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Query: UMLS:C0240066 (iron deficiency)
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A brief survey of the literature on the side effects of oral contraceptives is given. Of the many influences on laboratory results those related to (reversible) cholestasis or to a change in protein synthesis are the most important ones. A decrease of the tolerance for glucose is sometimes observed. Few of the clinical side effects attributed to oral contraceptives can be directly correlated with the pharmaceutical action of these drugs. Many so-called side effects of the pill are due to other factors such as altered psychosociological or sexual behavior, etc. However, among users of oral contraceptives there is a significant decrease in the number of benign tumors, particularly of the breast, the uterus and the ovaries. It is still an open question if this also signifies protection against cancer. Anemias due to iron deficiency are less frequent among users of the pill. According to recent studies arterial hypertension and cholecystopathies are probably directly related to oral contraceptives, but a causal relation has not been proven for migraine, headaches, depression etc. An elevated risk for vascular complications seems to be well established: there is a 4-6-fold increase of the estimated risk for venous thrombo-embolism and a 4-9-fold increase for cerebrovascular accidents among users of oral contraceptives when compared with nonpregnant women of the same age not using the pill. Oral contraceptives act as a supplementary factor of risk which may cumulate with other similar factors, such as arterial hypertension, hyperlipidemia, overweight, smoking etc. Mortality due to oral contraceptives is very much 10-50 x) inferior to the one caused by delivery and the post partum state. Since the number of failures in prevention of pregnancies is less for oral contraceptives than for any other method of contraception, the overall risk of death under oral contraceptives in this age group of women is least.
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PMID:[Real and seeming side-effects of oral contraceptives with an emphasis on medical and haematological problems. Review of literature (author's transl)]. 79 Mar 74

Various factors are involved in the pathogenesis of anemia in dialysis patients. Reduced erythropoiesis is mainly attributed to erythropoietin deficiency. Stimulation of erythropoiesis may be promoted by androgens. Substitution of iron is recommended in case of iron deficiency. As a rule, supplementation of vitamin B12 is not necessary, but administration of folic acid is recommended. Treatment of anemia in renal failure is rendered more effective by increased technical efficiency in hemodialysis permitting a relatively protein-rich diet. Blood transfusions are not necessary during routine treatment of dialysis. Since bilateral nephrectomy will always provoke severe anemia, it should be reserved to special cases of severe hypertension. Until now, no conservative therapy has been developed which would allow optimal treatment of anemia in dialysis patients. Successful renal transplantation still is, and will be, the best therapeutic intervention.
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PMID:[Anemia in terminal kidney failure. Pathogenesis and therapy]. 83 56

Eleven anemic children and adolescents with a median age of 14 years (range six months-20 years) on chronic hemodialysis were treated with recombinant human erythropoietin (rHuEPO) intravenously three times a week for an average of 9.2 months. After eight weeks of therapy, hematocrit rose from 20.3 +/- 1.4% to 31.7 +/- 0.7% (0.20 +/- 0.01 to 0.31 +/- 0.007, p less than 0.001, mean +/- SEM). After reaching the target hematocrit of 30% to 33% (0.30 to 0.33), doses were adjusted individually. Blood transfusions were eliminated in all but one patient. All patients experienced an increase in appetite and energy level. Serum ferritin concentrations decreased in all patients who reached target hematocrit and seven required iron supplementation. Hypertension worsened in two patients and developed in two others. One patient's vascular access clotted. Dialysis efficiency and heparin requirements during dialysis did not change significantly. We conclude that rHuEPO is safe, effective, and should be recommended as treatment for anemia in children and adolescents on hemodialysis, but close monitoring for the development of hypertension and/or iron deficiency is necessary.
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PMID:Therapy of renal anemia in children and adolescents with recombinant human erythropoietin (rHuEPO). 154 82

Chronic renal failure is almost invariably accompanied by symptomatic anemia. It has been demonstrated that the primary cause of this anemia is inadequate production of erythropoietin by the diseased kidneys. The isolation of erythropoietin, followed by the cloning and expression of the human erythropoietin gene, made possible clinical trials of rHuEPO in uremic patients. rHuEPO produced dramatic increases in the hematocrit in almost all patients treated and also ameliorated many symptoms, such as lethargy, dizziness, and poor appetite, that had long been attributed to the effect of uremic toxins. Adverse effects of treatment with rHuEPO noted in the early clinical trials included hypertension, seizures, arteriovenous fistula or shunt thrombosis, and hyperkalemia. Further study of rHuEPO has shown that many of these side effects may be no more frequent in patients receiving rHuEPO than in other uremic patients not receiving rHuEPO. Reduction of the rHuEPO dosage and subcutaneous administration produce less rapid increases in the hematocrit and may lessen the incidence and severity of these side effects. rHuEPO therapy places great demands on both the body's iron stores and the capacity to rapidly transfer iron from storage sites to the erythroid progenitor cells. Thus, almost all patients treated with rHuEPO become iron deficient and require oral or parenteral iron replacement. Response to rHuEPO in uremic patients is diminished if the anemia is complicated by iron deficiency, inflammatory disorders, aluminum overload, or deficiency of folate or vitamin B12. rHuEPO therapy is safe and effective in the treatment of the anemia of chronic renal failure. The use of rHuEPO leads to enhanced quality of life and eliminates the need for red cell transfusions. In addition to hemodialysis patients, predialysis patients and those on CAPD benefit from and are candidates for rHuEPO therapy.
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PMID:Anemia of renal failure. Use of erythropoietin. 157 66

This multicentre study in 142 transfusion-dependent patients with chronic renal failure maintained by haemodialysis was performed to establish the appropriate dose regimen of rHuEpo and define its long-term safety profile. Only one of 132 patients eligible for efficacy analysis did not achieve the haemoglobin target of greater than or equal to 10 g/dl; this particular patient had folate deficiency and overt hyperparathyroidism. Regular blood transfusions were no longer necessary in any patients, however five patients needed blood transfusions only once, not due to rHuEpo failure: two for iron deficiency and three for intercurrent disease. In parallel with the haemoglobin increase a statistically significant improvement in quality of life scores was observed. The weekly dose required to maintain median haemoglobin between 10 and 10.5 g/dl for 1 year (n = 79) was 200-225 U/kg, applied as two or three i.v. injections. Mean serum ferritin decreased from 1900 to 1300 ng/ml and transferrin saturation from 60% to 30%; this feature was associated with statistically significant decrease of pre-study elevated liver enzymes. The treatment had no untoward effect on the outcome of renal transplantation (n = 24). Of the 56 patients who experienced hypertensive episodes during rHuEpo therapy, 47 had a history of hypertension and nine had not. The patient incidence during the first 3 months was 28.9% and fell markedly to 4% after 1 year. Only two hypertensive episodes could not be controlled and the patients dropped out. Seizures occurred in 11 patients, most of them during early treatment; annualised incidence during the first 3 months was 7.78 per year vs 2.07 per year for seizures beyond 3 months treatment. Clinical presentation, patients' history, haemoglobin pattern, BP recordings, brain scan, and EEG indicated that the pathophysiology is multifactorial, with emphasis on rate of haemoglobin increase. Therefore a smooth haemoglobin increase rate, induced by a conservative starting dose regimen (50 U/kg thrice weekly) is recommended, to allow the circulation to adapt to changes in haematocrit/viscosity and O2 delivery. The majority of the observed adverse reactions were related to rHuEpo's therapeutic effect, i.e. increase the haematocrit. The side-effects are therefore largely predictable and can be successfully managed.
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PMID:Treatment of transfusion-dependent anaemia of chronic renal failure with recombinant human erythropoietin. A European multicentre study in 142 patients to define dose regimen and safety profile. 179 95

The efficacy of recombinant human erythropoietin in correcting the anemia of the uraemic patient has been thoroughly confirmed. Iron deficiency, aluminum intoxication, severe hyperparathyroidism and infections are some of the main factors limiting patients' response to the drug. Worsening or de novo formation of arterial hypertension generally makes it necessary to diminish the degree of correction of anaemia. It is commonly accepted that anaemia should be only partially corrected and that the target haemoglobin level should be defined patient by patient.
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PMID:[Factors limiting the correction of anemia with recombinant human erythropoietin]. 181 32

During pregnancy because of physiologic hemodiluition and changes in various plasma protein levels, plasma viscosity is decreased compared to the non pregnant condition. Specifically the whole blood viscosity profile throughout pregnancy follows that of the hematocrit. However some pathological condition like pregnancy induced hypertension and intrauterine growth retardation are characterized by an increase of plasma viscosity. In order to evaluate the effect of plasma viscosity on placental perfusion, in 41 patients affected by pregnancy induced hypertension and with no iron deficiency we compared maternal hemoglobin and hematocrit to the birth weight. High maternal hemoglobin and hematocrit levels were associated to an increased frequency of low weight for date newborns (less than or equal to 10th centile), although the relationship with the hemoglobin levels is stronger (p less than or equal to 0.02) than the one with the hematocrit (p less than or equal to 0.05). In contrast, high weight for date newborns (greater than or equal to 90th centile) were not related to maternal hemoglobin and hematocrit parameters. We found that maternal hemoglobin and hematocrit, indicators of plasma viscosity, are useful in predicting low birth weight, but not high birth weight. We speculate that hypoxia due to the modification of microcirculation is a very important factor in determining the low birth weight; in contrast the oxygen is not the only factor involved in determining the high birth weight.
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PMID:[Hematocrit and hemoglobin, parameters of hematic viscosity, in pregnancy-induced hypertension]. 188 67

The use of recombinant human erythropoietin (rhEPO) for the treatment of renal anemia is well accepted. However, the lowest effective dose for subcutaneous (SC) administration has not been determined. This study documents that a dose of 50 U/kg administered three times a week was effective in 10 children (age range, 13 days to 18.6 years) receiving continuous cycling peritoneal dialysis (CCPD) for a period ranging from 0.25 to 23.5 months. Their hematocrit (hct) increased at an average rate of 0.26% points per day from a baseline of 19.8% +/- 3.1% to a value of at least 30% after a mean of 7.4 +/- 2.5 weeks of treatment. When compared with other studies, this response was more rapid than what has been observed with the same dose administered intravenously (IV). This response was similar to that seen with larger IV doses. Hypertension and functional iron deficiency were the most common complications. Two patients with previously controlled hypertension developed elevation in blood pressure that was easily controlled by oral antihypertensives. Six patients required IV iron dextran to reestablish treatment response. A SC rhEPO dose less than 50 U/kg three times a week may be effective in children and should be investigated.
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PMID:Use of low-dose subcutaneous recombinant human erythropoietin in end-stage renal disease: experience with children receiving continuous cycling peritoneal dialysis. 192 63

The article gives an account of contemporary knowledge of the treatment of anaemia in dialyzed patients by human recombinant erythropoietin. It was obtained by genetic engineering. It is very effective in the treatment of anaemia in patients included in a dialyzation programme, unless factors are present which reduce its effect (iron deficiency, Al cumulation and others). Along with red cell haematopoiesis, some other organs and systems are affected. The main undesirable effects may be hypertension and vascular thrombosis. In case of correct treatment and careful monitoring of treatment, these effects are outweighed by the assets of treatment. The drug is very expensive and it is important to pay attention to its effective use not only with regard to the patients but also to wider aspects associated with the care of dialyzed patients and the operation of dialyzation centres.
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PMID:[Chronic kidney failure, anemia and erythropoietin]. 235 Jul 72

The development of hypoproliferative anemia with generally normocytic red blood cells in most patients with chronic renal failure impairs the success of maintenance dialysis therapy, particularly hemodialysis. Anemia can be a complication of the hemodialysis procedure itself, with its associated blood losses and mild effect on oxygen transport functioning. However, the primary cause of anemia in the chronic dialysis patient is decreased erythropoiesis. The most important mechanism leading to decreased erythropoiesis involves the production of subnormal levels of erythropoietin (EPO). Insufficient nephric output of EPO or, possibly, suppression of the effect of EPO by uremic inhibitors may cause this decreased erythropoiesis. Other factors, such as iron deficiency, hyperparathyroidism, systemic infections, and aluminum toxicity may contribute to anemia in some patients. Increased hemolysis, a comparatively mild factor in the anemia of chronic dialysis patients, may be related to retention of protein metabolism products, hypersplenism, hypophosphatemia, drugs, or other conditions in affected patients. There are several traditional treatment options for anemia: transfusions; iron, vitamin B12, or folic acid supplementation when indicated; a change to peritoneal dialysis; parathyroidectomy; and administration of androgens. None of these treatments have proved satisfactory, and some, such as transfusions and androgen therapy, pose risks and have serious side effects. A comparatively new approach, administration of genetically engineered erythropoietin (r-HuEPO; EPOGEN, AMGEN inc, Thousand Oaks, CA), has been found effective in treating anemia in clinical trials. Patients have shown improved cardiac performance as well as enhanced quality of life, and hypertension appears to be the most serious side effect of r-HuEPO therapy.
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PMID:Overview of anemia associated with chronic renal disease: primary and secondary mechanisms. 264 18


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