Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

More than 200 hemoglobin variants with high oxygen affinity have been reported since 1966. In about one third of these, the increase in oxygen affinity is responsible for a compensatory erythrocytosis. The degree of erythrocytosis depends primarily upon the molecular defect of the hemoglobin molecule. Measurement of the oxygen binding properties of the blood (or of the stripped lysate) is a convenient test both for the diagnosis of these variants and for evaluation of their severity. In the severe cases the affinity of the abnormal hemoglobin is identical to that of isolated subunits and the heme heme interaction is abolished; erythrocythemia is usually observed. Conversely, when the increase in oxygen affinity is moderate no clinical abnormal features are noticed. A high oxygen affinity variant has to be suspected when the hemoglobin level is at the upper limits of the normal in females or individuals with a mild iron deficiency. Several high oxygen affinity hemoglobins are also unstable and a hemolytic process may mask the increase of the Hb level. These patients, despite Hb levels close to the normal, are anemic from a functional view point. Examples have been reported in the literature in which the high oxygen affinity hemoglobin was found in coincidence with another red cell abnormality: such a situation lead usually to a more severe syndrome than the simple heterozygous state.
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PMID:Abnormal hemoglobins with high oxygen affinity and erythrocytosis. 889 22

Red cell indices and discriminant functions were studied in 463 heterozygous beta-thalassaemics (337 without iron deficiency, 126 with iron deficiency) and 195 patients of iron deficiency anaemia (IDA) to ascertain their utility in the detection of betathalassaemia trait (BTT). Majority of traits in both groups had an elevated RBC count (> or = 5.0 x 10(12)/L). The counts were significantly higher than of patients with IDA, only 4.6% of whom had this degree of erythrocytosis. Mean Hb concentration was significantly higher in traits as compared to iron deficient subjects (p < 0.0001). Mean MCV and MCH were significantly (p < 0.0001) lower in traits more so in those with ID as compared to patients of IDA. MCV < 80 fl and MCH < 27 pg were found to be sensitive markers in the detection of traits even in the presence of ID. Of the four discriminant functions studied MCSQ was found to be most sensitive in detection of BTT and it identified 97.9% traits. DF of England and Fraser was most specific for BTT being < 8.4 in only 6.2% patients with IDA. Detection of erythrocytosis especially in the presence of mild anaemia and calculation of discriminant functions derived from red cell indices were found to play an important role in screening for BTT even in the presence of ID and helped identify those patients who required further laboratory evaluation.
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PMID:Red cell indices and discriminant functions in the detection of beta-thalassaemia trait in a population with high prevalence of iron deficiency anaemia. 1042 Jun 85

Erythrocytosis, thrombocytopenia, platelets function defects, coagulation factors deficiencies are the main haematologic disorders in patients with cyanotic congenital heart disease. They are responsible for increased bleeding tendency and contraindication of anticoagulation. Phlebotomy in this group of patients should be recommended when erythrocytosis is accompanied by clinical symptoms. Excessive phlebotomy can lead to iron deficiency and cause hyperviscosity symptoms. The iron supplementation should be closely monitored.
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PMID:[Hematologic disorders in patients with cyanotic congenital heart disease]. 1052 25

n vitro, rheological studies establish that whole blood viscosity and yield stress are high in patients with an erythrocytosis. However, a number of factors ensure that these patients, under physiological conditions, do not show the clinical features observed in other hyperviscosity states. These include red cell axial migration in flowing blood and "plug flow" in the largest vessels. In addition, a small increase in vessel diameter leads to large increases in blood flow, and generally high blood flows produce the lowest blood viscosity values. The increased hemoglobin levels and the increase in oxygen-carrying capacity at high hematocrit values compensate for the tissue hypoxia. In the "non-hypoxemic" erythrocytoses (polycythemia vera, idiopathic and apparent erythrocytosis), there is an increased incidence of vascular occlusion in untreated patients. The reasons for this include reduced peripheral blood flow, increased platelet-vessel wall interactions, and the demonstrated in vitro hyperviscosity which comes into play with abnormally low flow, seen in vivo under pathological conditions. In the erythrocytosis of hypoxemic lung disease and its associated hypoxemia, pulmonary vasoconstriction enhances susceptibility to hyperviscosity effects in particular. Moreover, the vasoconstriction caused by the hypoxemia prevents the normal adaptive changes of increased vessel diameter. Microcytic hypochromic red cell changes of iron deficiency do not cause a higher viscosity value at any given hematocrit value compared with normal red cells. However, in hypoxemic states oxygen-carrying capacity should be maximized, since the hemoglobin value is disproportionately lower at any given hematocrit in the presence of microcytic hypochromic cells compared with normal red cells.
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PMID:Hemorheology in the erythrocytoses. 1137 90

We describe, in Ethiopia, a third successful pattern of human adaptation to high-altitude hypoxia that contrasts with both the Andean "classic" (erythrocytosis with arterial hypoxemia) and the more recently identified Tibetan (normal venous hemoglobin concentration with arterial hypoxemia) patterns. A field survey of 236 Ethiopian native residents at 3,530 m (11,650 feet), 14-86 years of age, without evidence of iron deficiency, hemoglobinopathy, or chronic inflammation, found an average hemoglobin concentration of 15.9 and 15.0 gdl for males and females, respectively, and an average oxygen saturation of hemoglobin of 95.3%. Thus, Ethiopian highlanders maintain venous hemoglobin concentrations and arterial oxygen saturation within the ranges of sea level populations, despite the unavoidable, universal decrease in the ambient oxygen tension at high altitude.
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PMID:An Ethiopian pattern of human adaptation to high-altitude hypoxia. 1247 Nov 59

The Philadelphia chromosome-negative chronic myeloproliferative disorders (CMPD), polycythemia vera (PV), essential thrombocythemia (ET) and chronic idiopathic myelofibrosis (IMF), have overlapping clinical features but exhibit different natural histories and different therapeutic requirements. Phenotypic mimicry amongst these disorders and between them and nonclonal hematopoietic disorders, lack of clonal diagnostic markers, lack of understanding of their molecular basis and paucity of controlled, prospective therapeutic trials have made the diagnosis and management of PV, ET and IMF difficult. In Section I, Dr. Jerry Spivak introduces current clinical controversies involving the CMPD, in particular the diagnostic challenges. Two new molecular assays may prove useful in the diagnosis and classification of CMPD. In 2000, the overexpression in PV granulocytes of the mRNA for the neutrophil antigen NBI/CD177, a member of the uPAR/Ly6/CD59 family of plasma membrane proteins, was documented. Overexpression of PRV-1 mRNA appeared to be specific for PV since it was not observed in secondary erythrocytosis. At this time, it appears that overexpression of granulocyte PRV-1 in the presence of an elevated red cell mass supports a diagnosis of PV; absence of PRV-1 expression, however, should not be grounds for excluding PV as a diagnostic possibility. Impaired expression of Mpl, the receptor for thrombopoietin, in platelets and megakaryocytes has been first described in PV, but it has also been observed in some patients with ET and IMF. The biologic basis appears to be either alternative splicing of Mpl mRNA or a single nucleotide polymorphism, both of which involve Mpl exon 2 and both of which lead to impaired posttranslational glycosylation and a dominant negative effect on normal Mpl expression. To date, no Mpl DNA structural abnormality or mutation has been identified in PV, ET or IMF. In Section II, Dr. Tiziano Barbui reviews the best clinical evidence for treatment strategy design in PV and ET. Current recommendations for cytoreductive therapy in PV are still largely similar to those at the end of the PVSG era. Phlebotomy to reduce the red cell mass and keep it at a safe level (hematocrit < 45%) remains the cornerstone of treatment. Venesection is an effective and safe therapy and previous concerns about potential side effects, including severe iron deficiency and an increased tendency to thrombosis or myelofibrosis, were erroneous. Many patients require no other therapy for many years. For others, however, poor compliance to phlebotomy or progressive myeloproliferation, as indicated by increasing splenomegaly or very high leukocyte or platelet counts, may call for the introduction of cytoreductive drugs. In ET, the therapeutic trade-off between reducing thrombotic events and increasing the risk of leukemia with the use of cytoreductive drugs should be approached by patient risk stratification. Thrombotic deaths seem very rare in low-risk ET subjects and there are no data indicating that fatalities can be prevented by starting cytoreductive drugs early. Therefore, withholding chemotherapy might be justifiable in young, asymptomatic ET patients with a platelet count below 1500000/mm(3) and with no additional risk factors for thrombosis. If cardiovascular risk factors together with ET are identified (smoking, obesity, hypertension, hyperlipidemia) it is wise to consider platelet-lowering agents on an individual basis. In Section III, Dr. Gianni Tognoni discusses the role of aspirin therapy in PV based on the recently completed European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP) Study, a multi-country, multicenter project aimed at describing the natural history of PV as well as the efficacy of low-dose aspirin. Aspirin treatment lowered the risk of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke (relative risk 0.41 [95% CI 0.15-1.15], P =.0912). Total and cardiovascular mortality were also reduced by 46% and 59%, respectively. Major bleedings were slightly increased nonsignificnsignificantly by aspirin (relative risk 1.62, 95% CI 0.27-9.71). In Section IV, Dr. Giovanni Barosi reviews our current understanding of the pathophysiology of IMF and, in particular, the contributions of anomalous megakaryocyte proliferation, neoangiogenesis and abnormal CD34(+) stem cell trafficking to disease pathogenesis. The role of newer therapies, such as low-conditioning stem cell transplantation and thalidomide, is discussed in the context of a general treatment strategy for IMF. The results of a Phase II trial of low-dose thalidomide as a single agent in 63 patients with myelofibrosis with meloid metaplasia (MMM) using a dose-escalation design and an overall low dose of the drug (The European Collaboration on MMM) will be presented. Considering only patients who completed 4 weeks of treatment, 31% had a response: this was mostly due to a beneficial effect of thalidomide on patients with transfusion dependent anemia, 39% of whom abolished transfusions, patients with moderate to severe thrombocytopenia, 28% of whom increased their platelet count by more than 50 x 10(9)/L, and patients with the largest splenomegalies, 42% of whom reduced spleen size of more than 2 cm.
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PMID:Chronic myeloproliferative disorders. 1463 83

The state of iron deposits in long-term kidney graft recipients is not well-known. Angiotensin enzyme inhibitors (ACEIs) reduce hematocrit levels in patients with posttransplant erythrocytosis (PTE), but their action on iron deposits has not been sufficiently evaluated. We designed this study to investigate the prevalence of iron deficiency among patients without anemia, the efficacy of ACEI treatment and its influence on iron deposits, and the risks of iron treatment in patients with symptomatic iron deficiency but no anemia. One hundred thirty eight patients were included if they had a kidney transplant for more than a year, with good renal function, with no anemia, and with neither iron nor rHuEpo, ARA, or ACEI treatment. One hundred seventeen had a normal Ht (group 1) and 21 had PTE (group 2). Iron deficiency was found in 73 (62.4%) group 1 patients and in 10 (47%) group 2 patients. Two group 1 patients with symptoms of iron deficiency were treated with oral iron. Their symptoms disappeared, but one developed PTE. Enalapril treatment decreased Ht levels in PTE but not in control patients. Furthermore, this drug increased iron deposits in PTE and controls with a baseline iron deficiency. We conclude that there is a high prevalence of iron deficiency in long-term transplanted patients without anemia. Furthermore, iron treatment must be carefully administered because of the risk of PTE. Enalapril treatment decreased Ht levels in PTE but not in control patients and increased iron deposits in patients with baseline iron deficiency.
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PMID:Iron deficiency--an underrecognized problem in nonanemic and erythrocytic kidney transplant recipients: risks and effects of ACEI and of iron treatment. 1584 6

The authors describe a 19 year old male with an isolated but absolute erythrocytosis with iron deficiency without evidence for polycythemia vera as well as another causes of erythrocytosis. The polycythemia was due to a recently described von Hippel-Lindau (VHL) mutation. By stopping iron therapy there was no more requirements for phlebotomy in this patient.
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PMID:Clinical presentation of a patient with congenital polycythemia. 1661 1

Erythrocytosis is an adaptive response to improve oxygen transport in cyanotic congenital heart disease (CCHD). However, at highly increased hematocrit levels patients may experience hyperviscosity symptoms. Iron deficiency in CCHD patients is often overlooked due to elevated hemoglobin concentrations. A 29-year-old male with CCHD was readmitted to our outpatient clinic. Red blood cells (11.65*10(12)/L), hemoglobin (25.7 g/dL), and hematocrit (80%) were extremely elevated. Measurements of iron supply showed a constellation typical for iron deficiency with low ferritin (13.2 microg/L), and high sTfR (20 mg/L). We present a case of extremely high red blood cell counts with concomitant iron deficiency. For appropriate management and to avoid misinterpretation of the iron status, ferritin and sTfR should always accomplish laboratory examination of CCHD patients.
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PMID:Iron deficiency in a patient with extreme erythrocytosis due to cyanotic congenital heart disease. 1709 63

Complications of chronic hypoxia, including erythrocytosis, hyperviscosity, abnormalities of hemostasis, cerebral abscesses, stroke, and endocarditis, are among the most common consequences of cyanotic heart disease in adults. The compensatory erythrocytosis of cyanotic heart disease can become pathologic by causing an increase in blood viscosity, thereby decreasing perfusion and resulting in decreased total oxygen delivery and increased risk of venoocclusive/hyperviscosity syndrome. Treatment of hyperviscosity secondary to erythrocytosis in cyanotic heart disease is controversial. Data is limited but suggest that phlebotomy has the potential to increase exercise capacity, reduce the symptoms of hyperviscosity, and reduce the potential risk of vasoocclusive disease in selected patients with polycythemia secondary to cyanotic heart disease. Unfortunately, repeated phlebotomy can quickly lead to iron deficiency, resulting in microcytic erythrocytes that induce higher viscosity than normocytic erythrocytes, which may increase the risk for venoocclusive events. There are limited data on the use of hydroxyurea to suppress erythrocytosis in this patient population. The authors conclude that until newer approaches to decreasing hematocrit without inducing iron deficiency are shown to be safe and efficacious, phlebotomy should only be used for the acute resolution of hyperviscosity symptoms. In addition, the use of hydroxyurea should be limited to patients with recurrent symptoms.
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PMID:Blood is thicker than water: the management of hyperviscosity in adults with cyanotic heart disease. 1717 81


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