Pediatric immune thrombocytopenia (ITP) is an acquired disorder associated with autoimmune destruction and impairment of platelet production in children. Some children exhibit poor or transient response to ITP-directed treatments and are referred to as having refractory ITP (rITP). There is currently no consensus on the definition of rITP, nor evidence-based treatment guidelines for patients with rITP. After a survey of pediatric ITP experts demonstrated lack of consensus on pediatric rITP, we pursued a systematic review to examine the reported clinical phenotypes and treatment outcomes in pediatric rITP. The search identified 253 relevant manuscripts; following review, 11 studies proposed a definition for pediatric rITP with no consensus amongst them. Most definitions included sub-optimal response to medical management, while some outlined specific platelet thresholds to define this sub-optimal response. Common attributes identified in this study should be used to propose a comprehensive definition, which will facilitate outcome comparisons of future rITP studies.

Pyruvate kinase (PK) deficiency is an important cause of hereditary non-spherocytic hemolytic anemia caused by a defect in the glycolytic pathway in red blood cells. PK deficient erythrocytes have impaired ATP production and resultant difficulty maintaining normal cell integrity and function, leading to mild to severe anemia due to increased extravascular hemolysis and splenic destruction. Sequelae of chronic hemolysis can result in severe and occasionally life-threatening complications such as hepatobiliary disease, iron overload, bone and cardiopulmonary disease, as well as often markedly impaired quality of life. While the mainstay of management of PK deficiency involves supportive care, comprehensive screening recommendations and disease modifying therapies in development are likely to significantly improve the management of patients. Here, we provide a case-based comprehensive review of the diagnostic evaluation, complications, monitoring recommendations and management of PK deficiency in children.

Background: Autoimmune hemolytic anemia (AIHA) after allogeneic hematopoietic stem cell transplant (HSCT) is a rare but complex and serious complication. Detailed descriptions of cases and management strategies are needed due to lack of prospective trials. Objectives: Describe the incidence, clinical characteristics, and management of AIHA after HSCT in a pediatric cohort. Methods: This is a retrospective cohort study of 33 pediatric patients with AIHA after HSCT at an academic tertiary care center from 2003 to 2019. A case-control analysis was performed to compare outcomes. Results: The overall incidence of AIHA after allogeneic HSCT was 3.8% (33/868). AIHA was significantly more common after transplant for non-malignant versus malignant diagnoses (7.0% (26/370) vs. 1.4% (7/498), p<0.0001). AIHA developed at a median of 4.7 months (range: 1.0-29.7) after transplant. Sixteen of 33 patients (48.5%) required new AIHA-directed pharmacologic therapy; 17 (51.5%) were managed on their current immunosuppression and supportive care. Patients managed without additional therapy were significantly older, more likely to have a malignant diagnosis, and tended to develop AIHA at an earlier timepoint after transplant. Patients received a median of 2 red blood cell transfusions within the first two weeks of diagnosis and a median of one AIHA-directed medication (range: 1-4), most commonly corticosteroids and rituximab. Conclusions: AIHA after HSCT is rare but occurs more commonly in patients transplanted for non-malignant diagnoses. While some patients can be managed on current immunosuppression and supportive care, many require AIHA-directed therapy including second-line medications.