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British Journal of Haematology Feb 2013αIIbβ3 integrin mutations that result in the complete loss of expression of this molecule on the platelet surface cause Glanzmann thrombasthenia. This is usually...
αIIbβ3 integrin mutations that result in the complete loss of expression of this molecule on the platelet surface cause Glanzmann thrombasthenia. This is usually autosomal recessive, while other mutations are known to cause dominantly inherited macrothrombocytopenia (although such cases are rare). Here, we report a 4-generation pedigree including 10 individuals affected by dominantly inherited thrombocytopenia with anisocytosis. Six individuals, whose detailed clinical and laboratory data were available, carried a non-synonymous ITGB3 gene alteration resulting in mutated integrin β3 (ITGB3)-L718P. This mutation causes partial activation of the αIIbβ3 complex, which promotes the generation of abnormal pro-platelet-like protrusions through downregulating RhoA (RHOA) activity in transfected Chinese Hamster Ovary cells. These findings suggest a model whereby the integrin β3-L718P mutation contributes to thrombocytopenia through gain-of-function mechanisms.
Topics: Adult; Child; Child, Preschool; DNA Mutational Analysis; Down-Regulation; Erythrocytes, Abnormal; Exome; Female; Humans; Integrin beta3; Male; Pedigree; Polymorphism, Single Nucleotide; Signal Transduction; Thrombocytopenia; rhoA GTP-Binding Protein
PubMed: 23253071
DOI: 10.1111/bjh.12160 -
Clinical Hemorheology and... 2010Hemorheological abnormalities such as elevated whole blood viscosity, plasma viscosity, erythrocyte deformability and platelet aggregation, hematocrit and fibrinogen... (Review)
Review
Hemorheological abnormalities such as elevated whole blood viscosity, plasma viscosity, erythrocyte deformability and platelet aggregation, hematocrit and fibrinogen levels, are frequently examined as diagnostic tool and prognostic relevance in socially important hemorheological disorders. Distinct biological - morphological and functional platelet alterations, have been described in different addictions (heroin-, cocaine-, nicotine-, alcohol-, etc.). Chronic addictions could cause biochemical and conformational changes in platelets and their membranes, thus modulating platelet receptor expression, morphology (anisocytosis, giant platelets) and activation (alpha-granule release), platelet aggregation and hemorheological properties. Some of these alterations in chronic addicts - documented at cellular- and molecular level, could be easily used as a precise diagnostic tool with regard to thromboembolic complications and microcirulation injuries attributable to addictions. The present review focuses on some changes in platelet morphological, functional and rheological properties induced by chronic opiate/opioid abuse. Hypothesis is accumulated that free fatty acids (FFAs) and especially oleic acid (OA) could cause positive molecular and conformational changes in platelets of addicts with hemorheological disorders.
Topics: Blood Platelets; Fatty Acids, Nonesterified; Hemorheology; Humans; Microcirculation; Oleic Acid; Opioid-Related Disorders; Substance-Related Disorders; Thromboembolism
PubMed: 20675906
DOI: 10.3233/CH-2010-1305 -
Annals of Translational Medicine Jul 2017Red blood cell distribution width (RDW) is a simple, inexpensive, routinely measured and automatically reported blood test parameter, which reflects the degree of... (Review)
Review
Red blood cell distribution width (RDW) is a simple, inexpensive, routinely measured and automatically reported blood test parameter, which reflects the degree of anisocytosis of red blood cells in peripheral blood. RDW was found to be associated with and retain clinical significance for assessing disease severity and outcomes in a number of hematological and solid malignancies. Motley of interacting clinical and biochemical factors have an impact on the red cell population biology. Malignancies per se can act as a causative factor, or anisocytosis may develop as a result of chronic inflammation. RDW has also been shown to be affected by nutritional status, which is typically deranged in malignancies. RDW is shown to be a clinically useful marker of disease severity and level of fibrosis in liver cirrhosis of various causes such as hepatitis B, hepatitis C and non-alcoholic fatty liver disease. Whether liver cirrhosis patients with higher RDW are at increased risk of hepatocellular cancer is yet to be determined, but several lines of evidence confirm that RDW has clinical significance in hepatocellular carcinoma (HCC). In this review, we specifically discuss the current literature about the association between RDW and HCC. The available evidences were summarized and the potential underlying mechanisms were analyzed.
PubMed: 28758097
DOI: 10.21037/atm.2017.06.30 -
Indian Journal of Critical Care... Jan 2020Red cell distribution width (RDW), which is a quantitative method applied for the measurement of anisocytosis, is the most reliable and inexpensive method for... (Review)
Review
UNLABELLED
Red cell distribution width (RDW), which is a quantitative method applied for the measurement of anisocytosis, is the most reliable and inexpensive method for differentiation of iron deficiency anemia and thalassemia trait. An increase in its rate reflects a great heterogeneity in the size of red blood cells (RBCs). Recent studies have shown a significant relationship between RDW and the risk of morbidity and mortality in patients with multiple diseases. A strong association is established between changes in RDW and the risk of adverse outcome in patients with heart failure in multiple studies. In this review, we try to focus on the association and correlation between the increase in RDW and different outcomes of common diseases that may be related to RDW and based on the results of various studies, we are trying to introduce RDW as a diagnostic indicator for these diseases.
HOW TO CITE THIS ARTICLE
Yousefi B, Sanaie S, Ghamari AA, Soleimanpour H, Karimian A, Mahmoodpoor A. Red Cell Distribution Width as a Novel Prognostic Marker in Multiple Clinical Studies. Indian J Crit Care Med 2020;24(1):49-54.
PubMed: 32148349
DOI: 10.5005/jp-journals-10071-23328 -
Acta Haematologica Mar 1964
Topics: Anemia; Animals; Erythrocytes; Erythropoiesis; Hematocrit; Hemoglobins; Pharmacology; Phenylhydrazines; RNA; Rabbits; Research; Reticulocytes
PubMed: 14168027
DOI: 10.1159/000209622 -
The American Journal of Surgical... Nov 2018In our routine and consultative pathology practices, we have repeatedly encountered an unusual subcutaneous fatty tumor with notable anisocytosis, single-cell fat...
Dysplastic Lipoma: A Distinctive Atypical Lipomatous Neoplasm With Anisocytosis, Focal Nuclear Atypia, p53 Overexpression, and a Lack of MDM2 Gene Amplification by FISH; A Report of 66 Cases Demonstrating Occasional Multifocality and a Rare Association With Retinoblastoma.
In our routine and consultative pathology practices, we have repeatedly encountered an unusual subcutaneous fatty tumor with notable anisocytosis, single-cell fat necrosis, and patchy, often mild, adipocytic nuclear atypia. Because of the focal atypia, consultative cases have most often been received with concern for a diagnosis of atypical lipomatous tumor. Similar tumors have been described in small series under the designations "subcutaneous minimally atypical lipomatous tumors" and "anisometric cell lipoma." Sixty-six cases of this tumor type were collected and reviewed. Immunohistochemistry for p53, MDM2, CDK4, Retinoblastoma 1 (RB1) protein, CD34, S100, and CD163 was performed. Cases were tested for MDM2 gene amplification and RB1 gene deletion with fluorescence in situ hybridization (FISH) and for TP53 mutations by Sanger sequencing. Next-generation sequencing analysis using a panel of 271 cancer-related genes, including TP53, RB1, and MDM2, was also carried out. Our patient cohort included 57 male patients, 8 female patients, and 1 patient of unstated sex, who ranged in age from 22 to 87 years (mean: 51.2 y). All tumors were subcutaneous, with most examples occurring on the upper back, shoulders, or posterior neck (86.4%). Ten patients had multiple (2 to 5) lipomatous tumors, and the histology was confirmed to be similar in the different sites in 4 of them, including 1 patient who had a retinoblastoma diagnosed at age 1. The tumors were generally well circumscribed. At low magnification, there was notable adipocytic size variation with single-cell fat necrosis in the background associated with reactive histiocytes. Adipocytic nuclear atypia was typically patchy and characterized by chromatin coarsening, nuclear enlargement, and focal binucleation or multinucleation. Focal Lochkern change was frequent. In most instances, the degree of atypia was judged to be mild, but in 3 instances, it was more pronounced. Spindle cells were sparse or absent, and when present, cytologically bland. Thick ropy collagen bundles were absent. In all cases, p53 immunoexpression was noted (range: 2% to 20% of adipocytic nuclei), characteristically highlighting the most atypical cells. Twenty of 50 cases had MDM2 immunoreactivity, usually in <1% of the neoplastic cells, but in 4 cases, up to 10% of the cells were positive. Of 32 cases tested, 22 showed a near total loss of RB1 immunoexpression, and the remainder showed partial loss. Three of 13 cases showed RB1 gene deletion in >45% of the cells by FISH (our threshold value for reporting a positive result) with an additional 3 cases being very close to the required cutoff value. MDM2 gene amplification was absent in all 60 cases tested, including those with the greatest MDM2 immunoexpression and most pronounced atypia. All 5 tested cases showed no TP53 mutation with Sanger sequencing. Because of material quality issues, next-generation sequencing analysis could be performed in only 3 cases, and this did not reveal any recurrent mutations. All tumors were managed by simple local excision. Follow-up was available for 47 patients (range: 1 to 192 mo; mean: 27 mo) and revealed 2 local recurrences and no metastases. Dysplastic lipoma is a distinctive atypical fatty tumor variant that has p53 overexpression and RB1 gene abnormalities and lacks MDM2 gene amplification by FISH. These tumors have a strong male predominance and a notable tendency to involve the subcutaneous tissue of the shoulders, upper back and posterior neck. Multifocality is frequent (18.9% of patients with follow-up information), and there is a rare association with retinoblastoma. This tumor warrants separation from ordinary lipoma with fat necrosis, fat-rich spindle cell lipoma and the conventional form of atypical lipomatous tumor that features MDM2 gene amplification.
Topics: Adipocytes; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; DNA Mutational Analysis; Diagnosis, Differential; Europe; Fat Necrosis; Female; Gene Amplification; Genetic Predisposition to Disease; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Liposarcoma; Male; Middle Aged; Mutation; Neoplasms, Multiple Primary; Predictive Value of Tests; Proto-Oncogene Proteins c-mdm2; Retinoblastoma; Retinoblastoma Binding Proteins; Retrospective Studies; Tumor Suppressor Protein p53; Ubiquitin-Protein Ligases; Up-Regulation; Young Adult
PubMed: 30001242
DOI: 10.1097/PAS.0000000000001129 -
Annales de Biologie Clinique 2000Myelodysplastic syndromes (MDS) are clonal disorders of pluripotent hematopoietic stem cells. MDS occur predominantly over the age of 60 years. The diagnosis of MDS is... (Review)
Review
Myelodysplastic syndromes (MDS) are clonal disorders of pluripotent hematopoietic stem cells. MDS occur predominantly over the age of 60 years. The diagnosis of MDS is based on the examination of both blood films and bone marrow aspirate. Diseases such as vitamin B12 and/or folate deficiency, or cytotoxic therapy leading to a marrow dysplasia should be ruled out. Five subtypes are described in the FAB classification : refractory anaemia or refractory cytopenia, refractory sideroblastic anaemia, refractory anaemia with excess of blasts, refractory anaemia with excess of blasts in transformation, chronic myelomonocytic leukaemia. This FAB classification is based on a small number of parameters: percentage of blood and marrow blasts, percentage of ringed sideroblasts and blood monocytes. The anaemia is typically normo- or macrocytic, non regenerative, and in half cases is associated with neutropenia and/or thrombocytopenia. During blood film examination, cell abnormalities have to be notified, i.e. anisocytosis, poikilocytosis of red cells, morphological abnormalities of neutrophils including hypogranulation, hypolobulation, abnormal large platelets. The prognostic and the treatment of MDS depend on the subtype of the FAB classification, the patient's age, the percentage of marrow blasts, the importance of cytopenia, the presence or not of cytogenetic abnormalities and the existence or not of HLA-identical donor.
Topics: Diagnosis, Differential; Hematopoietic Stem Cells; Humans; Myelodysplastic Syndromes
PubMed: 10932040
DOI: No ID Found -
Annals of Translational Medicine Oct 2019Red blood cell distribution width (RDW) reflects erythrocyte size distribution, thus representing a reliable index of anisocytosis, widely used for the differential... (Review)
Review
Red blood cell distribution width (RDW) reflects erythrocyte size distribution, thus representing a reliable index of anisocytosis, widely used for the differential diagnosis of micro- and normocytic anaemias. Along with the large use in diagnostic hematology, RDW has been associated with presence and complications of a vast array of human pathologies during the last decades, including cardiovascular (CV) diseases. This article is hence aimed to provide an overview of important studies and systematic reviews with meta-analysis, in which RDW has been associated with CV events and mortality, in the attempt of establishing whether enough evidence exists for supporting its routine use in clinical practice. According to available data it seems reasonable to conclude that although the diagnostic specificity is low, and this measure is still plagued by important lack of standardization, RDW can be regarded as an index of enhanced patient fragility and higher vulnerability to adverse outcomes. Abnormal RDW values shall hence persuade physicians to broaden the diagnostic reasoning over anaemias, especially those due to malnutrition or malabsorption, encompassing a comprehensive assessment of traditional and non-traditional CV risk factors.
PubMed: 31807562
DOI: 10.21037/atm.2019.09.58 -
The American Journal of the Medical... Jan 1999There has been little systematic study of the clinical spectrum of pancytopenia, and the optimal diagnostic approach to pancytopenia remains undefined.
BACKGROUND
There has been little systematic study of the clinical spectrum of pancytopenia, and the optimal diagnostic approach to pancytopenia remains undefined.
METHODS
The authors studied 134 hospitalized pancytopenic patients in Zimbabwe in both consecutive and nonconsecutive fashion.
RESULTS
The most common cause of pancytopenia was megaloblastic anemia, followed by aplastic anemia, acute leukemia, acquired immunodeficiency syndrome (AIDS), and hypersplenism. Severe pancytopenia was usually due to aplastic anemia. Patients with aplastic anemia and acute leukemia were usually children, whereas those with megaloblastic anemia were adults. Moderate to severe anemia was noted throughout the series, but was most striking in patients with megaloblastic anemia, aplastic anemia, and acute leukemia. The mean corpuscular volume (MCV) was elevated in most patients with megaloblastic hematopoiesis, aplastic anemia, and acute nonlymphocytic leukemia. Normal or low MCV values were noted in almost one third of patients with megaloblastic anemia. Anisocytosis, poikilocytosis, macroovalocytosis, microcytosis, fragmentation, and teardrop erythrocytes were more prominent on the blood films of patients with megaloblastic anemia.
CONCLUSIONS
Megaloblastic anemia, aplastic anemia, and AIDS are the most common causes of pancytopenia in Zimbabwe. Aplasia is the most frequent cause of severe pancytopenia. The authors have formulated tentative guidelines for the evaluation of pancytopenic patients in this setting.
Topics: Acquired Immunodeficiency Syndrome; Acute Disease; Adolescent; Adult; Aged; Anemia, Aplastic; Anemia, Megaloblastic; Child; Child, Preschool; Diagnosis, Differential; Female; Humans; Hypersplenism; Infant; Leukemia; Male; Middle Aged; Pancytopenia; Predictive Value of Tests; Risk Factors; Sensitivity and Specificity; Severity of Illness Index; Zimbabwe
PubMed: 9892268
DOI: 10.1097/00000441-199901000-00004 -
Cancer Jan 1979This study is based upon an analysis of the hematologic and pathologic material from seven patients with acute myelosclerosis, as well as a review of the literature of... (Review)
Review
This study is based upon an analysis of the hematologic and pathologic material from seven patients with acute myelosclerosis, as well as a review of the literature of 49 cases reported under this designation, or one of its synonyms. Patients with this disease characteristically present with pancytopenia, minimal or absent anisocytosis and poikilocytosis, and a fibrotic bone marrow showing hyperplasia and immaturity of all three cell lines, with particular prominence of megakaryocytes and their precursors. In addition, clinical splenomegaly is almost always absent, and the disease has a rapidly fatal course. We consider only one-fourth of the cases reported in the literature to have the clinical and hematologic features consistent with the diagnosis of acute myelosclerosis; the remainder represent a variety of myeloproliferative disorders, including chronic myelosclerosis with an accelerated terminal phase, acute myeloblastic leukemia with bone marrow fibrosis, myeloproliferative diseases that cannot be subclassified, and cases in which the data are insufficient for analysis. Using strict clinical and hematological criteria, acute myelosclerosis can be separated from other myeloproliferative disorders as a distinct clinicopathologic entity.
Topics: Acute Disease; Adult; Aged; Bone Marrow; Erythroblasts; Female; Humans; Male; Megakaryocytes; Middle Aged; Primary Myelofibrosis; Prognosis; Spleen; Terminology as Topic
PubMed: 367569
DOI: 10.1002/1097-0142(197901)43:1<279::aid-cncr2820430141>3.0.co;2-l