Infiltrative Cardiomyopathies
Andreas P. Kalogeropoulos, Hal A. Skopicki, Javed Butler in Heart Failure, 2023
The most common causes of acquired iron overload are transfusion-dependent anemias, such as thalassemia and sickle cell disease (Table 36.1). Thalassemia is characterized by a deficiency in the synthesis of one or more globin chains of haemoglobin.44 It is estimated that 1–5% of the world population are carriers of a mutant thalassemia allele; the disease is mostly prevalent in sub-Saharan Africa, the Mediterranean region, the Middle East, the Indian subcontinent, and East and Southeast Asia. Similarly, sickle cell disease, which results from mutations altering the β-globin chain of hemoglobin, is also known to be highly prevalent in Africa, India, the Mediterranean region, and the Middle East.45 With migration, sickle cell disease has been introduced to areas in which it was not historically endemic, such as northern Europe and North America. In addition to thalassemia and sickle cell anemia, other hematological conditions, such as myelodysplastic syndrome, sideroblastic anemia, acute myeloid leukemia, and congenital dyserythropoietic anemia, are all associated with secondary iron overload resulting from frequent blood transfusion.42,43 Additionally, iron overload has also been recognized in dialysis patients due to administration of erythropoiesis-stimulating agents and supplemental iron.46
Hemolytic Anemia Associated with Red Cell Membrane Defects
Harold R. Schumacher, William A. Rock, Sanford A. Stass in Handbook of Hematologic Pathology, 2019
The diagnosis of PNH is established using tests that examine patient red cells for sensitivity to lysis by complement. Maneuvers that activate serum complement produce lysis of PNH red cells. A commonly used screening test is the sucrose hemolysis test, also called the sugar water test. The ionic strength of serum is reduced by dilution with an isoosmotic solution of sucrose. The sucrose hemolysis test is not specific for PNH, but is quite sensitive. In patients with a positive result, a more specific confirmatory test is recommended, the classical Ham test. In this test, the serum is acidified and the Mg2+ level is adjusted to achieve maximal sensitivity. The only known false positive Ham test occurs in type II congenital dyserythropoietic anemia. Some research laboratories use the more precise complement lysis sensitivity test that identifies three different populations of PNH red cells based on their differential sensitivity to complement lysis.
Myelodysplastic Syndromes
Wojciech Gorczyca in Atlas of Differential Diagnosis in Neoplastic Hematopathology, 2014
The presence of dysplastic features (morphology and/or FC immunophenotyping) does not per se is diagnostic of MDS. Dysmaturation may be seen in healthy individuals and in conditions other than MDS, for example, B12/folate deficiency, deficiency of essential elements, certain drugs (e.g., cotrimoxazole), treatment with G-CSFs, exposure to heavy metals (especially arsenic), drugs and toxins, PNH, viral infections, immunologic disorders, and hereditary conditions (e.g., congenital dyserythropoietic anemia). Antibiotic cotrimoxazole causes prominent neutrophilic nuclear hypolobation similar to changes seen in MDS. Parvovirus B19 infection may be associated with erythroblastopenia with giant megaloblastoid erythroblasts. Identification of ALIP is not specific for MDS, as it can be seen in reactive conditions with increased blasts (e.g., BM regeneration after treatment of toxic insult), after treatment with Neupogen, or in myeloproliferative neoplasms.
Hb Calgary (HBB: c.194G>T): A Highly Unstable Hemoglobin Variant with a β-Thalassemia Major Phenotype
Published in Hemoglobin, 2021
Georgina Martin, Runa M. Grimholt, Doan Le, Anne G. Bechensteen, Olav Klingenberg, Bente Fjeld, Thomas Fourie, Renee Perrier, Melanie Proven, Shirley J. Henderson, Noémi B. A. Roy
Hb Calgary presents with a phenotype of severe dyserythropoiesis and transfusion dependence in early infancy. In both cases, given the age of presentation and the findings on bone marrow examination, the diagnosis of congenital dyserythropoietic anemia type II was entertained. Similar to other hyperunstable Hb variants resulting from heterozygous β-globin variants, this variant was not isolated on Hb electrophoresis [2] and is not associated with an elevated Hb A2 [4–6,8], and therefore, β-globin gene sequencing is critical for diagnosis. The presentation of both infants with Hb Calgary in the neonatal period is rather unusual for a β-globin mutation, given the presence of relatively high Hb F values at this age. It could be that the degree of instability of Hb Calgary results in such severe dyserythropoiesis that it interferes with red cell production, even when making up less than half of the fraction of total Hb being made.
Fetal hydrops – a review and a clinical approach to identifying the cause
Published in Expert Opinion on Orphan Drugs, 2020
Esther Dempsey, Tessa Homfray, John M Simpson, Steve Jeffery, Sahar Mansour, Pia Ostergaard
Congenital dyserythropoietic anemia type 1 (CDA I) is another rare bone marrow failure syndrome. Complications include macrocytic anemia, bony abnormalities and secondary hemochromatosis. Most cases are caused by mutations in CDAN1 [51]. The product of CDAN1, codanin-1 is important for terminal erythrocyte differentiation, disruption of which leads to dyserythropoiesis [52]. So far fewer than ten cases of CDA I presenting as fetal hydrops have been reported in the literature, only two of those had a molecular genetic diagnosis, both with mutations in CDAN1 [52,53]. Intrauterine blood transfusions have been used as a bridge to postnatal allogenic bone marrow transplant with varying degrees of success. Additional genes have been implicated in CDA (types 2 and 3 and rarer variants) although these have been less frequently associated with fetal hydrops, and tend to have a milder phenotype.
Fetal-onset congenital dyserythropoietic anemia type 1 due to CDAN1 mutations presenting as hydrops fetalis
Published in Pediatric Hematology and Oncology, 2018
Sha Liu, Ying-Na Liu, Li Zhen, Dong-Zhi Li
Congenital dyserythropoietic anemia (CDA) is a rare hematologic disorder characterized by ineffective erythropoiesis with dysplastic morphologic features.1 It is classified into types 1, 2, and 3, along with some variants. The anemia is usually mild to moderate in patients with CDA; however, it may be more serious and required transfusion. Anemia is rarely very severe, and the affected patient can develop fatal hydrops fetalis in utero.2–4 We report on a case of CDA type 1 with hydrops fetalis detected by ultrasound, which subsequently was confirmed by genetic testing using whole-exome sequencing (WES).
Related Knowledge Centers
- Anemia
- Congenital Dyserythropoietic Anemia Type II
- Fatigue
- Ineffective Erythropoiesis
- Red Blood Cell
- Thalassemia
- Congenital Dyserythropoietic Anemia Type I
- Congenital Dyserythropoietic Anemia Type II
- Congenital Dyserythropoietic Anemia Type III
- Congenital Dyserythropoietic Anemia Type IV
- Weakness