losartan-potassium and Heart-Defects--Congenital

Topics: Bone Marrow; Erythrocyte Count; Erythropoiesis; Erythropoietin; Female; Fetus; Gestational Age; Glycerophosphates; Heart Defects, Congenital; Hematocrit; Hemoglobinometry; Humans; Hypoxia; Infant; Infant, Newborn; Infant, Premature; Kidney; Liver; Oxygen; Oxygen Consumption; Placenta; Pregnancy; Vitelline Membrane

Neonates undergoing complex congenital heart surgery have a significant incidence of neurologic problems. Erythropoietin has antiapoptotic, antiexcitatory, and anti-inflammatory properties to prevent neuronal cell death in animal models, and improves neurodevelopmental outcomes in full-term neonates with hypoxic ischemic encephalopathy. We designed a prospective phase I/II trial of erythropoietin neuroprotection in neonatal cardiac surgery to assess safety and indicate efficacy.. Neonates undergoing surgery for D-transposition of the great vessels, hypoplastic left heart syndrome, or aortic arch reconstruction were randomized to 3 perioperative doses of erythropoietin or placebo. Neurodevelopmental testing using the Bayley Scales of Infant and Toddler Development III was performed at age 12 months.. Fifty-nine patients received the study drug. Safety profile, including magnetic resonance imaging brain injury, clinical events, and death, was not different between groups. Three patients in each group died. Forty-two patients (22 in the erythropoietin group and 20 in the placebo group; 79% of survivors) returned for 12-month follow-up. In the group receiving erythropoietin, mean Cognitive Scale scores were 101.1 ± 13.6, Language Scale scores were 88.5 ± 12.8, and Motor Scale scores were 89.9 ± 12.3. In the group receiving placebo, Cognitive Scale scores were 106.3 ± 10.8 (P = .19), Language Scores were 92.4 ± 12.4 (P = .33), and Motor Scale scores were 92.6 ± 14.1 (P = .51).. Safety profile for erythropoietin administration was not different than placebo. Neurodevelopmental outcomes were not different between groups; however, this pilot study was not powered to definitively address this outcome. Lessons learned suggest optimized study design features for a larger prospective trial to definitively address the utility of erythropoietin for neuroprotection in this population.

Topics: Cardiac Surgical Procedures; Erythropoietin; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Nervous System Diseases; Neuroprotective Agents; Prospective Studies; Single-Blind Method

Preoperative autologous blood donation with recombinant human erythropoietin (rHuEPO) is effective in adults. However, there are problems concerning the blood access, cost, and blood storage in children. The purpose of this study was to evaluate the efficacy of administering a single dose of rHuEPO without blood donation in children undergoing pediatric cardiac surgery.. Eighty-two children (72 with noncyanotic heart disease, and 10 with cyanotic heart disease) whose hematocrit values were less than 45% were included in this prospective, nonrandomized study. The children were divided into 3 groups: group E0 (n = 20) was not treated with rHuEPO and iron sulfate; group E2 (n = 27) was treated with 200 IU/kg of rHuEPO and 2 mg/kg of iron sulfate; and group E4 (n = 35) was treated with 400 IU/kg of rHuEPO and 4 mg/kg of iron sulfate. Administration of rHuEPO was performed subcutaneously 7 days before the operation. The hematological and iron parameters were measured perioperatively.. A lower proportion of children treated with rHuEPO (group E2, 14.8%; group E4, 22.9%) than children without rHuEPO (group E0, 40.0%) were exposed to RBC transfusions; however, there was no significance. The elevations of the hematocrit levels were 0.7% in group E0, 1.3% in group E2, and 1.9% in group E4. The elevation of the hematocrit was greater in patients with anemia (hematocrit < or =37%).. Although the effectiveness for avoiding transfusion was not clear, the administration of a single dose of rHuEPO without autologous blood donations had an effect by increasing hematocrit levels.

Topics: Blood Chemical Analysis; Cardiac Surgical Procedures; Child; Child, Preschool; Confidence Intervals; Cyanosis; Dose-Response Relationship, Drug; Erythropoietin; Female; Follow-Up Studies; Heart Defects, Congenital; Hematocrit; Humans; Injections, Subcutaneous; Male; Postoperative Period; Preoperative Care; Probability; Prospective Studies; Recombinant Proteins; Treatment Outcome

We assessed the feasibility and efficacy of subcutaneous erythropoietin alpha (EPO) therapy and preoperative autologous blood donation (ABD) in children undergoing open heart surgery. Thirty-nine children were treated consecutively with EPO (100 U x kg(-1) s.c. three times a week in the 3 weeks preceding the operation and i.v. on the day of surgery) and two ABDs were made (Group 1). As controls to compare transfusion requirements, 39 consecutive age-matched patients who had undergone open heart surgery during the two preceding years were selected (Group 2). In a mean time of 20 (SD 5) days, 96% of scheduled ABDs were performed and only three mild vasovagal reactions were observed. The mean volume of autologous red blood cells (RBC) collected was 6 (1) ml x kg(-1) and the mean volume of autologous RBC produced as a result of EPO therapy before surgery was 7 (3) ml x kg(-1), corresponding to a 28 (11)% increase in circulating RBC volume. The mean volume of autologous RBC collected was not different from that produced [6 (1) vs 7 (3) ml x kg(-1), P=0.4]. Allogenic blood was administered to three out of 39 children in Group 1 (7.7%) and to 24 out of 39 (61.5%) in Group 2. Treatment with subcutaneous EPO increases the amount of autologous blood that can be collected and minimizes allogenic blood exposure in children undergoing open heart surgery.

Topics: Adolescent; Blood Loss, Surgical; Blood Transfusion, Autologous; Cardiopulmonary Bypass; Child; Child, Preschool; Erythropoietin; Feasibility Studies; Female; Heart Defects, Congenital; Hemoglobins; Humans; Infant; Male; Platelet Count; Preoperative Care; Tissue and Organ Harvesting

The authors present results of using recombinant human erythropoietin in patients operated on the heart under conditions of extracorporeal blood circulation. It was found that the intravenous infusions of erythropoietin at the postoperative period accelerated the restitution of circulating erythron indices. The volume of transfusion of the donor erythrocyte-containing media to the patient is given erythropoietin was reliably less than that in the control group. The results obtained allow using erythropoietin to be recommended as an effective method of prophylactics and treatment of anemia in cardiosurgical patients.

Topics: Adult; Anemia; Cardiac Surgical Procedures; Endocarditis, Bacterial; Erythropoietin; Extracorporeal Circulation; Female; Heart Defects, Congenital; Humans; Hypothermia, Induced; Male; Postoperative Care; Postoperative Complications; Recombinant Proteins; Rheumatic Heart Disease

Between August 1989 and July 2003 14 Jehovah's Witness children with congenital heart defects (CHD) aged under 14 years (median 2.9 years) and with a median weight of 14 kg underwent 16 operations with cardiopulmonary bypass (CPB). Five children had been operated on previously between one to three times. Preoperatively, 7 children were prepared with oral iron supplementation and 10 received erythropoietin. Mean hemoglobin (Hb) at admission was 14.4 g/dl (range 10.9 - 19.2). The cardiopulmonary bypass (CPB) circuit was modified to reduce total priming volume. High doses of aprotinin were administered. The modified ultrafiltration (MUF) circuit, used in 7 patients, was parallel to the ECC circuit with continuous circulation of the blood through a small shunt between the arterial and venous lines. Operations performed consisted of VSD closure (3 pts.), ASD closure (3 pts.), Fontan operation (2 pts.), and complete AV canal correction, aortic commissurotomy, Ross operation, Glenn shunt, cor triatriatum correction, MV reconstruction combined with left outflow tract stenosis resection, correction of absent pulmonary valve syndrome, and correction of tetralogy of Fallot in one patient each. There were no deaths. Mean duration of CPB was 192 min and mean aortic cross-clamp time 40 min. The Hb value at the end of the operation was 4.9 - 14.5 g/dl (mean 9.6) and at discharge it was 7.1 - 14.5 g/dl (mean 15.5). No blood or blood products were used in any patient.. Bloodless cardiac surgery with and without CPB can be safely performed in Jehovah's Witness infants and children.

Topics: Aprotinin; Cardiopulmonary Bypass; Child; Child, Preschool; Deamino Arginine Vasopressin; Erythropoietin; Heart Defects, Congenital; Heart Septal Defects, Atrial; Heart Septal Defects, Ventricular; Hemoglobins; Hemostatics; Humans; Infant; Jehovah's Witnesses

Erythropoietin is an essential growth factor that promotes survival, proliferation, and differentiation of mammalian erythroid progenitor cells. Erythropoietin(-/-) and erythropoietin receptor(-/-) mouse embryos die around embryonic day 13.5 due, in part, to failure of erythropoiesis in the fetal liver. In this study, we demonstrated a novel role of erythropoietin and erythropoietin receptor in cardiac development in vivo. We found that erythropoietin receptor is expressed in the developing murine heart in a temporal and cell type-specific manner: it is initially detected by embryonic day 10.5 and persists until day 14.5. Both erythropoietin(-/-) and erythropoietin receptor(-/-) embryos suffered from ventricular hypoplasia at day 12-13 of gestation. This defect appears to be independent from the general state of hypoxia and is likely due to a reduction in the number of proliferating cardiac myocytes in the ventricular myocardium. Cell proliferation assays revealed that erythropoietin acts as a mitogen in cells isolated from erythropoietin(-/-) mice, while it has no effect in hearts from erythropoietin receptor(-/-) animals. Erythropoietin(-/-) and erythropoietin receptor(-/-) embryos also suffered from epicardium detachment and abnormalities in the vascular network. Finally, through a series of chimeric analysis, we provided evidence that erythropoietin acts in a manner which is non-cell-autonomous. Our results elucidate a novel role of erythropoietin in cardiac morphogenesis and suggest a combination of anemia and cardiac failure as the cause of embryonic lethality in the erythropoietin(-/-) and erythropoietin receptor(-/-) animals.

Topics: Animals; Cell Differentiation; Cell Division; Cells, Cultured; Chimera; Erythropoietin; Gene Expression Regulation, Developmental; Heart; Heart Defects, Congenital; Mice; Mice, Knockout; Morphogenesis; Myocardium; Receptors, Erythropoietin; Stem Cells

Topics: Blood Preservation; Blood Transfusion, Autologous; Cardiac Catheterization; Child; Child, Preschool; Erythropoietin; Female; Heart Defects, Congenital; Humans; Infant; Male; Preoperative Care; Recombinant Proteins

Open-heart surgery has been performed since 1975 on 25 patients who are Jehovah's Witnesses by religion. The patients' ages ranged from 6-60 years, and their body weights from 18-51 kg. Surgical procedures included correction of congenital heart disease in 14 patients and valve repair or replacement in 11. Six procedures were reoperations. The lowest mean haematocrits, during perfusion and the postoperative period, were 22.7% (range 15.0-31.0%) and 27% (range 16.0-36.0%), respectively. Twenty-four patients survived and are alive and well. One patient died of low output failure before discharge. The blood return system reduced blood loss. Five of the patients who underwent cardiac surgery received recombinant erythropoietin before and after surgery, leading to higher postoperative haematocrits. In one patient, a haematocrit which fell to 16.9% after surgery was raised to 27% by administration of erythropoietin, without blood transfusion. In two recent cases, high doses of aprotinin were used during surgery, resulting in better haemostasis after cardiopulmonary bypass.

Topics: Adolescent; Adult; Blood Loss, Surgical; Child; Christianity; Erythropoietin; Female; Heart Defects, Congenital; Heart Valve Diseases; Hematocrit; Humans; Male; Middle Aged; Platelet Count; Postoperative Hemorrhage; Recombinant Proteins; Religion and Medicine; Reoperation; Survival Rate

To determine the safety and efficacy of epoetin alfa therapy in infants awaiting heart transplantation to minimize the need for blood transfusions.. Prospective case series analysis.. Pediatric tertiary care center.. Eleven term infants (4 to 54 days old) awaiting heart transplantation.. Infants received 16 courses of daily epoetin therapy and four subsequent courses of alternate-day epoetin therapy.. Daily epoetin therapy was instituted at 23.6 +/- 4.5 days of age, and the duration of treatment was 13.8 +/- 3.9 days (mean +/- SEM). During daily epoetin therapy, the hematocrit increased from 0.42 +/- 0.015 to 0.50 +/- 0.019 (P < .001), and the reticulocyte count increased from 58 +/- 9 x 10(-3) to 105 +/- 16 X 10(-3) (P < .05). There were no significant changes in leukocyte count (13.4 +/- 1.0 X 10(9)/L vs 15.1 +/- 0.9 X 10(9)/L), platelet count (402 +/- 43 X 10(9)/L vs 387 +/- 39 X 10(9)/L), or creatinine (53 +/- 9 mumol/L [0.6 +/- 0.1 mg/dL] vs 53 +/- 9 mumol/L [0.6 +/- 0.1 mg/dL]) (not significant). Four patients received blood transfusions during daily epoetin therapy, but the amount of blood administered to patients was significantly less (0.9 +/- 0.5 mL/kg per day) than the phlebotomy losses (1.8 +/- 0.4 mL/kg per day) (P < .01). During alternate-day epoetin therapy, the hematocrit decreased from 0.53 +/- 0.014 to 0.43 +/- 0.019 (P < .05).. Daily epoetin therapy appears to be effective in maintaining stable hematocrit in infants awaiting heart transplantation, who generally require multiple transfusions secondary to iatrogenic blood losses.

Topics: Anemia; Blood Transfusion; Drug Administration Schedule; Erythropoietin; Feasibility Studies; Heart Defects, Congenital; Heart Transplantation; Hematocrit; Humans; Infant; Infant, Newborn; Prospective Studies; Recombinant Proteins

Fetal hemoglobin (HbF) synthesis in children with congenital cyanotic heart disease was compared that in normal children. Children with hypoxemia had higher levels of hemoglobin, total HbF, and HbF synthesis. In these children there was also an inverse correlation between HbF synthesis and oxygen content, as well as between HbF synthesis and hemoglobin concentration. Thus hypoxemia increases HbF synthesis.

Topics: Child; Child, Preschool; Cyanosis; Erythropoietin; Fetal Hemoglobin; Heart Defects, Congenital; Humans; Hypoxia; Infant

Haematological features of 64 patients suffering from non operable cyanotic congenital heart disease (CCHD) treated with hydroxyurea (HU) were compared with those of 43 patients suffering from the same disorder who had not yet received this drug. Patients with subclinical renal dysfunction were excluded by measuring plasma creatinine levels. MCV and HbF were higher among patients receiving HU, the increase in MCV being cumulative with HU dosage but the rise in HbF dose independent. HbF response to HU was found to be due to the coordinated increase in F-cell and F-reticulocyte production rather than to a selective survival of F-cells. Absence of a relationship between plasma erythropoietin and HbF levels excluded a dominant role of the former in increasing F-cell production and results determined after doubling the HU dosage or immediately after initiating therapy suggested genetic differences to be responsible for the individual variations in Hb F response. No irreversible toxic effects or malignancies were noted in this series of patients. HU was administered for a relatively long period of time, the mean duration of treatment exceeding 5 years, while the study also included patients below the age of 10 years.

Topics: Adolescent; Adult; Child; Cyanosis; Erythroid Precursor Cells; Erythropoietin; Female; Fetal Hemoglobin; Globins; Heart Defects, Congenital; Hematocrit; Humans; Hydroxyurea; Kidney Function Tests; Male; Middle Aged; Oxygen; Polymorphism, Restriction Fragment Length; Retrospective Studies

Plasma erythropoietin (Ep) was determined in umbilical cord blood in 18 infants with Down's syndrome. The 16 infants with Down's syndrome who were delivered after labor had significantly elevated plasma Ep levels compared to 36 control infants born after labor (p < 0.001). Six of the ten infants with Down's syndrome who had their packed cell volume (PCV) measured in the first 24 h of life were polycythemic based on a PCV of > or = 0.65. The presence of congenital heart disease in 9 of the 18 infants with Down's syndrome was not associated with a higher plasma Ep or PCV levels. Plasma Ep was correlated with neonatal PCV in the combined group of control and Down's syndrome infants (p = 0.003). Increased plasma Ep levels observed in infants with Down's syndrome suggested chronic fetal hypoxemia as a likely explanation for the high incidence of neonatal polycythemia observed in this group.

Topics: Down Syndrome; Erythropoietin; Fetal Blood; Heart Defects, Congenital; Hematocrit; Humans; Infant, Newborn; Polycythemia

To avoid using the homologous blood, 11 children between the age of 5 and 15 years donated autologous blood of 10 ml/kg of body weight (upper limit 400 ml) once a week for two weeks prior to elective open heart surgery. Five of 11 children received erythropoietin (100 U/kg of body weight) intravenously three times a week for two weeks. Only one patient experienced a mild donor reaction but no adverse effects occurred in erythropoietin therapy. In all the patients cardiac operations were able to be completed without homologous blood transfusion. Patients treated with erythropoietin were not anemic despite of preoperative donation although without erythropoietin therapy patients were mildly anemic. Our experience documents safety and effectiveness of predeposit autologous blood transfusion and erythropoietin therapy in pediatrics.

Topics: Adolescent; Blood Transfusion, Autologous; Cardiac Surgical Procedures; Child; Child, Preschool; Erythropoietin; Female; Heart Defects, Congenital; Humans; Male; Recombinant Proteins

Topics: Androgens; Endocrine System Diseases; Erythropoietin; Heart Defects, Congenital; Humans; Hypoventilation; Kidney Transplantation; Lung Diseases; Neoplasms; Polycythemia; Smoking

Serum immunoreactive erythropoietin (siEPO) was determined in cord serum from neonates (n = 97, gestational age 36-43 weeks), in healthy children from birth to adolescence (n = 260) and in children with haematological (n = 30), renal (n = 10) and congenital heart diseases (n = 70). In healthy children siEPO levels decreased after birth (geometric mean cord siEPO 35.6 mU/ml with 95% range of 17-56 mU/ml in eutrophic, nondistressed fetuses) and reached lowest values during the first 2 months (geometric mean siEPO 11.5 mU/ml). Thereafter siEPO levels increased slightly and were constant between 2 months and adolescence. The geometric mean siEPO for healthy children after birth was 18.8 mU/ml with 95% range of 7-47 mU/ml. These estimates were not significantly different from normal adult values. In newborns with fetal distress (n = 15) cord siEPO was significantly elevated (geometric mean 63.0 mU/ml; P less than 0.001). In children with haematological disease, siEPO and Hb concentration were inversely correlated (log siEPO (mU/ml) = 4.1-0.20 x Hb (g/dl); r = -0.62; P less than 0.0005). This relationship was significantly different in children with chronic renal failure (log siEPO (mU/ml) = 0.67 + 0.035 x Hb (g/dl); r = 0.50; P = 0.1). In children with heart disease the geometric mean siEPO was 19.2 mU/ml with 95% range 8-65 mU/ml for cyanotic (SaO2 less than 94%) and 17.7 mU/ml with 95% range of 12-36 mU/ml for acyanotic patients. In this group siEPO values were inversely correlated to the arterial oxygen content (log siEPO (mU/ml) = 1.61-2.04 x oxygen content (l/l); r = -0.28; P less than 0.02).

Topics: Adolescent; Adult; Analysis of Variance; Anemia; Child; Child, Preschool; Erythropoietin; Female; Fetal Distress; Heart Defects, Congenital; Hemoglobins; Humans; Infant; Infant, Newborn; Infant, Small for Gestational Age; Kidney Diseases; Male; Normal Distribution; Oxygen; Pregnancy; Reference Values; Regression Analysis

We hypothesized that children with cyanotic congenital heart disease and moderate hypoxemia, as a result of erythrocytosis, and adequate iron stores would have low serum erythropoietin titers, low tissue oxygen delivery, and normal red cell 2,3-diphosphoglycerate (DPG) concentrations. We assessed hemoglobin levels, aortic oxygen saturation, iron stores, red cell 2,3-DPG, oxygen consumption, and systemic O2 transport in 19 hypoxemic patients, aged 3 months to 8 years. Low erythropoietin titers (less than 30 mU/dl) were found in 14 patients. Patients with high erythropoietin titers had lower Pao2 (36 +/- 7 vs 49 +/- 7 mm Hg, p less than 0.01), lower aortic saturation (68 +/- 12 vs 81 +/- 9%, p less than 0.01), and higher red cell 2,3-DPG (2.47 +/- 0.34 vs 3.23 +/- 0.73 mumol/ml, p less than 0.01). Aortic oxygen saturation higher than 80% was associated with a low erythropoietin titer and a hemoglobin level below that associated with hyperviscosity. The relationship between aortic oxygen saturation and hemoglobin concentration was strong (r = 0.77). These data suggest that for children less than 8 years of age, adequate compensation for moderate hypoxemia can occur with moderate increases in hemoglobin levels.

Topics: 2,3-Diphosphoglycerate; Child; Child, Preschool; Cyanosis; Diphosphoglyceric Acids; Erythropoietin; Female; Heart Defects, Congenital; Hemoglobins; Humans; Hypoxia; Infant; Iron; Male; Oxygen; Oxygen Consumption; Polycythemia

Serum immunoreactive erythropoietin (siEp) levels were measured in 35 full-term infants aged 0-13 weeks, 31 of whom had congenital heart disease. The infants displayed a wide range in arterial oxygen tension (PaO2) and oxygen saturation (SaO2). During the first days of life siEp varied widely with a range from less than 3 to more than 10,000 mIU/ml. The wide variation is consistent with findings in cord blood at term. The siEp levels did not correlate significantly with haemoglobin, haematocrit, PaO2, SaO2, or arterial oxygen content in the total sample, nor when the cohort was split up into different age groups. Cyanotic infants aged 2-13 weeks had significantly higher siEp concentrations than normal adults (p less than 0.001) and than children with cyanotic congenital heart disease, aged 4 months-10 years (p less than 0.001). The raised siEp levels in cyanotic children aged 2-13 weeks found in this study and the normal levels found in their older counterparts (4 months-10 years) (reported elsewhere) are consistent with the pattern observed in man and animals exposed to prolonged hypobaric hypoxia, in which after an initial rise in erythropoietin concentrations the levels fall to normal while increased erythropoiesis is sustained.

Topics: Cross-Sectional Studies; Erythropoietin; Heart Defects, Congenital; Hemoglobins; Humans; Hypoxia; Infant; Infant, Newborn; Male; Oxygen; Radioimmunoassay

Serum erythropoietin levels were measured by radioimmunoassay in 146 children and young adults with congenital heart disease to assess the relationship between erythropoietin and clinical factors (heart failure, anemia, cyanosis) and hemodynamic variables affecting oxygen delivery and utilization. Erythropoietin values were in the normal range (10 to 30 microU/mL) in 73% (58 of 80) of the patients with and 82% (54 of 66) of those without cyanosis. Elevated erythropoietin values in cyanotic patients were associated with lower mixed venous oxygen saturation and tension than in cyanotic patients with normal erythropoietin levels, even though the degree of polycythemia was similar. In contrast, most of the acyanotic patients who had elevated erythropoietin levels were anemic. Of the blood oxygen measurements, mixed venous oxygen saturation and tension had the closest inverse correlation with erythropoietin values. The normal erythropoietin values in most patients are in accord with other observations that show that an elevation in erythropoietin level in response to hypoxia will be transient if it results in a rise in hemoglobin concentration "appropriate" to the degree of hypoxia. Persistent elevation of erythropoietin in patients with congenital heart disease may indicate harmful impairment of hemoglobin production that is potentially correctable.

Topics: Adolescent; Adult; Cardiac Catheterization; Child; Child, Preschool; Erythrocyte Indices; Erythropoietin; Ferritins; Heart Defects, Congenital; Hemoglobins; Humans; Infant; Infant, Newborn; Oxygen

Serum immunoreactive erythropoietin (siEp) was measured in 27 cyanotic and 21 acyanotic children with congenital heart disease, age 4 months to 10 years. The geometric mean value was 9 mIU/mL for each group with 95% range from 3 to 26 mIU/mL and 4 to 22 mIU/mL for the cyanotic and acyanotic subjects, respectively. The levels are similar to those found in normal adults using the same assay system. Three cyanotic subjects showed increased siEp values. One was anemic relative to his hypoxemia, and the other two showed signs of increasing hypoxia. There was a significant negative correlation between siEp and arterial oxygen content. However, siEp did not correlate significantly with hemoglobin, hematocrit, PaO2, or SaO2. Despite normal siEp levels, the cyanotic children showed compensatory erythropoiesis with significantly elevated hemoglobin and hematocrit levels, which did correlate inversely with PaO2 and SaO2. Arterial oxygen content was also significantly higher in the cyanotic subjects (p less than 0.02). The cyanotic children seemed to display the same pattern as observed in man and animals exposed to prolonged hypobaric hypoxia, where after an initial rise in erythropoietin values the levels fall to normal, while increased erythropoiesis is sustained.

Topics: Arteries; Child; Child, Preschool; Cyanosis; Erythropoietin; Heart Defects, Congenital; Hematocrit; Hemoglobins; Humans; Infant; Oxygen; Partial Pressure; Radioimmunoassay

An increase in hemoglobin concentration characterizes the normal compensatory response to chronic tissue hypoxia. We observed no such increase in 42 chronically hypoxic patients with cystic fibrosis, in whom the mean concentration was 12.6 gm/dl; one third of the patients were anemic. Compared with patients with cyanotic heart disease, patients with cystic fibrosis did not have a compensatory increase in P50 or 2,3-diphosphoglycerate. Despite anemia, erythropoietin levels in patients with cystic fibrosis were not significantly different from normal control values. The growth of colony-forming units-erythroid in patients with cystic fibrosis was similar to that in control subjects, and there was no inhibition of growth with the addition of autologous serum. Erythropoietin sensitivity, determined by measuring the CFUe dose response curve, was normal in both patients and controls. Results of iron studies were consistent with iron deficiency in the majority of patients. Impaired absorption of iron was observed in six of 13 iron-deficient patients with cystic fibrosis. An inverse correlation between erythrocyte sedimentation rate and peak serum iron was obtained during the iron absorption study. Eight patients who underwent a therapeutic trial of iron demonstrated a 1.8 gm/dl rise in hemoglobin concentration. Two patients with previously documented iron malabsorption responded to parenteral iron therapy after failure to respond to oral supplementation. These studies demonstrate that patients with cystic fibrosis not only have an impaired erythroid response to hypoxia, but are frequently anemic. Their inadequate erythroid response to hypoxia results in part from disturbances in erythropoietin regulation and iron availability.

Topics: 2,3-Diphosphoglycerate; Adolescent; Adult; Biological Availability; Blood Sedimentation; Child; Child, Preschool; Cystic Fibrosis; Diphosphoglyceric Acids; Erythropoietin; Heart Defects, Congenital; Hematopoietic Stem Cells; Hemoglobins; Humans; Hypoxia; In Vitro Techniques; Intestinal Absorption; Iron; Oxygen Consumption

An in vitro bioassay has been used to measure erythropoietin levels in extracts of serum from 74 patients with polycythaemia. Patients with polycythaemia vera in relapse had subnormal or undetectable levels which did not increase after challenge by venesection. In polycythaemia secondary to hypoxaemia serum erythropoietin concentrations were generally elevated with a further elevation occurring after venesection. Where polycythaemia was secondary to renal polycystic disease or tumours increased levels of erythropoietin could not be consistently demonstrated. In these patients the serum erythropoietin was unaffected by venesection. In other patients in whom the cause for polycythaemia was unknown examples of each of the above patterns were seen. Erythropoietin investigations in such patients may help in the elucidation of the underlying pathology.

Topics: Adult; Aged; Biological Assay; Bloodletting; Child; Diagnosis, Differential; Erythropoietin; Female; Heart Defects, Congenital; Humans; Male; Middle Aged; Polycythemia; Polycythemia Vera

Topics: Adolescent; Adult; Blood Volume; Child; Child, Preschool; Erythrocyte Aging; Erythropoiesis; Erythropoietin; Female; Heart Defects, Congenital; Humans; Infant; Male

Topics: Adolescent; Adult; Animals; Blood; Child; Child, Preschool; Cyanosis; Erythropoietin; Heart Defects, Congenital; Humans; Hypoxia; In Vitro Techniques; Infant; Infant, Newborn; Polycythemia; Rats; Umbilical Cord

Topics: Animals; Asphyxia Neonatorum; Blood; Epoetin Alfa; Erythroblastosis, Fetal; Erythropoietin; Fetal Blood; Fetus; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Mice; Research; Umbilical Cord