Good engraftment after reduced intensity targeted busulfan-based conditioning and matched related donor hematopoietic cell transplantation in hemoglobinopathies.

Background: Hematopoietic cell transplantation (HCT) is an established curative therapy for transfusion-dependent thalassemia (TDT) and sickle cell disease (SCD). The latest American Society of Hematology guidelines recommend myeloablative preparative regimen in patients under 18 years of age.

Procedure: The objective was to demonstrate safety and efficacy of a reduced intensity conditioning (RIC) regimen including high-dose fludarabine, anti-thymocyte globulin, and targeted busulfan as a single alkylator to sub-myeloablative exposures.

IVIg treatment increases thrombin activation of platelets and thrombin generation in paediatric patients with immune thrombocytopenia.

Clinical manifestations and laboratory parameters of haemostasis were investigated in 23 children with newly diagnosed immune thrombocytopenia (ITP) before and after intravenous immunoglobulin (IVIg) treatment. ITP patients with platelet counts of less than 20 × 10 /L and mild bleeding symptoms, graded by a standardized bleeding score (BS), were compared with healthy children with normal platelet counts and children with chemotherapy-related thrombocytopenia. Markers of platelet activation and platelet apoptosis in the absence and presence of platelet activators were analysed by flow cytometry; thrombin generation in plasma was determined.

Using the hemolysis index of Abbott's Alinity c for the measurement of plasma free hemoglobin in ECMO patients.

Objectives: Quantitative measurement of plasma free hemoglobin (fHb) concentrations is essential for monitoring pediatric ECMO patients, since hemolysis has a great impact on the patient's clinical outcome. The aim of this study was to validate the hemolysis index (HI) assay on Abbott's Alinity c system as a quantitative method to measure fHb.

Methods: The performance of the HI assay, based on an automated spectrophotometric method recording the absorption at four different wavelength pairs, was evaluated using the 20 × 2 × 2 design according to the CLSI-EP05-A3 guidelines.

Comparison between intraoperative bleeding score and ROTEM® measurements to assess coagulopathy during major pediatric surgery.

Purpose: Intraoperative bleeding should be regularly assessed visually to guide coagulation management. Whereas viscoelastic testing with ROTEM® measurement has been proven to be useful in detecting coagulopathies, the visual assessment is not standardized. This study therefore aims to compare a standardized visual assessment with ROTEM® results.

The landscape of pediatric Diamond-Blackfan anemia in Switzerland: genotype and phenotype characteristics.

Diamond-Blackfan anemia (DBA) is caused mainly by genetic mutations in large (RPL) or small ribosomal subunit genes (RPS) and presents with macrocytic anemia and congenital malformations. Clinical differences between genotypes are insufficiently understood. The aim of this study was to assess clinical features, treatment strategies, and genotypes in the Swiss pediatric DBA population.

Platelets express adaptor proteins of the extrinsic apoptosis pathway and can activate caspase-8.

Background: Apoptotic pathways in platelets are important for their survival and function. Platelet apoptosis may be involved in the pathogenesis of immune thrombocytopenia (ITP), an autoimmune-mediated disease. In contrast to the intrinsic apoptosis pathway, not much is known about the extrinsic pathway mechanisms in platelets.

Synonymous GATA2 mutations result in selective loss of mutated RNA and are common in patients with GATA2 deficiency.

Deficiency of the transcription factor GATA2 is a highly penetrant genetic disorder predisposing to myelodysplastic syndromes (MDS) and immunodeficiency. It has been recognized as the most common cause underlying primary MDS in children. Triggered by the discovery of a recurrent synonymous GATA2 variant, we systematically investigated 911 patients with phenotype of pediatric MDS or cellular deficiencies for the presence of synonymous alterations in GATA2.

Increased levels of IL-10 and IL-1Ra counterbalance the proinflammatory cytokine pattern in acute pediatric immune thrombocytopenia.

Immune thrombocytopenia (ITP) is an autoimmune disease which leads to accelerated platelet clearance. We investigated the plasma cytokine, chemokine and growth factor signatures and their clinical significance in pediatric ITP patients during acute, chronic and follow-up stages as well as the effects of intravenous immunoglobulin (IVIg) treatment, by using the Multiplex technology. In acute ITP before and/or after IVIg treatment we found significantly increased plasma levels of the pro- (tumour necrosis factor-α (TNF-α), interleukin IL-15) and anti- (IL-1 receptor antagonist (Ra), IL-10 and the growth factor interferon γ-induced protein (IP-10)) inflammatory cytokines, compared to healthy controls.

Risk factors and outcomes of postoperative emergency response team activation: a matched case-control study.

Objective: To determine patient and perioperative characteristics associated with unexpected postoperative clinical deterioration as determined for the need of a postoperative emergency response team (ERT) activation.

Design: Retrospective case-control study.

Setting: Tertiary academic hospital.

Diagnosis and management of iron deficiency in children with or without anemia: consensus recommendations of the SPOG Pediatric Hematology Working Group.

Iron deficiency is the most prevalent nutritional deficiency affecting children and adolescents worldwide. A consistent body of epidemiological data demonstrates an increased incidence of iron deficiency at three timepoints: in the neonatal period, in preschool children, and in adolescents, where it particularly affects females.Conclusion: This narrative review focuses on the most suggestive symptoms of iron deficiency in childhood, describes the diagnostic procedures in situations with or without anemia, and provides Swiss expert-based management recommendations for the pediatric context.

Newborn screening for sickle cell disease in Europe: recommendations from a Pan-European Consensus Conference.

Sickle Cell Disease (SCD) is an increasing global health problem and presents significant challenges to European health care systems. Newborn screening (NBS) for SCD enables early initiation of preventive measures and has contributed to a reduction in childhood mortality from SCD. Policies and methodologies for NBS vary in different countries, and this might have consequences for the quality of care and clinical outcomes for SCD across Europe.

Usefulness of multiple electrode aggregometry as a screening tool for bleeding disorders in a pediatric hospital.

Platelet function testing is a cornerstone in the diagnostic investigation of patients with a bleeding history. Multiple electrode aggregometry (MEA) has been shown to detect von Willebrand disease (VWD), platelet function disorders, and drug-induced bleeding disorders. However, there are few studies supporting its successful use in children.

RAS-pathway mutation patterns define epigenetic subclasses in juvenile myelomonocytic leukemia.

Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative disorder of early childhood characterized by mutations activating RAS signaling. Established clinical and genetic markers fail to fully recapitulate the clinical and biological heterogeneity of this disease. Here we report DNA methylome analysis and mutation profiling of 167 JMML samples.

Impact of genetic variants on haematopoiesis in patients with thrombocytopenia absent radii (TAR) syndrome.

Thrombocytopenia absent radii (TAR) syndrome is clearly defined by the combination of radial aplasia and reduced platelet counts. The genetics of TAR syndrome has recently been resolved and comprises a microdeletion on Chromosome 1 including the RBM8A gene and a single nucleotide polymorphism (SNP) either at the 5' untranslated region (5'UTR) or within the first intron of RBM8A. Although phenotypically readily diagnosed after birth, the genetic determination of particular SNPs in TAR syndrome harbours valuable information to evaluate disease severity and treatment decisions.

Severe glucose-6-phosphate dehydrogenase deficiency leads to susceptibility to infection and absent NETosis.

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymatic disorder of red blood cells in human subjects, causing hemolytic anemia linked to impaired nicotinamide adenine dinucleotide phosphate (NADPH) production and imbalanced redox homeostasis in erythrocytes. Because G6PD is expressed by a variety of hematologic and nonhematologic cells, a broader clinical phenotype could be postulated in G6PD-deficient patients. We describe 3 brothers with severe G6PD deficiency and susceptibility to bacterial infection.

Prevalence, clinical characteristics, and prognosis of GATA2-related myelodysplastic syndromes in children and adolescents.

Germline GATA2 mutations cause cellular deficiencies with high propensity for myeloid disease. We investigated 426 children and adolescents with primary myelodysplastic syndrome (MDS) and 82 cases with secondary MDS enrolled in 2 consecutive prospective studies of the European Working Group of MDS in Childhood (EWOG-MDS) conducted in Germany over a period of 15 years. Germline GATA2 mutations accounted for 15% of advanced and 7% of all primary MDS cases, but were absent in children with MDS secondary to therapy or acquired aplastic anemia.