Clinical features and neurological outcomes in pediatric immune‐mediated thrombotic thrombocytopenic purpura: A report from a large pediatric hematology center

Abstract

Background: Thrombotic thrombocytopenic purpura (TTP) is a potentially lifethreatening disorder characterized by microangiopathic hemolytic anemia, thrombocytopenia, and severely reduced or absent ADAMTS13 (A disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) activity, with varying degrees of organ dysfunction. As TTP is rare in pediatrics, most of the medical and scientific literature has largely reported on adult patients. As a result, limited data exist regarding the clinical features, comorbidities, treatment response, and long-term outcomes in pediatric patients with immune-mediated TTP.Methods: A single-center retrospective cohort study was conducted of all children and adolescents presenting to Children's Healthcare of Atlanta, Atlanta, Georgia, between the years 2001 and 2021 with immune-mediated TTP (iTTP). Clinical features, treatments, and outcomes, including long-term neurocognitive function, were analyzed.Results: Eighteen individuals were identified, six of whom had a total of 10 relapses, amounting to 28 episodes overall. Thirty-eight percent of the patients experienced exacerbations but, ultimately, 85% achieved a clinical response and clinical remission. Only one in-hospital death occurred (mortality rate 5.5%). Seventy-three percent of analyzed patients demonstrated long-term neurocognitive abnormalities, including cognitive delay, learning difficulties, and severe depression. Conclusions:Children and adolescents recovering from iTTP are at high risk for neurocognitive deficits from initial and possibly ongoing microvascular disease. Due to risk for long-term neurological deficits, we recommend neuropsychological testing in addition to monitoring of other organ functions in all children with TTP, as well as long-term

Paediatric patients with suspected immune thrombotic thrombocytopenic purpura also experience treatment delays

“…2 Even when iTTP is suspected, treatment initiation with TPE is often postponed pending confirmational testing. 2,10 In this study, we saw no significant differences between children <10 or ≥10 year (see Table 1). Therefore, among paediatric patients, opportunities exist to improve strategies for early TTP diagnosis and treatment.…”

Immune and Hereditary Thrombotic Thrombocytopenic Purpura: Can ADAMTS13 Deficiency Alone Explain the Different Clinical Phenotypes?

“…TRPC5 participates in endothelial cell injury and dysfunction, migration and proliferation of vascular smooth muscle cells, cardiac hypertrophy, and lipid deposition. Moreover, a pharmacological block of the TRPC5 channels can inhibit atherosclerotic plaque progression, improve renal function, play a synergistic role in improving the prognosis of CVD patients, and, importantly, prevent depression and anxiety [75], the latter being a common symptom of the long-term effects of iTTP [76]. Thus, TRPC inhibitors may represent an intriguing target for the pharmacological control of cardiovascular morbidity and mortality in iTTP.…”

Complement‐driven hemolytic uremic syndrome

“…‐A few case series and isolated case reports suggest that the recovery of renal dysfunction and extra‐renal ischemic lesions could be hastened by eculizumab 120–123 . Notably most of the reported cases had low C3 at presentation…”

“…Similarly, in order to identify complement-driven TMA, a newlydeveloped assay has been established to quantify complement [120][121][122][123] Notably most of the reported cases had low C3 at presentation -Yet, two other cases with low C3 did not improve their clinical condition upon eculizumab 124 None Gemcitabine -Small case series and isolated case reports suggest that eculizumab/ravulizumab could promptly obtain the hematological response, decrease the transfusion need, and improve renal recovery 56,125-127 -Eculizumab was also successfully used in one case to mitigate the risk of gemcitabine-associated HUS relapse following gemcitabine re-challenge 127 None HSCT -The response rate to eculizumab was estimated from small retrospective studies at 67%-78% and 33%-60% in children and adults, respectively 128 -A recent meta-analysis including 116 patients from 6 retrospective studies suggest that eculizumab could improve the course of HSCT-related TMA and survival rate 129…”