Atypical hemolytic uremic syndrome (aHUS) is an infrequently encountered complement-mediated thrombotic microangiopathy (TMA) usually associated with germline variants in genes of the complement system. Clinical findings of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI) with severe hypertension arise due to aberrant complement protein activation in the circulation and significant endothelial damage. Transplant-associated thrombotic microangiopathy has been increasingly recognized after high dose carboplatin, etoposide, and melphalan-chemotherapy followed by autologous hematopoietic stem cell rescue for treatment of children with neuroblastoma (NB). We report the case of a 13-month-old boy with metastatic neuroblastoma who developed aHUS during the first cycle of induction chemotherapy. Germline testing revealed a Complement factor H (CFH) gene mutation, Cys357Arg, which is currently classified as a variant of uncertain significance (VUS), although likely pathogenic based on molecular modeling as well as this patient’s clinical presentation. The patient has been successfully managed with complement blockade therapy with no recurrence of disease. We review presentations of neuroblastoma with hypertension, along with AKI and thrombocytopenia, to raise awareness about the potential for aHUS in patients with newly diagnosed NB.

Background: Flow artifact, intrinsic to Magnetic Resonance Angiography (MRA), is dependent on technical parameters and can lead to overinterpretation of stenosis. Degree of cerebrovascular stenosis in pediatric patients with sickle cell anemia (SCA) informs need for chronic transfusion therapy, which may have significant risks. The primary objective of this study was to document any change in stroke prevention therapy that could be attributed to the implementation of a standardized MRA scanning protocol. Procedure: A standardized MRA scanning protocol with an echo time of <5 msec was implemented at Montefiore Medical Center in May 2016. Retrospective chart review identified 29 patients ≤ 21 years with SCA cerebral vasculopathy and an MRA head pre- and post-May 2016. Level of arterial stenosis on MRA, echo time, and treatment plans were documented both pre- and post-implementation. McNemar analysis determined the significance of change in treatment plans before and after implementation of the standardized scanning protocol. Results: Previously seen stenosis was re-classified to a lower degree in 12/29 patients (41%). Notably, 6 patients had a reclassification of vasculopathy leading to discontinuation of chronic transfusion therapy whereas 0 patients required escalation of therapy to chronic transfusions. McNemar analysis showed this difference to be statistically significant (p = 0.042). Conclusion: Minimizing flow artifact with echo time <5msec improves accurate interpretation of true cerebrovascular disease and ensures appropriate treatment plans are in place for stroke prevention. This is especially important when trying to implement “TCD With Transfusions Changing to Hydroxyurea (TWiTCH)” clinical trial results in the real-world setting.

We report the clinical and laboratory coagulation characteristics of 27 pediatric and young adult patients (2 months to 21 years) treated for symptomatic COVID-19 at a children’s hospital in the Bronx, New York between March 1 and May 31, 2020. D-Dimer was > 0.5 ug/mL (upper limit of normal) in 25 (93%) patients at admission; 11 (41%) developed peak D-Dimer > 5 ug/mL during admission. Seven (26%) patients developed venous thromboembolism: three with deep vein thrombosis and four with pulmonary embolism. Requirement of increased ventilatory support was a risk factor for thrombosis (p=0.006). Three of eight (38%) patients on prophylactic anticoagulation developed thrombosis, however no patients developed VTE on low molecular weight heparin prophylaxis titrated to anti-Xa level. Manifestation of COVID-19 disease was severe or critical in 16 (59%) patients. Four (15%) patients died of COVID-19 complications: all had comorbidities. Elevated D-dimer and increased VTE rate were observed in this young cohort, particularly in those with severe respiratory complications suggesting thrombotic coagulopathy. More data is needed to guide thromboprophylaxis in this age group.