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Clinical uses for recombinant human erythropoietin (rHuEPO) therapy continue to expand. Initial use was in anaemia associated with end-stage renal disease, but more recently there have been many reports of the benefits of erythropoietin in other clinical situations such as cancer-related anaemia. Recombinant erythropoietin reduces the need for blood transfusion and hence exposure to donor blood products as well as improving quality of life. We report four patients who were transfusion dependent, none of whom had licensed indications for the use of recombinant erythropoietin. Two patients had microangiopathic haemolytic anaemia secondary to mechanical valve haemolysis and were unsuitable for any further cardiac intervention. One patient had anaemia of chronic disease and anti-Vel red cell antibodies, making compatible blood transfusions difficult to obtain. The fourth patient had primary thrombocythaemia and developed transfusion-dependent anaemia secondary to myelosuppressive agents. All four patients had a relative deficiency in endogenous erythropoietin levels ranging between 7 and 41?IU/l. After commencing recombinant erythropoietin therapy, all had a response in haemoglobin of at least 1?g/dl with an overall improvement in their quality of life. We conclude that rHuEPO is a very convenient and useful form of treatment in transfusion-dependent anaemia and in some cases beyond the licensed indications.The Hematology Journal (2004) 5, 181-185. doi:10.1038/sj.thj.6200350 [ABSTRACT FROM AUTHOR]

A previous literature review found at least 4/9 (>=44.4%) CMMRD-associated ALL were T-ALL [[1]], and 8/88 (9.1%, 95% CI: 0.4-17.1%) childhood T-LBL patients were diagnosed with CMMRD in a consecutive series between 2007 and 2020 [[15]], suggesting an association of CMMRD with T cell lineage malignancies. For example, PCR-fragment length analysis has been shown to be insensitive to MSH6 deficiency in ALL relapse samples [[3]], and detected increased MSI in only 27% of CMMRD haematological malignancies and in 0% of non-neoplastic CMMRD tissues [[9]]. Here, 1/17 (5.9%, 95% CI: 0.2-28.7%) ALL patients with SMN had CMMRD, which is similar to the 14/189 (7.4%, 95% CI: 4.1-12.1%) pediatric non-Hodgkin lymphoma patients with SMN who had CMMRD in another recent study [[16]]. Constitutional mismatch repair deficiency (CMMRD, MIM #276300) is a rare, recessive pediatric and adolescent cancer syndrome, caused by pathogenic variants in a mismatch repair (MMR) gene: I MLH1 i , I MSH2 i , I MSH6 i , or I PMS2 i . [Extracted from the article]

Thrombosis in children is becoming more prevalent due to increased awareness of these issues in the pediatric population and advances in medicine. Management of affected children are challenging due to differences in their hemostatic system compared with adults. Prospective, controlled trials for management/treatment of children with thrombosis are lacking. Many of the available guidelines for treatment of thrombosis in children are extrapolated from adult data and do not account for the uniqueness of the pediatric hemostatic system, although more research and data are becoming available. This review will focus on children over 1 year of age, including adolescents, looking at the etiology of thrombosis, diagnosis, management options, and any associated complications in this pediatric population. [ABSTRACT FROM AUTHOR]

The presence of multiple bleeding symptoms and/or severe bleeding symptom(s) contribute to a higher score and therefore a greater chance of a bleeding disorder diagnosis. There is bleeding at a critical site (e.g., ICH, retinal haemorrhage, gastrointestinal haemorrhage, intraspinal haemorrhage, haemarthrosis) with no correlating history of trauma or other explanation that adequately accounts for the bleeding. ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders. A standardised bleeding assessment tool, e.g., the International Society for Haemostasis and Thrombosis Bleeding Assessment Tool (ISTH-BAT), can be used to quantitate bleeding symptoms in order to generate a bleeding score. [Extracted from the article]

The article discusses the British Society for Haematology's (BSH) guidelines on the management of thrombotic and haemostatic issues in paediatric malignancy. Topics discussed include the methodology for the creation of the guidelines, venous thromboembolism (VTE) and bleeding as serious complications of cancer and its treatment, assessing and reducing the risk of VTE, treatment of various types of VTE, management of thrombocytopenia and coagulopathy and therapy for menstrual suppression.

Hexokinase (HK) is a key enzyme of glycolysis, the only metabolic pathway able to provide the red blood cell with ATP. HK deficiency is a very rare hereditary disorder with severe chronic nonspherocytic hemolytic anemia (HNSHA) as a major clinical feature. To date, only 24 patients with HK deficiency have been identified. Here, we report the molecular analysis of six new cases of HK deficiency. A total of six different mutations were detected in HK1 , four of them described here for the first time: c.2599C > T p.(His867Tyr), c.1799C > T p.(Thr600Met), c.873-2A > G and c.493-1G > A. The pathogenic nature of the identified missense mutations was confirmed by biochemical and 3-dimensional structural analysis. The effects of the novel splice site mutation c.873-2A > G were studied at the level of pre-mRNA processing, and confirmed at the protein level. All together, these results provide a better insight into the pathogenesis of this rare red cell disorder, and contribute to a better understanding of the genotype-phenotype correlation in HK deficiency. [ABSTRACT FROM AUTHOR]