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            "title": "Circulating red cell-derived microparticles in human malaria",
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                    "firstName": "Arjen M",
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            "abstractNote": "In patients with falciparum malaria, plasma concentrations of cell-derived microparticles correlate with disease severity. Using flow cytometry, we quantified red blood cell-derived microparticles (RMPs) in patients with malaria and identified the source and the factors associated with production. RMP concentrations were increased in patients with Plasmodium falciparum (n = 29; median, 457 RMPs/μL [range, 13-4,342 RMPs/μL]), Plasmodium vivax (n = 5; median, 409 RMPs/μL [range, 281-503/μL]), and Plasmodium malariae (n = 2; median, 163 RMPs/μL [range, 127-200 RMPs/μL]) compared with those in healthy subjects (n = 11; median, 8 RMPs/μL [range, 3-166 RMPs/μL]; P = .01). RMP concentrations were highest in patients with severe falciparum malaria (P = .01). Parasitized red cells produced >10 times more RMPs than did unparasitized cells, but the overall majority of RMPs still derived from uninfected red blood cells (URBCs). In cultures, RMP production increased as the parasites matured. Hemin and parasite products induced RMP production in URBCs, which was inhibited by N-acetylcysteine, suggesting heme-mediated oxidative stress as a pathway for the generation of RMPs.",
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            "title": "Red blood cell vesiculation in hereditary hemolytic anemia",
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                    "creatorType": "author",
                    "firstName": "Amr",
                    "lastName": "Alaarg"
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                    "lastName": "Schiffelers"
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                    "firstName": "Wouter W",
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                    "creatorType": "author",
                    "firstName": "Richard",
                    "lastName": "van Wijk"
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            "abstractNote": "Hereditary hemolytic anemia encompasses a heterogeneous group of anemias characterized by decreased red blood cell survival because of inherited membrane, enzyme, or hemoglobin disorders. Affected red blood cells are more fragile, less deformable, and more susceptible to shear stress and oxidative damage, and show increased vesiculation. Red blood cells, as essentially all cells, constitutively release phospholipid extracellular vesicles in vivo and in vitro in a process known as vesiculation. These extracellular vesicles comprise a heterogeneous group of vesicles of different sizes and intracellular origins. They are described in literature as exosomes if they originate from multi-vesicular bodies, or as microvesicles when formed by a one-step budding process directly from the plasma membrane. Extracellular vesicles contain a multitude of bioactive molecules that are implicated in intercellular communication and in different biological and pathophysiological processes. Mature red blood cells release in principle only microvesicles. In hereditary hemolytic anemias, the underlying molecular defect affects and determines red blood cell vesiculation, resulting in shedding microvesicles of different compositions and concentrations. Despite extensive research into red blood cell biochemistry and physiology, little is known about red cell deformability and vesiculation in hereditary hemolytic anemias, and the associated pathophysiological role is incompletely assessed. In this review, we discuss recent progress in understanding extracellular vesicles biology, with focus on red blood cell vesiculation. Also, we review recent scientific findings on the molecular defects of hereditary hemolytic anemias, and their correlation with red blood cell deformability and vesiculation. Integrating bio-analytical findings on abnormalities of red blood cells and their microvesicles will be critical for a better understanding of the pathophysiology of hereditary hemolytic anemias.",
            "publicationTitle": "Frontiers in physiology",
            "publisher": "",
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            "partTitle": "",
            "pages": "365",
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            "DOI": "10.3389/fphys.2013.00365",
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            "title": "Flow cytometric quantitation of red blood cell vesicles in thalassemia",
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                    "creatorType": "author",
                    "firstName": "Kovit",
                    "lastName": "Pattanapanyasat"
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                    "firstName": "Egarit",
                    "lastName": "Noulsri"
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                    "lastName": "Fucharoen"
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                    "firstName": "Surada",
                    "lastName": "Lerdwana"
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                    "firstName": "Pornvaree",
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                    "firstName": "Napadol",
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                    "creatorType": "author",
                    "firstName": "H Kyle",
                    "lastName": "Webster"
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            ],
            "abstractNote": "BACKGROUND: Thalassemia is a hereditary hemolytic anemia caused by mutations in the globin gene complex. Circulatory disturbances including arterial and venous thrombosis have also been noted in these patients. Aggregability of abnormal RBC and the high level of membrane-derived microparticles stemming from activated platelets and other blood cells are thought to be responsible for the associated thrombotic risk. Destruction of RBC is also thought to be an important pathophysiological consequence, particularly through the formation of circulating vesicles. To our knowledge, there has been no attempt to quantitatively evaluate the number of RBC vesicles in thalassemia. This prompted us to study the level of RBC vesicles in the peripheral blood of thalassemia patients using quantitative flow cytometry.\nMETHODS: Whole blood from each subject was doubly stained for RBC and platelet or annexin V markers, together with the known density TruCount beads. RBC vesicles were gated according to their forward/side scatter and RBC marker. Percentage of RBC vesicles and their absolute number were analyzed by flow cytometry.\nRESULTS: Our data indicated that RBC vesicles were annexin V-positive. The number of annexin V-positive events was higher than their intact RBCs. RBC vesicles were present in both normal and thalassemic blood samples, but the numbers of RBC vesicles were significantly higher in thalassemia. Both the percentage and the absolute number of RBC vesicles were especially marked in splenectomized subjects with beta-thalassemia/Hemoglobin E. When clinical and hematological indices were compared with RBC vesicles, there was an inverse relationship between the degree of severity in thalassemia patients and the number of RBC vesicles.\nCONCLUSION: Flow cytometric quantitation of RBC vesicles is simple, reliable and may offer new insights in to study of the relationship between defective hemoglobin synthesis, RBC perturbation and pathophysiological complications in thalassemia.",
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            "extra": "PMID: 14696060",
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                    "tag": "Adolescent",
                    "type": 1
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                {
                    "tag": "Adult",
                    "type": 1
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                    "tag": "Annexin A5",
                    "type": 1
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                {
                    "tag": "Biological Markers",
                    "type": 1
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                {
                    "tag": "Erythrocyte Count",
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            "creators": [
                {
                    "creatorType": "author",
                    "firstName": "Mutlu",
                    "lastName": "Kasar"
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                {
                    "creatorType": "author",
                    "firstName": "Can",
                    "lastName": "Boğa"
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                {
                    "creatorType": "author",
                    "firstName": "Mahmut",
                    "lastName": "Yeral"
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                {
                    "creatorType": "author",
                    "firstName": "Suheyl",
                    "lastName": "Asma"
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                {
                    "creatorType": "author",
                    "firstName": "Ilknur",
                    "lastName": "Kozanoglu"
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                {
                    "creatorType": "author",
                    "firstName": "Hakan",
                    "lastName": "Ozdogu"
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            "abstractNote": "Increased thrombocyte activation leads to a higher likelihood of coagulation in sickle-cell disease. On the other hand, chronic inflammation and endothelial cell activation promote vaso-occlusion. The effect of circulating microparticles derived from erythrocytes, monocytes, thrombocytes, and endothelial cells on the vaso-occlusive process is unclear. This study aims to analyze the relationship between sickle-cell disease and miscellaneous organ complications by defining the circulating microparticles during the steady-state and painful crisis periods in 45 patients with sickle-cell disease. Microparticle analysis was conducted using an eight-parameter flow cytometric method, using CD61 PERCP, CD142PE, CD106 FITC, CD14 APC-H7, CD235a FITC, and Annexin-V APC monoclonal antibodies. Microparticle levels of sickle-cell patients were found to be significantly higher during both painful crisis and steady-state situations compared with the control group (for all, p < 0.001). Among these microparticles, levels of erythrocyte microparticles (eMPs) were significantly higher during crisis than in the steady-state period (eMP steady state vs. painful crisis: 7.59 ± 12.24 vs. 7.59 ± 12.24, respectively; p < 0.01). Microparticles, including eMPs, were not affected by hydroxyurea treatment. Their level did not reflect the high frequency of crisis (>3 times/year). Thrombocyte microparticle levels were found to be higher in patients with nephropathia than in those without (48.05 ± 40.23 vs. 7.67 ± 6.75, respectively; p < 0.049). Circulating microparticles seem to be involved in the pathogenesis of sickle-cell disease. eMPs may help with the management of crisis. Thrombocyte microparticles might predict renal damage induced by vaso-occlusion.",
            "publicationTitle": "Journal of thrombosis and thrombolysis",
            "publisher": "",
            "place": "",
            "date": "Nov 20, 2013",
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            "issue": "",
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            "journalAbbreviation": "J. Thromb. Thrombolysis",
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            "PMCID": "",
            "ISSN": "1573-742X",
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            "language": "ENG",
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            "title": "Rapid, sensitive diagnosis of hemolytic anemia using antihemoglobin antibody in hypotonic solution",
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                    "firstName": "Wonbae",
                    "lastName": "Lee"
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                {
                    "creatorType": "author",
                    "firstName": "Yonggoo",
                    "lastName": "Kim"
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                {
                    "creatorType": "author",
                    "firstName": "Jihyang",
                    "lastName": "Lim"
                },
                {
                    "creatorType": "author",
                    "firstName": "Myungshin",
                    "lastName": "Kim"
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                {
                    "creatorType": "author",
                    "firstName": "Eun Jung",
                    "lastName": "Lee"
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                {
                    "creatorType": "author",
                    "firstName": "Ahwon",
                    "lastName": "Lee"
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                {
                    "creatorType": "author",
                    "firstName": "Kyo Young",
                    "lastName": "Lee"
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                {
                    "creatorType": "author",
                    "firstName": "Chang Suk",
                    "lastName": "Kang"
                },
                {
                    "creatorType": "author",
                    "firstName": "So-Young",
                    "lastName": "Kim"
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                {
                    "creatorType": "author",
                    "firstName": "Kyungja",
                    "lastName": "Han"
                },
                {
                    "creatorType": "author",
                    "firstName": "Soo Hwan",
                    "lastName": "Pai"
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            ],
            "abstractNote": "We have developed a new and simple flow cytometric method to detect damaged red blood cells (RBCs) using anti-Hb in hypotonic solution. We studied a total of 200 patients, including 62 patients with schistocytosis, 8 postsplenectomy patients, and 108 healthy controls. Peripheral blood (2 microl) was stained with phycoerythrin-conjugated (PE) antihemoglobin antibody (anti-Hb) in 0.6% (w/v) NaCl solution, and analyzed by flow cytometry omitting the washing step. The proportion of RBCs stained by anti-Hb was 0.55% (SD +/-0.23%) in normal controls and was significantly higher in patients with schistocytosis (2.95+/-2.95%, p <0.001). Six of 108 blood samples from normal controls and 60 of 62 samples from schistocytosis patients showed > or =1.01% stained RBCs (ie, values > mean+2SD of normal controls). The number of schistocytes counted by microscopic examination correlated with the proportion of RBCs stained by anti-Hb (r = 0.637, p <0.001). The proportions of stained RBCs in blood samples with malaria, spherocytosis, and elliptocytosis were also significantly higher than in normal controls. However, the results in postsplenectomy and iron-deficiency anemia (IDA) patients were not significantly different from the normal controls; the number of schistocytes in postsplenectomy patients was not related to the proportion of RBCs stained by anti-Hb. Based on these findings, flow cytometry of damaged RBCs using anti-Hb in hypotonic solution is a simple, sensitive, and accurate method to detect active hemolysis.",
            "publicationTitle": "Annals of clinical and laboratory science",
            "publisher": "",
            "place": "",
            "date": "2002",
            "volume": "32",
            "issue": "1",
            "section": "",
            "partNumber": "",
            "partTitle": "",
            "pages": "37-43",
            "series": "",
            "seriesTitle": "",
            "seriesText": "",
            "journalAbbreviation": "Ann. Clin. Lab. Sci.",
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            "accessDate": "",
            "PMID": "",
            "PMCID": "",
            "ISSN": "0091-7370",
            "archive": "",
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            "shortTitle": "",
            "language": "eng",
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            "callNumber": "",
            "rights": "",
            "extra": "PMID: 11848616",
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                {
                    "tag": "Anemia, Hemolytic",
                    "type": 1
                },
                {
                    "tag": "Anemia, Iron-Deficiency",
                    "type": 1
                },
                {
                    "tag": "Antibodies",
                    "type": 1
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                {
                    "tag": "Elliptocytosis, Hereditary",
                    "type": 1
                },
                {
                    "tag": "Erythrocytes",
                    "type": 1
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                {
                    "tag": "Erythrocytes, Abnormal",
                    "type": 1
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                {
                    "tag": "Flow Cytometry",
                    "type": 1
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                {
                    "tag": "Hemoglobins",
                    "type": 1
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                    "tag": "Hemolysis",
                    "type": 1
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                    "tag": "Humans",
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                    "tag": "Hypotonic Solutions",
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                    "tag": "Postoperative Period",
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                    "tag": "Reference Values",
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                    "tag": "Sensitivity and Specificity",
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                    "tag": "Staining and Labeling",
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            "title": "The production of schistocytes by fibrin strands (a scanning electron microscope study)",
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                    "firstName": "B S",
                    "lastName": "Bull"
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            "date": "Jan 1970",
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            "pages": "104-111",
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            "creatorSummary": "Klein et al.",
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            "title": "[Quantitative determination of fragment erythrocytes (schistocytes) in healthy subjects and patients after surgery]",
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                {
                    "creatorType": "author",
                    "firstName": "P J",
                    "lastName": "Klein"
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                {
                    "creatorType": "author",
                    "firstName": "H",
                    "lastName": "Pullman"
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                {
                    "creatorType": "author",
                    "firstName": "W F",
                    "lastName": "de Lacroix"
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                {
                    "creatorType": "author",
                    "firstName": "V",
                    "lastName": "Pahnke"
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                {
                    "creatorType": "author",
                    "firstName": "H",
                    "lastName": "Imig"
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                {
                    "creatorType": "author",
                    "firstName": "R",
                    "lastName": "Fischer"
                }
            ],
            "abstractNote": "Fragmented erythrocytes (schistocytes) were counted in blood subjects and from 50 patients who underwent various surgical procedures. The results showed to be as follows: 1. The average number of schistocytes in healthy controls of both sexes was 1-20/00 (medium in Thoma chamber 1.4%0/00, in blood smears 2.030/00, with a range from 0-50/00 and 0-60/00, respectively). 2. There was an increase in the number of schistocytes two hours after a surgical procedure (average 60/00), the degree of which correlated with the extent of the operation. Higher values of fragmented erythrocytes were counted after intraoperative blood transfusion (average 100/00). In most cases schistocyte values returned to normal at about 24 hours after surgery. 3. The highest schistocyte counts (18-350/00) were observed in two patients undergoing splenectomy with persistence of elevated counts for a longer period. 4. The average schistocyte number in stored blood of various age was 2.50/00. 5. Both counting of schistocytes in Thoma chambers and in blood smears are applicable, though the values obtained with the latter technique are slightly higher. Quantitative estimtion of schistocytes proves a useful method for evaluating disturbances in microcirculation.",
            "publicationTitle": "Klinische Wochenschrift",
            "publisher": "",
            "place": "",
            "date": "Sep 15, 1975",
            "volume": "53",
            "issue": "18",
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            "partNumber": "",
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            "pages": "847-851",
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            "extra": "PMID: 1165626",
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                {
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                    "type": 1
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                {
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