- An update on the pathogenesis and diagnosis of Diamond-Blackfan anemia. [Review]
- FF1000Res 2018; 7
- Diamond-Blackfan anemia (DBA) is a rare congenital hypoplastic anemia characterized by a block in erythropoiesis at the progenitor stage, although the exact stage at which this occurs remains to be f...
Diamond-Blackfan anemia (DBA) is a rare congenital hypoplastic anemia characterized by a block in erythropoiesis at the progenitor stage, although the exact stage at which this occurs remains to be fully defined. DBA presents primarily during infancy with macrocytic anemia and reticulocytopenia with 50% of cases associated with a variety of congenital malformations. DBA is most frequently due to a sporadic mutation (55%) in genes encoding several different ribosomal proteins, although there are many cases where there is a family history of the disease with varying phenotypes. The erythroid tropism of the disease is still a matter of debate for a disease related to a defect in global ribosome biogenesis. Assessment of biological features in conjunction with genetic testing has increased the accuracy of the diagnosis of DBA. However, in certain cases, it continues to be difficult to firmly establish a diagnosis. This review will focus on the diagnosis of DBA along with a description of new advances in our understanding of the pathophysiology and treatment recommendations for DBA.
- Hemolytic anemia potentially associated with Aripiprazole - a case report. [Letter]
- PCPsychiatry Clin Neurosci 2018 Sep 18
- We report a case of a female patient, 48yo, medicated for depressive features with Clomipramine 75mg 1id and Bromazepam 6mg 3id, with the recent addition (8 weeks at admission time) of Aripiprazole 1...
We report a case of a female patient, 48yo, medicated for depressive features with Clomipramine 75mg 1id and Bromazepam 6mg 3id, with the recent addition (8 weeks at admission time) of Aripiprazole 10mg 1id. She started experiencing fatigue, tachycardia, and paleness (symptoms suggestive of anemia) as well as weight loss and dark coloured urine. She presented with macrocytic anemia (Hb 7.7 g/dL, MGV 108.1 fL), leucocytosis (17.160/L), thrombocytosis (612 x109/L) and hyperbilirubinemia (total 1.86mg/dL, direct 0.46mg/dL). This article is protected by copyright. All rights reserved.
- Hemolytic Anemia: Evaluation and Differential Diagnosis. [Journal Article]
- AFAm Fam Physician 2018 Sep 15; 98(6):354-361
- Hemolytic anemia is defined by the premature destruction of red blood cells, and can be chronic or life-threatening. It should be part of the differential diagnosis for any normocytic or macrocytic a...
Hemolytic anemia is defined by the premature destruction of red blood cells, and can be chronic or life-threatening. It should be part of the differential diagnosis for any normocytic or macrocytic anemia. Hemolysis may occur intravascularly, extravascularly in the reticuloendothelial system, or both. Mechanisms include poor deformability leading to trapping and phagocytosis, antibody-mediated destruction through phagocytosis or direct complement activation, fragmentation due to microthrombi or direct mechanical trauma, oxidation, or direct cellular destruction. Patients with hemolysis may present with acute anemia, jaundice, hematuria, dyspnea, fatigue, tachycardia, and possibly hypotension. Laboratory test results that confirm hemolysis include reticulocytosis, as well as increased lactate dehydrogenase, increased unconjugated bilirubin, and decreased haptoglobin levels. The direct antiglobulin test further differentiates immune causes from nonimmune causes. A peripheral blood smear should be performed when hemolysis is present to identify abnormal red blood cell morphologies. Hemolytic diseases are classified into hemoglobinopathies, membranopathies, enzymopathies, immune-mediated anemias, and extrinsic nonimmune causes. Extrinsic nonimmune causes include the thrombotic microangiopathies, direct trauma, infections, systemic diseases, and oxidative insults. Medications can cause hemolytic anemia through several mechanisms. A rapid onset of anemia or significant hyperbilirubinemia in the neonatal period should prompt consideration of a hemolytic anemia.
- Differential diagnosis of anemia. [Journal Article]
- VLVnitr Lek 2018; 64(5):468-475
- Anemia, defined as hemoglobin level under lower normal limit, is a symptom of different pathologic conditions and the accurate differential diagnosis is necessary to determine the cause of anemia. Th...
Anemia, defined as hemoglobin level under lower normal limit, is a symptom of different pathologic conditions and the accurate differential diagnosis is necessary to determine the cause of anemia. The article uses the morphological classification of anemia to distinguish macrocytic, normocytic and microcytic types of anemias and divides anemias with increased amount of peripheral blood reticulocytes as a special group. It describes commonly known clinical units as iron deficiency anemia or anemia of chronic disease, as so as rare clinical units, which are always need to think about in a differential diagnosis of an anemic patient. There is an increasing incidence of rare blood disorders due to introduction of molecular genetics methods into diagnostics, prolonged overall survival of patients and increasing migration from areas with endemic occurrence of these diseases. Etiology, basic pathophysiological mechanisms, main clinical features together with important diagnostic examinations are described by each clinical unit. Due to the differential diagnostic focus of the article only basic knowledge about therapy is mentioned. The authors are members of the IHBT Center for Rare Disorders of Hematopoiesis, which is focused mainly on congenital and acquired disorders of red blood cell. Key words: anemia - differential diagnosis - enzymopathies - hemoglobinopathies - iron - macrocytosis - microcytosis - rare blood disorders - reticulocytosis.
- Genotype-phenotype correlation and risk stratification in a cohort of 123 hereditary stomatocytosis patients. [Journal Article]
- AJAm J Hematol 2018 Sep 06
- Hereditary stomatocytoses (HSt) are a wide spectrum of hemolytic anemias in which the erythrocyte membrane cation permeability is increased. Dehydrated hereditary stomatocytosis is the most frequent ...
Hereditary stomatocytoses (HSt) are a wide spectrum of hemolytic anemias in which the erythrocyte membrane cation permeability is increased. Dehydrated hereditary stomatocytosis is the most frequent among hereditary stomatocytoses. It is caused by missense mutations in PIEZO1 and KCNN4 genes. We described 123 patients enrolled in our Genetic Unit from 2013 to 2017. Overall HSt subjects exhibit macrocytic mild anemia. We found that PIEZO1 is the most frequent mutated gene within our families (47% of pedigrees). In 59.1% of cases the mutations localized in the non-pore protein domain, while in 40.9% of patients they localized in the central pore region. The genotype-phenotype correlation analysis on 29 PIEZO1-patients demonstrated that most of severely affected patients carried mutations in the pore domain, suggesting that the severity of this condition is related to the pore properties and intracellular domain that could be responsible of interactions with intracellular components. This is the first cohort study on a large set of hereditary stomatocytosis patients, stratified according their causative gene useful for diagnosis, prognosis, and management of these patients. This article is protected by copyright. All rights reserved.
- My tummy hurts - a case report of abdominal pain and macrocytic anemia caused by hypothyroidism. [Journal Article]
- EDEndocrinol Diabetes Metab Case Rep 2018; 2018
- A 6-year-old female presented with chronic intermittent abdominal pain for 1 year. She underwent extensive investigation, imaging and invasive procedures with multiple emergency room visits. It cause...
A 6-year-old female presented with chronic intermittent abdominal pain for 1 year. She underwent extensive investigation, imaging and invasive procedures with multiple emergency room visits. It caused a significant distress to the patient and the family with multiple missing days at school in addition to financial burden and emotional stress the child endured. When clinical picture was combined with laboratory finding of macrocytic anemia, a diagnosis of hypothyroidism was made. Although chronic abdominal pain in pediatric population is usually due to functional causes such as irritable bowel syndrome, abdominal migraine and functional abdominal pain. Hypothyroidism can have unusual presentation including abdominal pain. The literature on abdominal pain as the main presentation of thyroid disorder is limited. Pediatricians should exclude hypothyroidism in a patient who presents with chronic abdominal pain. Contrast to its treatment, clinical presentation of hypothyroidism can be diverse and challenging, leading to a delay in diagnosis and causing significant morbidity.
- Mice lacking the transcobalamin-vitamin B12 receptor, CD320, suffer from anemia and reproductive deficits when fed vitamin B12-deficient diet. [Journal Article]
- HMHum Mol Genet 2018 Aug 15
- In humans, poor nutrition, malabsorption and variation in cobalamin (vitamin B12) metabolic genes are associated with hematological, neurological and developmental pathologies. Cobalamin is transport...
In humans, poor nutrition, malabsorption and variation in cobalamin (vitamin B12) metabolic genes are associated with hematological, neurological and developmental pathologies. Cobalamin is transported from blood into tissues via the transcobalamin (TC) receptor encoded by the CD320 gene. We created mice carrying a targeted deletion of the mouse ortholog, Cd320. Knockout (KO) mice lacking this TC receptor have elevated levels of plasma methylmalonic acid and homocysteine but are otherwise healthy, viable, fertile and not anemic. To challenge the Cd320 KO mice we maintained them on a vitamin B12-deficient diet. After 5 weeks on this diet, reproductive failure develops in Cd320 KO females but not males. In vitro, homozygous Cd320 KO embryos from cobalamin-deficient Cd320 KO dams develop normally to embryonic day (E) 3.5, while in vivo, few uterine decidual implantation sites are observed at E7.5, suggesting that embryos perish around the time of implantation. Dietary restriction of vitamin B12 induces a severe macrocytic anemia in Cd320 KO mice after 10-12 months while control mice on this diet are anemia-free up to 2 years. Despite the severe anemia, cobalamin-deficient KO mice do not exhibit obvious neurological symptoms. Our results with Cd320 KO mice suggest that an alternative mechanism exists for mice to transport cobalamin independent of the Cd320 encoded receptor. Our findings with deficient diet are consistent with historical and epidemiological data suggesting that low vitamin B12 levels in humans are associated with infertility and developmental abnormalities. Our Cd320 KO mouse model is an ideal model system for studying vitamin B12 deficiency.
- Significantly higher frequencies of anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody positivity in atrophic glossitis patients. [Journal Article]
- JFJ Formos Med Assoc 2018 Aug 04
- CONCLUSIONS: There are significantly higher frequencies of anemia, serum iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity in AG patients than in healthy control subjects. The normocytic anemia and iron deficiency anemia are the two most common types of anemia in our 1064 AG patients.
- [Diagnostic targets and exosome sequence analysis of Diamond-Blackfan anemia in Japan]. [Journal Article]
- RKRinsho Ketsueki 2018; 59(7):945-952
- Diamond-Blackfan anemia (DBA) is a rare, inherited, congenital bone marrow failure syndrome, which typically manifests in infancy. In addition, the disease is often accompanied by normochromic macroc...
Diamond-Blackfan anemia (DBA) is a rare, inherited, congenital bone marrow failure syndrome, which typically manifests in infancy. In addition, the disease is often accompanied by normochromic macrocytic anemia and acute reticulocytopenia in the peripheral blood and by selective deficiency of erythroid precursors in the normocellular bone marrow. Approximately 50% of patients with DBA exhibit growth retardation and multiple congenital anomalies, which primarily include craniofacial dysmorphism, upper-limb abnormalities, urogenital malformations, and congenital heart defects. In addition, heterozygous mutations in genes encoding ribosomal proteins (RP) that lead to a loss of function of the genes are detected in nearly 60% of patients with DBA. As a majority of identified causative genes belong to RP genes, the impairment of ribosome biogenesis is considered accountable for the disease. This study aims to outline the molecular pathology of DBA and the causative gene RPS15A isolated using our exosome analysis.
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- Anti-Inflammatory, Immunomodulatory, and Antioxidant Activities of Allicin, Norfloxacin, or Their Combination against Pasteurella multocida Infection in Male New Zealand Rabbits. [Journal Article]
- OMOxid Med Cell Longev 2018; 2018:1780956
- The present study investigated the efficacy of allicin as an antibacterial, anti-inflammatory, antioxidant, and immunostimulant agent in reducing the severity of Pasteurella multocida (P. multocida) ...
The present study investigated the efficacy of allicin as an antibacterial, anti-inflammatory, antioxidant, and immunostimulant agent in reducing the severity of Pasteurella multocida (P. multocida) type B infection in rabbits. Fifty New Zealand rabbits, 5 weeks old, were divided equally into five groups. Except for group 1, all groups were intranasally infected with P. multocida type B (2 × 105 colony forming units/ml/rabbit). Then, group 3 rabbits were orally treated with allicin (50 mg/kg BW) for 5 days, group 4 rabbits received a single oral dose of norfloxacin 30% (100 mg/kg BW), while group 5 rabbits were treated with a combination of norfloxacin and allicin. Hematological, serum biochemical, inflammatory cytokine, immunological, and histopathological analyses were performed. Results revealed that rabbits, infected with P. multocida type B, exhibited macrocytic hypochromic anemia and leukocytosis with a significant elevation in the phagocytic percentage and index. Moreover, significant reductions in serum total protein, albumin, globulin, and immunoglobulin (IgG and IgM) levels were observed in infected rabbits. Infected rabbits showed significant increases in serum inflammatory cytokine (TNF-α and IL-6), alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, and serum bilirubin (total, direct, and indirect) levels. Further, P. multocida infection induced oxidative stress as demonstrated by the significant reduction in serum levels of reduced glutathione and superoxide dismutase enzyme and marked elevation in serum malondialdehyde. Treatment with allicin, norfloxacin, or their combination significantly ameliorated the alterations in all studied parameters. In conclusion, allicin could ameliorate the inflammation and oxidative stress, induced by P. multocida type B infection in rabbits.