Need For Erythrocyte Transfusions Research Articles

Anemia of Prematurity Management in the Tertiary Neonatology Centre of Clinical Emergency County Hospital Constanta

Abstract Objective: Preterm neonates represent a category of neonates at high risk for anemia. Due to particular pathologic processes and clinical presentation in preterm neonates, this type of anemia is described as a separate entity named anemia of prematurity (AOP). The population represented by very low birthweight (VLBW) neonates is at the highest risk of developing anemia of prematurity. Reduced tissue oxygenation due to anemia can have short-term consequences (growth restriction, apnea episodes) or long-term consequences such as delayed neurological development, rapid detection, and management of AOP is needed to avoid its complications. Material and methods: We describe the particularities of this condition and the interventions for its prevention or correction in a group of premature infants born at less than 32 weeks of gestation discharged home during 2021. Results: We assessed the presence of anemia and the need for erythrocyte transfusion in 32 VLBW neonates, separated into two groups based on the gestational age: 24-29 gestational weeks (GW) and 30-31 GW. The number of neonates receiving a transfusion and the number of transfusion events was higher in the former, more immature group. We also identified more significant phlebotomy losses in the first group, contributing to a higher proportion of AOP cases needing erythrocyte transfusion. Conclusions: Although our protocols for transfusion at this moment recommend lower hemoglobin thresholds, we tend to transfuse above those levels based mainly on clinical signs and symptoms. We need better prevention strategies for AOP, both by using cord blood and more strict monitoring of phlebotomy losses.

Investigation of risk factors associated with erythrocyte engraftment after ABO-incompatible hematopoietic stem cell transplantation.

ABO-incompatible hematopoietic stem cell transplantations (HSCTs) are widely practiced; however, the delay in erythrocyte engraftment can be problematic. While erythrocyte engraftment is usually indicated by an increase in reticulocyte levels without the need for erythrocyte transfusions, the disappearance of recipient-derived anti-A/B isoagglutinin and detection of donor-derived A/B antigens can also be used as other parameters. We conducted a retrospective analysis of 68 ABO-incompatible HSCTs, focusing on major and bidirectional mismatch. We analyzed known clinical risk factors associated with delayed erythrocyte engraftment using the three parameters (disappearance of anti-A/B isoagglutinin in recipient, detection of donor-derived A/B antigen, and reticulocyte levels >1%). Although the three parameters were well correlated, the results showed heterogeneity when analyzing the associated risk factors for delayed erythrocyte engraftment. In the analysis of all cases, the requirement for an HLA-matched platelet transfusion was a common risk factor. Furthermore, erythrocyte engraftment was slower in adults than in children. In adults, cytomegalovirus antigenemia was a risk factor for two parameters; however, in children, underlying disease was a common risk factor for all parameters. There is a complex relationship between erythrocyte engraftment and various factors related to HSCTs. Our results suggest that greater accuracy is possible by using analysis methods other than the measurement of reticulocyte levels.

Sezaryen sırasında miyomektomi: Perioperatif sonuçların değerlendirilmesi

Aim: To compare the perioperative outcomes between patients who underwent myomectomy during cesarean section and those without myomectomy during cesarean section retrospectively.
 Materials and Methods: In our study, a total of 187 patients, including 125 patients who underwent myomectomy (case) during cesarean section and 62 patients who had not undergone myomectomy (control) during cesarean section, were included in our clinic between February 2015- October 2019. Basic demographic characteristics of the patients, gestational week at the time of operation, the mean number of myoma and size, locations of myoma, mean differences between hemoglobin and hematocrit levels postoperatively, mean operation time, need for erythrocyte transfusion, and mean hospitalization time were retrospectively evaluated.
 Results: The mean diameter of the myoma in the control group is significantly higher than that of the myomectomy group (5.75 ± 3.71 cm and 4.73 ± 3.76 cm, respectively; p:0.0057). The mean operation time was 82.81 ± 28.69 min. and 70.08 ± 17.89 min. in the myomectomy and control groups, respectively (p: 0.003). There was no statistically significant difference between the two groups in the other parameters (Mean Hb, Htc differences postoperatively, mean hospitalization time, etc.).
 Conclusion: Our results support that myomectomy performed during the cesarean section does not increase perioperative morbidity and may be useful when it is performed by experienced surgeons. In addition, myomectomy during cesarean section can decrease the need for secondary surgery due to the myoma.

Heparin-coated vs. Non-coated Cardiopulmonary Bypass Circuits: Comparing Immediate Results with Different Target Activated Clotting Time.

ObjectiveTo compare immediate postoperative results in patients receiving heparin-albumin-coated and non-coated circuits.MethodsA total of 241 patients undergoing on-pump cardiac surgery were divided into two groups: those receiving heparin-coated circuits (Bioline®, Maquet Cardiopulmonary AG., Hirrlingen, Germany) and those receiving non-coated circuits (Maquet Cardiopulmonary AG., Hirrlingen, Germany).ResultsActivated clotting times (ACT) during cardiopulmonary bypass (CPB) were significantly shorter in the heparin-albumin-coated group than in the non-coated group (355.64±34.12 vs. 560.38±90.20, respectively, P=0.001). In-hospital mortality and postoperative stroke rates and lengths of intensive care unit stay were similar between the groups; in contrast, in the heparin-albumin-coated group, patients had significantly better outcomes for hospital stay, drainage, and need for erythrocyte transfusion.ConclusionHeparin-coated circuits and reduced level of systemic heparinization with 300 seconds of target ACT level in cardiac surgery under CPB are safe and result in a very satisfactory clinical course.

Risk factors associated with clinically significant gastrointestinal bleeding in pediatric ED

IntroductionGastrointestinal bleeding is a common problem in pediatric emergency department (PED). Some of these patients can lose significant amount of blood which may lead to shock. The aim of this study is to determine the risk factors predicting clinically significant gastrointestinal (GIS) bleeding in patients presenting to PED. MethodsThis study was performed prospectively from January 1st 2013 to December 31th 2013 in patients with upper or lower GIS bleeding. Clinically significant GIS bleeding was defined as >2g/dL hemoglobin decrease at any time during observation in PED, need for erythrocyte transfusion or need for rapid endoscopic evaluation. Results105 patients were enrolled, 81 of which were eligible for the study. Twenty two patients (26,8%) had clinically significant GIS bleeding. These patients have significantly more commonly have upper GI bleeding and symptoms of melena, pallor and tachycardia. Initial laboratory findings revealed lower hemoglobin, RBC and albumin levels with higher WBC and BUN levels. They need significantly more nasogastric tube placement and PPI and H2 blocker treatment. Final diagnosis included more gastritis and peptic ulcers. These patients have less hematochezia, less lower gastrointestinal bleeding and less commonly diagnosed as acute gastroenteritis or Mallory Weiss tear as a final diagnosis. ConclusionsPediatric emergency physicians should be aware of clinical and laboratory parameters of patients with clinically significant GIS bleeding to predict which patients are under risk of life threatening blood loss. Patients who have melena, pallor, tachycardia, anemia and uremia at presentation are more prone to have significant GIS bleeding.

Evaluation of the Correlation between Echocardiographic Findings and Serum Ferritin in Thalassemia Major Patients

<p><strong>INTRODUCTION: </strong>Thalassemia is a disorder that affects beta globin gene production and the resultant need for erythrocyte transfusions puts the patient at risk for iron loading, especially cardiac iron loading. Cardiac complications are the most serious ones accompanied by morbidity and mortality. The most harm to the heart is caused by iron overload. Ferritin is generally associated with the amount of stored iron in the body. The aim of this study was to investigate the relationship between echocardiographic findings and serum ferritin level.</p><p><strong>MATERIALS & METHODS:</strong> 107 patients with thalassemia major were enrolled in this prospective analytical study. Serum ferritin levels and echocardiographic findings (diastolic, systolic, pulmonary artery pressure, valvular dysfunctions) were assessed. The data were analyzed by spearman statistical test.</p><p><strong>RESULTS:</strong> Serum ferritin levels of the thalassemia major patients in the study were 2419.13±1772.65 ng/ml. there wasn’t any significant relationship between echocardiographic findings and serum ferritin level.</p><p><strong>CONCLUSION:</strong> Although our findings didn’t support the association between ferritin level and echocardiographic data but we suggest serial cardiac assessment to prevent the effect of increasing iron on the heart.</p>

A Clinical Trial to Detect Subclinical Transfusion-induced Lung Injury during Surgery.

Transfusion-related acute lung injury incidence remains the leading cause of posttransfusion mortality. The etiology may be related to leukocyte antibodies or biologically active compounds in transfused plasma, injuring susceptible recipient's lungs. The authors have hypothesized that transfusion could have less severe effects that are not always appreciated clinically and have shown subtly decreased pulmonary oxygen gas transfer in healthy volunteers after transfusion of fresh and 21-day stored erythrocytes. In this study, the authors tested the same hypothesis in surgical patients. Ninety-one patients undergoing elective major spine surgery with anticipated need for erythrocyte transfusion were randomly allocated to receive their first transfusion of erythrocytes as cell salvage (CS), washed stored, or unwashed stored. Clinicians were not blinded to group assignment. Pulmonary gas transfer and mechanics were measured 5 min before and 30 min after erythrocyte transfusion. The primary outcome variable, gas transfer, as assessed by change of PaO2/FIO2, with erythrocyte transfusion was not significant in any group (mean ± SD; CS: 9 ± 59; washed: 10 ± 26; and unwashed: 15 ± 1) and did not differ among groups (P = 0.92). Pulmonary dead space (VD/VT) decreased with CS transfusion (-0.01 ± 0.04; P = 0.034) but did not change with other erythrocytes; the change from before to after erythrocyte transfusion did not differ among groups (-0.01 to +0.01; P = 0.28). The authors did not find impaired gas exchange as assessed by PaO2/FIO2 with transfused erythrocytes that did or did not contain nonautologous plasma. This clinical trial did not support the hypothesis of erythrocyte transfusion-induced gas exchange deficit that had been found in healthy volunteers.

Preclinical Screening for Retinopathy of Prematurity Risk Using IGF1 Levels at 3 Weeks Post-Partum

Following current recommendations for preventing retinopathy of prematurity (ROP) involves screening a large number of patients. We performed a prospective study to establish a useful screening system for ROP prediction and we have determined that measuring serum levels of IGF1 at week three and the presence of sepsis have a high predictive value for the subsequent development of ROP. A total of 145 premature newborn, with birthweight <1500 g and/or <32 weeks gestational age, were enrolled. 26.9% of them showed some form of retinopathy. A significant association was found between the development of retinopathy and each of the following variables: early gestational age, low birthweight, requiring mechanical ventilation, oxygen treatment, intracranial haemorrhage, sepsis during the first three weeks, bronchopulmonary dysplasia, the need for erythrocyte transfusion, erythropoietin treatment, and low levels of serum IGF1 in the third week. A multiple logistic regression analysis was used to obtain curves for the probability of developing ROP, based on the main factors linked with ROP, namely serum levels of IGF1 and presence of sepsis. Such preclinical screening has the ability to identify patients with high-risk of developing retinopathy and should lead to better prediction for ROP, while at the same time optimising the use of clinical resources, both human and material.

Comparison of New Technology Integrated and Nonintegrated Arterial Filters Used in Cardiopulmonary Bypass Surgery: A Randomized, Prospective, and Single Blind Study

Background. Innovative cardiopulmonary bypass (CPB) settings have been developed in order to integrate the concepts of “surface-coating,” “blood-filtration,” and “miniaturization.” Objectives. To compare integrated and nonintegrated arterial line filters in terms of peri- and postoperative clinical variables, inflammatory response, and transfusion needs. Material and Methods. Thirty-six patients who underwent coronary bypass surgery were randomized into integrated (Group In) and nonintegrated arterial line filter (Group NIn) groups. Arterial blood samples for the assessments of complete hemogram, biochemical screening, interleukin-6, interleukin-2R, and C-reactive protein were analyzed before and after surgery. Need for postoperative dialysis, inotropic therapy and transfusion, in addition to extubation time, total amount of drainage (mL), length of intensive care unit, and hospital stay, and mortality rates was also recorded for each patient. Results. Prime volume was significantly higher and mean intraoperative hematocrit value was lower in Group NIn, but need for erythrocyte transfusion was significantly higher in Group NIn. C-reactive protein values did not differ significantly except for postoperative second day's results, which were found significantly lower in Group In than in Group NIn. Conclusion. Intraoperative hematocrit levels were higher and need for postoperative erythrocyte transfusion was decreased in Group In.

Erythrocyte Transfusion

Erythrocyte Transfusion

Postpartum Hemorrhage Update on Problems of Definitions and Diagnosis

Maternal mortality due to postpartum hemorrhage (PPH) continues to be one of the most important causes of maternal death worldwide. PPH is a significantly underestimated obstetric problem, primarily because a lack of definition and diagnosis. The 'traditional' definition of primary PPH based on quantification of blood loss has several limitations. Notoriously, blood loss is not measured or is significantly underestimated by visual estimation and there are no generally accepted cut-offs limits for estimated blood loss. A definition based on hematocrit change is not clinically useful in an emergency such as PPH, as a fall in hematocrit postpartum shows poor correlation with acute blood loss. The need for erythrocyte transfusion alone to define PPH is also of limited value, as the practice of blood transfusion varies widely. Definitions based on symptoms of hemodynamic instability are problematic, as they are late signs of depleted blood volume and commencing failure of compensatory mechanisms threatening the mother's life. There is thus currently no single, satisfactory definition of primary PPH. Proper and timely diagnosis of PPH should above all include accurate estimation of blood loss before vital signs change. Estimation of blood loss by calibrated bags has been shown to be significantly more accurate than visual estimation at vaginal delivery. Careful monitoring of the mother's vital signs, laboratory tests, in particular coagulation testing, and immediate diagnosis of the cause of PPH are important key factors to reduce maternal morbidity and mortality.

Postpartum hemorrhage - update on problems of definitions and diagnosis*

Maternal mortality due to postpartum hemorrhage (PPH) continues to be one of the most important causes of maternal death worldwide. PPH is a significantly underestimated obstetric problem, primarily because a lack of definition and diagnosis. The 'traditional' definition of primary PPH based on quantification of blood loss has several limitations. Notoriously, blood loss is not measured or is significantly underestimated by visual estimation and there are no generally accepted cut-offs limits for estimated blood loss. A definition based on hematocrit change is not clinically useful in an emergency such as PPH, as a fall in hematocrit postpartum shows poor correlation with acute blood loss. The need for erythrocyte transfusion alone to define PPH is also of limited value, as the practice of blood transfusion varies widely. Definitions based on symptoms of hemodynamic instability are problematic, as they are late signs of depleted blood volume and commencing failure of compensatory mechanisms threatening the mother's life. There is thus currently no single, satisfactory definition of primary PPH. Proper and timely diagnosis of PPH should above all include accurate estimation of blood loss before vital signs change. Estimation of blood loss by calibrated bags has been shown to be significantly more accurate than visual estimation at vaginal delivery. Careful monitoring of the mother's vital signs, laboratory tests, in particular coagulation testing, and immediate diagnosis of the cause of PPH are important key factors to reduce maternal morbidity and mortality.

Serum levels of IGF1 are a useful predictor of retinopathy of prematurity

To ascertain whether insulin-like growth factor 1 (IGF1) is associated with retinopathy of prematurity (ROP) and is a useful predictor of the disease. Although its aetiopathogenesis is multifactorial, development of the disease appears to be related to a deficiency in IGF1, a hormone that acts together with vascular endothelial growth factor in the normal angiogenesis in the retina. Prospective study for a 30-month period. A total of 74 premature newborn babies, of less than 1500 g and/or 32 weeks' gestational age or less. To determine the development and severity of ROP. Serum levels of IGF1 were measured once a week from birth until 40 weeks corrected gestational age in each subject. Of our subjects, 32.4% developed some form of ROP, and all those ROP patients had the following characteristics at birth (median +/- standard deviation scores): low weight (1098 +/- 188 vs. 1393 +/- 285 g), short length (36.74 +/- 1.77 vs. 38.89 +/- 3.08 cm), small cranial perimeter (26.03 +/- 1.74 vs. 27.93 +/- 1.81 cm) and young gestational age (29.7 +/- 1.78 vs. 31.3 +/- 1.79 weeks) (p < 0.05). Other factors previously associated with ROP that were also observed with statistically significant frequency in our ROP patients were bronchopulmonary dysplasia, intracranial haemorrhage, the need for erythrocyte transfusion or treatment with erythropoietin and sepsis (all p < 0.05). Levels of IGF1 at the 3rd week post-partum, independent of gestational age at birth, were clearly lower in the group who developed ROP (29.13 vs. 43.16 ng/mL, p < 0.05). A value of 30 ng/mL of IGF1 in the third week post-partum was found to have a 90% sensitivity in the diagnosis of ROP. A rapid rise in IGF1 levels between the 3rd and 5th weeks appeared to be related to the development of a higher stage of ROP. Determination of IGF1 serum levels in the 3rd week post-partum, independent of gestational age at birth, provides a sufficient and reliable prognostic tool and allows the identification of a group of patients at high risk of developing the disease.

Long-term Efficacy of Pegylated Recombinant Human Megakaryocyte Growth and Development Factor in Therapy of Aplastic Anemia

Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) potently stimulates platelet production in humans, mitigates thrombocytopenia associated with nonmyeloablative chemotherapy, and reduces the need for platelet transfusions. Its long-term effect in patients, however, is not well understood. We report a patient with aplastic anaemia who received 3 cycles of PEG-rHuMGDF 3 times a week for up to 2 years. Platelet counts slightly increased 1 week after the initiation of PEG-rHuMGDF therapy, bleeding episodes decreased, and there was no need for platelet transfusion. Administration of PEG-rHuMGDF increased not only platelet numbers but also reticulocyte counts, and reduced the need for erythrocyte transfusions as well. There were no significant adverse events, and no neutralizing antibodies were detected in the patient.

Serum erythropoietin (EPO) levels correlate with survival and independently predict response to EPO treatment in patients with myelodysplastic syndromes.

Treatment with recombinant erythropoietin (EPO) can alleviate anaemia in patients with myelodysplastic syndromes (MDS). The present study, based on a long-term follow-up of 68 MDS patients (26RA, 16 RAS, 26 RAEB) treated with EPO alone, pinpoints pre-treatment variables associated with response induction, response duration and overall survival. Response, defined as an increase in haemoglobin >15gL1 or eliminated erythrocyte transfusion requirements, was observed in 22 of 66 (33%) evaluable patients. The median response duration was 15 (range 3-64+) months. Using univariate logistic regression models, responders displayed significantly lower baseline serum EPO levels (S-EPO), more often normal bone marrow blast cell content (RA/RAS vs. RAEB), normal cytogenetics and no need for erythrocyte transfusion. In a multiple logistic regression model, S-EPO (P=0.009), marrow blast content (P=0.031) and erythrocyte transfusion need (P=0.024) remained associated with response induction. The probability of response for a patient with S-EPO >50UL1, RA/RAS and no transfusion need was 0.79 (0.53-0.93, 95% CI). The median overall survival time from start of EPO treatment was 26 months, significantly longer for responders than for non-responders (49 vs. 18 months, P=0.018). Survival was also predicted by baseline S-EPO; patients with S-EPO >50UL1 (n=50) had a median survival of 17 months, as compared to 65 months for those with S-EPO >50UL1 (n=14, P=0.024). The international prognostic scoring system (IPSS) for MDS predicted survival (P=0.003) and progression to acute leukemia (P<0.001) but not response to EPO treatment. Furthermore, in a logistic regression model with S-EPO and IPSS, S-EPO (but not IPSS) was again a significant predictor for response (P=0.007). Our data facilitate the optimal selection of MDS patients suitable for EPO treatment and pinpoint S-EPO as a powerful predictor of response and overall survival in MDS.

Erythropoietin Administration in Term Infants with Hemolytic Anemia. 792

Administration of recombinant erythropoietin (EPO) has been shown to decrease or eliminate the need for erythrocyte transfusion (Tx) in preterm infants and to decrease the need for Tx in late anemia due to Rh or ABO hemolytic disease. The objective of this study was to determine if EPO administration to infants with hemolytic anemia before one month of age will prevent severe anemia and avoid the need for Tx. A planned randomized, controlled study could not be done due to parents' preference for EPO therapy once relative risks of EPO vs transfusion had been explained. Eighteen term infants were treated with EPO between 8/96 and 11/97. The etiology of the hemolytic anemia was as follows: 10 ABO incompatibility (7/10 with positive direct Coombs), 1 hemolytic elliptocytosis, 1 G6PD deficiency, 2 alpha thal. trait, 4 unknown (1 had Hb SS). At the start of EPO therapy, ages were 1.5-3.5 wks (med 2 wks), Hb levels 9-13.5 gm/dL (med 10.1; all but 1 had Hb < 11.4), reticulocytes 0.6-2.6% (med 1.5%). Serum EPO levels in 10 of these infants ranged from 2.5-20.3 mU/mL (med 9.6 mU/mL). All infants received EPO 200 u/kg SC TIW for a duration of 2-5.5 wks (med 3 wks) with oral iron 3 mg/kg day during EPO therapy and for an additional 6 wks. The reticulocyte counts increased 2-10 fold from pre-EPO values in 1-2 wks. Hb levels remained stable or increased during EPO therapy except in 1 infant with OB hemolytic disease who developed a UTI and was transfused for worsening anemia. In most infants the Hb level remained stable or declined slightly (< 1 gm/dL) after EPO was discontinued, but EPO administration was resumed in 1 infant when the Hb level dropped from 11.4 to 10.1 gms/dL during the first week off therapy. No adverse effects were observed from EPO administration. We conclude that serum EPO levels are not increased in term infants with hemolytic anemia. EPO administration results in brisk reticulocyte response with stable or increasing Hb levels and, thus, is likely to prevent or reduce the need for Tx.

Recombinant Human Erythropoietin Stimulates Erythropoiesis and Reduces Erythrocyte Transfusions in Very Low Birth Weight Preterm Infants

We hypothesized that treatment with recombinant human erythropoietin (r-HuEPO) would stimulate erythropoiesis and would thereby reduce the need for erythrocyte transfusions in preterm infants. We treated 157 preterm infants born at 26.9 +/- 1.6 weeks of gestation who weighed 924 +/- 183 g at birth with either subcutaneous r-HuEPO (100 U/kg/d, 5 days per week) or placebo for 6 weeks in a randomized, double-blind, controlled clinical trial. All patients received oral iron and were managed according to uniform conservative transfusion guidelines. Treatment with r-HuEPO was associated with fewer erythrocyte transfusions (1.1 +/- 1.5 per infant in the r-HuEPO group versus 1.6 +/- 1.7 per infant in the placebo group; P = .046) and with a reduction in the volume of packed erythrocytes transfused (16.5 +/- 23.0 mL versus 23.9 +/- 25.7 mL per infant; P = .023). Overall, 43% of the infants in the r-HuEPO group and 31% of placebo-treated infants were transfusion-free during the study (P = .18). The volume of blood removed for laboratory tests and the need for respiratory support at the start of treatment had major effects on transfusion requirements independent of r-HuEPO. Reticulocyte counts were higher during treatment in the r-HuEPO group (P = .0001), and r-HuEPO-treated infants had higher hematocrit values at the end of the study (32% versus 27.3% in the placebo group; P = .0001). We found no differences in the incidence of major complications of prematurity between the treatment groups. We conclude that treatment with r-HuEPO at a weekly dose of 500 U/kg stimulates erythropoiesis, moderates the course of anemia, is associated with a reduction in erythrocyte transfusions, and appears safe in very low birth weight preterm infants who are receiving iron supplements. Conservative transfusion criteria, minimization of phlebotomy losses, and treatment with r-HuEPO are complementary strategies to reduce erythrocyte transfusions in these infants.

Butyrate in the treatment of sickle cell disease and beta-thalassemia.

The search for, and discovery of, a physiologic model in which the developmentally regulated switch from fetal to adult globin gene expression could be prevented has resulted in the development of a new class of therapeutic agents, consisting of simple fatty acids, such as butyric acid, for the treatment of the beta-hemoglobinopathies. Butyrate and related drugs stimulate fetal (gamma-) globin gene expression in erythroid cells cultured from patients, and in chicken, ovine, and primate animal models. The butyrates are perhaps the first class of drugs designed to transcriptionally activate specific genes--in this particular case, to reactivate the developmentally silenced fetal globin genes. Phase I-II clinical trials resulting from this basic research have been initiated on a small scale during the past 3 years. Analysis of two butyrate-derived therapeutic agents, one delivered intravenously and one orally, has shown initial efficacy in stimulating fetal hemoglobin expression in 50% to 85% of patients. Correction of the anemia from the beta-hemoglobinopathy has followed induction of fetal globin, and has been adequate to eliminate the need for erythrocyte transfusions in some patients with beta-thalassemia. These compounds have been relatively safe and without generalized cytotoxicity in patients, but drug tolerance develops in some patients after prolonged therapy. Third-generation, small two- to five-carbon butyrate derivatives are in development. The molecular basis for butyrate action is being defined. Binding of putative regulatory proteins to a specific region of the gamma-globin promoter is altered in vivo in patients receiving butyrate therapy. Further analysis of the mode of action may contribute to development of other therapeutic agents designed to regulate gene transcription.

Erythropoietin prevents chemotherapy-induced anemia: Case report

A thirty-seven year old male patient with heavily pretreated metastatic testicular carcinoma received escalating doses of recombinant human erythropoietin (EPO) before and throughout chemotherapy. Whereas previous chemotherapy regimens repeatedly caused anemic situations in this patient (hemoglobin (HB) 7.0 g/dl requiring multiple transfusions of red blood cells), EPO given as an i.v. bolus injection at escalating doses of 150 to 300 U/kg body weight (BW) twice/week, starting two weeks prior to the identical myelosuppressive treatment protocol, maintained HB at levels above 8.8 g/dl and thus obviated the need for erythrocyte transfusion. EPO was discontinued after 9 weeks of administration when the patient had achieved a hematocrit (HCT) of 41.1% and a HB of 12.7 g/dl. However, erythropoiesis continued to recover for the next 7 weeks reaching a HCT of 42.4% and a HB of 14.3 g/dl, although the next identical chemotherapy cycle had been given within this period. Along with the rise in HB, ferrokinetics changed significantly as measured by serum ferritin, which was reduced to one third at the end of EPO therapy after only 9 weeks (from 979 ng/ml to 320 ng/ml). No side effects due to EPO administration occurred. These data provide first evidence for efficacy of EPO in chemotherapy-induced anemia and may open new avenues for its clinical application.