Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pseudotumor cerebri (PC) is a clinical syndrome characterized by increased intracranial pressure with a normal cerebrospinal fluid cell count and protein level in the absence of a space-occupying lesion or apparent obstruction to the cerebrospinal fluid pathway. Although PC is described in patients with various hematological diseases including iron-deficiency anemia, megaloblastic anemia, acquired aplastic anemia, hemolytic anemia, sickle cell disease, and paroxysmal nocturnal hemoglobinuria, there is no case of PC with Fanconi anemia in the English literature. Here, we report a first case of PC in an 11-year-old boy with a diagnosis of Fanconi anemia.
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PMID:Pseudotumor cerebri in a Turkish boy with Fanconi anemia. 2243 May 86

Similar to nucleated cells, erythrocytes may undergo suicidal death or eryptosis, which is characterized by cell shrinkage, cell membrane blebbing and cell membrane phospholipid scrambling. Eryptotic cells are removed and thus prevented from undergoing hemolysis. Eryptosis is stimulated by Ca(2+) following Ca(2+) entry through unspecific cation channels. Ca(2+) sensitivity is enhanced by ceramide, a product of acid sphingomyelinase. Eryptosis is triggered by hyperosmolarity, oxidative stress, energy depletion, hyperthermia and a wide variety of xenobiotics and endogenous substances. Eryptosis is inhibited by nitric oxide, catecholamines and a variety of further small molecules. Erythropoietin counteracts eryptosis in part by inhibiting the Ca(2+)-permeable cation channels but by the same token may foster formation of erythrocytes, which are particularly sensitive to eryptotic stimuli. Eryptosis is triggered in several clinical conditions such as iron deficiency, diabetes, renal insufficiency, myelodysplastic syndrome, phosphate depletion, sepsis, haemolytic uremic syndrome, mycoplasma infection, malaria, sickle-cell anemia, beta-thalassemia, glucose-6-phosphate dehydrogenase-(G6PD)-deficiency, hereditary spherocytosis, paroxysmal nocturnal hemoglobinuria, and Wilson's disease. Enhanced eryptosis is observed in mice with deficient annexin 7, cGMP-dependent protein kinase type I (cGKI), AMP-activated protein kinase AMPK, anion exchanger AE1, adenomatous polyposis coli APC and Klotho as well as in mouse models of sickle cell anemia and thalassemia. Eryptosis is decreased in mice with deficient phosphoinositide dependent kinase PDK1, platelet activating factor receptor, transient receptor potential channel TRPC6, janus kinase JAK3 or taurine transporter TAUT. If accelerated eryptosis is not compensated by enhanced erythropoiesis, clinically relevant anemia develops. Eryptotic erythrocytes may further bind to endothelial cells and thus impede microcirculation.
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PMID:Killing me softly - suicidal erythrocyte death. 2256 48

The recent availability of eculizumab as the first complement inhibitor renewed the interest for complement-mediated damage in several human diseases. Paroxysmal nocturnal hemoglobinuria (PNH) may be considered the paradigm a disease caused by complement dysregulation specifically on erythrocytes; in fact, PNH is a clonal, non-malignant, hematological disorder characterized by the expansion of hematopoietic stem cells and progeny mature blood cells which are deficient in some surface proteins, including the two complement regulators CD55 and CD59. As a result, PNH erythrocytes are incapable to modulate on their surface physiologic complement activation, which eventually enables the terminal lytic complement leading to complement-mediated intravascular anemia - the typical clinical hallmark of PNH. In the last decade the anti-C5 monoclonal antibody has been proven effective for the treatment of PNH, resulting in a sustained control of complement-mediated intravascular hemolysis, with a remarkable clinical benefit. Since then, different diseases with a proved or suspected complement-mediated pathophysiology have been considered as candidate for a clinical complement inhibition. At the same time, the growing information on biological changes during eculizumab treatment in PNH have improved our understanding of different steps of the complement system in human diseases, as well as their modulation by current anti-complement treatment. As a result, investigators are currently working on novel strategy of complement inhibition, looking at the second generation of anti-complement agents which hopefully will be able to modulate distinct steps of the complement cascade. Here we review PNH as a disease model, focusing on the observation that led to the development of novel complement modulators; the discussion will be extended to other hemolytic disorders potentially candidate for clinical complement inhibition.
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PMID:Paroxysmal nocturnal hemoglobinuria and other complement-mediated hematological disorders. 2296 33

Paroxysmal nocturnal hemoglobinuria (PNH) is a progressive, life-threatening disorder characterized by chronic intravascular hemolysis caused by uncontrolled complement activation. Hepatic vein thrombosis (Budd-Chiari syndrome) is common in PNH patients. This case report describes the response to eculizumab (a humanized monoclonal antibody that inhibits terminal complement activation) in a 25-year-old male with progressive liver function deterioration despite standard anticoagulation therapy and transjugular intrahepatic porto-systemic shunt. The patient presented with anemia, severe thrombocytopenia, headache, abdominal pain, and distention. He was diagnosed with PNH, cerebral vein thrombosis, and Budd-Chiari syndrome. Despite adequate anticoagulation, diuretic administration, and placement of a transjugular shunt, additional thrombotic events and progressive liver damage were observed. Eculizumab therapy was initiated, resulting in rapid blockade of intravascular hemolysis, increased platelet counts, ascites resolution, and liver function recovery, all of which are presently sustained. Since starting eculizumab the patient has had no further thrombotic events and his quality of life has dramatically improved. This is the first report to confirm the role of complement-mediated injury in the progression of Budd-Chiari syndrome in a patient with PNH. This case shows that terminal complement blockade with eculizumab can reverse progressive thromboses and hepatic failure that is unresponsive to anticoagulation therapy and suggests that early initiation of eculizumab should be included in the therapeutic regimen of patients with PNH-related Budd-Chiari syndrome.
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PMID:Eculizumab in paroxysmal nocturnal hemoglobinuria with Budd-Chiari syndrome progressing despite anticoagulation. 2321 Apr 33

The term "unexplained anemia" appears frequently in a request for a hematology consultation. Although most anemia consultations are fairly routine, they occasionally represent challenging problems that require an amalgam of experience, insight, and a modicum of "out-of-the-box" thinking. Problem anemia cases and pitfalls in their recognition can arise for one of several reasons that are discussed in the cases presented herein. "Anemias beyond B12 and iron deficiency" covers a vast domain of everything that lies beyond the commonly encountered anemias caused by simple deficiencies of 2 currently major hematologically relevant micronutrients. However, even these deficiencies may be obscured when they coexist or are not considered because of misleading distractions. They may also be mistakenly identified when other less common nutrient deficiencies occur. I present herein case examples of such situations: a young patient with pancytopenia and schistocytes who was responsive to plasmapheresis, but in whom pernicious anemia was not suspected because of ethnicity and age; a bicytopenic patient with anemia and myelodysplastic features caused by copper deficiency after gastric reduction surgery; and a patient with BM hypoplasia and a dimorphic blood smear who was found to have paroxysmal nocturnal hemoglobinuria. These "pearls" represent but 3 examples of the many varieties of problems in anemia diagnosis and are used to illustrate potential pitfalls and how to avoid them.
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PMID:Anemias beyond B12 and iron deficiency: the buzz about other B's, elementary, and nonelementary problems. 2323 24

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired disorder characterized by chronic intravascular hemolysis as the primary clinical manifestation and morbidities that include anemia, thrombosis, renal impairment, pulmonary hypertension, and bone marrow failure. The prevalence of the PNH clone (from <1-100% PNH granulocytes) is approximately 16 per million, and careful monitoring is required. The average age of onset of the clinical disease is the early 30s, although it can present at all ages. PNH is caused by the acquisition of a somatic mutation of the gene phosphatidylinositol glycan anchor (PIG-A) in a multipotent hematopoietic stem cell (HSC), with clonal expansion of the mutated HSC. The mutation causes a deficiency in the synthesis of glycosylphosphatidylinositol (GPI). In cells derived from normal HSCs, the complement regulatory proteins CD55 and CD59 are anchored to the hematopoietic cell membrane surface via GPI, protecting the cells from complement-mediated lysis. However, in patients with PNH, these 2 proteins, along with numerous other GPI-linked proteins, are absent from the cell surface of red cells, granulocytes, monocytes, and platelets, resulting in complement-mediated intravascular hemolysis and other complications. Lysis of red blood cells is the most obvious manifestation, but as other cell lineages are also affected, this complement-mediated attack contributes to additional complications, such as thrombosis. Eculizumab, a humanized monoclonal antibody against the C5 complement protein, is the only effective drug therapy for PNH patients. The antibody prevents cleavage of the C5 protein by C5 convertase, in turn preventing generation of C5b-9 and release of C5a, thereby protecting from hemolysis of cells lacking the CD59 surface protein and other complications associated with complement activation. Drs. Ilene C. Weitz, Anita Hill, and Jeff Szer discuss 3 recent cases of patients with PNH.
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PMID:Clinical roundtable monograph: Paroxysmal nocturnal hemoglobinuria: a case-based discussion. 2327 Nov 56

Acute renal failure (ARF) is a well-recognized complication of paroxysmal nocturnal hemoglobinuria (PNH). The predominant mechanism is intravascular hemolysis resulting in massive hemoglobinuria ARF. We report a case of acute tubular necrosis (ATN) developed in the absence of overwhelming evidence of intravascular hemolysis in a 21-year-old man with anemia, who was eventually diagnosed to have PNH. The patient presented with rapidly deteriorating renal functions in the background of iron deficiency anemia, which was attributed to reflux esophagitis. There was no clinical or laboratory evidence of intravascular hemolysis. Renal biopsy revealed ATN with deposition of hemosiderin in the proximal tubular epithelial cells. Diagnosis of PNH was confirmed with a positive Ham's test and flow cytometry. Our case emphasizes the need to consider ATN as a possible cause for ARF in patients suspected to have PNH even in the absence of overwhelming evidence of intravascular hemolysis.
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PMID:Acute tubular necrosis in a patient with paroxysmal nocturnal hemoglobinuria. 2335 3

Paroxysmal nocturnal hemoglobinuria (PNH) is a hematological disorder characterized by complement-mediated hemolytic anemia, thrombophilia, and bone marrow failure. PNH is due to a somatic, acquired mutation in the X-linked phosphatidylinositol glycan class A (PIG-A) gene, which impairs the membrane expression on affected blood cells of a number of proteins, including the complement regulators CD55 and CD59. The most evident clinical manifestations of PNH arise from dysregulated complement activation on blood cells; in fact, the hallmark of PNH is chronic, complement-mediated, intravascular hemolysis, which results in anemia, hemoglobinuria, fatigue, and other hemolysis-related disabling symptoms. In addition, the peculiar thromboembolic risk typical of PNH patients is thought as secondary to the complement-mediated hemolysis itself and/or to a complement-mediated activation of platelets. Thus, as a complement-mediated disease, PNH was an appropriate medical condition to develop and to investigate therapeutical complement inhibitors. Indeed, the first complement inhibitor eculizumab, a humanized anti-C5 monoclonal antibody, has been proven safe and effective for the treatment of PNH patients. Chronic treatment with eculizumab results in sustained control of intravascular hemolysis, leading to hemoglobin stabilization and transfusion independence in more than half of the patients. However, recent observations have demonstrated that residual anemia may persist in some patients regardless of sustained fluid-phase terminal complement inhibition. Indeed, persistent dysregulated activation of the early phases of the complement cascade on PNH erythrocytes may lead to progressive C3 deposition on affected cells, which become susceptible to subsequent extravascular hemolysis through the reticuloendothelial system. These findings have renewed the interest for the development of novel complement inhibitors which aim to modulate early phases of complement activation, more specifically at the level of C3 activation. As proof of principle of this concept, an anti-C3 monoclonal antibody has been proven effective in vitro to prevent hemolysis of PNH erythrocytes. More intriguingly, a human fusion protein consisting of the iC3b/ C3d-binding region of complement receptor 2 and of the inhibitory domain of the CAP regulator factor H has been recently shown effective in inhibiting, in vitro, both intravascular hemolysis of and surface C3-deposition on PNH erythrocytes, and is now under investigation in phase 1 clinical trials.
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PMID:Paroxysmal nocturnal hemoglobinuria and the complement system: recent insights and novel anticomplement strategies. 2340 25

Hidden blood loss (HBL), commonly seen post total knee or hip arthroplasty, causes postoperative anemia even after reinfusion or blood transfusion based on the visible blood loss volume. The mechanism of HBL remains unclear although more than one theory had tried to explain it. Free fatty acids, metabolites of fatty emboli that are generated during TKA, THA and other surgery manipulating the medullary canal of femur, had been demonstrated to stimulate the neutrophils in producing reactive oxygen species such (ROS) as hydrogen peroxide and chlorous peroxide. Erythrocytes injury was also shown in parasitic infection, chronic renal disease and paroxysmal nocturnal hemoglobinuria in a mechanism of oxidation of membrane polyunsaturated fatty acids and cytosolic hemoglobin by ROS. Based on these results we hypothesize that free fatty acids generated from fatty emboli in blood circulation are responsible for the hidden blood loss through peroxidating injury of membrane molecules of RBC and hemoglobin. Antioxidants administered intra- or post-operatively are predicted to play a protective role in erythrocytes oxidation and potentially reduce the volume of hidden blood loss after arthroplasty.
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PMID:Free fatty acids are responsible for the hidden blood loss in total hip and knee arthroplasty. 2362 96

This study was aimed to explore the transcription level of WT1 and PRAME two genes in bone marrow and peripheral blood samples of patients with myelodysplastic syndrome(MDS) and their relationship with bone marrow dysplasia and karyotype. The quantitative expression of WT1 and PRAME transcripts detected by RQ-PCR in the bone marrow samples of 203 MDS patients and 19 aplastic anemia(AA), 6 other benign anemia(BA), 4 paroxysmal nocturnal hemoglobinuria(PNH) patients from July 2009 to June 2012 and 14 healthy donors, and in 92 peripheral blood samples. The results showed that WT1 and PRAME expression levels in both BM and PB samples of MDS group were higher than those in normal controls, AA, and BA patients (BM: WT1:P = 0.000, 0.000, 0.000, PRAME: P = 0.048, 0.000, 0.064; PB: WT1:P = 0.012, 0.000, 0.011, PRAME: P = 0.020, 0.004, 0.003). What is more, this expression in high risk MDS group (RAEB1, RAEB2, MDS-AML) were higher than those in low risk group (RCUD, RCMD, MDS-U) and AA and BA. The WT1 and PRAME mRNA expression levels in PB and BM were well correlated (WT1:r = 0.6028, P = 0.001; PRAME: r = 0.7628, P = 0.000), as well as the WT1 expression levels in BM samples with the Karyotype (P = 0.049). In addition, the same positive rate of WT1 or PRAME expression existed in BM and PB samples of MDS patients. It is concluded that the WT1 and PRAME gene expression levels in both BM and PB samples of MDS patients are higher than those in healthy controls, AA and other benign anemia patients, and increase with the progression of the disease. The WT1 and PRAME transcripts constitute good molecular markers for the clinical diagnosis and prognosis and monitoring minimal residual disease after treatment of MDS. What is more, when bone marrow is not so convenient to get, the transcript levels of PB samples can be detected.
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PMID:[Expression of WT1 and PRAME gene in bone marrow and peripheral blood samples of patients with myelodysplastic syndrome]. 2476 7


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