Hereditary spherocytosis (HS) is a prevalent inherited hemolytic disorder primarily reported in Caucasians. Recently, next‐generation sequencing (NGS) techniques have shown tremendous potential in the diagnosis of HS. HS commonly originates from variants in ANK1, SPTB, SLC4A1, SPTA1, and EPB42. This review is focused on 13 previous clinical studies on genotype–phenotype correlation, which might promote the role of causative variants in the diagnosis and prognosis of HS. Most studies have focused on the pediatric population and Asian countries. The occurrence of novel variants was common in each cohort, and variants with a high frequency of causative genes were demonstrated. In conclusion, patients with variants in SPTA1 and SLC4A1 were reported to have more severe and milder anemia, respectively. ANK1 and SPTB are the most common variants in patients with HS, and no significant difference in phenotypes was observed between patients with variants in ANK1 versus SPTB. The types and locations of variants might influence the phenotype of each genotype, whereas the roles of concomitant pathogenic genes and the source of variants deserve further investigation.

In this study, we assessed the health-related quality of life (QoL) in children with immune thrombocytopenia (ITP) and their parents in China using a disease-specific QoL measure, the Kids' ITP Tools (KIT). Forty-three Children less than 18 years of age with newly diagnosed ITP and their parents were recruited to complete the KIT study. The children’s version of the KIT consisted of 26 items which divided into 5 domains: treatment side effects, intervention-related, disease-related, activity-related, and family-related concerns. Parental version of KIT consisted of 26 items which divided into 6 domains: diagnosis-related, monitoring-related, child’s restricted activity-related, daily life-related, disease outcome, and emotional impact. Each item was rated on a 6-point Likert scale from 1 (not at all) to 6 (a great deal). A high score represented a high concern level. Scores for the individual domains were summed to yield a total KIT score. The reliability of KIT was found to be high in assessing QoL of children with ITP and their parents in China (children’s version: Cronbach’s a=0.933, parents’ version: Cronbach’s a=0.905). Parent KIT scores was significantly higher than child KIT scores, (31.46±14.58）vs（79.05±14.99）Z=7.625，P=0.000. Which suggested that QoL of parents was significantly lower than children’s. Among the children KIT, the highest mean score was noted in the “intervention-related” (1.92±1.30) and “activity related (1.82±1.47)”. Among the parents KIT, the highest mean score was noted in the “emotional impact（4.88±0.97)” and “disease outcome (4.78±1.01)”; (3) The KIT scores for different age groups of children with ITP were significantly different which showed that the older the children were, they cared for more and worried more about the disease. But the KIT scores for parents were no different in different age groups, which suggested that whatever their children are old or young, Chinese parents worried about ITP disease in the same degree. The QoL of children with ITP and their parents were remarkably lower in Chinese, especially for parents. The cross-culturally translated KIT was a valid and reliable disease-specific measure of health-related quality of life for children with ITP. KIT could be used as an tool in clinical trials and management of childhood ITP. Disclosures No relevant conflicts of interest to declare.

Background and ObjectiveIt is urgent to find out an alternative therapy for Kawasaki disease (KD) since around 20% patients are resistant to intravenous immunoglobulin (IVIG) or aspirin. Tanshinone IIA is the active component of the traditional Chinese medicine Danshen (Salvia miltiorrhiza), which has anti-inflammatory and anti-platelet properties; however, whether or not tanshinone IIA has a therapeutic effect on KD remains unclear. Therefore, the present study aimed to examine the effect of tanshinone IIA on KD patients and rabbits with immune vasculitis, and to identify the potential mechanisms with special emphasis on megakaryopoiesis and megakaryocytic apoptosis.MethodsKawasaki disease patients were recruited and prescribed with tanshinone IIA in the absence or presence of aspirin and IVIG, and the inflammatory responses and platelet functions were determined. Megakaryocytes (MKs) isolated from rabbits with immune vasculitis and human megakaryocytic CHRF-288-11 cells were treated with tanshinone IIA to examine the colony forming unit (CFU) and apoptosis, respectively. Microarray assay was conducted to identify potential targets of tanshinone IIA-induced apoptosis.ResultsTanshinone IIA reduced the serum levels of C-reactive protein (CRP), interleukin (IL)-1β, IL-6, and P-selectin in KD patients; such inhibitory effect was more significant compared to aspirin and IVIG. It also dose-dependently lowered the levels of tumor necrosis factor (TNF)-α and IL-8 in peripheral blood mononuclear cells isolated from KD patients. In rabbits with immune vasculitis, tanshinone IIA significantly reduced the serum levels of proinflammatory cytokines and platelet functions. In addition, tanshinone IIA significantly decreased the number of bone marrow MKs and inhibited the Colony Forming Unit-Megakaryocyte (CFU-MK) formation. In human megakaryocytic CHRF-288-11 cells, tanshinone IIA induced caspase-dependent apoptosis, probably through up-regulating TNF receptor superfamily member 9 (TNFRSF9) and the receptor (TNFRSF)-interacting serine/threonine-protein kinase 1 (RIPK1), which may contribute to its anti-platelet and anti-inflammatory properties.ConclusionTanshinone IIA exerts better anti-inflammatory and anti-platelet effects in treating KD patients than aspirin and IVIG. It attenuates immune vasculitis likely by inhibiting IL-mediated megakaryopoiesis and inducing TNFRSF9/RIPK1/caspase-dependent megakaryocytic apoptosis. The findings therefore suggest that tanshinone IIA may be a promising alternative therapy for the treatment of KD.