losartan-potassium and ferrous-sulfate

Iron supplementation is required in a preponderance of peritoneal dialysis (PD) patients treated with erythropoietic stimulatory agents (ESAs). Although many authors and clinical practice guidelines recommend primary oral iron supplementation in ESA-treated PD patients, numerous studies have clearly demonstrated that, because of a combination of poor bioavailability of oral iron, gastrointestinal intolerance, and noncompliance, oral iron supplementation is insufficient for maintaining a positive iron balance in these patients over time. Controlled trials have demonstrated that, in iron-deficient and iron-replete PD patients alike, intravenous (IV) iron supplementation results in superior iron stores and hemoglobin levels with fewer side effects than oral iron produces. Careful monitoring of iron stores in patients receiving IV iron supplementation is important in view of conflicting epidemiologic links between IV iron loading and infection and cardiovascular disease. Emerging new iron therapies such as heme iron polypeptide and ferumoxytol may further enhance the tolerability, efficacy, and ease of administration of iron in PD patients.

Topics: Administration, Oral; Clinical Trials as Topic; Darbepoetin alfa; Erythropoietin; Ferric Compounds; Ferritins; Ferrous Compounds; Hemoglobins; Humans; Infusions, Intravenous; Iron; Peritoneal Dialysis; Recombinant Proteins; Transferrin

The ability of epoetin alfa to increase hematopoiesis in a dose-dependent manner when administered by the intravenous (i.v.) or subcutaneous (s.c.) route has been demonstrated in pharmacokinetic studies in healthy volunteers. Epoetin alfa may therefore be a useful adjunct to autologous blood (AB) donation. By facilitating AB donation, the use of allogeneic blood could be reduced. In patients scheduled to undergo orthopedic surgery, i.v. administration of epoetin alfa 600 IU/kg twice weekly for 3 weeks prior to surgery (in conjunction with oral iron supplementation) significantly increased the number of AB units and total red blood cell (RBC) volume donated and increased the number of patients able to donate > or = 4 AB units. However, there was no difference between epoetin alfa and placebo groups with respect to allogeneic blood exposure.

Topics: Anemia; Blood Transfusion, Autologous; Epoetin Alfa; Erythropoiesis; Erythropoietin; Ferrous Compounds; Hematocrit; Hemoglobins; Humans; Injections, Intravenous; Injections, Subcutaneous; Orthopedics; Premedication; Recombinant Proteins

The production of red cells can be stimulated by pharmacologic doses of recombinant human erythropoietin (rHu-EPO), provided EPO-sensitive precursors and iron are available. Its side effects are negligible when used in patients with nonrenal anemia. Antibodies against rHu EPO are a rare event. Iron supplementation is routinely necessary in patients with low iron stores, since availability of iron is a rate-limiting cofactor for red cell production. The rationale for treating patients with anemia of cancer or chronic inflammation is to avoid homologous blood transfusion. However, it is not proven whether a raising of the hemoglobin concentration by 2 or 3 g% will improve the quality of life in these multimorbid patients who undergo palliative treatment. There is no evidence yet that rHu-EPO has reduced morbidity and mortality in such patients. Another question is the cost effectiveness of EPO particularly in patients who suffer from an incurable disease. EPO has also been used as an adjuvant in autologous preoperative transfusion programs and has increased the available volume of red cells for transfusion particularly in conjunction with intravenous iron supplementation. EPO given for 14 days preoperatively in patients with elective hip replacement reduced the need for transfusion by nearly 50%. A high dose of oral ferrous sulfate (300 mg) was given 11 days in advance of rHu EPO. Randomized trials are needed for patients with an initial low Hb (< 13.5 g/dl) to study the efficacy and cost effectiveness of different strategies avoiding homologous transfusion and also the risk-benefit ratio of such strategies versus homologous transfusions, since the risk of homologous transfusions has decreased considerably in recent years.

Topics: Anemia; Blood Transfusion; Combined Modality Therapy; Dose-Response Relationship, Drug; Erythropoiesis; Erythropoietin; Ferrous Compounds; Hemoglobinometry; Humans; Palliative Care; Recombinant Proteins

Gestational anemia increases the incidence of maternal and fetal complications. Adjuvant recombinant human erythropoietin (rHuEPO) has been used in patients who refuse blood transfusions, have a low response to treatment with iron sulfate, have limited time before birth, or have other illnesses that complicate the anemia. We demonstrated that the use of adjuvant rHuEPO with iron sulfate reduces the anemia time period and is innocuous to the fetus.. An experimental longitudinal prospective study; 100 pregnant women in their third trimester were included. Group 1 (n=50) was set as control for prevalence of anemia and establish hematological maternal and fetal parameters at delivery for our population; 50 women diagnosed with iron deficiency anemia were randomly assigned to treatment groups. Group 2 (n=25) third trimester women with a hemoglobin of <11g/dL were treated with iron sulfate, 600mg administered orally daily for 4 weeks, evaluating the hematologic response for the mother weekly and for both mother and fetus at birth; Group 3 (n=25) women similar to group 2, treated in addition with adjuvant rHuEPO, 4000 units subcutaneously, three times a week, for 4 weeks evaluating the same parameters.. Group 2 and 3 showed a corrected anemia before delivery (mean 11.1 vs 11.4g/dL), but Group 3 showed a statistically broader and more rapid increase in hemoglobin (1.22 vs 1.92g/dL, p value 0.013) with an rHuEPO dose of 4000 units, three times a week for 1 month. No clinical or hematologic difference or changes in growth were observed in the fetus.. Erythropoietin is safe and effective for both mother and fetus, although an ideal pregnancy dose has not yet been established.

Topics: Adult; Anemia, Iron-Deficiency; Drug Therapy, Combination; Erythropoietin; Female; Ferrous Compounds; Humans; Pregnancy; Pregnancy Trimester, Third; Prospective Studies; Recombinant Proteins; Treatment Outcome

Preliminary clinical evidence suggests that heme iron polypeptide (HIP) might represent a promising, novel oral iron supplementation strategy in chronic kidney disease. The aim of this multi-centre randomized controlled trial was to determine the ability of HIP administration to augment iron stores in darbepoetin (DPO)-treated patients compared with conventional oral iron supplementation.. Adult peritoneal dialysis (PD) patients treated with DPO were randomized 1:1 to receive two capsules daily of either HIP or ferrous sulphate per os for 6 months. The primary outcome measure was transferrin saturation (TSAT). Secondary outcomes comprised serum ferritin, haemoglobin, DPO dose and responsiveness, and adverse events.. Sixty-two patients were randomized to HIP (n = 32) or ferrous sulphate (n = 30). On intention-to-treat analysis, the median (inter-quartile range) TSAT was 22% (16-29) in the HIP group compared with 20% (17-26) in controls (P = 0.65). HIP treatment was not significantly associated with TSAT at 6 months on multivariable analysis (P = 0.95). Similar results were found on per-protocol analysis and subgroup analysis in iron-deficient patients. Serum ferritin levels at 6 months were significantly lower in the HIP group (P = 0.003), while the cost of HIP was 7-fold higher than that of ferrous sulphate. No other differences in secondary outcomes were observed.. HIP showed no clear safety or efficacy benefit in PD patients compared with conventional oral iron supplements. The reduction in serum ferritin levels and high costs associated with HIP therapy suggest that this agent is unlikely to have a significant role in iron supplementation in PD patients.

Topics: Administration, Oral; Adult; Aged; Anemia, Iron-Deficiency; Darbepoetin alfa; Dietary Supplements; Erythropoietin; Female; Ferritins; Ferrous Compounds; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peptide Fragments; Peritoneal Dialysis; Treatment Outcome

The main hypothesis of this study is that oral heme iron polypeptide (HIP; Proferrin ES) administration will more effectively augment iron stores in erythropoietic stimulatory agent (ESA)-treated peritoneal dialysis (PD) patients than conventional oral iron supplementation (Ferrogradumet).. Inclusion criteria are peritoneal dialysis patients treated with darbepoietin alpha (DPO; Aranesp(R), Amgen) for >or= 1 month. Patients will be randomized 1:1 to receive either slow-release ferrous sulphate (1 tablet twice daily; control) or HIP (1 tablet twice daily) for a period of 6 months. The study will follow an open-label design but outcome assessors will be blinded to study treatment. During the 6-month study period, haemoglobin levels will be measured monthly and iron studies (including transferring saturation [TSAT] measurements) will be performed bi-monthly. The primary outcome measure will be the difference in TSAT levels between the 2 groups at the end of the 6 month study period, adjusted for baseline values using analysis of covariance (ANCOVA). Secondary outcome measures will include serum ferritin concentration, haemoglobin level, DPO dosage, Key's index (DPO dosage divided by haemoglobin concentration), and occurrence of adverse events (especially gastrointestinal adverse events).. This investigator-initiated multicentre study has been designed to provide evidence to help nephrologists and their peritoneal dialysis patients determine whether HIP administration more effectively augments iron stores in ESP-treated PD patients than conventional oral iron supplementation.. Australia New Zealand Clinical Trials Registry number ACTRN12609000432213.

Topics: Administration, Oral; Adult; Anemia; Australia; Chronic Disease; Darbepoetin alfa; Delayed-Action Preparations; Erythropoietin; Ferritins; Ferrous Compounds; Hematinics; Hemeproteins; Hemoglobins; Humans; Iron; Kidney Diseases; Peritoneal Dialysis; Treatment Outcome

Topics: Adult; Antioxidants; Brain Chemistry; Brain Ischemia; Catalysis; Chelating Agents; Erythropoietin; Ferritins; Ferrous Compounds; Hematocrit; Hemoglobins; Humans; Iron; Male; Neuroprotective Agents; Oxidation-Reduction; Oxidative Stress; Recombinant Proteins; Transferrin

The religious beliefs of Jehovah's Witnesses who refuse homologous and autologous blood transfusion poses serious problems for surgeons when operating on patients requiring a mean transfusion requirement of =/>2 units of blood.. After a number of encouraging studies in a randomised sample of patients 2-3 and after the treatment of some Jehovah's Witnesses 1, a group of 45 patients (23 females and 22 males) underwent elective heart surgery between June 1998 and December 2000. The patients, who were all Jehovah's Witnesses, received pre-treatment with epoetin alpha and ferrous sulphate. In the light of recent studies, it was also decided to repeat medullary preconditioning using the same intervals but with a higher dose. The patients underwent surgery involving myocardial revascularisation, mitral and/or aortic valve replacement, associated interventions, valvuloplasty and ascending aortic aneurysms. After obtaining informed and signed consent, the treatment protocol comprised the administration of 140 IU/kg epoetin alpha three times a week for 3 weeks associated with oral ferrous sulphate 3 times a day. Hematochemical levels (hemoglobin, free hemoglobin, hematocrit, ferritin, transferrin, haptoglobin, reticulocytes, iron levels) were monitored from admission to Day Hospital to discharge.. No patient in the study required blood transfusion.. The short, medium and long-term follow-up reconfirmed the substantial reliability of this drug linked to the absence of collateral effects.

Topics: Administration, Oral; Aged; Anemia, Hypochromic; Blood Transfusion; Christianity; Coronary Artery Bypass; Elective Surgical Procedures; Epoetin Alfa; Erythropoietin; Female; Ferrous Compounds; Heart Valve Prosthesis Implantation; Heart Valves; Hematinics; Hematocrit; Hemoglobins; Humans; Male; Middle Aged; Recombinant Proteins; Religion and Medicine; Treatment Outcome; Vascular Surgical Procedures

Correction of anaemia as a result of renal failure improves cardiovascular function and also provides significant cognitive and emotional benefits. The most appropriate route for iron supplementation has not been determined for patients with chronic renal failure who are not yet on dialysis.. Forty-five anaemic patients with progressive renal insufficiency (PRI) were prospectively randomized to receive oral (ferrous sulphate 200 mg tds) or intravenous (300 mg iron sucrose monthly) iron treatment. Erythropoietin (rHuEpo) was simultaneously commenced and the dose adjusted according to a pre-established protocol.. There were no significant differences in baseline patient characteristics between the two groups. The average follow-up was 5.2 months. Three patients suffered possible allergic reactions to iron sucrose. Haemoglobin response and changes in red cell hypochromasia were similar in the two groups, but serum ferritin was significantly higher in the intravenous group. The starting dose of rHuEpo could be temporarily discontinued in 43% of patients on oral iron and 33% of patients receiving iron sucrose (NS). rHuEpo was increased after 3 months in 9% of patients on oral iron and 19% of patients receiving iron sucrose (NS). Final doses of rHuEpo were 33.5 (0-66) and 41.6 (0-124) U/kg/week respectively in the oral and intravenous groups (NS). Although gastro-intestinal symptoms were more commonly reported in patients taking oral iron, these were mild according to scores on visual analogue scales. Dietary protein and energy intake were not significantly different in the two groups at 0, 3 and 6 months.. In pre-dialysis patients, the efficacy of monthly 300 mg iron sucrose given intravenously is not superior with regard to haemoglobin response and rHuEpo dose as compared with a daily oral dose of 600 mg of ferrous sulphate or equivalent. Where intravenous iron is preferred, lower doses may help to reduce the incidence of allergic or "free iron" reactions, especially in patients with low body mass.

Topics: Administration, Oral; Aged; Disease Progression; Dose-Response Relationship, Drug; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Ferrous Compounds; Gastrointestinal Diseases; Glucaric Acid; Hemoglobins; Humans; Injections, Intravenous; Male; Middle Aged; Recombinant Proteins; Renal Insufficiency

Autologous blood transfusion presents few infectious or immunologic side effects. The aim of the present study was to determine the impact of autologous blood transfusion with or without recombinant human erythropoietin (rHuEPO) in patients who underwent elective maxillofacial operations.. Seventy eight consecutive patients (29 men and 49 women) underwent elective maxillofacial operations during the years 1990-95.. The patients were randomly assigned to three groups: In group 1, 30 patients preoperatively underwent autologous blood predonation with intravenous injection of erythropoietin 600 lU/kg after each blood predonation and autologous blood transfusion intraoperatively; in group 2, 28 patients underwent the same procedure without erythropoietin and in group 3, 20 patients underwent homologous transfusion serving as control group. All patients received ferrous sulphate daily by mouth, preoperatively until one week postoperatively.. Group 1 patients showed higher levels of haematocrit, haemoglobin and red blood cell count pre- and postoperatively than the group 2 patients. It was also shown that the use of rHuEPO contributed to an improvement of the blood parameters of the patients in the group 1 compared with those of the patients in groups 2 and 3.

Topics: Administration, Oral; Adolescent; Adult; Analysis of Variance; Blood Transfusion; Blood Transfusion, Autologous; Elective Surgical Procedures; Erythrocyte Count; Erythropoietin; Facial Bones; Female; Ferrous Compounds; Follow-Up Studies; Head and Neck Neoplasms; Hematocrit; Hemoglobins; Humans; Injections, Intravenous; Male; Middle Aged; Orthognathic Surgical Procedures; Osteotomy; Premedication; Reactive Oxygen Species; Recombinant Proteins; Statistics as Topic

This study evaluates the real effectiveness of epoetin-alpha associated with ferrous sulphate, in reducing blood transfusion in patients undergoing elective open heart surgery not treated with autologous donation.. Sixty patients had been divided into 2 groups: group A (30 patients) treated with 525 mg ferrous sulphate three time a day per os for 3 weeks; group B (30 patients) treated with epoetin-alpha 10,000 UI twice a week and 525 mg ferrous sulphate 3 times a day. Grouping of patients has been randomized. In both groups hemoglobin, hematocrit, reticulocytes, iron values, ferritine, transferrine, and serological values, have been evaluated sequentially before treatment, before surgery, day of operation, 1st, 2nd, 3rd, 7th postoperative days and at discharge.. In group A 86% patients needed blood transfusion (26 out of 30); in group B only 3% of patients needed blood transfusion (1 patient). One year follow up didn't show side effects related to epoetin-alpha.. This study confirms the real effectiveness of epoetin-alpha in reducing the postoperative need for homologous blood transfusion. No side effects due to epoetin-alpha treatment have been proved. The conclusion is drawn that epoetin-alpha can be used as an alternative to blood transfusion or in association with predeposit and in the treatment of basal anemia.

Topics: Blood Loss, Surgical; Coronary Disease; Elective Surgical Procedures; Epoetin Alfa; Erythropoietin; Female; Ferrous Compounds; Heart Valve Diseases; Hematinics; Humans; Male; Middle Aged; Recombinant Proteins

Iron replacement therapy reduces the demand for erythropoietin (EPO) in some dialysis patients. It has been postulated that iron supply to the bone marrow is a rate-limiting step in the process of erythropoiesis under erythropoietin stimulation.. We evaluated the economic benefit of intravenous iron therapy for this purpose in a prospective, non-blinded study of 22 haemodialysis patients, 16 male, six female, mean age 62 years (range 24-80 years). All patients had a serum ferritin (SF) of < or = 60 microg/L, despite oral iron therapy. Patients with high aluminium and/or parathyroid hormone (PTH) levels, underlying bleeding/haematological disorders or active inflammatory diseases were excluded. Patients were established on subcutaneous EPO and given intravenous iron over seven consecutive dialysis sessions (total dose 1050 mg) and supplemental monthly doses with regular monitoring for 4 months.. The median EPO dose was 4000 units/week (mean 6050 units/week) pre-treatment and 2000 units/week (mean 3700 units) at 6 weeks post intravenous iron therapy (P=0.03). No serious adverse events occurred in the 154 treatment sessions of intravenous iron. Mean haemoglobin (Hb) level remained constant at 6 and 12 weeks (P=0.087). Serum ferritin levels (P< 0.0001) rose significantly, while a reduction in transferrin saturation (TS) became significant at the end of the study (P=0.0047). The use of intravenous iron allowed a substantial monthly cost saving per patient in our unit.. Intravenous iron therapy is a safe and cost-effective method for maintaining or improving Hb levels with a more effective utilization of EPO in patients with low SF levels despite oral iron therapy.

Topics: Adult; Aged; Aged, 80 and over; Erythropoietin; Female; Ferritins; Ferrous Compounds; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Iron-Dextran Complex; Iron, Dietary; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis

Topics: Administration, Oral; Anemia; Anemia, Iron-Deficiency; Delayed-Action Preparations; Drug Administration Schedule; Erythropoietin; Female; Ferritins; Ferrous Compounds; Humans; Injections, Intravenous; Iron; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

The ability of epoetin alfa to increase hematopoiesis in a dose-dependent manner when administered by the intravenous (i.v.) or subcutaneous (s.c.) route has been demonstrated in pharmacokinetic studies in healthy volunteers. Epoetin alfa may therefore be a useful adjunct to autologous blood (AB) donation. By facilitating AB donation, the use of allogeneic blood could be reduced. In patients scheduled to undergo orthopedic surgery, i.v. administration of epoetin alfa 600 IU/kg twice weekly for 3 weeks prior to surgery (in conjunction with oral iron supplementation) significantly increased the number of AB units and total red blood cell (RBC) volume donated and increased the number of patients able to donate > or = 4 AB units. However, there was no difference between epoetin alfa and placebo groups with respect to allogeneic blood exposure.

Topics: Anemia; Blood Transfusion, Autologous; Epoetin Alfa; Erythropoiesis; Erythropoietin; Ferrous Compounds; Hematocrit; Hemoglobins; Humans; Injections, Intravenous; Injections, Subcutaneous; Orthopedics; Premedication; Recombinant Proteins

Predonation of autologous blood (AB) represents an attractive alternative to allogeneic blood transfusion in patients scheduled for elective orthopedic surgery. However, anemic patients may not be able to donate sufficient AB prior to surgery, thus increasing the risk of exposure to allogeneic blood. This group of patients may benefit from the administration of epoetin alfa to facilitate AB donation. A recent multicenter, double-blind, placebo-controlled study in 204 patients with a low hematocrit (Hct; < or = 39%) scheduled for orthopedic surgery demonstrated that the intravenous administration of epoetin alfa (600 IU/kg twice weekly for 3 weeks) significantly increased the number of AB units predeposited and the percentage of patients able to donate > or = 4 AB units. Furthermore, epoetin alfa attenuated the decrease in Hct associated with AB donation and significantly (P = .027) reduced allogeneic blood exposure in these patients.

Topics: Anemia; Blood Transfusion; Blood Transfusion, Autologous; Double-Blind Method; Elective Surgical Procedures; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Ferrous Compounds; Hematocrit; Humans; Male; Orthopedics; Premedication; Recombinant Proteins; Treatment Outcome

In order to avoid exposure to allogeneic blood, perisurgical administration of epoetin alfa has been proposed as an alternative to autologous blood (AB) predonation in patients who are unable or unwilling to donate AB prior to elective surgery. The efficacy of perisurgical epoetin alfa to reduce allogeneic blood exposure was investigated in a randomized, double-blind, placebo-controlled study in 200 patients unable to participate in an AB predonation program who were scheduled for orthopedic surgery with expected blood loss > or = 2 units. Epoetin alfa (100 IU/kg or 300 IU/kg) was administered daily by subcutaneous (s.c.) injection, commencing 10 days preoperatively and continuing until day 4 postoperatively (15 doses in total). All patients received oral iron supplementation. Patients treated with epoetin alfa required significantly fewer (P < .001) allogeneic transfusion compared with placebo, and this effect of epoetin alfa was particularly evident in the subgroup of patients with baseline hemoglobin (Hb) levels of more than 10 to < or = 13 g/dL. In terms of the reduction in allogeneic blood exposure, no significant difference was evident between epoetin alfa regimens. Epoetin alfa was well tolerated. Although 15 s.c. doses of epoetin alfa 100 IU/kg appears to be the optimum dosage regimen in patients scheduled for orthopedic surgery, a presurgical simulation study in 24 healthy volunteers suggested that two s.c. doses of epoetin alfa 600 IU/kg in 10 days prior to expected surgery may be a suitable regimen for further study. However, the optimum timing of epoetin alfa administration in relation to surgery remains to be established. A finding consistent to all studies is that adequate iron supplementation (most probably in parenteral form) is necessary to optimize the erythropoietic response to epoetin alfa in the surgical setting.

Topics: Anemia; Blood Transfusion; Dose-Response Relationship, Drug; Double-Blind Method; Elective Surgical Procedures; Epoetin Alfa; Erythropoiesis; Erythropoietin; Ferrous Compounds; Humans; Injections, Subcutaneous; Orthopedics; Premedication; Recombinant Proteins; Transferrin; Treatment Outcome

We prospectively compared the absorption of ferrous sulfate to that of a polysaccharide ferric complex (Niferex) in 5 healthy controls and 7 stable patients on continuous ambulatory peritoneal dialysis (CAPD). All study subjects received an equivalent of 150 mg of elemental iron of either preparation, in a random fashion. After a baseline fasting serum iron level was obtained, the serum iron concentration was measured at 2 h in the control group and at 2 and 4 h in the CAPD patients. One to 2 months later, all study subjects received the alternative iron compound and were studied in an identical manner. A significant rise in serum iron was only observed in the healthy subjects after the ingestion of ferrous sulfate and not Niferex (ferrous sulfate 102 +/- (SE) 9 vs. 142 +/- 7 Mg/dl, p = 0.0005; Niferex 96 +/- (SE) 10 vs. 102 +/- 12 mg/dl; baseline vs. 2 h, respectively). The absorption of both compounds was poor in the patients on CAPD, with the 2- and 4-hour serum iron levels not significantly higher than the baseline values (ferrous sulfate 73 +/- 7 vs. 107 +/- 21 vs. 109 +/- 21 mg/dl, p = NS; Niferex 57 +/- 11 vs. 65 +/- 14 vs. 60 +/- 11 mg/dl, p = NS; baseline vs. 2 vs. 4 h, respectively). Our data suggest that the absorption of both ferrous sulfate and ferric polysaccharide complex is poor in patients on CAPD.

Topics: Administration, Oral; Adult; Erythropoietin; Female; Ferrous Compounds; Humans; Intestinal Absorption; Iron; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Polysaccharides; Prospective Studies; Recombinant Proteins; Reference Values; Time Factors

Iron supplementation is required by most dialysis patients receiving recombinant human erythropoietin. The efficacy of oral iron is variable in these patients, and many require the use of intravenous iron dextran to maintain adequate iron levels, defined as transferrin saturation greater than 20%, serum ferritin greater than 100 ng/mL, and serum iron greater than 80 micrograms/dL. To determine the efficacy of different oral iron preparations in maintenance of iron status, we prospectively studied 46 recombinant human erythropoietin-treated patients and randomized them to receive different oral iron preparations. These four preparations included Chromagen (ferrous fumarate; Savage Laboratories, Melville, NY), Feosol (ferrous sulfate; SmithKline Beecham, Inc, Pittsburgh, PA), Niferex (polysaccharide; Central Pharmaceuticals, Inc, Seymour, IN), or Tabron (ferrous fumarate; Parke-Davis, Morris Plains, NJ). All patients were prescribed approximately 200 mg of elemental iron daily of their assigned iron preparation with at least 100 mg ascorbic acid daily for 6 months. At baseline and bimonthly during the study, serum iron, transferrin saturation, ferritin, hematocrit, and recombinant human erythropoietin dose were monitored; in addition, compliance and side effects were recorded by patient interview. All patients were able to maintain target hematocrit during the 6 months of study. However, there were differences in the trends of serum iron, percent transferrin saturation, and ferritin when considered singly or in combination between the four groups of iron medications. The percent of laboratory values measured over the study period in each group that met the criteria of transferrin saturation more than 20% was greatest in the Tabron group (58%), followed by the Feosol (47%), Chromagen (33%), and Niferex (31%) groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Anemia; Anemia, Iron-Deficiency; Delayed-Action Preparations; Erythropoietin; Female; Ferrous Compounds; Hematocrit; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Patient Compliance; Polysaccharides; Prospective Studies; Recombinant Proteins; Renal Dialysis

The hemoglobin (Hgb) level of patients during radiation therapy is associated with both survival and local tumor control in several organ sites. This clinical trial tested whether administering recombinant human erythropoietin (r-HuEPO) to cancer patients would increase their Hgb level during the course of radiation therapy without adverse effects.. The 40 participating patients had a Hgb value < 13.5 g/dL and a malignant tumor located above the diaphragm without evidence of distant metastasis for which they were scheduled to undergo a 5-8 week course of daily radiation therapy. All 40 patients were given oral ferrous sulfate throughout their radiation therapy course. Half the patients also received 150-300 mg/kg of r-HuEPO subcutaneously three times per week starting 0-10 days prior to the first dose of radiation.. The r-HuEPO and control groups did not differ significantly in patient age, gender, tumor type, initial hemoglobin, erythropoietin, or iron bioavailability. The Hgb level increased more than 6% during radiation therapy in all 20 of the r-HuEPO patients but in only 2/20 of the control patients (p < 0.001). The Hgb rose from a mean +/- standard deviation of 11.9 +/- 1.3 g/dL to > 14 g/dL during radiation therapy in 80% of the r-HuEPO group compared to in 5% of the control group (p < 0.001). The mean +/- s.d. change in Hgb concentration during radiation therapy was 27 +/- 15% (an average rise of 5% per week) in the r-HuEPO group and 0 +/- 6% in the control group (p < 0.001). r-HuEPO had no significant measurable effect on blood pressure, white blood cell, neutrophil or platelet count, or liver or renal function. The only reported adverse effect of r-HuEPO administration was an asymptomatic skin rash in one patient.. r-HuEPO with ferrous sulfate significantly increased the Hgb level in cancer patients without interfering with their course of radiation therapy, whereas ferrous sulfate alone did not. r-HuEPO appears to be a safe and effective means of increasing red cell mass during radiation therapy.

Topics: Erythropoietin; Female; Ferrous Compounds; Hemoglobins; Humans; Leukocyte Count; Male; Middle Aged; Neoplasms; Platelet Count; Radiotherapy; Recombinant Proteins

Studies on baboons and preliminary observations in three patients with sickle cell anemia (SS) suggested that high doses of pulse administered recombinant human erythropoietin (rHuEPO) stimulate F-reticulocyte production. We now report on the administration of rHuEPO in a double-blind format to ascertain frequency of response and potential precipitation of side effects. Ten patients were enrolled, but one was discontinued due to the indication of a blood transfusion. Of the other nine, five received rHuEPO in escalating doses (from 400 to 1,500 U per kg twice daily [BID] per week), alternating with a placebo, in blinded fashion. The second group, consisting of four patients, followed an identical protocol (except starting dose was 1,000 U/Kg, BID per week) and were iron supplemented during treatment. The criterion of response was a transient doubling (as a minimum) of the steady-state F-reticulocyte level. We found that none of the five patients in the first group responded to rHuEPO, and two of them became iron deficient, as judged by a significant decrease in ferritin. Of the second group, four patients responded with F-reticulocyte increases. In three patients, open label administration of rHuEPO confirmed the effect. We observed seven painful episodes during this study, two during the EPO administration and five during the placebo arm. Three patients were phlebotomized because the hemoglobin level increased 1.5 g/dL more than steady-state levels. Of the six patients followed-up by percent dense cell determinations, one exhibited increased levels during periods of the treatment, whereas the other five showed no change. No anti-rHuEPO antibodies were detected. We conclude that rHuEPO can stimulate F-reticulocyte response in some patients with sickle cell anemia, without apparent negative clinical side effects. The state of iron stores may be critical. Whether higher doses of rHuEPO and/or a different regimen might induce sustained F cells and fetal hemoglobin increases remains to be determined.

Topics: Adolescent; Adult; Anemia, Sickle Cell; Double-Blind Method; Erythrocyte Count; Erythropoietin; Female; Ferritins; Ferrous Compounds; Humans; Male; Middle Aged; Recombinant Proteins; Reticulocytes

Approximately one in 2000 babies are born with craniosynostosis, and primary open repair is typically performed before 1 year of age. Historically, the procedure has been associated with nearly 100 percent transfusion rates. To decrease the rates of transfusion, the authors' center has developed a novel multimodal blood conservation protocol.. The authors administered their standard of care to children aged 1 year or younger undergoing primary repair of craniosynostosis between 2008 and 2014. In 2014, the authors implemented the following protocol: (1) preoperative erythropoietin and ferrous sulfate, (2) local anesthetic with epinephrine infiltration of the incision, (3) PlasmaBlade incision and subgaleal dissection, (4) hypervolemic hemodilution, and (5) intravenous tranexamic acid. Procedures performed before the protocol implementation served as controls. The authors performed classic fronto-orbital advancement with anterior cranial vault remodeling for coronal and metopic craniosynostosis. For lambdoid and sagittal craniosynostosis, barrel stave osteotomies, cranial base outfracture, and interposition bone grafting were performed.. A total of 279 children with a mean age of 6 months who had craniosynostosis repairs were included. One hundred forty-five underwent repair before the authors' protocol, and 134 had repairs during the authors' blood conservation protocol. Both groups were similar in demographics. Overall blood loss and operative times were significantly reduced by 73 percent and 11 percent, respectively. Blood transfusion rate decreased 92 percent (p < 0.001).. These results show a strong association between the authors' blood conservation protocol and significantly reduced transfusion rates. The authors believe this is a significant step forward and can be safely applied in the great majority of children undergoing craniosynostosis repairs.. Therapeutic, III.

Topics: Blood Loss, Surgical; Craniosynostoses; Dissection; Epinephrine; Erythropoietin; Female; Ferrous Compounds; Hemodilution; Humans; Infant; Infant, Newborn; Male; Osteotomy; Plastic Surgery Procedures; Vasoconstrictor Agents

To assess the effects of protocolized recombinant human erythropoietin (r-HuEPO) therapy and standardized high dose iron supplementation on hematologic and iron status measures in a cohort of extremely low gestational age newborns (ELGANs).. Charts of extremely low gestational age newborns admitted from 2006 to 2016 and who had received r-HuEPO per neonatal intensive care unit protocol were reviewed. The r-HuEPO was started at a dose of 900 IU/kg per week after 7 days of age and continued until 35 weeks postmenstrual age. Oral iron supplementation at 6-12 mg/kg per day was used to maintain a transferrin saturation of >20% during r-HuEPO treatment. Data on demographic features, hematologic and iron panel indices, red blood cell transfusions, and clinical outcomes were collected. Quartile groups were created based on serum ferritin levels at the conclusion of the r-HuEPO treatment and the quartiles were compared.. The cohort included 116 infants with mean gestational age 25.8 ± 1.5 weeks and birth weight 793 ± 174.1 g. The r-HuEPO promoted erythropoiesis as indicated by increasing hemoglobin, hematocrit, and reticulocyte count. Serum ferritin decreased over time and was ≤75 ng/mL in 60.2% of infants at the conclusion of r-HuEPO therapy; 87% received packed red blood cell transfusions. Transfusion volume, total iron intake, total iron binding capacity, and transferrin concentration differed among infants in the different serum ferritin quartiles (P < .05).. In extremely low gestational age newborns, r-HuEPO therapy promoted erythropoiesis. Despite a biomarker-based standardized high-dose iron supplementation, the majority of infants had evidence of iron deficiency to a degree that is associated with reduced brain function.

Topics: Anemia, Iron-Deficiency; Drug Therapy, Combination; Erythropoietin; Female; Ferrous Compounds; Hematinics; Humans; Infant, Extremely Premature; Infant, Newborn; Iron-Dextran Complex; Male; Prevalence; Recombinant Proteins; Retrospective Studies

Strategies to prevent anaemia in preterm infants include drawing fewer blood samples, the use of recombinant human erythropoietin and iron supplementation. Although iron sulfate is the most commonly used pharmaceutical formulation for iron supplementation, there are few studies comparing different iron salts in infants.. This is a study of retrospective data comparison of two groups of preterm infants receiving erythropoietin to evaluate the efficacy of iron bisglycinate chelate to iron sulfate.. Three-hundred infants of gestational age ≤32 weeks were enrolled: 225 were supplemented with iron sulfate (3 mg/kg/day) and 75 were supplemented with iron bisglycinate chelate (0.75 mg/kg/day). The effect on erythropoiesis was assessed with a general linear model that estimates the response variables (values for Haemoglobin, Haematocrit, absolute values and percentage Reticulocytes, Reticulocyte Haemoglobin content) based on treatment, time, birth weight, and gestational age.. Supplementation with iron bisglycinate chelate at a dose of 0.75 mg/kg/day demonstrated an efficacy comparable to iron sulfate at a dose of 3 mg/kg/day in both populations of preterm infants. The two cohorts had similar erythropoietic response, without significant differences.. The higher bioavailability of iron bisglycinate chelate resulted in a lower load of elemental iron, a quarter of the dose, and achieved equivalent efficacy compared to iron sulfate. Iron bisglycinate chelate may appear to be an alternative to iron sulfate in the prevention and treatment of preterm newborn anaemia.

Topics: Anemia, Iron-Deficiency; Drug Administration Schedule; Drug Therapy, Combination; Erythropoietin; Female; Ferrous Compounds; Hematinics; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Retrospective Studies; Treatment Outcome

Iron is integral for erythropoietic adaptation to hypoxia, yet the importance of supplementary iron compared with existing stores is poorly understood. The aim of the present study was to compare the magnitude of the hemoglobin mass (Hbmass) in response to altitude in athletes with intravenous (IV), oral, or placebo iron supplementation.. Thirty-four, nonanemic, endurance-trained athletes completed 3 wk of simulated altitude (3000 m, 14 h·d), receiving two to three bolus iron injections (ferric carboxymaltose), daily oral iron supplementation (ferrous sulfate), or a placebo, commencing 2 wk before and throughout altitude exposure. Hbmass and markers of iron regulation were assessed at baseline (day -14), immediately before (day 0), weekly during (days 8 and 15), and immediately, 1, 3, and 6 wk after (days 22, 28, 42, and 63) the completion of altitude exposure.. Hbmass significantly increased after altitude exposure in athletes with IV (mean % [90% confidence interval (CI)], 3.7% [2.8-4.7]) and oral (3.2% [2.2-4.2]) supplementation and remained elevated at 7 d postaltitude in oral (2.9% [1.5-4.3]) and 21 d after in IV (3.0% [1.5-4.6]) supplementation. Hbmass was not significantly higher than baseline at any time point in placebo.. Iron supplementation appears necessary for optimal erythropoietic adaptation to altitude exposure. IV iron supplementation during 3 wk of simulated live high-train low altitude training offered no additional benefit in terms of the magnitude of the erythropoietic response for nonanemic endurance athletes compared with oral supplementation.

Topics: Adaptation, Physiological; Administration, Intravenous; Administration, Oral; Adult; Altitude; Dietary Supplements; Erythropoietin; Female; Ferric Compounds; Ferrous Compounds; Hemoglobins; Humans; Hypoxia; Male; Maltose; Physical Conditioning, Human; Physical Endurance; Young Adult

Iron and oxygen are essential substance for cellular activity in body tissues. Hypoxia-inducible factors (HIFs) can respond to available oxygen changes in the cellular environment and regulate the transcription of a series of target genes. The study was conducted to investigate the effects of iron supplementation on the expression of hypoxia-inducible factor-1 alpha (HIF-1α) and antioxidant status in rats exposed to high-altitude hypoxia environment. Forty rats were divided into control (CON), hypobaric hypoxia (HH), and hypobaric hypoxia plus ferrous sulfate (FeSO4) (9.93 mg/kg body weight (BW)/day) (HFS) and hypobaric hypoxia plus iron glycinate chelate (Fe-Gly) (11.76 mg/kg BW/day) (HFG) groups. Results showed that Fe-Gly effectively alleviated weight loss and intestinal mucosa damage induced by hypobaric hypoxia, whereas FeSO4 aggravated hypobaric hypoxia-induced weight loss, liver enlargement, spleen atrophy, and intestinal damage. Iron supplementation decreased liver superoxide dismutase (T-SOD) and catalase (CAT) activity (P < 0.01) and increased iron concentration in the liver compared to HH group (P < 0.001). Moreover, Fe-Gly upregulated liver transferrin expression in messenger RNA (mRNA) level (P < 0.05) and downregulated serum erythropoietin (EPO) concentration (P < 0.01) and liver HIF-1α expression level (P < 0.05 in mRNA level; P < 0.001 in protein level) compared to HH group. The study indicated that FeSO4 supplementation at high altitudes aggravated the oxidative damage of tissues and organs that could be mediated through production of malondialdehyde (MDA) and inhibition antioxidant enzyme activities. Fe-Gly can protect hypobaric hypoxia-induced tissues injury. Moreover, iron supplementation at high altitudes affected HIF-1α-mediated regulating expression of targeting genes such as EPO and transferrin. The study highlights that iron supplementation under hypobaric hypoxia environment has possible limitation, and efficient supplementation form and dosage need careful consideration.

Topics: Altitude; Animals; Antioxidants; Erythropoietin; Ferrous Compounds; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Liver; Male; Malondialdehyde; Rats; Rats, Sprague-Dawley; RNA, Messenger; Transferrin

Topics: Adult; Anemia, Iron-Deficiency; Epoetin Alfa; Erythropoietin; Ferric Compounds; Ferric Oxide, Saccharated; Ferrous Compounds; Fluid Therapy; Glucaric Acid; Hematinics; Humans; Jehovah's Witnesses; Male; Oxygen Inhalation Therapy; Recombinant Proteins; Severity of Illness Index; Vitamin B 12; Vitamin B Complex

Our aim was to evaluate the effectiveness of two different dosing regimens of human recombinant erythropoietin (rHu-EPO) for preoperative autologous blood collection in patients undergoing total hip arthroplasty (THA).. Prospective randomised trials in which erythropoietin 15,000 IU was administered intravenously twice a week or 30,000 IU once a week (total 90,000 IU) combined with ferrous II sulphate (Ferro-Gradumet 2) orally and compared with Ferro-Gradumet 2 alone.. Although different dosing regimens of rHu-EPO administration during preoperative autologous blood donation have similar effects on the collection of two units of autologous blood, preoperative haemoglobin level and perioperative allogenic blood transfusion, a once weekly dose regimen of rHu-EPO was more convenient (although not statistically significantly) for patients.. We recommend the more practical and comfortable but yet highly effective therapeutic regimen with a single weekly intravenous administration of rHu-EPO for patients scheduled for THA.

Topics: Administration, Oral; Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Blood Transfusion, Autologous; Drug Administration Schedule; Drug Therapy, Combination; Erythropoietin; Female; Ferrous Compounds; Hemoglobins; Humans; Injections, Intravenous; Male; Middle Aged; Osteoarthritis, Hip; Preoperative Care; Recombinant Proteins

ESA therapy can increase hemoglobin, decrease blood transfusions, and improve quality of life in patients with chemotherapy induced anemia (CIA). Despite its benefits, ESA therapy increases the risk of venous thromboembolism (VTE) in cancer patients by 50% and can also cause iron restricted erythropoiesis in CIA patients, which may augment the tendency to develop VTE. We postulated that thrombocytosis, a risk factor for VTE in cancer patients, in CIA patients on ESA therapy might be a result of ESA induced iron restricted erythropoiesis. We performed a retrospective analysis of 187 CIA patients who were randomized to receive weekly Epoetin and IV ferric gluconate, oral ferrous sulfate, or no iron for 8 weeks. Nineteen patients experienced 29 VTEs, and patients, whose platelets increased to ≥350,000 cells/uL were three times more likely to experience a VTE (OR 2.9, P = 0.036, logistic regression) with a four times greater incidence of VTE (IRR 4.4, P = 0.001, Poisson regression). Patients treated with IV iron were significantly less likely to develop platelets of ≥350,000 cells/uL (IRR 0.7, P = 0.013, Poisson regression) and had a decreased incidence of VTE. Our study suggests that ESA associated VTE in CIA patients may be, in part, related to the thrombocytosis of ESA induced iron restricted erythropoiesis and may be countered by IV iron.

Topics: Aged; Anemia; Anemia, Iron-Deficiency; Antineoplastic Agents; Double-Blind Method; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Ferric Compounds; Ferrous Compounds; Hematinics; Hemoglobins; Humans; Iron; Male; Meta-Analysis as Topic; Middle Aged; Multicenter Studies as Topic; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins; Retrospective Studies; Thrombocytosis; Thrombophilia; Venous Thromboembolism

Anemia of chronic kidney disease (CKD) has been traditionally treated by erythropoiesis-stimulating agents (ESAs) and/or iron following manual determination of dose. We hypothesized that once-monthly (QM) algorithmically dosed darbepoetin α (DA) and iron administration would successfully treat anemia of CKD in ESA-naïve CKD subjects.. QM DA and iron doses were determined via a computerized program targeting a hemoglobin (Hb) of 10.5 - 12.5 g/dl in anemic, ESA-naïve, CKD Stages 3 - 5 subjects. Six consecutive QM doses were administered. Hb, ferritin, and transferrin saturation were recorded. Data are presented as means ± standard deviation.. Anemia was identified in 133 subjects, with a mean follow-up of 188 days. DA doses and Hb were significantly greater at Months 3 and 6 compared to baseline (p < 0.05); DA doses were 109 ± 68 μg and 118 ± 91, respectively, at Months 3 and 6. Hemoglobin levels were correspondingly 11.3 ± 1.1 g/dl and 11.3 ± 1.0. 78% of patients achieved the target Hb by 6 months of therapy. The elevation of Hb was greater in non-proteinuric than proteinuric subjects at 6 months of treatment (11.6 ± 0.8 g/dl vs. 11.0 ± 1.1; p < 0.05), despite lower DA dose (96 ± 76 μg vs. 139 ± 98; p < 0.05).. Successful treatment of the anemia of CKD by QM DA based upon a computerized dosing program was achieved by 6 months in 78% of ESA-naïve, CKD subjects.

Topics: Algorithms; Anemia; Chronic Disease; Darbepoetin alfa; Drug Administration Schedule; Drug Therapy, Computer-Assisted; Erythropoietin; Female; Ferritins; Ferrous Compounds; Hematinics; Hemoglobins; Humans; Kidney Diseases; Male; Transferrin

The efficiency of therapy with the iron-containing preparation Ferro-Folgamma (Vervag Pharma, Germany) was evaluated in 62 men and women aged from 18 to 82 years with iron-deficiency anemia. Criteria for the efficiency were changes in clinical symptoms of anemia, hemoglobin level, erythrocyte and reticulocyte counts, packed cell volume, erythrocyte indices (mean erythrocyte volume, average content and concentration of hemoglobin in erythrocytes), erythropoietin level, and characteristics of iron metabolism (serum iron and ferritin levels, total iron-binding capacity of the serum, coefficient of ferritin saturation with iron), and drug tolerance. It was shown that Ferro-Folgamma is fairly well tolerated by the patients and produces good therapeutic effect when used to treat and prevent iron-deficiency anemia. Also, the study demonstrated that blood erythropoietin level being a sensitive indicator of hypoxia, it may be used as one of the most important criteria for the assessment of treatment efficiency in patients with iron-deficiency anemia.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Dose-Response Relationship, Drug; Erythropoietin; Female; Ferrous Compounds; Follow-Up Studies; Hemoglobins; Humans; Iron; Male; Middle Aged; Treatment Outcome; Young Adult

Anaemia is a common and serious complication in patients with end-stage renal disease. Iron therapy is crucial in managing anaemia and maintenance of haemodialysis (HD) patients. This study investigated the efficacy of both oral and intravenous (i.v.) therapies, and the possible factors deleteriously affecting patient response to iron therapy. Forty patients on maintenance HD from a single institution were enrolled in this 6-month retrospective study. Group I (n = 20) received i.v. two ampoules of atofen (ferric chloride hexahydrate 193.6 mg) per week for a total of 6 weeks (total dosage, 960 mg). Group II (n = 20) received oral ferrous sulphate S.C. Tab (ferrous sulphate 324 mg) one pill three times daily (total dosage, 63,000 mg). Patients whose haematocrit (Hct) level increased at minimum 3% within the period were classified as responders. Iron i.v. ferric chloride (960 mg) was more effective than oral ferrous sulphate (63,000 mg) in correcting anaemia in HD patients with iron deficiency. In group I, serum triglyceride (TG) levels were significantly lower in patients responding to i.v. iron therapy than in patients with no response. In group II, serum high-sensitive C-reactive protein (hs-CRP) level was significantly lower in patients responding to oral iron therapy than patients with no response. The i.v. ferric chloride is more effective than oral ferrous sulphate in treating anaemia in HD patients with iron deficiency. Serum hs-CRP and TG levels may be parameters for predicting hyporesponsiveness to oral and i.v. iron therapies, respectively.

Topics: Administration, Oral; Anemia, Iron-Deficiency; C-Reactive Protein; Chlorides; Erythropoietin; Female; Ferric Compounds; Ferritins; Ferrous Compounds; Hematinics; Hematocrit; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Retrospective Studies; Treatment Outcome

Jehovah's Witnesses' religious convictions disallow blood transfusion. Major surgery in these patients is therefore problematic. The objective of this study is to describe our experience with microvascular reconstruction of complex head and neck defects in Jehovah's Witness patients.. This was a retrospective review of all Jehovah's Witnesses' patients undergoing head and neck free-flap reconstruction at a tertiary academic referral center from 1997 to 2006.. Five Jehovah's Witnesses patients underwent a total of 7 free-flap reconstructions (6 radial, 1 rectus). Four flaps were immediate: 1 osteocutaneous radial forearm, 2 fasciocutaneous radial forearm, and 1 rectus abdominus myocutaneous. One fasciocutaneous radial forearm flap was staged. Two patients were planned secondary reconstructions, both facsciocutaneous radial forearm. Iron supplements and/or erythropoietin were administered perioperatively in 6 of the 7 microvascular reconstructions. Selective external carotid embolization was performed preoperatively in 1 patient. Hematocrit levels were 36% to 46% preoperatively and 30% to 41% postoperatively. Immediate postoperative hematocrit decline was 5.2% (3.0% to 6.0%). No transfusions or blood products were administered.. Our case series supports the feasibility of head and neck free-flap reconstruction in these challenging patients.

Topics: Adenocarcinoma; Aged; Carcinoma, Squamous Cell; Carotid Artery, External; Embolization, Therapeutic; Erythropoietin; Female; Ferrous Compounds; Head and Neck Neoplasms; Hematocrit; Humans; Jehovah's Witnesses; Male; Microsurgery; Middle Aged; Perioperative Care; Preoperative Care; Retrospective Studies; Surgical Flaps; Treatment Outcome

Anemia is common in patients with chronic kidney disease (CKD) and those who have received a kidney allograft. Anemia is most prevalent in kidney transplant recipients before and immediately after transplantation, but also can occur months after transplantation if the donor kidney begins to fail. Replacement therapy for CKD-related and posttransplantation anemia is effective through the administration of exogenous erythropoiesis-stimulating proteins. Darbepoetin alfa (Aranesp; Amgen Inc, Thousand Oaks, CA) is a unique erythropoiesis-stimulating protein that can be administered at an extended dosing interval relative to recombinant human erythropoietin because of its approximately 3-fold longer serum half-life. Although darbepoetin alfa has been shown to be an effective treatment for patients with anemia of CKD and anemia after kidney transplantation, limited data have been published showing efficacy in treating women with anemia of these conditions during pregnancy. We report a case of successful darbepoetin alfa treatment for severe anemia in a pregnant transplant recipient.

Topics: Adult; Anemia; Cesarean Section; Contraindications; Cyclosporine; Darbepoetin alfa; Erythropoietin; Female; Ferrous Compounds; Humans; Hydronephrosis; Immunosuppressive Agents; Kidney Transplantation; Nephrostomy, Percutaneous; Postoperative Complications; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy, High-Risk; Puerperal Disorders; Seizures; Sirolimus; Stents; Treatment Refusal

To eliminate the need for allogeneic blood transfusion in patients undergoing elective total knee arthroplasty, we established and tried a protocol of combined methods, which is characterized by effectiveness, ease in application, and safety. It is based on perioperative administration of human recombinant erythropoietin plus iron and folic acid, mild acute normovolemic hemodilution, meticulous surgical technique, postoperative blood salvage through a closed-wound drainage system, and lower transfusion triggers.. Sixty-one patients entered the protocol, and the results were retrospectively compared with the ones obtained from 58 consecutive patients who were operated on in the past before the use of any blood saving technique.. Only 5 patients of those who entered the protocol finally needed allogeneic blood transfusion, receiving a total number of 7 units, which is remarkable when compared with the 50 patients before the application of the protocol who required 111 units. Consequently, the utilization of allogeneic blood was reduced by 94%, a statistically quite significant result (P <0,001). We believe the protocol should be included in orthopedic surgeons' alternatives for blood saving in elective total knee arthroplasty.

Topics: Aged; Aged, 80 and over; Arthroplasty, Replacement, Knee; Blood Transfusion; Blood Transfusion, Autologous; Clinical Protocols; Erythropoietin; Female; Ferrous Compounds; Folic Acid; Hematinics; Hemostasis, Surgical; Hemostatic Techniques; Humans; Male; Middle Aged; Recombinant Proteins; Retrospective Studies

Topics: Allopurinol; Animals; Cat Diseases; Cats; Erythropoietin; Euthanasia, Animal; Female; Ferrous Compounds; Interferon alpha-2; Interferon-alpha; Leishmaniasis; Male; Recombinant Proteins

Zinc protoporphyrin/heme ratio (ZnPP/H) has been well established as an indicator of functional iron deficiency in subjects 6 months of age to adult. The primary objective of this study was to establish normative values for ZnPP/H in NICU patients and secondarily to explore the utility of this test as an indicator of iron deficiency in neonates. Study design ZnPP/H and complete blood counts were obtained weekly on consecutive NICU patients. Gestational age, growth variables, iron supplementation, erythropoietin treatment, and blood transfusions were documented. Results are reported as mean +/- SD. A value of P <.05 was considered significant.. ZnPP/H ratios (n = 639) were evaluated from 143 infants. During the first week of life, ZnPP/H was inversely correlated with gestational age (n = 78, P <.001, r = -0.72). Maternal diabetes, growth retardation, and exposure to chorioamnionitis were independent risk factors for high ZnPP/H. Both iron supplementation and blood transfusion decreased ZnPP/H (P <.001). Erythropoietin treatment was associated with an increase in reticulocyte count and ZnPP/H (P <.001).. ZnPP/H is inversely correlated with gestational age, and the range in all newborn infants is higher than in adults. ZnPP/H is elevated in certain infant subpopulations, which suggests that they may require additional iron supplementation.

Topics: Biomarkers; Blood Cell Count; Erythrocyte Transfusion; Erythropoietin; Ferrous Compounds; Gestational Age; Heme; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Iron Deficiencies; Protoporphyrins; Recombinant Proteins; Reference Values; Risk Factors

Topics: Adult; Anticoagulants; Bandages; Blood Loss, Surgical; Cesarean Section; Christianity; Dalteparin; Erythropoietin; Extracorporeal Circulation; Female; Ferrous Compounds; Humans; Pregnancy; Pregnancy Outcome; Pregnancy, Multiple; Recombinant Proteins; Triplets

The vast majority of erythropoietin (EPO)-treated peritoneal dialysis (PD) patients require iron supplementation. Most authors and clinical practice guidelines recommend primary oral iron supplementation in PD patients because it is more practical and less expensive. However, numerous studies have clearly demonstrated that oral iron therapy is unable to maintain EPO-treated PD patients in positive iron balance. Once patients become iron-deficient, intravenous iron administration has been found to more effectively augment iron stores and hematologic response than does oral therapy. We recently performed a prospective, cross-over trial in 28 iron-replete PD patients and showed that twice-monthly outpatient iron polymaltose infusions (200 mg) were a practical and safe alternative to oral iron. That treatment produced significant increases in hemoglobin concentration and body iron stores. The additional expense of intravenous iron therapy was completely offset by reductions in EPO dosage. Careful monitoring of iron stores is important in patients receiving intravenous iron supplementation in view of epidemiologic links with infection and cardiovascular disease. Nevertheless, a growing body of evidence suggests that, as has been found for hemodialysis patients, intravenous iron therapy is superior to oral iron supplementation in EPO-treated PD patients.

Topics: Administration, Oral; Erythropoietin; Ferric Compounds; Ferritins; Ferrous Compounds; Hemoglobins; Humans; Infusions, Intravenous; Iron; Peritoneal Dialysis; Recombinant Proteins; Transferrin

Hemodialysis (HD) patients are prone to develop iron deficiency because of consumption of iron stores during erythropoietin (EPO) therapy. Data are needed to establish the factors involved in the different iron needs among these patients. Sixty-five HD patients were prospectively studied during a year. The subjects were dialyzed through polytetrafluoroethylene (PTFE) grafts (n = 23), arteriovenous native fistulae (n = 41), and a Permcath (n = 1). Twenty-four patients were administered aspirin; 23 patients, ticlopidine; 1 patient, dipyridamole; and 4 patients, anticoagulation with acenocoumarol. Iron supplementation (oral or parenteral) and laboratory parameters were recorded monthly. Significant differences in iron requirements, depending on the use of antiplatelet and/or anticoagulation agents, were found. Total parenteral iron supplements were greater in patients on antiplatelet therapy with either native or graft vascular accesses compared with the rest (2,406 +/- 1,445 versus 1,562 +/- 858 mg; P = 0.0081). Twelve of 52 patients on antiplatelet therapy required oral iron and only 1 of 13 patients not on antiplatelet therapy was administered oral iron supplements (P < 0.05). Patients on antiplatelet therapy were administered more transfusions (1.9 +/- 3.8 transfusions/y) than individuals not on antiplatelet therapy (0.15 +/- 0.3 transfusions/y; P = 0.0015). However, only patients with PTFE grafts on antiplatelet therapy had a post-HD bleeding time longer than patients not on antiplatelet therapy (9.1 +/- 3.6 versus 5.7 +/- 3.9 minutes; P < 0.0001). Multiple logistic regression analysis showed that the use of antiplatelet agents (P < 0.05) is an independent factor that increased the probability of requiring greater parenteral iron supplements (>2.5 g/y). Patients with PTFE grafts required more EPO than those with autologous fistulae (160 +/- 93 versus 100 +/- 63 U/kg/wk; P = 0.012). No differences between groups were found that could explain this finding. Antiplatelet and/or anticoagulation therapy implied the use of greater amounts of iron supplements in HD patients. Although these greater requirements of iron occurred in parallel with bleeding from the vascular access, additional data favor the existence of other factors, eg, interdialytic blood losses. The present study suggests that antiplatelet therapy may be an important factor in determining iron requirements in HD patients. Moreover, our data relate for the first time the use of prosthetic grafts

Topics: Administration, Oral; Arteriovenous Shunt, Surgical; Blood Vessel Prosthesis Implantation; Erythropoietin; Female; Ferric Compounds; Ferrous Compounds; Humans; Infusions, Parenteral; Iron Deficiencies; Kidney Failure, Chronic; Male; Middle Aged; Nutritional Requirements; Platelet Aggregation Inhibitors; Prospective Studies; Renal Dialysis

Leptin is a 16 kDa protein hormone involved in food intake, energy expenditure regulation and numerous other physiological processes. Recently, leptin has been demonstrated to stimulate hematopoietic stem cells in vitro. The aim of our study was to measure serum leptin and erythropoietin levels in patients with sideropenic (n = 18) and pernicious anemia (n=7) before and during anemia treatment. Blood samples for the blood count, leptin and erythropoietin determinations were obtained by venepunction at the time of the diagnosis of anemia and after partial and complete anemia recovery. The relationships of serum leptin levels to erythropoietin levels and blood count parameters were also studied. No significant differences in serum leptin levels between the groups studied were found. The serum leptin levels in none of groups were modified by treatment of anemia (basal levels, the levels during treatment and after anemia recovery were 13.1+/-14.5 vs 12.8+/-15.6 vs 12.0+/-14.8 ng/ml in patients with sideropenic anemia and 7.8+/-8.5 vs 9.5+/-10.0 vs 8.9+/-6.6 ng/ml in patients with pernicious anemia). The erythropoietin levels were higher at the time of anemia in both groups and decreased significantly after partial or complete recovery. Serum leptin levels in both groups correlated positively with the body mass index. No significant relationships were found between serum leptin levels and erythropoietin values or various parameters of the peripheral blood count. We conclude that serum leptin levels in patients with sideropenic and pernicious anemia positively correlate with the body mass index but are not influenced by the treatment of anemia.

Topics: Adult; Aged; Anemia, Pernicious; Anemia, Sideroblastic; Body Mass Index; Erythrocyte Count; Erythropoietin; Female; Ferrous Compounds; Hemoglobins; Humans; Leptin; Male; Middle Aged; Vitamin B 12

Topics: Adult; Anemia; Blood Transfusion; Chronic Disease; Delayed-Action Preparations; Epidermolysis Bullosa Dystrophica; Erythropoietin; Female; Ferrous Compounds; Folic Acid; Hematinics; Humans; Recombinant Proteins

Topics: Adolescent; Anemia, Aplastic; Delayed-Action Preparations; Erythropoietin; Ferrous Compounds; Glomerulonephritis; Humans; Kidney Failure, Chronic; Male; Parvoviridae Infections; Parvovirus B19, Human; Renal Dialysis; Uremia

Recombinant erythropoietin (rHuEPO) is well established in the management of anemia of chronic renal disease. However, a number of clinical issues, including the best laboratory indicators of an imminent marrow response to rHuEPO replacement, the ideal measurements to detect masked iron deficiency, and optimal methods of iron replacement, remain unanswered. To investigate these issues, studies were performed in anemic chronic hemodialysis patients. A number of standard hematologic measurements in addition to automated reticulocyte counts (Sysmex R-1000) and serum transferrin receptors (TfR) were obtained in these patients. A response to initiation of rHuEPO administration could be predicted if the serum TfR concentration was less than 6 mg/L (normal, 3.8 to 8.5 mg/L). In patients on rHuEPO, an imminent hemoglobin response to an increased rHuEPO dose could be predicted after 1 week based on a greater than 20% increase from baseline in the serum TfR or absolute reticulocyte count, with a sensitivity of 92%. In patients on rHuEPO replacement with serum ferritin levels greater than 30 microg/L, none of the panel of tests, including serum TfR, reliably detected masked iron deficiency. In a long-term study over 5 months in patients on a stable maintenance dose of EPO, a gradual decline in total body iron occurred, even in subjects with initial adequate iron stores, and despite taking 50 mg elemental iron daily as oral ferrous sulphate. The serum TfR is useful for predicting a hemoglobin response when initiating rHuEPO therapy, and combined with automated reticulocyte counting it is valuable for predicting a hemoglobin response when increasing the dose of rHuEPO. The serum TfR loses its specificity for detecting tissue iron deficiency in patients on maintenance rHuEPO therapy because of increased erythropoiesis, which itself raises serum TfR levels.

Topics: Adult; Aged; Anemia; Anemia, Iron-Deficiency; Erythropoiesis; Erythropoietin; Female; Ferritins; Ferrous Compounds; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Receptors, Transferrin; Recombinant Proteins; Renal Dialysis; Reticulocyte Count; Sensitivity and Specificity; Time Factors

Two siblings were identified with severe hypoproliferative microcytic anemia and iron malabsorption, in the absence of any gastrointestinal disorder or blood loss. These children had severe microcytosis (MCV 48 fl, hemoglobin 7.5 g/dl) with decreased serum iron, elevated serum TIBC, and decreased serum ferritin, despite prolonged treatment with oral iron. An iron challenge study with an oral dose of 2 mg/kg elemental iron as ferrous sulfate documented iron malabsorption. After treatment with intravenous iron dextran, there was an absence of the expected reticulocytosis and only a partial correction of the hemoglobin, hematocrit, and microcytosis. The bone marrow was hypocellular with abnormal iron incorporation into erythroid precursor cells. This appears to be a rare form of inherited anemia characterized by iron malabsorption and disordered iron metabolism that only partially corrects after the administration of parenteral iron. These features resemble those found in the microcytic mouse (mk/mk), which also has severe microcytic anemia and iron malabsorption that partially responds to parenteral iron.

Topics: Administration, Oral; Anemia, Iron-Deficiency; Animals; Biological Transport; Bone Marrow; Cell Compartmentation; Cell Size; Child; Child, Preschool; Colony-Forming Units Assay; Craniosynostoses; Drug Resistance; Erythrocytes, Abnormal; Erythroid Precursor Cells; Erythropoietin; Female; Ferrous Compounds; Humans; Infusions, Intravenous; Intestinal Absorption; Intracellular Fluid; Iron; Iron-Dextran Complex; Malabsorption Syndromes; Male; Mice; Mice, Mutant Strains

Iron deficiency may develop in hemodialysis patients, especially when erythropoietin is given. The role of iron deficiency in the anemia of predialysis chronic renal failure (CRF), however, is much less clear. We have intravenously (IV) administered iron as ferric saccharate in a total dose of 200 mg elemental iron monthly for 5 months to 33 CRF patients who remained anemic despite oral iron supplementation and who had no laboratory signs of iron overload. None was receiving erythropoietin therapy. In 22 of the patients there was an increase in the hematocrit values by the end of the study. These patients were considered responders to intravenous iron (IV Fe) therapy. In 11 patients the iron administration was not associated with improvement of the anemia (nonresponders). Before onset of the IV Fe therapy there were no differences between the responders and nonresponders with regard to degree of anemia, serum ferritin, iron saturation, renal function, or blood pressure. One additional patient was excluded from the study because of a mild reaction during an IV test dose before the study. No worsening of kidney function and no other side effects were noted. In four patients (three responders and one nonresponder) the control of blood pressure necessitated antihypertensive drug therapy adjustment. In conclusion, IV Fe supplementation in two thirds of anemic CRF patients not receiving dialysis resulted in a significant improvement of the anemia, thus avoiding the necessity of erythropoietin or blood administration. This could be achieved by increasing the plasma ferritin levels to 200 to 400 microns/L and/or increasing the iron saturation to 25% to 35%. Intravenous ferric saccharate appears to be a safe and effective method of administering iron for the correction of anemia in CRF patients not receiving dialysis.

Topics: Administration, Oral; Adult; Aged; Anemia; Anemia, Iron-Deficiency; Delayed-Action Preparations; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferrous Compounds; Follow-Up Studies; Glucaric Acid; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Time Factors

Autologous blood (AB) donation can minimize exposure to allogeneic blood in patients scheduled for coronary artery bypass graft (CABG) surgery. During AB donation in this group of patients, minimization of the accompanying decrease in hemoglobin (Hb) levels is important to reduce the risk of provoking silent myocardial ischemia and/or arrhythmias. Recombinant human erythropoietin (rHuEPO) has been used to facilitate AB donation and minimize the accompanying decrease in Hb levels in patients scheduled for cardiac surgery. In 24 patients scheduled for CABG surgery, once-weekly subcutaneous (s.c.) administration of rHuEPO (epoetin alfa 400 IU/kg) plus oral iron supplementation for 4 weeks prior to surgery caused marked stimulation of erythropoiesis and significantly increased collection of autologous red blood cells (RBCs) compared with oral iron alone. Furthermore, epoetin alfa minimized the decrease in Hb levels associated with AB donation and significantly attenuated allogeneic blood requirements by facilitating the collection of 4 AB units prior to surgery. During AB donation, no changes in the incidence or severity of ischemic attacks or ST-segment changes were observed using electrocardiographic monitoring. Epoetin alfa was well tolerated. Once-weekly s.c. administration of epoetin alfa for 4 weeks therefore represents a practical means of facilitating AB donation by patients scheduled for CABG surgery.

Topics: Anemia; Blood Transfusion, Autologous; Coronary Artery Bypass; Elective Surgical Procedures; Epoetin Alfa; Erythropoiesis; Erythropoietin; Ferrous Compounds; Hemodilution; Hemoglobins; Humans; Injections, Subcutaneous; Male; Premedication; Recombinant Proteins; Treatment Outcome

Red blood cell formation relies on the contributions of a variety of substances, including iron, vitamins, and protein. Therapeutic intervention with Epoetin alfa changes the requirements for these erythropoietic ingredients, frequently necessitating modifications in nutritional prescriptions. Nursing knowledge and management of the nutritional components that affect erythropoiesis can help ensure optimal patient response to therapy. Case study illustrations of iron deficiency and potassium excess are used to demonstrate potential nursing interventions.

Topics: Aged; Anemia, Iron-Deficiency; Erythropoiesis; Erythropoietin; Female; Ferrous Compounds; Humans; Kidney Failure, Chronic; Nutritional Support; Patient Compliance

Topics: Administration, Oral; Anemia; Anemia, Iron-Deficiency; Colitis, Ulcerative; Crohn Disease; Erythropoietin; Ferrous Compounds; Humans; Inflammatory Bowel Diseases; Injections, Subcutaneous; Recombinant Proteins

The superimposition of human immunodeficiency virus (HIV) infection, associated opportunistic infections, and anti-retroviral therapy further worsens the severity of anemia in patients also suffering from end-stage renal disease. A major cause of anemia in renal failure is a deficiency of erythropoietin. The causes of anemia in HIV disease include direct and indirect stem cell inhibition by the virus, increased peripheral destruction of red blood cells, and bone marrow suppression by various opportunistic infections and therapeutic drugs, particularly zidovudine. We compared the efficacy of recombinant human erythropoietin (rHuEPO) therapy in improving the anemia in HIV-infected end-stage renal disease patients (group I) with that in nondiabetic (group II) and diabetic (group III) hemodialysis patients without HIV infection. All three groups of patients were comparable in dialysis prescription and serum iron studies. Iron supplementation was prescribed to all patients, and none received blood transfusions. After 8 weeks of rHuEPO therapy (administered intravenously in a dose of 100 U/kg body weight thrice weekly), the mean increase in hematocrit was similar in all responders (5.8% increase in hematocrit in 23 of 30 HIV patients and 6.7% increase in 24 of 30 non-HIV patients). Response in hematocrit was noted in HIV patients despite the presence of opportunistic infections in 15 and zidovudine administration in 11. Seven HIV-positive patients and six non-HIV patients failed to respond to rHuEPO. Irrespective of the HIV status, the baseline serum EPO levels in patients responding to rHuEPO were significantly lower than those in nonresponders.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; AIDS-Associated Nephropathy; Anemia; Case-Control Studies; Diabetic Nephropathies; Erythropoietin; Female; Ferrous Compounds; Hematocrit; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Zidovudine

Six sickle cell/beta-thalassemia patients (3 males and 3 females) were treated with 500 U/kg body weight human recombinant erythropoietin (h-rEPO) along with 300 mg/day iron sulfate in two phases, for a period of 90 days. Fetal hemoglobin (HbF) was assayed every 2 weeks and the gamma-chain ratio at three successive intervals during the treatment. All patients showed a moderate to high increase in their HbF values (1.25- to 12-fold). The gamma-chain ratio, as determined by high performance liquid chromatography was found to be unaffected by the HbF increase. Two patients with the newborn gamma-chain ratio, responded faster to the h-rEPO treatment and achieved higher HbF values than the rest of the group. The h-rEPO treatment was very well tolerated and had a positive effect on the general clinical condition of all the patients.

Topics: Adolescent; Adult; Anemia, Sickle Cell; beta-Thalassemia; Child; Drug Evaluation; Drug Therapy, Combination; Erythrocyte Indices; Erythropoietin; Female; Ferrous Compounds; Fetal Hemoglobin; Globins; Humans; Male; Middle Aged; Recombinant Proteins; Stimulation, Chemical; Time Factors

In two previous studies, we observed that recombinant human interleukin-3 (IL-3) induced an increase in marrow burst-forming unit-erythroid-derived colonies in vitro in some patients with Diamond-Blackfan anemia (DBA). To determine whether a similar erythropoietic response could be induced in vivo, we treated 13 patients with DBA (aged 4 to 19 years) with two preparations of IL-3. All patients had absent absolute reticulocyte counts and markedly reduced to absent recognizable bone marrow erythroid elements; patients with circulating reticulocytes in the previous 12 months were excluded from study. All patients except 1 had failed steroid therapy and had been transfusion-dependent since infancy; 1 patient was maintained on high-dose prednisone at the time of enrollment. On the first arm of the study, IL-3 (Immunex Corp, Seattle, WA) was administered subcutaneously using a dose escalation regimen of 125 to 500 micrograms/m2/day in divided dosage at 12-hour intervals, coadministered with 1.5 mg/kg/d of oral ferrous sulphate. Of the 13 patients that entered the trial, 4 stopped prematurely because of adverse side effects. In the other 9 evaluable cases, reticulocytes increased transiently in 1 patient from 0 to 65 x 10(9)/L after 35 days of IL-3 therapy at 250 micrograms/m2, but transfusion dependency persisted. One transient peak in absolute reticulocyte count was noted in 6 other patients, but no erythroid response was observed after completion of a full course of IL-3. Oral prednisone at 0.5 mg/kg/d was then coadministered with IL-3 at 500 micrograms/m2 to 5 of the patients without effect, and treatment was stopped. In 2 patients, a second preparation of IL-3 (Sandoz Canada Inc, Dorval, Quebec, Canada) was initiated in a dose escalation regimen of 2.5 to 10 micrograms/kg and was coadministered with ferrous sulphate. No erythroid response was observed in either patient, and in one of the two, alternate-day subcutaneous recombinant erythropoietin at 300 U/kg was administered for 3 weeks in combination with daily IL-3 at 10 micrograms/kg, but no increased erythropoiesis was seen. Significant increases in white blood cell and eosinophil counts during administration of both preparations of IL-3 were observed in all patients. These data show that the response of DBA patients to IL-3 in vivo is heterogeneous and cannot be predicted from in vitro studies. The absence of a corrective effect of IL-3 in these patients with DBA indicates that a deficiency of the cytok

Topics: Adolescent; Bone Marrow; Child; Child, Preschool; Erythrocyte Count; Erythropoiesis; Erythropoietin; Fanconi Anemia; Female; Ferrous Compounds; Humans; Interleukin-3; Male; Prednisone; Recombinant Proteins; Reticulocytes

Hydroxyurea increases the production of fetal hemoglobin in patients with sickle cell anemia, inhibiting the polymerization of hemoglobin S and potentially improving vaso-occlusive manifestations and hemolysis. Recombinant erythropoietin increases the number of reticulocytes containing fetal hemoglobin in laboratory animals and in humans. We studied whether hydroxyurea and erythropoietin might have a potentiating effect on the production of fetal hemoglobin in patients with sickle cell disease.. We treated four patients who were receiving hydroxyurea for sickle cell disease (three who were homozygous for sickle cell anemia and one with sickle beta zero-thalassemia) with escalating doses of intravenous erythropoietin for seven weeks, along with oral iron sulfate. Doses of hydroxyurea on four consecutive days were alternated with doses of erythropoietin on three consecutive days.. There was a 28 percent increase in the number of reticulocytes containing fetal hemoglobin and a 48 percent increase in the percentage of fetal hemoglobin, as compared with the maximal values obtained with hydroxyurea alone. The percentage of erythrocytes containing fetal hemoglobin (F cells) increased from 64 to 78 percent. As compared with hydroxyurea alone, treatment with hydroxyurea and erythropoietin decreased the mean (+/- SD) serum indirect bilirubin level from 0.8 +/- 0.2 to 0.5 +/- 0.1 mg per deciliter (13.3 +/- 2.9 to 8.9 +/- 2.2 mumol per liter) (P = 0.02), suggesting a further decrease in hemolysis. Red-cell filterability improved.. Intravenous recombinant erythropoietin with iron supplementation alternating with hydroxyurea elevates fetal-hemoglobin and F-cell levels more than hydroxyurea alone. Such increases decrease intracellular polymerization of hemoglobin S and improve the overall rheologic characteristics of erythrocytes. A reduced dosage of hydroxyurea alternating with erythropoietin may prove less myelotoxic than hydroxyurea given daily or in pulsed-dose regimens. It may also increase levels of fetal hemoglobin in patients with sickle cell disease who have not been helped by hydroxyurea alone.

Topics: Adult; Anemia, Sickle Cell; beta-Thalassemia; Drug Synergism; Drug Therapy, Combination; Erythrocyte Count; Erythrocyte Indices; Erythropoietin; Ferrous Compounds; Fetal Hemoglobin; Humans; Hydroxyurea; Male; Recombinant Proteins; Reticulocytes

Major blood loss following trauma is common, but severe anemia is generally not life-threatening when managed with the administration of blood and blood products. Severe anemia becomes particularly challenging and potentially lethal when the patient is a Jehovah's Witness, for whom receiving a transfusion is contrary to religious principles. This case report describes the management and hospital course of a Jehovah's Witness who was seriously injured in an airplane crash.

Topics: Anemia; Blood Transfusion; Christianity; Clinical Protocols; Critical Care; Delayed-Action Preparations; Enteral Nutrition; Erythropoietin; Ferrous Compounds; Hemoglobins; Humans; Male; Middle Aged; Multiple Trauma; Oxygen Consumption; Treatment Refusal; Vitamin B 12

Limited red blood cell (RBC) regeneration often prevents collection of sufficient blood from autologous donors. We studied the effects of subcutaneous recombinant erythropoietin (rEPO) in subjects making frequent blood donations. Six healthy iron-replete male subjects took rEPO (200 U/kg) subcutaneously daily, and donated blood (450 mL) twice a week for 3 weeks. During a control study, these subjects also attempted twice-weekly blood donations without rEPO. Four other males given rEPO, including one with idiopathic hemochromatosis, waited until day 8 to begin blood donations. All healthy subjects took oral ferrous sulfate. Subcutaneous rEPO given with blood donations resulted in a marked reticulocytosis (mean peak value 568 +/- 159 x 10(9)/L v 235 +/- 77 x 10(9)/L, control study; P < .05), and enhanced RBC production at 28 days (1,208 +/- 227 mL v 719 +/- 161 mL, P < .05). rEPO in advance of blood donations was slightly less effective in normal subjects (941 +/- 139 mL, P < .05); however, the subject with hemochromatosis produced substantially more RBCs (1,764 mL) than any normal subject. rEPO-treated normal subjects (but not the rEPO-treated patient with hemochromatosis or untreated controls) produced iron-deficient RBCs with elevated zinc protoporphyrin levels and low hemoglobin content. These cells appeared within 1 week of rEPO administration and before laboratory confirmation of depleted iron stores. Thus, subcutaneous rEPO is an effective stimulant of erythropoiesis in nonanemic blood donors. However, in addition to eventual depletion of iron stores, early functional iron deficiency affects response to the drug.

Topics: Blood Donors; Erythrocyte Count; Erythrocyte Indices; Erythropoiesis; Erythropoietin; Ferritins; Ferrous Compounds; Folic Acid; Hematocrit; Hemochromatosis; Hemoglobins; Humans; Iron; Iron Deficiencies; Male; Recombinant Proteins; Reticulocytes; Transferrin; Vitamin B 12

To examine the influence of erythropoiesis on iron absorption, radioiron absorption tests were performed in normal subjects before and after a course of recombinant erythropoietin. The absorption of heme and nonheme iron from a standard meal was measured in nine subjects, and the absorption of a therapeutic dose of ferrous sulfate given with or without food was determined in an additional 11 subjects. The subcutaneous administration of 100 U recombinant human erythropoietin/kg body weight given on 10 successive days over a 2-week period induced a brisk increase in erythropoiesis and a sharp decrease in iron stores. With the standard meal, there was a modest increase in heme iron absorption from 47.0% to 58.6% (p < 0.05) and a dramatic five-fold rise in nonheme iron absorption from 5.9% to 31.8% (p < 0.001). The absorption of 50 mg iron as ferrous sulfate increased from 2.0% to 17.9% when given with food (p < 0.001) and from 7.0% to 24.6% when given with water (p < 0.001). To assess the effect of erythropoiesis independently of the induced changes in iron status, the absorption data were adjusted to a common serum ferritin level. The relative increase in iron absorption was still significant for both dietary nonheme iron (ratio 2.51, p < 0.02) and ferrous sulfate given with food (ratio 2.99, p < 0.01). It is concluded that the striking enhancement of iron absorption following regular erythropoietin administration in normal subjects is related to the combined effect of diminished iron stores and augmented erythropoiesis.

Topics: Adult; Erythropoiesis; Erythropoietin; Female; Ferritins; Ferrous Compounds; Food; Heme; Humans; Intestinal Absorption; Iron; Iron Radioisotopes; Male; Recombinant Proteins; Transferrin

Treatment with recombinant human erythropoietin (r-HuEPO; EPOGEN [epoetin alfa], AMGEN Inc, Thousand Oaks, CA) rapidly corrects the anemia associated with end-stage renal disease during the acute phase of therapy and supports hematocrit levels throughout the maintenance phase. However, during the acute phase of therapy, iron deficiency will develop in most patients; it is therefore initially essential to monitor body iron stores monthly. A plasma ferritin level of less than 30 ng/mL or a transferrin saturation level of less than 20% confirms the diagnosis of iron deficiency. Microcytic, hypochromic red cell morphology appears only after prolonged iron deficiency due to inadequate monitoring and insufficient iron supplementation; alternatively, microcytosis in the presence of adequate iron stores suggests aluminum toxicity. In all patients except those with transfusional iron overload, prophylactic supplementation with ferrous sulfate (325 mg up to three times daily) is recommended. When oral supplements, which are poorly tolerated at high doses, are insufficient to meet the extraordinary needs resulting from r-HuEPO-induced erythropoiesis, intravenous iron dextran (500 to 1,000 mg administered in five to ten doses) may be required. During the maintenance phase of therapy, it may be necessary to continue iron supplementation to counteract ongoing loss of iron associated with blood loss through dialyzers and gastrointestinal bleeding. At the other extreme of iron balance, iron overload in transfusion-dependent patients, recent studies suggest that the ability of r-HuEPO to mobilize iron stores can be harnessed with therapeutic phlebotomy to reverse transfusional iron overload.

Topics: Adult; Anemia; Anemia, Hypochromic; Delayed-Action Preparations; Erythropoietin; Ferrous Compounds; Hematocrit; Humans; Iron-Dextran Complex; Kidney Failure, Chronic; Male; Recombinant Proteins