Does Autoimmunity in Family Members of Children with Immune Thrombocytopenia Help Identify Patients at Higher Risk of Chronic Immune Thrombocytopenia?
Authors: Lozano Chinga Michell , Fluchel Mark , Meznarich Jessica 
Published: November 2021

Abstract
Background
Immune thrombocytopenia (ITP) is the most common cause of thrombocytopenia during childhood. Approximately 10-30% of pediatric patients will develop chronic ITP (cITP), which is defined as thrombocytopenia lasting over 12 months, and constitutes a significant burden for patients and their caregivers. Patients with cITP may require ongoing medications to treat symptomatic thrombocytopenia, may have asymptomatic thrombocytopenia not requiring medical interventions, or may experience complete resolution of their ITP. There are not specific patient nor disease characteristics that can help us predict how cITP may progress, and which patients are more likely to require ongoing treatments. ITP can be a manifestation of immune dysregulation in patients with other autoimmune conditions or primary immunodeficiency disorders (PIDDs). We aimed to assess the characteristics of patients with cITP including the presence of autoimmune or allergic disorders in the patients and in first-, second-, and third-degree family members. We hypothesized that patients with cITP may have a higher incidence of immune dysregulation in family members in contrast to patients with acute aITP.
Methods
The study was approved by the institutional review and ethics boards at the University of Utah. We queried the Primary Children's Hospital database for cases of "immune thrombocytopenia" from January 1 st, 2001 to January 1 st,2021. Retrospective chart review was done to confirm the diagnosis. Patient demographics, clinical presentation, and family history of patients were reviewed. Data was collected in RedCap at the University of Utah. Descriptive summaries of data were done.
Results
Medical charts from 266 ITP patients diagnosed during the study period were reviewed; 182/266 (68.5%) had acute ITP (aITP) and 84/266 (31.5%) patients had cITP, defined as platelet count &lt;150 K/µl for &gt;12 months. Resolution of ITP occurred in 28/84 (33.3%) patients with cITP (resolved cITP), while 56/84 (66.7%) had ongoing thrombocytopenia (unresolved cITP). Mean duration of ITP in patients with resolved cITP was 2.9 years, and 4.6 years in patients with unresolved cITP at the time of the last known platelet count. Mean age at diagnosis was 7.4 years in the cITP group and 5.1 years in the aITP group.
Concurrent allergic conditions were identified in 10/84 (12%) of patients with cITP and 5/182 (2.7%) of patients with aITP. Autoimmune conditions were identified in 3 patients (3.5%) with cITP, and 4 patients (2.2%) with aITP. First-degree family members of cITP patients were more likely to be reported with an autoimmune condition than first-degree family members of aITP patients (15.5% vs. 5.5%, p=0.007 using Chi-square test); this effect was not seen amongst second- or third-degree relatives. The most common autoimmune condition reported in family members was autoimmune thyroid disease in both cohorts (2.7% in aITP and 9.5% in cITP). Common variable immunodeficiency (CVID) was reported in second degree relatives of 3/84 (3.6%) patients with cITP; no relatives of patients with aITP had a report of PIDD. Additionally, we identified 14 patients with Evans syndrome (ES), all with chronic immune thrombocytopenia and all patients had been followed for over a year at the time of the chart review. Four ES patients were previously diagnosed with 22q11.2 deletion, and one with CVID. In patients with ES, 4/14 (28.6%) and 5/14 (35.7%) had first- and second-degree family members with a reported autoimmune condition, respectively. No PIDDs were identified in first, second-, or third-degree relatives of patients with ES.
Conclusions
There is increasing evidence that patients with chronic ITP may exhibit polyautoimmunity or other signs of immune dysregulation, suggesting that ITP may be the initial manifestation of another autoimmune process or PIDD. We evaluated medical histories of patients with ITP and their family members. Patients with cITP have a history of autoimmunity in their family stronger than in patients with aITP. This association was even stronger in patients with ES.

Disclosures
No relevant conflicts of interest to declare.