Three-dimensional appearance of Langerhans cells in human gingival epithelium as revealed by confocal laser scanning microscopy

Despite the reducing exposure to allogeneic blood in cardiac surgery, most of patients with anemia still require allogeneic blood. In this study, we have attempted to harvest the blood from cardiac patients with baseline hemoglobin levels below 11.0 g/dl using recombinant human erythropoietin (rHuEPO). 29 anemic patients undergoing cardiac surgery at our hospital between January 1994 and March 1997 were divided into two groups: 3 weeks' treatment with recombinant human erythropoietin (rHuEPO) and blood donation (group 1, n = 15) and iron supplementation alone (group 2, n = 14). There were no statistically significant differences among the two groups in patients characteristic and surgical data. No serious adverse events after phlebotomy were apparent in patients donating autologous blood. Patients in group 1 had significantly higher hemoglobin levels than patients in group 2 at 7 days before operation. The number of reticulocytes were increased at just before operation in group 1, whereas group 2 showed no significant increase. The estimated hemoglobin increase in group 1 were higher at 7 days and just before operation. In 75% of group 1, allogeneic blood transfusion could be avoided, while all patients in group 2 received allogeneic blood transfusion. This study suggests that the combination of rHuEPO administration and autologous blood donation would be beneficial for anemic patients in elective cardiac surgery. The use of rHuEPO should not be restricted to anemic patients.     

Prospective validation of a point score system for predicting blood transfusion following hip or knee replacement

BACKGROUND: The purpose of this study was to validate a previously published point score system for predicting the likelihood of a postoperative blood transfusion following hip or knee replacement. STUDY DESIGN AND METHODS: Data were collected prospectively on 460 sequential patients undergoing elective hip and knee replacement at two academic hospitals. Blood transfusion frequency was determined for patients in each of the four risk strata, as defined by the point score system. The accuracy of the system was validated by calculating the area under the receiver operating characteristic (ROC) curve for each site. Data were then combined and inappropriate blood transfusions were eliminated, by using the American College of Physicians guidelines. The frequencies of blood transfusion within each strata were recalculated along with an ROC curve. RESULTS: The point score system accurately predicted the likelihood of blood transfusion at both hospitals, despite marked differences in overall transfusion frequencies. The calculated areas under the ROC curves were 0.78 and 0.79 for the two sites. The point score system also proved valid when only appropriate blood transfusions were considered, with a calculated area under the ROC curve of 0.74. CONCLUSION: The point score system can accurately predict the likelihood of postoperative blood transfusion following hip or knee replacement. Such a system can be used to target high-risk patients for preoperative autologous blood donation.     

Epoetin alfa. A bloodless approach for the treatment of perioperative anemia

Under normal physiologic conditions the level of circulating red blood cells is regulated precisely by the glycoprotein erythropoietin. In major elective surgery, patients who are participating in preoperative autologous blood donation or who are anemic may not have the capacity to manufacture sufficient red blood cells in response to increases in endogenous erythropoietin that is sufficient to avoid perioperative allogeneic blood transfusion. In these patients pharmacologic doses of recombinant human erythropoietin (Epoetin alfa) have been shown to accelerate erythropoiesis, thereby increasing preoperative red blood cell production, hematocrit level, and hemoglobin concentration and reducing exposure to allogeneic blood transfusion. In four large multicenter studies, 869 patients undergoing major elective surgery were treated with a daily regimen (300 or 100 IU/kg x 14 or 15 doses) or a weekly regimen (600 IU/kg x 4 doses) of subcutaneous Epoetin alfa beginning either 2 or 3 weeks before surgery, respectively. Although all Epoetin alfa regimens were effective at accelerating erythropoiesis and increasing red blood cell production, the weekly regimen was the most patient friendly, cost effective regimen for treating preoperative anemia and minimizing patient risk of allogeneic blood transfusion.     

Autologous blood donation prior to anatomical radical retropubic prostatectomy: is it necessary?

OBJECTIVES: To determine if autologous blood donation prior to anatomical radical retropubic prostatectomy, given current improvements in surgical technique, is necessary. METHODS: The medical records of 200 consecutive patients undergoing radical retropubic prostatectomy for clinically localized prostate cancer were reviewed with regard to (1) preoperative hematocrit (HCT); (2) estimated blood loss (EBL); (3) postoperative HCT prior to discharge; (4) number of units of autologous blood donated; and (5) number of units of autologous and homologous blood transfused. In addition, the charges associated with autologous blood donation were determined via telephone interview with 14 blood donation centers across the United States. RESULTS: Overall, 189 patients (95%) did not require a homologous blood transfusion. Sixty-four patients (32%) donated autologous units and 136 patients (68%) did not. Of the patients who had donated, only 17 (27%) received their blood back, and none (0%) received any homologous blood. Eleven (8%) of the 136 nondonors received a blood transfusion. The autologous donors, in comparison with nondonors, were found to have a significantly lower preoperative HCT (mean +/- standard deviation: 40 +/- 4.0% versus 42 +/- 2.9%, P < 0.05). However, there was no statistically significant difference in the mean EBL between the two groups, autologous donors versus nondonors (771 +/- 370 versus 737 +/- 425 cc, P = 0.23). The autologous donors had a smaller mean change in HCT versus the nondonors (-9.3 +/- 5.1% versus -11.2 +/- 4.4%, P < 0.05), reflecting an increased willingness to transfuse patients who have autologous units available. With regard to cost, patients, on average, can expect to be charged as much as $745 per unit of autologous blood donated. CONCLUSIONS: These findings suggest that preoperative blood donation prior to radical prostatectomy may not be necessary, because 95% of the patients did not require a homologous blood transfusion. In addition, autologous blood donation can be associated with substantial costs in both time and money. Thus, autologous donation should be left as an option for the patient and should not be considered routine practice.     

Effect of plumbagin on the radiation induced cytogenetic and cell cycle changes in mouse Ehrlich ascites carcinoma in vivo

BACKGROUND: Controversy exists concerning whether the costs and potential risks outweigh the potential benefits of "crossover" use in the general blood supply of unutilized blood that was donated for autologous transfusion. STUDY DESIGN AND METHODS: Published articles and reports were identified through systematic search of MEDLINE and review of references cited in previously identified articles, textbooks, and reports. Consultation was made with experts in blood donation and transfusion. Additional peer review was received from the American Medical Association (AMA) Council on Scientific Affairs RESULTS: Concern over infectious disease transmission has led to increased interest in and support for autologous transfusion for individuals having planned surgeries. Different requirements exist for collection, labeling, and screening of blood to be used for autologous versus allogeneic transfusions; therefore, procedures for diverting autologous blood donations to the general blood supply involve considerable expense. Several cost-effectiveness studies of autologous blood donation and transfusion conclude that currently this "crossover" appears to be an expensive procedure yielding little increased benefit from a societal perspective. CONCLUSIONS: The recommendations in this report were adopted as AMA Policy at the AMA Annual Meeting in June 1997. The AMA does not encourage blood collection programs to "cross over" units donated for autologous use to the allogeneic blood supply. Practice guidelines are needed, and should be utilized to ensure parsimony in the use of autologous blood donations and transfusions.     

Red blood cell transfusion practices in patients undergoing orthopedic surgery: a multi-institutional analysis

This retrospective review analyzed and compared transfusion practices in patients undergoing orthopedic surgery in five Massachusetts hospitals with current practice guidelines; opportunities for improvement were identified. Patient-specific clinical information and data about transfusion practices were obtained from the medical records of 384 Medicare patients undergoing orthopedic surgery between January 1992 and December 1993. The number of patients who donated autologous blood preoperatively differed significantly among hospitals as did the number of autologous units that were unused. The number of blood units transfused at each transfusion event also differed significantly; some surgeons transfused > or =2 units in the majority of their patients, while others transfused 1 unit at a time. This variation in practice was not explained by differences in patients' clinical status. The mean pretransfusion hematocrit was higher for autologous versus allogeneic blood, suggesting more liberal criteria to transfuse autologous blood. Nearly half of all transfusion events were determined to have been potentially avoidable. Avoidable transfusions were also three to seven times more likely with autologous than with allogeneic blood. Significant inter-hospital differences existed in the number of elective surgery patients exposed to allogeneic blood. The major determinant of allogeneic blood use in these patients was the availability of autologous blood. Each additional autologous blood unit available decreased the odds of allogeneic blood exposure twofold. Differences in intraoperative and postoperative blood salvage use also were noted. These findings indicate that significant variations in practice exist. Comparative data enabled hospitals to identify and target specific areas for improvement.     

Transfusion management in pediatric and adolescent scoliosis surgery. Efficacy of autologous blood

STUDY DESIGN: A retrospective review of consecutive pediatric and adolescent patients who required posterior spinal fusion to correct scoliosis. OBJECTIVES: To 1) measure the participation of pediatric patients in predeposit programs for autologous and directed blood donation 2) to assess the success of autologous predonation in preventing allogeneic blood use, 3) to determine whether transfusion indications differed between patients who received allogeneic blood and those who received autologous blood, and 4) to assess factors that predict transfusion requirements during scoliosis surgery. SUMMARY OF BACKGROUND DATA: Authors of recent studies in adults have questioned whether transfusion of autologous blood is a cost-effective therapy when compared with the less-expensive alternative--transfusion of allogeneic blood. In children, the efficacy of autologous blood has not been assessed in a large population of surgical patients. In adults, the frequency of patient participation, the success of autologous donors in avoiding allogeneic transfusion, and the proportion of collected autologous units used during the perioperative period are measures used to establish the efficacy of autologous predonation programs. METHODS: Hospital and clinic records for each patient who underwent posterior spinal fusion from September 1, 1989 through September 1, 1994 were reviewed. Blood bank consultation, autologous donation records, anesthesia records, surgical reports, and hospital records were reviewed. Seventy percent of patients (164 of 243) participated in autologous donation. RESULTS: More than 90% of autologous donors successfully avoided receiving allogeneic blood. Patients with idiopathic scoliosis (n = 168) were more likely to participate in autologous donation (n = 144) and to avoid allogeneic blood (n = 135). Patients with neurologic causes of scoliosis more commonly used allogeneic or directed donation (56 of 75 patients). Nineteen patients with neuromuscular causes of scoliosis participated in autologous donation, but more than one half of this group (10 of 19 patients) required allogeneic blood in addition to autologous units. CONCLUSIONS: Using measures of efficacy similar to those reported in studies of adults, autologous blood was found to be more effective in meeting the transfusion needs of pediatric patients who required posterior spinal fusion than in meeting those needs in adult surgical patients in previous studies.     

Avoidance of homologous blood transfusion despite extreme blood loss

We report the case of a 22-year-old woman who underwent two-step scoliosis surgery without allogeneic transfusion, although the intraoperative blood loss (3500 ml) during the first procedure was higher than the calculated blood volume (3250 ml). Preoperatively the patient had donated four units of autologous blood. Intraoperatively blood-saving methods were combined. During the first operation acute normovolemic hemodilution (target hemoglobin 9.0 g/dl) was applied and during the second operation controlled hypotension (systolic blood pressure 80 mmHg). Intraoperative auto-transfusion was used in both procedures. During the first operation severe normovolemic anemia (minimal hemoglobin 3.5 g/dl) was accepted while the patient was ventilated with FiO2 1.0. The hemoglobin concentration was 8.6 g/dl after the first procedure and had increased to 11.6 g/dl 4 weeks after the second procedure. No severe complications occurred during the postoperative phase. This case report shows that also in surgical procedures with extreme blood loss any allogenic transfusion can be avoided by the combination of blood-saving methods, acceptance of low intraoperative transfusion trigger and ventilation with 100% oxygen.     

Preoperative recombinant human erythropoietin injection versus preoperative autologous blood donation in patients undergoing radical retropubic prostatectomy

OBJECTIVES: In an effort to avoid allogeneic transfusions, many patients scheduled for radical retropubic prostatectomy (RRP) participate in preoperative autologous donation (PAD) programs. Yet, PAD programs are costly, time-consuming, and not without risks. Perioperative administration of recombinant human erythropoietin (Epoetin alfa) also has been shown to reduce patients exposure to allogeneic transfusion. This study sought to compare the costs and transfusion rates associated with either PAD or perioperative Epoetin alfa in patients undergoing RRP. METHODS: The study population consisted of 120 men randomized to one of two treatment groups. Patients in group 1 donated up to 3 U of autologous blood preoperatively, provided that their hematocrit (HCT) was 33% or higher. Patients in group 2 received 600 IU/kg of Epoetin alfa on days -14 and -7 preoperatively, provided that their HCT was 46% or lower. RESULTS: Overall, 107 (89%) of 120 patients underwent RRP. In group 1, 5 (9.6%) of 52 patients received a total of 12 U of allogeneic blood (0.23 U/patient). In group 2, 5 (9.6%) of 52 patients received a total of 10 U of allogeneic blood (0.19 U/patient). Three patients in group 1 but no patients in group 2 experienced an adverse event. The average costs related to PAD and pharmacologic administration per patient were $540 in group 1 and $657 in group 2. Participation in PAD required an average of 5 hours more per patient compared with Epoetin alfa administration. CONCLUSIONS: Preoperative Epoetin alfa therapy is safe, well tolerated, and equally effective as PAD in reducing allogeneic blood transfusion requirements. Epoetin alfa therapy also is comparable in cost to PAD and offers patients greater convenience and less of a time commitment.     

Red blood cell transfusions for total hip replacement in a regional hospital. A six-year analysis

To evaluate changes in the need for homologous blood and to assess the impact of autologous blood transfusion, red cell transfusions in unilateral total hip replacement surgery, performed electively in the period 1986-1991, were studied in a regional hospital. Transfusion data, perioperative blood loss and post-operative haemoglobin concentration of 495 patients were analysed. From 1986 to 1991, the percentage of patients not transfused with homologous blood increased from 18.5 to 45.5%. After the introduction of an autologous blood transfusion programme in 1987, 116 of 430 patients (27.0%) donated autologous blood. No increase in the percentage of autologous donors was observed during the study. Most common reasons for nonparticipation were the patient's age, doctors' underordering and logistic limitations. 81.9% of autologous donors had total hip replacement surgery without homologous transfusions. Mean blood loss reduced significantly from 1,373 +/- 781 ml in 1986 to 958 +/- 582 ml in 1991 (p < 0.001). Transfusion requirement in the nonautologous patients fell from 2.6 +/- 1.8 units in 1986 to 1.4 +/- 1.4 units per patient in 1989 and increased thereafter to 2.2 +/- 2.1 units in 1991 (p < 0.01) and showed a strong correlation with blood loss (r = 0.58; p < 0.001). No changes in postoperative haemoglobin concentration were observed throughout the study. In conclusion, collection of autologous blood is effective, albeit still underutilized, to reduce homologous blood requirement. The close correlation between blood loss and transfusion requirement accentuates the role of surgical practice in the reduction of homologous transfusions.     

Shed mediastinal blood transfusion after cardiac operations: a cost-effectiveness analysis

BACKGROUND: Cardiac surgical patients consume a significant fraction of the annual volume of allogeneic blood transfused. Scavenged autologous blood may serve as a cost-effective means of conserving donated blood and avoiding transfusion-related complications. METHODS: This study examines 834 patients after cardiac operations at the University of Alabama Hospital. Data were collected on patients receiving unwashed, filtered, autologous transfusions from shed mediastinal drainage and those receiving allogeneic transfusions. The data were incorporated into clinical decision models; confidence intervals for parameters were estimated by bootstrapping sample statistics. Costs were estimated for transfusing both allogeneic and autologous blood. RESULTS: The study found a 54% reduction in transfusion risk or a mean reduction of 1.41 allogeneic units per case (95% confidence interval, 1.04 to 1.79 units). The process saved between $49 and $62 per case. CONCLUSIONS: The use of autologous blood has the potential to significantly reduce the costs and risks associated with transfusing allogeneic blood after cardiac operations.     

Recombinant human erythropoietin as adjuvant treatment for autologous blood donation in elective surgery with large blood needs (> or = 5 units): a randomized study

BACKGROUND: Autologous blood transfusion presents no infectious or immunologic side effects. The aim of this randomized study was to determine the impact of recombinant human erythropoietin (rHuEPO) on the donation of 5 units of autologous blood by nonanemic patients who were candidates for elective surgery with transfusion requirements of > or = 5 units. STUDY DESIGN AND METHODS: Starting on Day -35, 420 mL of blood was taken weekly. All patients received 200 mg of iron saccharose complex intravenously at each visit and six subcutaneous injections of rHuEPO (141 U/kg) or placebo between Days -21 and -7. RESULTS: Of 50 patients, 45 completed the study (placebo, 21; rHuEPO, 24). Total red cell production was higher in the rHuEPO group (p = 0.001). Donation of 5 units was possible for 67 percent (placebo group) and 79 percent (rHuEPO group) of patients (p = 0.5). The mean number of blood units donated was 4.6 (placebo group) and 4.7 (rHuEPO group). More patients in the placebo group received allogeneic blood (9/21 [43%] vs. 6/23 [26%]), although the difference did not reach significance (p = 0.34). CONCLUSION: In nonanemic patients donating 5 units of blood, rHuEPO associated with intravenous iron increased total red cell production. However, no difference was found between the rHuEPO and placebo groups with regard to the number of units of autologous blood donated of the number of patients receiving allogeneic blood transfusion.     

Immunization with the N-terminal region of the nonstructural protein NS1 promotes survival after challenge with lethal influenza A virus dose

We investigated the utilization patterns of autologous blood donation for radical retropubic prostatectomy (RRP) during a 6-year period. A total of 225 patients electing RRP with blood donation were identified for analysis. Group 1 consisted of 113 men who had an RRP from 1990 to 1993. Group 2 consisted of 112 men who had an RRP from 1993 to 1995. Charts were reviewed for the number of units transfused, number of autologous units donated, and operative blood loss. More patients autodonated blood in the later group (84% vs. 75%). Technical improvements and experience have significantly decreased blood loss and the need for transfusions (69% vs. 96% in the early group). In the more current series, only 14% of patients who autodonated blood required homologous transfusion vs. 42% in the earlier group. An increase in the amount of wasted blood (42% vs. 16% in the early group) also was noted. The 4-unit donors had the lowest homologous transfusion rate in both series (group 1 = 21%, group 2 = 5%); the 2-unit donors had the lowest units wasted per person (0.74). In addition, the 2-unit donors maintained a low homologous transfusion rate of 16%. These data suggest that 2 units of autologous blood donation has a reduced risk of homologous blood transfusion while the amount of autologous blood wasted is minimized.     

Preoperative autologous blood donation in patients with malignant tumors of the head and neck region

Twelve instances of preoperative autologous blood donation were assessed in 10 patients with malignant tumors of the head and neck region. All patients received preoperative radiation therapy and chemotherapy and most of the cases were also given recombinant human erythropoietin (EPO) and iron sulfate. Hemoglobin concentrations immediately before starting the 800ml blood donations were higher than 13g/dl in 5 cases and less than 13g/dl in 6 cases. The mean hemoglobin concentration just prior to donation and one week after donation in these two groups changed from 14.4g/dl to 12.5g/dl and 11.7g/dl to 11.7g/dl, respectively. A 1000ml blood donation was carried out in only one patient, and the hemoglobin concentrations just before donation and one week after donation were 11.4g/dl and 10.5g/dl, respectively. Only half of the blood volume scheduled, 400ml, was achieved in 3 of the 12 cases attempted because of fever, diarrhea and a change of the day of surgery, respectively. The mean estimated blood loss in the 10 patients that underwent surgery as planned was 898ml, and allogenic blood transfusion was avoided in all cases. We concluded that 800-1000ml preoperative autologous blood donation can be performed safely in patients with advanced malignant tumors of the head and neck region who have undergone preoperative radiation therapy and chemotherapy by giving EPO and iron sulfate.     

Acute normovolemic hemodilution can replace preoperative autologous blood donation as a standard of care for autologous blood procurement in radical prostatectomy

Predonation of autologous blood (PAD) is a standard of care for patients undergoing radical prostatectomy, but recent studies have shown that PAD is not cost-effective. Acute normovolemic hemodilution (ANH) is an alternative autologous blood procurement technique that is much less costly than PAD. We compared the efficacy and costs of ANH alone to ANH combined with PAD. Two hundred-fifty patients who predonated fewer than 3 units of autologous blood before radical prostatectomy underwent ANH to a target hematocrit of 28%. Perioperative hematocrit levels, transfusion outcomes and costs, and postoperative outcomes were compared for patients who predonated 0, 1, or 2 units of blood before surgery. A computer model was used to estimate the savings in red blood cells (RBC) associated with each autologous intervention. ANH alone resulted in a 21% allogeneic transfusion rate and contributed a mean net savings of 112 mL RBC in blood conservation (equivalent to 0.6 unit of blood). The addition of 1 or 2 units of PAD reduced allogeneic exposure rates to 6% or 0%, respectively. Overall, patients who predonated blood had a mean net loss of 198 mL of RBC (equivalent to 1 blood unit), due to both an absence in compensatory erythropoiesis and to the wastage of 60% of the blood units donated. Patients who underwent ANH alone had a 60% reduction in mean total transfusion costs ($103 +/- $102) compared with patients who predeposited 2 units of autologous blood in addition to ANH ($269 +/- $11, P < 0.05). We conclude that ANH can replace PAD as an autologous blood option because it is less costly and equally effective. A combination of ANH and PAD can further decrease allogeneic blood exposure, but it increases transfusion costs and wastage. IMPLICATIONS: A patient's own blood can be obtained for use in surgery by predonation or acute normovolemic hemodilution on the day of surgery. Both blood collection techniques decrease the need for blood bank transfusions, but acute normovolemic hemodilution is less expensive and more convenient for patients.     

Simultaneous bilateral versus unilateral total knee arthroplasty. Outcomes analysis

One hundred consecutive, primary simultaneous bilateral total knee arthroplasties were prospectively compared with 100 consecutive, primary unilateral total knee arthroplasties in reference to relative risk, complications, cost, and need for rehabilitation. All procedures were performed using identical preoperative, intraoperative, and postoperative protocols. Postoperative confusion was approximately four times greater in the simultaneous bilateral total knee arthroplasties group (29% versus 7%), which was thought to represent an increased incidence of fat embolism. Cardiopulmonary complications were approximately three times greater after simultaneous bilateral total knee arthroplasties (14% versus 5%), and most commonly involved arrhythmias. The increased stress on the cardiopulmonary system with simultaneous bilateral total knee arthroplasties may make this procedure contraindicated in certain patients with preexisting disease. There was an approximately 17 times greater need for banked blood in the simultaneous bilateral total knee arthroplasties group (17% versus 1%), which is alarming given the persistent concerns of transfusion related disease transmission. Although the length of hospitalization was similar (6.4 days simultaneous bilateral total knee arthroplasties versus 6 days unilateral total knee arthroplasty), 89% of the patients in the simultaneous bilateral total knee arthroplasties group required a rehabilitation stay versus 45% of the patients in the unilateral total knee arthroplasty group. Total hospital charges averaged $53,168 for simultaneous bilateral total knee arthroplasties versus $32,598 for unilateral total knee arthroplasty. Total rehabilitation charges were similar. The relative cost savings implicit by doing simultaneous bilateral total knee arthroplasties seem to be at least partially offset by the approximately two times greater need for rehabilitation in this group. The true safety, efficacy, relative risk, and total cost analysis of simultaneous bilateral total knee arthroplasties demands further critical evaluation.     

Lower homologous blood requirement in autologous blood donors after treatment with recombinant human erythropoietin

The risk of blood-borne diseases has substantially increased the use of autologous blood transfusion. Many autologous donors, however, still need homologous transfusions. To find out whether recombinant erythropoietin (rhEPO) reduces requirements for homologous blood transfusion, we carried out a randomised, controlled trial, in which patients were stratified according to blood volume. We studied 95 autologous blood donors undergoing elective hip surgery. 50 patients were randomly assigned 500 U/kg rhEPO subcutaneously twice a week for 3 weeks, and 45 patients received no treatment (control group). The patients each donated two units of blood before surgery. Only 5 (10%) rhEPO-treated patients received homologous transfusions compared with 16 (36%) controls (p < 0.01). rhEPO was most useful in patients with a blood volume below 4 L and an estimated blood loss below 2 L or with a blood volume of 4-5 L and blood loss of 1-2 L. Continued administration of rhEPO caused no further increase in reticulocyte counts after the fourth injection, which was accompanied by a pronounced depletion of storage iron. rhEPO treatment had no effect on renal function, platelet count, or blood pressure. Subcutaneous rhEPO is an effective and safe way to reduce exposure to homologous blood in autologous donors. Its use can be restricted to a subpopulation of autologous blood donors, which improves the cost-effectiveness of this expensive approach.     

Multicenter trials in the treatment of depression: some methodological issues

BACKGROUND: The indications for transfusion have never been evaluated in an adequately sized clinical trial. A pilot study was conducted to plan larger clinical trials. STUDY DESIGN AND METHODS: Hip fracture patients undergoing surgical repair who had postoperative hemoglobin levels less than 10 g per dL were randomly assigned to receive 1) symptomatic transfusion: that is, transfusion for symptoms of anemia or for a hemoglobin level that dropped below 8 g per dL or 2) threshold transfusion: that is, patients receive 1 unit of packed RBCs at the time of random assignment and as much blood as necessary to keep the hemoglobin level above 10 g per dL. Outcomes were 60-day mortality, morbidity, functional status, and place of residence. RESULTS: Among 84 eligible patients enrolled, mean (+/- SD) prerandomization hemoglobin was 9.1 (+/- 0.6) g/ dL. The median number of units transfused in the threshold transfusion group was 2 (interquartile range, = 1-2), and that in the symptomatic transfusion group was 0 (6; interquartile range, = 0-2) (p < 0.001). Mean hemoglobin levels were approximately 1 g per dL higher in the threshold group than in the symptomatic group: for example, on Day 2, 10.3 (+/- 0.9) g per dL versus 9.3 (+/- 1.2) g per dL, respectively (p < 0.001). At 60 days, death or inability to walk across the room without assistance occurred in 16 (39.0%) of the symptomatic transfusion group and 19 (45.2%) of the threshold transfusion group. Death occurred by 60 days in 5 (11.9%) of the symptomatic transfusion group and 2 (4.8%) in the threshold transfusion group (relative risk = 2.5; 95% CI, 0.5-12.2). Other outcomes were similar for the two groups. CONCLUSIONS: Symptomatic transfusion may be an effective blood-sparing protocol associated with the transfusion of appreciably fewer units of RBCs and lower mean hemoglobin levels than are associated with the threshold transfusion policy. However, it is unknown whether these two clinical strategies have comparable mortality, morbidity, or functional status. A definitive trial is needed.     

The ferredoxin:sulphite reductase gene from Synechococcus PCC7942

Conventional therapies with recombinant human erythropoietin (rHuEPO) to sustain preoperative autologous blood collection entail high doses of the drug at short intervals. To evaluate the efficacy of a single weekly dose of rHuEPO for autologous blood collection, we randomly assigned 24 male patients scheduled for coronary artery bypass surgery to receive 400 IU/kg rHuEPO subcutaneously once a week or iron only. Patients were examined weekly and a total of up to 4 units of autologous blood were obtained if the hemoglobin level exceeded 12 g/dL. Patients receiving rHuEPO had consistently higher hemoglobin values than those receiving iron only (P < 0.001). Consequently, more autologous red cells were obtained from this group (776 +/- 49 mL vs 682 +/- 91 mL; P < 0.05). One patient receiving rHuEPO and eight in the control group required homologous blood at surgery (P < 0.01). These results suggest that 400 IU/kg rHuEPO administered subcutaneously once a week efficiently stimulates erythropoiesis and compensates the hemoglobin decrease after autologous blood donation.     

Erythropoietin therapy in the perioperative setting

Recombinant human erythropoietin has been approved for use in patients undergoing autologous donation in Japan, Europe, and Canada since 1993, 1994, and 1996, respectively, and for perisurgical adjuvant therapy without autologous donation in Canada and the United States since 1996. Early clinical trials of erythropoietin therapy in the setting of autologous donation have provided important information regarding clinical safety, erythropoietin dose, and erythropoietic response. Later trials of perisurgical erythropoietin therapy without autologous donation provided data on efficacy (reduced allogeneic blood exposure) that led to approval of erythropoietin in patients undergoing surgery. However, the erythropoietin doses (300 U/kg subcutaneous x14 days) used in these trials, and their subsequent inclusion in labeling for the use of this product, are costly and tedious to administer. A recent study reported that a weekly regimen of erythropoietin (600 U/kg) for 4 weeks is less costly but just as effective at reducing allogeneic blood exposure in elective orthopaedic surgery. The most cost effective regimen that has been shown to minimize allogeneic exposure is preoperative erythropoietin therapy (600 U/kg subcutaneous weekly x2 and 300 U/kg subcutaneous on day of surgery) coupled with acute normovolemic hemodilution in patients undergoing radical retropubic prostatectomy. A similar regimen of erythropoietin therapy in patients undergoing coronary artery bypass grafting (2500 U/kg subcutaneous in divided doses for 2 weeks preoperatively) coupled with hemodilution also was effective. Low dose erythropoietin therapy coupled with acute normovolemic hemodilution ultimately may be shown to be cost equivalent to the predonation of three autologous blood units before elective surgery.