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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anemia is common in dialysis patients. Change in phospholipids asymmetry in red blood cells (RBCs) may affect the removal of RBCs from the circulation and thus shorten the lifespan of RBCs. In the present study, we investigated phospholipids asymmetry in RBCs in uremic patients and its relationship with anemia. We studied 34 continuous ambulatory peritoneal dialysis (CAPD) patients (age: 51 +/- 15 years), 73 hemodialysis (HD) patients (age: 48 +/- 12 years), 8 pre-dialysis renal-failure patients (age: 42 +/- 21 years), and 16 healthy controls (age: 32 +/- 9 years). All patients were clinically stable. Phospholipids asymmetry as measured by phosphatidylserine exposure was determined by a flow-cytometric annexin V-binding assay. Hemoglobin levels were 93 +/- 20 g/L, 83 +/- 17 g/L, 78 +/- 21 g/L, and 145.8 +/- 12.5 g/L for CAPD patients, pre-dialysis patients, HD patients, and healthy controls respectively. Phosphatidylserine exposure in RBCs was significantly higher in uremic patients as compared with healthy controls, especially in HD patients--whose values were significantly higher than values seen in CAPD patients and pre-dialysis patients. No significant difference was seen in RBC phosphatidylserine exposure between pre-dialysis patients and CAPD patients. Cells positive for annexin V binding were 1.58%, 1.40%, 2.11%, and 0.71% for CAPD patients, pre-dialysis patients, HD patients, and healthy controls respectively. Significant reverse correlations were seen between annexin V and hemoglobin (r = -0.381, p < 0.001), and between annexin V and hematocrit (r = -0.355, p < 0.001). Our results suggest that (1) anemia is common in our uremic patients, especially in HD patients; and (2) anemia in uremic patients may be partly related to the loss of phospholipids asymmetry in RBCs.
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PMID:Loss of phospholipids asymmetry in red blood cells contributes to anemia in uremic patients. 1151 Feb 98

Erythrocyte injury such as osmotic shock, oxidative stress or energy depletion stimulates the formation of prostaglandin E2 through activation of cyclooxygenase which in turn activates a Ca2+ permeable cation channel. Increasing cytosolic Ca2+ concentrations activate Ca2+ sensitive K+ channels leading to hyperpolarization, subsequent loss of KCl and (further) cell shrinkage. Ca2+ further stimulates a scramblase shifting phosphatidylserine from the inner to the outer cell membrane. The scramblase is sensitized for the effects of Ca2+ by ceramide which is formed by a sphingomyelinase following several stressors including osmotic shock. The sphingomyelinase is activated by platelet activating factor PAF which is released by activation of phospholipase A2. Phosphatidylserine at the erythrocyte surface is recognised by macrophages which engulf and degrade the affected cells. Moreover, phosphatidylserine exposing erythrocytes may adhere to the vascular wall and thus interfere with microcirculation. Erythrocyte shrinkage and phosphatidylserine exposure ('eryptosis') mimic features of apoptosis in nucleated cells which however, involves several mechanisms lacking in erythrocytes. In kidney medulla, exposure time is usually too short to induce eryptosis despite high osmolarity. Beyond that high Cl- concentrations inhibit the cation channel and high urea concentrations the sphingomyelinase. Eryptosis is inhibited by erythropoietin which thus extends the life span of circulating erythrocytes. Several conditions trigger premature eryptosis thus favouring the development of anemia. On the other hand, eryptosis may be a mechanism of defective erythrocytes to escape hemolysis. Beyond their significance for erythrocyte survival and death the mechanisms involved in 'eryptosis' may similarly contribute to apoptosis of nucleated cells.
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PMID:Mechanisms of suicidal erythrocyte death. 1595 82

Side effects of cytostatic treatment include development of anemia resulting from either decreased generation or accelerated clearance of circulating erythrocytes. Recent experiments revealed a novel kind of stress-induced erythrocyte death, i.e. eryptosis, which is characterized by enhanced cytosolic Ca(2+) levels, increased ceramide formation and exposure of phosphatidylserine at the cell surface. The present study explored whether cytostatic treatment with paclitaxel (Taxol) triggers eryptosis. Blood was drawn from cancer patients before and after infusion of 175 mg/m2 Taxol. The treatment significantly decreased the hematocrit and significantly increased the percentage of annexin-V-binding erythrocytes in vivo (by 37%). In vitro incubation of human erythrocytes with 10 microM paclitaxel again significantly increased annexin-V-binding (by 129%) and augmented the increase of annexin-V-binding following cellular stress. The enhanced phosphatidylserine exposure was not dependent on caspase-activity but paralleled by erythrocyte shrinkage, increase of cytosolic Ca(2+) activity, ceramide formation and activation of calpain. Phosphatidylserine exposure was similarly induced by docetaxel but not by carboplatin or doxorubicin. Moreover, eryptosis was triggered by the Ca(2+) ionophore ionomycin (10 microM). In mice, ionomycin-treated eryptotic erythrocytes were rapidly cleared from circulating blood and sequestrated into the spleen. In conclusion, our data strongly suggest that paclitaxel-induced anemia is at least partially due to induction of eryptosis.
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PMID:Stimulation of erythrocyte phosphatidylserine exposure by paclitaxel. 1691

Side effects of cyclosporine treatment include anemia. Most recent studies have found that anemia may be caused by triggering of suicidal erythrocyte death (eryptosis), i.e. activation of an erythrocyte scramblase and phosphatidylserine exposure at the erythrocyte surface. Phosphatidylserine exposing cells are rapidly cleared from circulating blood by phagocytosis. Stimulators of erythrocyte membrane scrambling include cytosolic Ca(2+) and ceramide, which are increased by entry through Ca2+-permeable cation channels and by activation of a sphingomyelinase, respectively. The present study has been performed to test for an effect of cyclosporine on eryptosis. Erythrocytes from healthy volunteers were exposed to cyclosporine, and phosphatidylserine exposure (annexin V binding), cell volume (forward scatter), cytosolic Ca2+ activity (Fluo3-dependent fluorescence), ceramide formation (anti-ceramide-FITC antibody), and 45Ca2+ uptake were determined by flow cytometry and tracer flux measurements, respectively. Exposure of erythrocytes to cyclosporine triggered annexin V binding and significantly enhanced the increased annexin V binding both following glucose depletion and after hyperosmotic or isotonic cell shrinkage. However, cyclosporine significantly decreased cytosolic Ca2+ activity and did not stimulate 45Ca2+ uptake. Instead, cyclosporine transiently stimulated ceramide formation, decreased the cytosolic ATP concentration and potentiated the decline of cytosolic ATP concentration following glucose depletion. Elevated ceramide levels and ATP depletion, in turn, sensitize the erythrocytes for the eryptotic effects of Ca2+. The present observations may provide a mechanistic explanation for the anemia following treatment with this important immunosuppressive drug.
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PMID:Induction of eryptosis by cyclosporine. 1701 14

Sequelae of sepsis include anemia which presumably results from accelerated clearance of erythrocytes from circulating blood. The underlying mechanisms, however, remained hitherto elusive. Most recent studies disclosed that increased cytosolic Ca2+ activity and ceramide both trigger suicidal erythrocyte death (i.e., eryptosis), which is characterized by lipid scrambling of the cell membrane leading to phosphatidylserine exposure at the erythrocyte surface. Phosphatidylserine exposing erythrocytes may adhere to vascular walls or may be engulfed by macrophages equipped with phosphatidylserine receptors. To explore whether sepsis leads to eryptosis, erythrocytes from healthy volunteers were exposed to plasma of patients suffering from sepsis, or to supernatants from sepsis producing pathogens. Then, phosphatidylserine exposure (annexin V binding), cell volume (forward scatter), cytosolic Ca2+ activity (Fluo3 fluorescence), and ceramide formation (anti-ceramide antibody) were determined by flow cytometry. Challenge of erythrocytes with plasma from the patients but not with plasma from healthy individuals triggered annexin V binding. The effect of patient plasma on erythrocyte annexin V binding was paralleled by formation of ceramide and a significant increase of cytosolic Ca2+ activity. Exposure of erythrocytes to supernatant of pathogens similarly induced eryptosis, an effect correlating with sphingomyelinase activity. The present observations disclose a novel pathophysiological mechanism leading to anemia and derangement of microcirculation during sepsis. Exposure to plasma from septic patients triggers phosphatidylserine exposure leading to adherence to the vascular wall and clearance from circulating blood.
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PMID:Suicidal erythrocyte death in sepsis. 1718 Mar 45

Wilson disease is caused by accumulation of Cu(2+) in cells, which results in liver cirrhosis and, occasionally, anemia. Here, we show that Cu(2+) triggers hepatocyte apoptosis through activation of acid sphingomyelinase (Asm) and release of ceramide. Genetic deficiency or pharmacological inhibition of Asm prevented Cu(2+)-induced hepatocyte apoptosis and protected rats, genetically prone to develop Wilson disease, from acute hepatocyte death, liver failure and early death. Cu(2+) induced the secretion of activated Asm from leukocytes, leading to ceramide release in and phosphatidylserine exposure on erythrocytes, events also prevented by inhibition of Asm. Phosphatidylserine exposure resulted in immediate clearance of affected erythrocytes from the blood in mice. Accordingly, individuals with Wilson disease showed elevated plasma levels of Asm, and displayed a constitutive increase of ceramide- and phosphatidylserine-positive erythrocytes. Our data suggest a previously unidentified mechanism for liver cirrhosis and anemia in Wilson disease.
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PMID:Liver cell death and anemia in Wilson disease involve acid sphingomyelinase and ceramide. 1769 26

Eryptosis, the suicidal death of erythrocytes, is characterised by cell shrinkage, membrane blebbing and cell membrane phospholipid scrambling with phosphatidylserine exposure at the cell surface. Phosphatidylserine-exposing erythrocytes are recognised by macrophages, which engulf and degrade the affected cells. Reported triggers of eryptosis include osmotic shock, oxidative stress, energy depletion, ceramide, prostaglandin E(2), platelet activating factor, hemolysin, listeriolysin, paclitaxel, chlorpromazine, cyclosporine, methylglyoxal, amyloid peptides, anandamide, Bay-5884, curcumin, valinomycin, aluminium, mercury, lead and copper. Diseases associated with accelerated eryptosis include sepsis, malaria, sickle-cell anemia, beta-thalassemia, glucose-6-phosphate dehydrogenase (G6PD)-deficiency, phosphate depletion, iron deficiency, hemolytic uremic syndrome and Wilsons disease. Eryptosis may be inhibited by erythropoietin, adenosine, catecholamines, nitric oxide (NO) and activation of G-kinase. Most triggers of eryptosis except oxidative stress are effective without activation of caspases. Their signalling involves formation of prostaglandin E(2) with subsequent activation of cation channels and Ca2+ entry and/or release of platelet activating factor (PAF) with subsequent activation of sphingomyelinase and formation of ceramide. Ca2+ and ceramide stimulate scrambling of the cell membrane. Ca2+ further activates Ca2+-sensitive K+ channels leading to cellular KCl loss and cell shrinkage and stimulates the protease calpain resulting in degradation of the cytoskeleton. Eryptosis allows defective erythrocytes to escape hemolysis. On the other hand, excessive eryptosis favours the development of anemia. Thus, a delicate balance between proeryptotic and antieryptotic mechanisms is required to maintain an adequate number of circulating erythrocytes and yet avoid noneryptotic death of injured erythrocytes.
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PMID:Erythrocyte programmed cell death. 1872 Apr 18

Side effects of peroxisome proliferator activated receptor gamma (PPARgamma) agonists such as ciglitazone include anemia, which in theory could be due to decreased formation or premature death of erythrocytes. A form of suicidal erythrocyte death is eryptosis, which is characterized by cell shrinkage and by breakdown of phosphatidylserine asymmetry leading to phosphatidylserine exposure at the cell surface. Phosphatidylserine-exposing erythrocytes are recognized by macrophages, engulfed, degraded and thus cleared from circulating blood. Triggers of eryptosis include increase in intracellular Ca(2+) concentration. The present study thus explored, whether the PPARgamma agonist ciglitazone or the natural PPARgamma ligand 15deoxy-delta12,14-prostaglandin J2 (15d-PGJ2) are capable to trigger eryptosis. Phosphatidylserine exposure was determined from annexin V binding and cell shrinkage from decrease of forward scatter of human erythrocytes in FACS analysis. Both, ciglitazone (>or= 5 microM) and 15d-PGJ2 (>or= 3 microM), within 24 hours increased phosphatidylserine exposure and at concentrations of 10 microM led to a significant loss of the cell volume. Ciglitazone further stimulated hemolysis, which, however, affected only a fraction of erythrocytes undergoing eryptosis. According to Fluo3 fluorescence of human erythrocytes, 10 microM ciglitazone or 15d-PGJ2 increased intracellular Ca(2+) activity. In conclusion, ciglitazone and 15d-PGJ2 trigger eryptosis at least in part by an increase in the cytosolic Ca(2+) concentration. The effect most likely contributes to the anemia observed following treatment with PPARgamma agonists.
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PMID:Ciglitazone and 15d-PGJ2 induced suicidal erythrocyte death. 1876 50

Eryptosis, the suicidal death of erythrocytes, is characterized by cell shrinkage and by cell membrane scrambling with phosphatidylserine exposure at the erythrocyte surface. Eryptosis is triggered by several stress conditions including isotonic cell shrinkage (Cl(-) removal) and energy depletion (glucose removal). Both are effective through an increase in the cytosolic Ca(2+) concentration. Phosphatidylserine-exposing erythrocytes are cleared from circulating blood. Enhanced eryptosis thus leads to anemia. Accordingly, drugs interfering with eryptosis may prove useful in the treatment of anemia. The present study explored, whether caffeine interferes with eryptosis. Erythrocyte phosphatidylserine exposure was estimated from annexin V-binding, cell volume from forward scatter and cytosolic Ca(2+) activity from Fluo3 fluorescence. Under control conditions, eryptosis affected less than 5% of the erythrocytes and was not significantly modified by the presence of caffeine (50-500 microM). Glucose depletion (for 48 hours) significantly increased Fluo3 fluorescence and annexin V-binding and decreased forward scatter, effects partially reversed by caffeine (500 microM). Low Cl(-) solution (Cl(-) exchanged by gluconate for 48 hours) similarly increased annexin V-binding and decreased forward scatter, effects again reversed by caffeine (50-500 microM). In conclusion, caffeine inhibits Ca(2+) entry following glucose depletion and thus counteracts eryptosis during isotonic cell shrinkage and energy depletion.
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PMID:Caffeine inhibits suicidal erythrocyte death. 1876 52

Methyldopa is used for treatment of hypertension in pregnancy. Side effects of methyldopa include anemia, which could result from decreased formation or accelerated death of circulating erythrocytes. Several drugs cause anemia by triggering of suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling, the latter leading to phosphatidylserine exposure at the erythrocyte surface. Stimulators of erythrocyte membrane scrambling include increased cytosolic Ca(2+) concentration ([Ca(2+)](i)) and ceramide. Phosphatidylserine-exposing cells are rapidly cleared from circulating blood. The present study explored whether eryptosis could be triggered by methyldopa. Erythrocytes from healthy volunteers were exposed to methyldopa, and phosphatidylserine exposure (annexin A5 binding), cell volume (forward scatter), [Ca(2+)](i) (Fluo3-dependent fluorescence), and ceramide formation (anti-ceramide-fluorescein isothiocyanate antibody) were determined by flow cytometry. Methyldopa (6 microg/ml) did not increase [Ca(2+)](i) but led to stimulation of ceramide formation resulting in significant phosphatidylserine exposure and, at higher concentrations, to cell shrinkage. Methyldopa further decreased the GSH/GSSG ratio, pointing to oxidative stress. The scavenger N-acetyl-L-cysteine significantly blunted methyldopa-induced eryptosis. Clearance of erythrocytes from circulating blood was significantly accelerated by treatment with methyldopa. The present observations disclose a novel action of methyldopa, which may well contribute to drug-induced anemia.
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PMID:Stimulation of erythrocyte cell membrane scrambling by methyldopa. 1877 3


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