Pediatric Evans syndrome (pES) is increasingly identified as the presenting manifestation of several inborn errors of immunity (IEI). Despite an improved understanding of genetic defects in pES, the underlying immunobiology of pES is poorly defined, and characteristic diagnostic immune parameters are lacking. We describe the immune characteristics of 24 patients with pES and compared them with 22 patients with chronic immune thrombocytopenia (cITP) and 24 healthy controls (HC). Compared to patients with cITP and HC, patients with pES had increased circulating T-follicular helper cells (cTfh), increased T cell activation, and decreased naïve CD4+ T cells for age. Despite normal or high IgG in the majority of pES at presentation, class-switched memory B cells (CSMB) were decreased. Within the cTfh subset, we noted features of post-activation exhaustion with upregulation of several canonical checkpoint inhibitors. TCR-b repertoire analysis of cTfh cells revealed increased oligoclonality in patients with pES compared with HC. Among patients with pES, those without a known gene defect had a similar characteristic immune abnormality as patients with defined genetic defects. Similarly, patients with pES with normal IgG had similar T cell abnormalities as patients with low IgG. Since genetic defects have been identified in only less than half of patients with pES, our findings of similar immune abnormalities across all pES patients help establish a common characteristic immunopathology in pES irrespective of the underlying genetic etiology.

Background Heavy menstrual bleeding (HMB) is often the first bleeding symptom for female individuals with inherited bleeding disorders. Guidelines recommend performing the hemostatic evaluation at HMB presentation. Von Willebrand factor (VWF) levels increase with stress, making it unclear if VWF studies during acute bleeding are beneficial in diagnosing von Willebrand disease (VWD). Objectives To determine the utility of testing for VWD during acute HMB. Patients/Methods This retrospective cohort study evaluated VWF levels of individuals presenting to the emergency department (ED) with HMB from January 1, 2017, to December 31, 2018, after prospective implementation of a clinical practice guideline recommending hemostatic evaluation in the ED. We compared VWF and factor VIII (FVIII) levels between acute presentation and follow‐up visit after bleeding resolution. We compared the diagnostic accuracy of initial and follow‐up labs. Results During the study period, 221 individuals were seen in the ED for acute HMB, and 39 had VWD testing at both time points. Median FVIII and VWF levels were higher during acute bleeding than at follow‐up. The difference in VWF levels between visits was negligible when initial FVIII value was normal. Overall incidence of VWD was 7.5%; 69% of those with VWD had low VWF levels during acute HMB. Conclusion VWD testing during acute HMB detects the majority of individuals with VWD but also leads to elevated levels of VWF, potentially limiting at the accuracy of diagnostic labs during acute bleeding episodes. Delayed testing until resolution of anemia and active bleeding may provide more accurate diagnostic evaluation for VWD.