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.     

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.     

Efficacy of oral iron supplementation is not enhanced by additional intravenous iron during autologous blood donation

BACKGROUND: The study compared the efficacy of oral iron combined with intravenous iron supplementation to that of oral iron supplementation alone in increasing the preoperative production of hemoglobin (Hb) in autologous blood donors with normal iron stores. STUDY DESIGN AND METHODS: One hundred eight iron-replete patients who were scheduled for donation of 3 units of autologous blood at weekly intervals were randomly assigned to receive, in a double-blind fashion, no iron supplementation (placebo, Group 1), oral iron supplementation (285.6 mg of elemental iron/day, Group 2), or oral iron plus intravenous iron supplementation (285.6 mg of elemental iron/day orally plus 102.5 mg of elemental iron/week intravenously, Group 3). The amount of Hb produced during the 21-day study period was determined by the total amount of Hb donated minus the change in the amount of circulating Hb between the first donation (Day 0) and the poststudy examination (Day 21). RESULTS: Hb production did not differ significantly in the two iron-supplemented groups (oral iron, 85 +/- 36 g; oral plus intravenous iron, 74 +/- 43 g). The patients in the oral iron group produced a significantly greater amount of Hb than those in the placebo group (85 +/- 36 g vs. 52 +/- 41 g, p < 0.01). CONCLUSION: Oral iron supplementation increased the production of Hb in autologous blood donors more than placebo did. Additional intravenous iron did not lead to a further increase in preoperative Hb production.     

Polymorphisms of the human beta-defensin-1 gene

Erythropoietin (EPO) plasma levels were monitored during the perioperative period in 61 consecutive patients (22 males - 39 females), aged 62.5 +/- 9.5 years, scheduled for hip arthroplasty. All patients underwent intraoperative blood salvage (IOBS) and were subdivided into three different groups according to their hemoglobin levels (Hb) 24 hours postoperatively (group A: Hb < 8 g/dl; group B: Hb between 8-9 g/dl; group C: HB > or = 9 g/dl). Seventy-two hours after surgery EPO levels were significantly different in group A (135 +/- 68) compared to group C (54.3 +/- 32), with a positive correlation (p < 0.01) between Hb and EPO levels. On the basis of these results we suggest that a programmed autologous red blood cell collection aimed at obtaining the lowest hemoglobin values during the first 24 hours after surgery, may be of clinical utility in preventing homologous blood needs.     

Predictors of transfusion risk in elective knee surgery

Two hundred seventy-nine patients undergoing primary unilateral total knee replacement and 280 patients undergoing primary bilateral total knee replacements were reviewed retrospectively. Patients' height, weight, hemoglobin level before donation, hemoglobin level before surgery, autologous donation, number and type of transfusions whether autologous or allogeneic, and hemoglobin at discharge were collected from hospital and clinic records. The average drop in hemoglobin was 3.85 g/dL in the group of patients undergoing unilateral total knee replacement and 5.42 g/dL in the group of patients undergoing bilateral total knee replacements. The preoperative hemoglobin and blood volume seemed to be very strong, statistically significant predictors of transfusion risk in single and bilateral knee replacements. In unilateral total knee replacement, patients with a hemoglobin of greater than 13 g/dL had only an 8% chance of transfusion and if they donated autologous blood, 66% of the blood was wasted. Preoperative anemia was a strong predictor of transfusion risk in patients undergoing unilateral and bilateral total knee replacements and carried a very high allogeneic transfusion exposure risk, even in patients who had donated blood preoperatively. A nomogram was developed using blood volume and predonation hemoglobin to predict transfusion risk and need to predeposit autologous blood in patients undergoing unilateral and bilateral total knee replacements.     

Intraoperative aspiration and reinfusion of autologous blood in resection of abdominal aortic aneurysms with Solcotrans plus

Quantitative and qualitative assessment of intraoperative aspiration and reinfusion of autologous blood with the Solcotrans was carried out in 11 males (52-79 years) undergoing elective resection of abdominal aortic aneurysms. Hematology, blood chemistry, coagulation parameters and complement activation were studied in the patient's blood at the following time points: preoperatively, before and after heparinisation, after retransfusion of the first and last Solcotrans, 6 and 20 hours postoperatively. In addition the same quality control was performed in the first and last Solcotrans blood. Results (mean values of 11 patients +/- 1 SD): Intraoperatively 2-3 Solcotrans units were salvaged (total 1039 +/- 565 ml) of which 805 +/- 487 ml were retransfused to the patients. As a mean patients required only 1 unit of homologous RBC's (395 +/- 781 ml) intraoperatively. Patient's intraoperative hemoglobin concentration amounted to 10 g/dl or more. Whereas the hemoglobin level in the Solcotrans attained only 8.2 g/dl. Thrombocyte counts (48 +/- 18 x 10(9)/l) and ionized calcium (0.2 +/- 0.4 mmol/l) were significantly depressed when compared to the preoperative patient values (p < 0.05). The protein concentration remained within normal limits in the patient's and in the Solcotrans blood. Complement activation (C4a, C5a [des Arg]) showed a significant increase after initiation of surgery and there was no significant difference between the solco- or patient blood. Whereas plasma free hemoglobin, coagulation and fibrinolysis parameters showed a significant elevation in the Solcotrans blood. In conclusion the solcotrans system offers a fast, efficient and simple method for salvage and retransfusion of intraoperative autologous blood.     

Computed tomography of the head by the accident and emergency department--why 24 hour access is vital

A 50-year-old man was admitted to our hospital for possible surgery. Echocardiogram showed severe calcification of the aortic valve, and cardiac catheter examination recorded a gradient greater than 150 mmHg across the valve. These results determined aortic valve replacement (AVR) to relieve the pressure-overloaded ventricle. Preoperative evaluations however, demonstrated anemia derived from hereditary spherocytosis (HS), an inherited hemolytic disorder. In order to avoid homologous blood transfusion, the following strategies were tried; 1) an iron supplement and an injection of recombinant human erythropoietin (rHuEPO); 2) pre- and perioperative autologous blood transfusion; and 3) an aggressive iron supplement just after the surgery. These raised the blood hemoglobin concentration to the criterion where autologous blood donation was started, and maintained the hemoglobin level stable, up to his discharge. In conclusion, bloodless cardiac surgery is possible for cases with anemia, and some strategies should be tried to raise and maintain the blood hemoglobin concentration well.     

Studies of the elderly in Boston. I. The effects of iron fortification on moderately anemic peole

It has been reported that large numbers of elderly Americans are moderately anemic because of iron deficiency anemia. In the present study, information has been obtained concerning blood composition, health, and nutritional habits of 779 people over 60 years of age, institutionalized or free-living in the Boston area. This paper presents the results of their blood examinations. Two hundred twenty-one of the free-living people examined who showed hemoglobin levels between 9 and 12.9 g/dl agreed to participate in an iron fortification study. Two-thirds of them received iron-fortified grain products daily for 6 to 8 months. The rest received the same foods without added iron. At the end of the experimental period a marked increase in hemoglobin levels averaging 1.4 g/dl was observed in both groups. This appeared to be attributable to an undefined intervention effect; no measurable effects attributable to the iron fortification were observed. Three months of daily ferrous sulfate administration to those whose hemoglobin levels remained below 13 g/dl was without effect. Examination of the data obtained suggests that the cause of the moderately low hemoglobin levels initially observed was not occult bleeding or folic acid or iron deficiency.     

Hemodilution in clinical surgery: state of the art 1996

Acute normovolemic hemodilution entails removal of blood from a patient either immediately before or shortly after induction of anesthesia and simultaneous replacement with cell-free fluid. Nowadays, because of their predictable volume effects, the synthetic colloids (6% dextran 60/70, 6% hydroxyethyl starch 200,000) are preferred as volume substitutes; albumin should be avoided because of its high cost. Hemodilution has experienced a renaissance in recent years, mainly due to the evolving discussion of legal aspects, immunologic changes, viral infections, and a potentially higher cancer recurrence rate associated with the transfusion of homologous blood. Hemodilution should be considered for elective surgical patients free of contraindications and presenting with an initial hemoglobin concentration >/= 12 g/dl and an anticipated blood loss of >/= 1500 ml. The efficacy of this method (judged by the need to give homologous blood transfusion) depends on the preoperative (initial) hematocrit, the target hematocrit (to which hemodilution is performed), and the preset intra- and postoperative transfusion trigger. In the past, data from clinical trials showed that in healthy subjects a target hematocrit of 20% to 25% (hemoglobin 7.0-8. 0 g/dl) is feasible and safe for the patient. The lower the target hematocrit accepted, the more extensive is the monitoring required: Intraoperative target hemoglobin concentrations of 5.0 g/dl and less have been tolerated by surgical patients without adverse effects. The safety and efficacy of acute normovolemic hemodilution in terms of reducing homologous blood transfusion requirements has been demonstrated in various clinical studies. Hemodilution therefore is regarded an integral part of programs aimed at reducing the need for homologous blood and can thus be successfully combined with preoperative autologous blood deposition, intraoperative blood salvage, and carefully adjusted surgical techniques. Hemodilution is feasible and relatively cost-effective, and it minimizes adverse effects associated with transfusion of homologous blood, particularly transmission of viral diseases, immunosuppression, and infectious complications.     

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.     

Zinc protoporphyrin (ZPP) in diagnosis of anemia

In iron deficiency, zinc protoporphyrin (ZPP) is produced instead of heme, and the ZPP concentration in erythrocytes increased (normal value < 2.3 micrograms ZPP/g Hb). The ZPP level and comparison with the other normally used tests in iron deficiency in the group of the patients with iron deficiency, ACD, MDS, AML, plasmocytoma was investigated. The ZPP level was determined by hematofluorometry in samples from 96 patients. Thirty five patients with iron depletion showed decreased both serum ferritin (median 5.9 ng/ml), and hemoglobin level (median 9.8 g/dl) with significantly increased ZPP level (median 8.5 micrograms/gHb). An increased level of ZPP (median 3.95 micrograms/gHb) with normal level of ferritin (median 24 ng/ml) and iron (median 50 (g/dl) in the serum of patients with ACD was determined. Measurement of ZPP level in the combination with ferritin and peripheral blood morphology allows to classify the degree of iron deficiency. The ZPP levels higher than 4.55 micrograms/gHb confirms iron deficiency in the group of anaemic patients.     

Anti-ulcerogenic activity of GABA and GABA mimetic agents in rats

Erythropoietin, the hematopoietic growth factor, is synthesised in the kidneys and liver and regulates red blood cell production. Within the last few years, recombinant DNA technology has produced synthetic erythropoietin (rhEPO). Some patients, especially Jehovah's Witnesses, will not accept blood transfusion. The perioperative administration of rhEPO increases the patients' hematocrit (HCt) to a higher than physiological level. METHODS AND RESULTS: We report a case of a 66-year-old female Jehovah's Witness who refused blood transfusions and responded favourably to rhEPO treatment. A total hip arthroplasty was planned. A pretreatment hemoglobin level (Hb) of 13.7 g/dl and HCt of 43% were documented. After preoperative subcutaneous application of 5000 I.E. rhEPO three times per week and daily oral substitution of 300 mg ferrous sulfate over a period of 3 weeks, the Hb increased to 15.5 g/dl and the HCt to 49%. The operation was carried out after the ninth application of rhEPO. Postoperatively, the Hb concentration was 11.8 g/dl and the HCt 35%. Therefore, postoperative administration of rhEPO was not considered indicated. No side effects of rhEPO application were noted. The patient left hospital on the 10th postoperative day. CONCLUSIONS: The case report describes perioperative management using human rhEPO in Jehovah's Witnesses. Treatment with rhEPO increases preoperative Hb levels to a point making it possible to compensate for operative blood loss. RhEPO combined with daily iron substitution may be useful in patients who refuse transfusion based on religious convictions.     

Increased autologous blood donation in rectal cancer by recombinant human erythropoietin (rhEPO)

A randomised, placebo-controlled trial was conducted to study whether the subcutaneous administration of recombinant human erythropoietin (rhEPO) increases the donated red cell blood volume in patients with rectal cancer. Patients with resectable rectal cancer and a haemoglobin (Hb) level > or = 12.5/ > 12 g/dl (males/females) were scheduled to receive pre-operatively either erythropoietin (200 U/kg body weight daily) (n = 28) or placebo (n = 26) subcutaneously for 11 days. During this period autologous blood was collected. No serious adverse events were attributed to erythropoietin. 20 of 28 patients treated with rhEPO were able to donate > or = 3 units (71%) compared with 11 of 26 control patients (42%). The mean cumulative volume of red cells donated was 29% higher in the patients who received rhEPO (571 versus 444 ml, P = 0.02). The change in the mean reticulocyte value from baseline to the last pre-operative value was significantly higher in the rhEPO group (10.4 to 61.6/1000 versus 11.0 to 20.1/1000, P = 0.0001). The fall in the mean haematocrit from baseline to the last pre-operative value was significantly lower in the rhEPO group (41.4 to 37.6% versus 41.8 to 34.8%, P = 0.0004). rhEPO increases the ability of cancer patients to donate autologous blood during a short pre-operative period and enhances the restoration of haematological values after the donation period.     

Hydrogen peroxide induces protection against lethal effects of cumene hydroperoxide in Escherichia coli cells: an Ahp dependent and OxyR independent system?

Despite a large body of evidence showing the beneficial effects of successful treatment of anemia with recombinant human erythropoietin (EPO) in patients with end-stage renal disease, controversy remains as to whether EPO treatment of anemia can improve the nutritional status in patients on maintenance hemodialysis. This prompted us to conduct a prospective study in 41 hemodialysis patients with basal hemoglobin less than 9 g/dl. The dose of EPO was increased for 12 weeks to achieve the target hemoglobin concentration of 10 g/dl and then titrated in the following 12 weeks to maintain the target value. Nutritional status was assessed at baseline and after 6 months of follow-up, using the global protein-calorie malnutrition (PCM) index proposed by Bilbrey and Cohen. A low global PCM score indicates better nutrition. The results showed that hemoglobin values significantly increased from 8.7 +/- 0.8 g/dl at baseline to 10.7 +/- 0.5 g/dl in the 6th month (p < 0.001). No significant changes were observed in the normalized protein catabolic rate and Kt/V during the study period. Global PCM scores improved from 30.0 +/- 7.5 to 23.6 +/- 3.1 (p < 0.001) and paralleled the correction of anemia by EPO treatment. The data were consistent with a major improvement in the nutritional markers of relative body weight, triceps skinfold, midarm circumference, midarm muscle circumference, serum albumin, serum transferrin and total lymphocyte count in the 6th month as compared to baseline. The percentages of mild and moderate-severe PCM at baseline were 32 and 58%, respectively. These percentages were significantly reduced during the 6th month to 20 and 30%, respectively (p = 0.0004). In summary, correction of renal anemia with EPO improves the nutritional status in hemodialysis patients. A postulated mechanism is that EPO may exhibit anabolic effects, with a better utilization of ingested protein.     

Lipids and stroke: a paradox resolved

The usual methods like hypotension, isovolaemic haemodilution, autologous transfusion and peri-operative blood salvage may significantly reduce the need for homologous blood transfusion in haemorrhagic surgery and also the risk of transmitting infectious agents. Erythropoietin (EPO) is now available and is used to stimulate red cell regeneration in pre-operative autologous blood donation. In acute anaemia, many studies have shown that the stimulation of endogenous erythropoietin production could be very high and accelerate red blood cell production. Taking higher quantities of blood than usual induces a secretion of endogenous erythropoietin, and could be an alternative for the utilization of exogenous EPO in 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.     

Autologous blood retransfusion in transurethral resection of prostate (TURP)]

Blood collected from the irrigation fluid used during TURP was retransfused in 17 patients. Of the 17 patients, 8 cases were also transfused preoperatively reserved blood. The weight of resected adenoma (g), resection time (minutes), the volume of salvaged blood (ml) of 9 cases who were transfused only salvaged autologous blood were 30.6 g, 63 min. and 355 ml, respectively, and those of 8 patients who were given both salvaged and preoperatively reserved autologous blood were 46.1 g, 78 min. and 703 ml, respectively. No patient was transfused homologous blood. Preoperative urine cultures showed contamination of bacteria in 12 cases (70.6%), and the blood concentrated from irrigated fluid was positive for bacteria in 2 cases (11.8%). Blood count (RBC, Hb, Ht) just after TURP, after blood retransfusion, at the next and the 7th day after the operation were compared to those of just before TURP (Blood Count Ratio). The ratio of the 9 cases who received only salvaged blood were 83.5%, 96.8%, 90.9%, 85.2% each and the ratio of the 8 cases who were transfused both salvaged and preserved blood were 86.9%, 102.6%, 101.4%, 97.5% each. There were no adverse effects due to the autologous blood retransfusion. Conclusion: Retransfusion of salvaged autologous blood from the irrigating fluid of TURP was clinically safe and effective. No homologous blood was transfused in TURP when salvaged autologous blood with or without preserved blood was retransfused to the patient.     

Intraoperative blood salvage in children and young adults undergoing spinal surgery with predeposited autologous blood: efficacy and cost effectiveness

We conducted a retrospective review of 155 spinal operations at our institution to determine the efficacy of intraoperative salvage. Addition of intraoperative salvage had little effect on the success of a preoperative autologous donation program. Only patients with operative blood loss > 2,000 ml (12% of patients) benefited from this expensive source of autologous blood. The technique tended to be most effective in children aged 16-18 years. Use of intraoperative salvage for all pediatric spinal procedures is neither necessary nor cost effective.     

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.