Real-World Data on the Effectiveness and Safety of wilate for the Treatment of von Willebrand Disease.

 The efficacy and safety of wilate (human von Willebrand factor/coagulation factor VIII) in patients with von Willebrand disease (VWD) has been demonstrated in clinical trials. Here, we present real-world data on the use of wilate for the routine care of patients with VWD.  The objectives of this observational, prospective, phase 4 study were to evaluate the safety, tolerability, and effectiveness of wilate in on-demand treatment of bleeding episodes (BEs), long-term prophylaxis, and surgical prophylaxis among patients with any type of VWD.

Pyruvate kinase deficiency in children.

Background: Pyruvate kinase deficiency (PKD) is a rare, autosomal recessive red blood cell enzyme disorder, which leads to lifelong hemolytic anemia and associated complications from the disease and its management.

Methods: An international, multicenter registry enrolled 124 individuals younger than 18 years old with molecularly confirmed PKD from 29 centers. Retrospective and prospective clinical data were collected.

Comorbidities and complications in adults with pyruvate kinase deficiency.

Objectives: Pyruvate kinase (PK) deficiency is caused by PKLR gene mutations, leading to defective red blood cell glycolysis and hemolytic anemia. Rates of comorbidities and complications by transfusion history and relative to the general population remain poorly quantified.

Methods: Data for patients aged ≥ 18 years with two confirmed PKLR mutations were obtained from the PK deficiency Natural History Study (NCT02053480).

Genotype-phenotype correlation and molecular heterogeneity in pyruvate kinase deficiency.

Pyruvate kinase (PK) deficiency is a rare recessive congenital hemolytic anemia caused by mutations in the PKLR gene. This study reports the molecular features of 257 patients enrolled in the PKD Natural History Study. Of the 127 different pathogenic variants detected, 84 were missense and 43 non-missense, including 20 stop-gain, 11 affecting splicing, five large deletions, four in-frame indels, and three promoter variants.

Safety and efficacy of turoctocog alfa in the prevention and treatment of bleeds in previously untreated paediatric patients with severe haemophilia A: Results from the guardian 4 multinational clinical trial.

Introduction: Turoctocog alfa is a recombinant, B domain-truncated factor VIII (FVIII) approved for patients with haemophilia A.

Aim: To evaluate the safety and efficacy of turoctocog alfa in previously untreated patients (PUPs) with severe haemophilia A.

Methods: Guardian 4 was a multicentre, multinational, non-randomized, open-label phase 3 trial comprising a main and extension phase.

Safety and Efficacy of Mitapivat in Pyruvate Kinase Deficiency.

Background: Pyruvate kinase deficiency is caused by mutations in and leads to congenital hemolytic anemia. Mitapivat is an oral, small-molecule allosteric activator of pyruvate kinase in red cells.

Methods: In this uncontrolled, phase 2 study, we evaluated the safety and efficacy of mitapivat in 52 adults with pyruvate kinase deficiency who were not receiving red-cell transfusions.

Ferritin in serum and urine: A pilot study.

Serum ferritin reflects total body iron stores, thus a low serum ferritin is used as a parameter of iron deficiency. In healthy adults in Japan, urine ferritin levels were about 5% of serum ferritin levels, with a correlation coefficient of 0.79.

Acute neonatal bilirubin encephalopathy in the State of Utah 2009-2018.

Herein we report a case series of seven newborn infants, all apparently well at birth, who in the period since 2009 were cared for in the State of Utah with acute bilirubin encephalopathy (ABE). This report summarizes our attempts to define common features of these seven through a state-wide voluntary registry, as a step toward devising new means of preventing such cases in the future. In previous reports of ABE, many of the affected neonates had no clearly defined explanation for their progressive hyperbilirubinemia.

Fetal presentation of congenital dyserythropoietic anemia type 1 with novel compound heterozygous CDAN1 mutations.

The congenital dyserythropoietic anemias are a heterogeneous group of disorders characterized by anemia and ineffective erythropoiesis. Congenital dyserythropoietic anemia type I (CDA1) can present in utero with hydrops fetalis, but more often it presents in childhood or adulthood with moderate macrocytic anemia, jaundice, and progressive iron-overload. CDA1 is inherited in an autosomal recessive manner, with biallelic pathogenic variants in CDAN1 or C15orf41.

Clinical spectrum of pyruvate kinase deficiency: data from the Pyruvate Kinase Deficiency Natural History Study.

An international, multicenter registry was established to collect retrospective and prospective clinical data on patients with pyruvate kinase (PK) deficiency, the most common glycolytic defect causing congenital nonspherocytic hemolytic anemia. Medical history and laboratory and radiologic data were retrospectively collected at enrollment for 254 patients with molecularly confirmed PK deficiency. Perinatal complications were common, including anemia that required transfusions, hyperbilirubinemia, hydrops, and prematurity.

Two novel mutations in TMPRSS6 associated with iron-refractory iron deficiency anemia in a mother and child.

In an iron deficient child, oral iron repeatedly failed to improve the condition. Whole exome sequencing identified one previously reported plus two novel mutation in the TMPRSS6 gene, with no mutations in other iron-associated genes. We propose that these mutations result in a novel variety of iron-refractory iron deficiency anemia.

Three Novel Spectrin Variants in Jaundiced Neonates.

Various mutations in the genes encoding alpha spectrin (SPTA1) or beta spectrin (SPTB) are known to cause erythrocyte membrane disorders, sometimes associated with severe neonatal jaundice and anemia. We used a next-generation sequencing panel to evaluate 3 unrelated neonates who had puzzling cases of nonimmune hemolytic jaundice. In each case, we identified novel mutations in either SPTA1 or SPTB.

Neonatal nonimmune hemolytic anemia.

Purpose Of Review: As in adults and older children, anemia in newborn infants can be the result of erythropoietic failure, hemorrhage, or hemolysis. When hemolysis is the prime consideration, it can be challenging for physicians caring for neonates to choose from the wide variety of available diagnostic tests. This review describes the authors' opinions regarding rational, consistent, and cost-effective means of making an exact diagnosis of a neonatal hemolytic condition.

Ringed sideroblasts in β-thalassemia.

Symptomatic β-thalassemia is one of the globally most common inherited disorders. The initial clinical presentation is variable. Although common hematological analyses are typically sufficient to diagnose the disease, sometimes the diagnosis can be more challenging.

Siblings with severe pyruvate kinase deficiency and a complex genotype.

Siblings presented as neonates with severe jaundice and transfusion-dependent hemolytic anemia. Next-generation sequencing revealed both to have three heterozygous mutations in the gene encoding erythrocyte pyruvate kinase (PKLR), plus a heterozygous splice mutation in the beta-spectrin gene (SPTB). In addition, both have a different 5th mutation in a gene encoding other erythrocyte membrane proteins.

Clinical utility of next-generation sequencing in the diagnosis of hereditary haemolytic anaemias.

Hereditary haemolytic anaemias are genetically and phenotypically heterogeneous disorders characterized by increased red cell destruction, with consequences ranging from innocuous to severe life-threatening anaemia. Diagnostic laboratories endeavour to assist clinicians reach the exact patient diagnosis by using tests principally based on morphological and biochemical techniques. However, these routine studies may be inconclusive, particularly in newborn infants and when transfusions have recently been administered.

Hemolysis in Preterm Neonates.

Hemolysis can be an important cause of hyperbilirubinemia in premature and term neonates. It can result from genetic abnormalities intrinsic to or factors exogenous to normal to red blood cells (RBCs). Hemolysis can lead to a relatively rapid increase in total serum/plasma bilirubin, hyperbilirubinemia that is somewhat slow to fall with phototherapy, or hyperbilirubinemia that is likely to rebound after phototherapy.

Improved harmonization of eosin-5-maleimide binding test across different instruments and age groups.

Background: The eosin-5'maleimide (EMA) binding test has been studied extensively for the detection of hereditary spherocytosis (HS). Its performance characteristics have been compared to NaCl-based or glycerol lysis-based red cell osmotic fragility tests and cryohemolysis. HS samples are also better identified when both mean channel fluorescence (MCF) of EMA relative to controls and the coefficient of variation (CV) are analyzed.

Hemolytic Disorders Causing Severe Neonatal Hyperbilirubinemia.

A shortened erythrocyte life span, because of hemolytic disorders, is a common cause of extreme neonatal hyperbilirubinemia. Clinical and laboratory examinations can frequently identify the underlying cause of extreme neonatal hyperbilirubinemia. In this article, several tests, techniques, and approaches have been reviewed, including red blood cell morphology assessment, end-tidal carbon monoxide quantification, eosin-5-maleimide flow cytometry, as well as next-generation DNA sequencing using neonatal jaundice panels.

Erythrocyte pyruvate kinase deficiency: 2015 status report.

Over the last several decades, our understanding of the genetic variation, pathophysiology, and complications of the hemolytic anemia associated with red cell pyruvate kinase deficiency (PKD) has expanded. Nonetheless, there remain significant gaps in our knowledge with regard to clinical care and monitoring. Treatment remains supportive with phototherapy and/or exchange transfusion in the newborn period, regular or intermittent red cell transfusions in children and adults, and splenectomy to decrease transfusion requirements and/or anemia related symptoms.

A pediatrician's practical guide to diagnosing and treating hereditary spherocytosis in neonates.

Newborn infants who have hereditary spherocytosis (HS) can develop anemia and hyperbilirubinemia. Bilirubin-induced neurologic dysfunction is less likely in these neonates if the diagnosis of HS is recognized and appropriate treatment provided. Among neonates listed in the USA Kernicterus Registry, HS was the third most common underlying hemolytic condition after glucose-6-phosphate dehydrogenase deficiency and ABO hemolytic disease.

Novel α-spectrin mutation in trans with α-spectrin causing severe neonatal jaundice from hereditary spherocytosis.

We evaluated a neonate with severe jaundice but a negative family history. Spherocytes were present and suspected hereditary spherocytosis was confirmed by osmotic fragility and eosin-5-maleimide erythrocyte staining. We found he was a compound heterozygote for two pathogenic mutations in the gene encoding α-spectrin: a previously reported α(LEPRA) inherited from his asymptomatic mother, and a novel α-spectrin mutation in intron 45 +1 disrupting the consensus splice site, from his asymptomatic father.