Background: The outcomes of deep vein thrombosis (DVT) in children with May-Thurner Syndrome (MTS) remain unclear. Objectives: This systematic review and patient-level meta-analysis aims to describe the outcomes of children with MTS presenting with DVT. Methods: A systematic review of the published literature was performed. Data related to patients <18 years diagnosed with MTS and DVT was extracted. Risk of bias was assessed using the Murad criteria. Outcomes included vessel patency post-treatment, DVT recurrence, and post-thrombotic syndrome (PTS). Predictive and explanatory models were developed for these outcomes. Results: In total, 109 cases were identified (age range 4–17 years; 77 females) in 28 studies; 75% of patients had ≥1 additional risk factor for DVT. PTS was seen in 61% of patients, DVT recurrence in 38%, and complete vessel patency post-treatment in 65%. The models developed to predict and explain PTS performed poorly overall. Recurrent thrombosis (adjusted for age and patency) predicted PTS (odds ratio [OR] 3.36, 95% confidence interval [CI] 1.28–8.82). DVT management strategies (adjusted for age and DVT characteristics) predicted vessel patency (OR 2.10, 95% CI 1.43–3.08). Lack of complete vessel patency (adjusted for age and thrombophilia) predicted recurrent DVT (OR 2.70, 95% CI 1.09–6.67). Sensitivity analyses showed the same direction of effects for all outcomes. Conclusions: PTS and DVT recurrence occur frequently in pediatric MTS. PTS prediction is complex and it was not possible to identify early predictors to guide clinical practice. Use of imaging-guided therapy and thrombus burden predicted venous patency, and lack of patency predicted DVT recurrence.

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.

Pediatric Evans syndrome (pES) is increasingly identified as the presenting manifestation of several inborn errors of immunity. 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 (HCs). Compared with 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 immunoglobulin G (IgG) in most pES at presentation, class-switched memory B cells were decreased. Within the cTfh subset, we noted features of postactivation exhaustion with upregulation of several canonical checkpoint inhibitors. T-cell receptor β chain (TCR-β) repertoire analysis of cTfh cells revealed increased oligoclonality in patients with pES compared with HCs. 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. Because genetic defects have been identified in less than half of patients with pES, our findings of similar immune abnormalities across all patients with pES help establish a common characteristic immunopathology in pES, irrespective of the underlying genetic etiology.

BACKGROUND: Thrombosis is common in infants undergoing staged surgeries for single-ventricle congenital heart disease. The reported incidence and timing of thrombosis varies widely, making it difficult to understand the burden of thrombosis and develop approaches for prevention. We aimed to determine the timing and cumulative incidence of thrombosis following the stage I Norwood procedure and identify clinical characteristics associated with thrombosis. METHODS AND RESULTS: We analyzed data from the Pediatric Heart Network Single Ventricle Reconstruction trial from 2005 to 2009 and identified infants with first-time thrombotic events. In 549 infants, the cumulative incidence of thrombosis was 21.2% (n=57) from stage I through stage II. Most events occurred during stage I (n=35/57, 65%), with a median time to thrombosis of 15 days. We used a Cox proportional hazards model to estimate the association of clinical variables with thrombosis. After adjusting for baseline variables, boys had a higher hazard of thrombosis (adjusted hazard ratio [HR], 2.69; 95% CI, 1.44–5.05; P=0.002), non–hypoplastic left heart syndrome cardiac anatomy was associated with a higher early hazard of thrombosis (adjusted HR, 3.93; 95% CI, 1.89–8.17; P<0.001), and longer cardiopulmonary bypass time was also associated with thrombosis (per 10-minute increase, adjusted HR, 1.07; 95% CI, 1.01–1.12; P=0.02). Lower oxygen saturation after the Norwood procedure increased the hazard for thrombosis in the unadjusted model (HR, 1.08; 95% CI, 1.02–1.14; P=0.011). CONCLUSIONS: Thrombosis affects 1 in 5 infants through Stage II discharge, with most events occurring during stage I. Male sex, non–hypoplastic left heart syndrome anatomy, longer cardiopulmonary bypass time, and lower stage I oxygen saturation were associated with thrombosis.

PURPOSE: T cell-Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (T cell-EBV-HLH) is prevalent in East Asia and has poor prognosis. Understanding of this disease is limited, and literature regarding prevalence in North America is scarce. Herein, we summarize our experience. METHODS: A retrospective analysis of T cell-EBV-HLH patients admitted to Children's Healthcare of Atlanta (GA, USA) from 2010 to 2020 was conducted. Additional immune studies were completed in a subset of patients. RESULTS: We report 15 patients (10 months-19 years of age) diagnosed with T cell-EBV-HLH. Nine patients were Hispanic, and the majority did not have primary HLH (p-HLH) gene defects. Soluble interleukin-2 receptor levels in T cell-EBV-HLH were significantly higher than other forms of secondary-HLH but comparable to p-HLH, and it correlated with disease severity at presentation. Natural killer cell function was decreased in most patients despite a negative workup for p-HLH. Depending on disease severity, initial therapy included dexamethasone or dexamethasone and etoposide. Refractory patients were managed with blended regimens that included one or more of the following therapies: combination chemotherapy, alemtuzumab, emapalumab, and nivolumab. Rituximab did not appreciably decrease EBV viremia in most patients. Non-critically ill patients responded well to immunosuppressive therapy and are long-term survivors without undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Alemtuzumab resulted in inflammation flare in two of the three patients. Three patients underwent allogeneic HSCT, with disease relapse noted in one. At a median follow-up of 3 years, 10 of the 15 patients are alive. CONCLUSION: T cell-EBV-HLH occurs in the USA among the non-Asian populations, especially in those who are Hispanic.

I noticed an error in the institutional affiliation of the authors. Deepak Kumar1,2 · Jenny Shim1,2 · Michael Briones1,2 Satheesh Chonat1,2 · Holly Edington1,2 · Michael H. White1,2 · Advay Mahajan1,2 The authors listed above should have only one institutional affiliation. They are only affiliated with Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta and Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA