmune diseases were the main causes for secondary ITP reported in 43 and 38 patients, respectively. Mean age of patients with infectious diseases was 4.3 years (SD 4.2) and 10 years (SD 4.5) for those with an autoimmune disorder. Other underlying causes were malignancy (n=6), aplastic anemia (n=7), immunodeficiency (n=4) and drugs (n=1). Mean platelet count at initial diagnosis was 22x10⁹/L (SD 24), and 62 patients had a platelet count of < 20x10⁹/l. Patients with malignancy and aplastic anemia had a higher initial platelet count (37 and 38x10⁹/l respectively), than patients with infection or autoimmune diseases (22 and 18x10⁹/l respectively). At the time point of reported secondary ITP the median platelet count was 171x10⁹/L (SD 124) with 59 patients exhibiting platelet counts > 100x10⁹/L. Patients with autoimmune diseases had a higher rate of persisting ITP (61%), than patients with infectious diseases (19%). Overall initial bleeding frequency (n=82) and bleeding location were similar to children with primary ITP. Wet bleeding defined as mucosal bleeding was initially reported in 36% of patients with no differences in the various subgroups. One patient exhibited an intracranial haemorrhage during the course of secondary ITP. A watch and wait strategy was initially applied in 34 patients (34%).

Discussion: The diagnosis of primary ITP appears to be accurate for most of the children reported to the PARC-ITP Registry, however, a minority of them experiences a correction of the diagnosis from primary into secondary ITP. Some differences were found for age, sex and initial platelet count in the subgroups of secondary ITP depending on etiology. The characteristics of patients with secondary ITP due to an infection are very similar to primary ITP, reflecting probably similar pathophysiological mechanisms of the immune system. Bleeding symptoms were very similar in all groups.

Conclusion: Little is known about patients with initial primary ITP and revision of the diagnosis. This is the first analysis of children with a critical appraisal of the diagnosis "primary ITP".