Publications by authors named "Rachael F Grace"

Objectives: Evidence-based protocols for managing bleeding emergencies in patients with immune thrombocytopenia (ITP) are lacking. We conducted a systematic review of treatments for critical bleeding in patients with ITP.

Methods: We included all study designs and extracted data in aggregate or individually for patients who received one or more interventions and for whom any of the following outcomes were reported: platelet count response, bleeding, disability, or death.

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  • Researchers conducted a genome-wide association study to identify genetic variants linked to pediatric immune thrombocytopenia (ITP) in a large group of patients.
  • Six significant genetic variants were found, particularly in the genes NAV2 and NKD1, which are associated with the Wnt signaling pathway and inversely correlated with ITP.
  • The study highlighted that no significant genetic variants were found to differentiate between those with ITP who recovered quickly and those who developed chronic ITP, suggesting a complex genetic influence on disease outcomes.
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  • Pyruvate kinase (PK) deficiency is a rare genetic anemia linked to the PKLR gene, leading to various health issues; however, its full impact is not fully understood.* -
  • The Peak Registry study analyzed 241 patients with PK deficiency, noting significant treatments like splenectomy (48.3%) and chelation therapy (50.5%), as well as common complications like iron overload and neonatal issues.* -
  • Adult patients also face serious complications, such as bone health problems and pulmonary hypertension, highlighting the need for better awareness and management strategies among healthcare providers.*
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The Kids ITP Tools (KIT) is a health-related quality of life (HRQoL) questionnaire that evaluates quality of life in children with immune thrombocytopenia (ITP). There are three formats: Child Self-Report, Parent Proxy-Report and Parent Impact-Report. This study aimed to develop a domain structure by grouping-related questions from the questionnaire into domains that independently reflect various aspects of HRQoL.

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  • * In 2023, the Pediatric ITP Consortium defined refractory pediatric ITP as no platelet response after treatment with all eligible emergent therapies.
  • * Patients with high disease burden or lack of platelet response, despite various treatments, are identified as a challenging group that requires further research and the potential for new treatment options.
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  • Mitapivat treatment showed significant improvements in the signs and symptoms of PK Deficiency in adult patients.* -
  • The results were based on data collected from disease-specific patient-reported outcome measures.* -
  • These findings were observed in two separate phase 3 clinical trials, indicating the potential effectiveness of mitapivat.*
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The 2019 American Society of Hematology (ASH) guidelines for immune thrombocytopenia (ITP) included recommendations on the management of adults (recommendations 1-9) and children (recommendations 10-21) with primary ITP . We describe here the results of a review of the 2019 guidelines by a working group of experts requested by ASH to inform decision-making about the need for and timing of a guideline revision. An updated Medline and Embase search applied the same search terms as in the 2019 ASH guidelines, limited to systematic reviews and clinical trials, from May 2017 to July 2022.

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Introduction: Autoimmune diseases are heterogeneous and often lack specific or sensitive diagnostic tests. Increased percentages of CD4CXCR5PD1 circulating T follicular helper (cTfh) cells and skewed distributions of cTfh subtypes have been associated with autoimmunity. However, cTfh cell percentages can normalize with immunomodulatory treatment despite persistent disease activity, indicating the need for identifying additional cellular and/or serologic features correlating with autoimmunity.

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  • Pyruvate kinase deficiency is a common cause of chronic congenital non-spherocytic hemolytic anemia, affecting about 1 in 100,000 to 1 in 300,000 people, leading to serious health issues.
  • The International Guidelines for the Diagnosis and Management of Pyruvate Kinase Deficiency were created to provide evidence-based recommendations for treating patients, developed by a global panel of 29 experts across multiple specialties.
  • The guidelines cover five key areas, including diagnosis, management of complications, anemia treatment, advanced therapies, and special populations, with a total of 31 recommendations aimed at improving patient care.
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Pyruvate kinase (PK) deficiency is a rare, hereditary disease characterized by chronic hemolytic anemia. Iron overload is a common complication regardless of age, genotype, or transfusion history. Mitapivat, an oral, allosteric PK activator, improves anemia and hemolysis in adult patients with PK deficiency.

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Pyruvate kinase (PK) deficiency is a congenital hemolytic anemia with wide-ranging clinical symptoms and complications associated with significant morbidity and reduced health-related quality of life in both children and adults. The management of patients with PK deficiency has been historically challenging due to difficulties in the diagnostic evaluation, heterogeneity of clinical manifestations, and treatment options limited to supportive care with transfusions and splenectomy. An oral allosteric PK activator, mitapivat, is now a clinically available disease-modifying treatment for adults with PK deficiency.

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Background: Pyruvate kinase (PK) deficiency is a rare hereditary disorder characterized by chronic hemolytic anemia and serious sequalae which negatively affect patient quality of life. This study aimed to psychometrically validate the first disease-specific patient-reported outcome (PRO) instruments: the 7-item PK Deficiency Diary (PKDD) and 12-item PK Deficiency Impact Assessment (PKDIA), designed to assess signs, symptoms, and impacts of PK deficiency in patients enrolled in the ACTIVATE global phase 3 study of mitapivat versus placebo (NCT03548220).

Methods: All validation analyses for the PKDD and PKDIA were performed on blinded data, with analyses on item integrity, scoring, reliability, and validity conducted on data from screening and baseline.

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Background: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is caused by antibodies against human platelet antigens (HPA). However, in many cases that meet clinical criteria for the condition, maternal sera do not have HPA antibodies. In studies examining whether human leukocyte antigen (HLA) antibodies cause FNAIT, the results are limited and inconclusive.

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Introduction: Pyruvate kinase (PK) deficiency is a rare, under-recognised, hereditary condition that leads to chronic haemolytic anaemia and potentially serious secondary complications, such as iron overload, cholecystitis, pulmonary hypertension and extramedullary haematopoiesis. It is an autosomal recessive disease caused by homozygous or compound heterozygous mutations in the gene. Due to its rarity and clinical heterogeneity, information on the natural history and long-term clinical course of PK deficiency is limited, presenting major challenges to patient management, the development of new therapies and establishing disease-specific treatment recommendations.

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Mutations in the PKLR gene lead to pyruvate kinase (PK) deficiency, causing chronic hemolytic anemia secondary to reduced red cell energy, which is crucial for maintenance of the red cell membrane and function. Heterogeneous clinical manifestations can result in significant morbidity and reduced health-related quality of life. Treatment options have historically been limited to supportive care, including red cell transfusions and splenectomy.

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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.

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Despite availability of epidemiologic studies and national guidelines for the management of newly diagnosed pediatric immune thrombocytopenia (ITP), practice variation exists among and within hematology practices. We previously described the development of an ITP pathway guiding management based on bleeding symptoms. Over an 8-year period, integration of this iterative ITP pathway into management of newly diagnosed ITP increased observation rates in children with no or mild bleeding symptoms and improved consistency of laboratory evaluation and treatment strategies without increasing adverse outcomes.

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Pyruvate kinase (PK) deficiency is a rare, congenital red blood cell disorder caused by a single gene defect. The spectrum of genotypes, variants, and phenotypes are broad, commonly requiring a multimodal approach including enzyme and genetic testing for accurate and reliable diagnosis. Similarly, management of primary and secondary sequelae of PK deficiency varies, mainly including supportive care with transfusions and surgical interventions to improve symptoms and quality of life.

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Article Synopsis
  • Pyruvate kinase deficiency is a rare genetic disorder leading to chronic hemolytic anemia, and the phase 3 trial assessed the impact of mitapivat, a new medication, on this condition.
  • In the trial, adults not on regular blood transfusions were randomized to receive either mitapivat or a placebo for 24 weeks, with the main goal of seeing significant increases in hemoglobin levels.
  • Results showed that 40% of patients on mitapivat achieved a notable hemoglobin response compared to none in the placebo group, with some common side effects including nausea and headaches, but overall, mitapivat demonstrated a better efficacy in treating this disorder.
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Background: Children with immune thrombocytopenia (ITP) may require second-line ITP therapies. The high remission rate in pediatric patients, need for extended-duration use of thrombopoietin receptor agonists (TPO-RAs), drug adherence, potential side effects, monitoring, and cost effectiveness are factors that should be considered in decision-making about second-line therapies. Rituximab (RTX) has been used off-label for years to treat ITP but there are limited studies about its efficacy and safety in children.

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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.

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