Miscellaneous Forms of Acquired Red Cell Aplasia and Erythropoietic Failure in Childhood
Stephen A. Feig, Melvin H. Freedman in Clinical Disorders and Experimental Models of Erythropoietic Failure, 2019
Red cell aplasia is a specific syndrome characterized by anemia, reticulocytopenia, and markedly reduced or absent erythroid precursor cells in the bone marrow with preservation of the lymphoid and other hematopoietic lineages. Although the aplasia is an end result of a wide variety of causes in adults, in children the etiologies are somewhat more restricted. As opposed to the syndrome of red cell aplasia, erythropoietic failure is defined in this chapter as a diminished but not necessarily absent marrow erythroid response to anemia, and as an entity is much more commonly seen in children. In this situation, reticulocytes are disproportionately low for the degree of anemia but are almost never completely absent. This is an anemia of underproduction, or alternatively, of ineffective erythropoiesis, and is almost always associated with a chronic severe underlying disease. Included in the classification of the causes of erythropoietic failure are chronic renal disease, cancer, chronic infection or inflammation, endocrine disease, and nutritional deficiencies. With regard to red cell aplasia, the two forms that are unique to pediatrics are Diamond-Blackfan anemia (DBA) and transient erythroblastopenia of childhood (TEC). Because these disorders are discussed in detail in Chapters 2 and 3, respectively, this chapter will address other miscellaneous forms of acquired (pure) red cell aplasia (PRCA) and erythropoietic failure that occur in patients younger than 20 years of age.
Venous anatomy
Joseph A. Zygmunt in Venous Ultrasound, 2020
The term peripheral is best used for the segment of the vein that is away from the heart; central, the segment of the vein toward the heart. With regard to a duplicated vein, this term is reserved for only when the two veins display the same path, topography, and relationships (like the tibial veins). If a vein is parallel but in a different compartment or plane, it cannot be considered double. Only those in the same space, and functionally duplicated, as in the case of the femoral vein, are truly duplicated. With regard to clinical practice, duplex ultrasound helps us understand terms relating to the diameter of veins in the lower limbs. Aplasia refers to the absence of a vein or segment of vein. Hypoplasia refers to a vein diameter 50%, whereas venomegalia is a diffuse dilation of one or more veins to >50% of their normal diameters [9]. In addition, as opposed to the arterial system which bifurcates or trifurcates as one moves distal when describing its anatomy, the venous system is best understood in accordance with direction of flow, and therefore distal veins join or “form a union” with other vessels as we move central in our descriptions (N. Labropoulos, personal communication).
Pediatric Oncology
Pat Price, Karol Sikora in Treatment of Cancer, 2020
The T-cells are most commonly autologous though allogeneic CarT have also been developed. The artificial engineered DNA construct is inserted into the T-cells by viral transfection. Critical to the success of CarT therapy are the proliferation, cytotoxicity, and persistence of the CarT in response to antigen stimulation as well as target cell capacity to downregulate the relevant target antigen. Many developments in the design of and methods to create CarT have been made to date. These include the choice of lentiviral or retroviral vectors, the design of the chimeric antigen receptor, linker molecule, and critically co-stimulatory molecules such as 4-1BB and CD28. As a result of different designs, some CarT are used as a bridge to transplant, whilst others are seen as a standalone therapy. The pivotal study for pediatric ALL is the Eliana study of CTL-019, Tisagenlecleucel. This study of 75 patients with relapsed refractory B-cell precursor ALL showed a 50% 12-month EFS in a group of patients with a median of three prior therapies. Importantly, there was no relationship between efficacy and the number of prior therapies including SCT. A common reason for failure was CD19-negative relapse. It should be noted that in all successful cases to date, prolonged B-cell aplasia has been a long-term side effect, though this has been effectively managed with immunoglobulin replacement therapy. It is to be hoped that further developments in CarT design including bi-specific CarT will reduce the risk of target antigen-negative escape.
Association between polymorphisms in PDCD1 gene and aplastic anemia in Chinese Han population
Published in Leukemia & Lymphoma, 2013
Zixia Wu, Miao Miao, Yuhua Qiu, Zhenghong Qin, Jin Wang, Yiguo Jiang, Zhijun Ming, Xueguang Zhang
Single nucleotide polymorphism (SNP) of programmed cell death 1 (PD-1, encoded by PDCD1) has been reported to be associated with several autoimmune diseases including rheumatoid arthritis (RA), Graves’ disease and multiple sclerosis (MS). In order to study the correlation between PD-1 gene polymorphism and aplastic anemia in a Chinese Han population, two SNPs, PD-1.1 G/A (rs36084323) and PD-1.6 G/A (rs10204525), were genotyped in 166 patients with aplastic anemia and 144 healthy controls by direct sequencing. All genotype distributions in both patients and controls were in Hardy–Weinberg equilibrium. Associations of genotypes and alleles with aplastic anemia were analyzed. The results suggested that the G allele of PD-1.1 was associated with an increased risk for aplastic anemia, while SNP of PD-1.6 was not associated with aplastic anemia in a Chinese Han population.
Aplasia Cutis Congenita with Ischemic Cortical Change and Normal Array Cytogenetic Analysis with a Fetus Papyraceus Twin
Published in Fetal and Pediatric Pathology, 2018
Laura A. Skillen, Damien Gates, Julie-Ann Collins, Nivedita Saxena, Daniel Hurrell, Kevin McKenna, Patrick J. Morrison
Background: Aplasia cutis congenita (ACC) is a heterogeneous condition that can be associated with fetus papyraceus. Few reports exist documenting genetic investigations in ACC or determining the etiology and recurrence risks. Objective: We present a Frieden group 5 ACC with fetus papyraceus along with molecular studies. Results: The newborn had multifocal aplasia cutis congenita involving the head, trunk, and limbs with cerebral ischemic changes demonstrated by imaging. The newborn had a monochorionic twin fetus papyraceus. The array cytogenetic analysis was normal. Conclusion: Supported by the ischemic cerebral damage, a monochorionic twin fetus papyraceus (monochorionic twins often have vascular anastomoses), and a normal cytogenetic array, this ACC with Frieden group 5 may have resulted from rapid but non-fatal exsanguination of the surviving twin into the dead twin. This type of ACC may have a low recurrence risk.
Low Expression of Basic Fibroblastic Growth Factor in Mesenchymal Stem Cells and Bone Marrow of Children with Aplastic Anemia
Published in Pediatric Hematology and Oncology, 2014
Sha yi Jiang, Xiao tian Xie, Hui Jiang, Ji ji Zhou, Fu xing Li, Ping Cao
Background: Our previous experiments with gene chip suggested that basic fibroblastic growth factor (FGF2) levels were lower in mesenchymal stem cell (MSC) from aplastic anemia patients. The purpose of this study was to determine the expression of FGF2 in MSC and in bone marrow of children with aplastic anemia to better understand the role of low FGF2 expression in the pathogenesis of aplastic anemia. Procedure: MSCs from the bone marrow of aplastic anemia children and control group were cultured in vitro. Growth curves of primary and passage MSC were plotted. FGF2 gene expression in MSCs was detected using quantitative real-time polymerase chain reaction (RT-PCR). FGF2 protein expression in mononuclear cells and FGF2 protein level in extracellular fluid of bone marrow were also investigated. Result: Decreased growth of MSCs from aplastic anemia children was observed after passage 8 in serial subcultivation, and FGF2 gene expression was downregulated. Within the patients’ bone marrow, low FGF2 expression was validated both in mononuclear cells and in the extracellular fluid. Conclusion: Low FGF2 gene expression in MSCs and low FGF2 protein level in bone marrow of aplastic anemia may involve to pathogenesis of aplastic anemia.
Related Knowledge Centers
- Aplasia Cutis Congenita
- Aplastic Anemia
- Hematology
- Embryology
- Organ
- Acquired Pure Red Cell Aplasia
- Sertoli Cell-Only Syndrome