Survey on the usage of therapeutic erythrocytapheresis in transfusion services in Italy for the treatment of polycythemia vera, secondary erythrocytosis and hemochromatosis.

INTRODUCTION: Erythrocytapheresis, an apheresis treatment which selectively removes red blood cells, is an alternative to therapeutic phlebotomy, over which it has several advantages. Actually there is a high degree of variability in the use of this treatment. This prompted SIdEM (Italian Society of Hemapheresis and Cell Manipulation) to conduct a survey on the use of erythrocytapheresis in the Italian Transfusion Services. The purpose is to monitor this activity in the treatment of Polycythemia Vera (pv), secondary erythrocytosis and hemochromatosis. MATERIALS AND METHODS: A data collection file was sent to the SIdEM regional delegates who, in turn, involved the Transfusion Centers in the areas they cover. The data collected were processed on a Microsoft Excel spreadsheet. RESULTS: 75 centers from 14 Italian regions responded to the Survey: 36 centers (48 %) use erythrocytapheresis (35 centers perform therapeutic apheresis and 1 center only donor apheresis), 39 centers (52 %) do not (15 centers perform therapeutic apheresis, 18 centers only donor apheresis and 6 centers do not perform either therapeutic apheresis or donor apheresis). Although most centers have a substantially uniform attitude concerning the indications for which erythrocytapheresis is used, the survey shows that there are still differences more evident in the treatment of secondary erythrocytosis than in the treatment of pv or hemochromatosis. CONCLUSIONS: This survey has been useful to document the current Italian reality and to raise awareness about the need for improvement in optimizing and standardizing the use of a therapy with a great potential to exploit properly.

Proposal of an algorithm to help the choice of the best transfusion strategy.

Autologous blood donation (ABD) reduces both the real and perceived risks of allogeneic blood exposure, although wasted units increase overall costs. Wastage of autologous blood can be contained by using rational blood ordering and collection strategies. These identify procedures with transfusion requirements, utilizing ABD predeposit in patients undergoing surgery for which the need for blood transfusion has been clearly established, and where the average blood loss for each procedure has been determined. ABD programmes can be optimized by adopting a personalized approach for each individual patient. The predicted and tolerated blood loss is calculated for each patient, and the difference between the two determines the patient's transfusion need. Taking into account the type of surgery, time to surgery and the clinical condition of the patient, the best and most cost-conscious transfusion strategy can then be determined. Options include: reducing the blood loss pharmacologically, transfusing allogeneic blood, using autologous blood from a variety of techniques, using recombinant erythropoietin (epoetin alfa) to increment baseline haematocrit (Hct) or to increase the volume of predonated blood, and using blood substitutes in addition to autotransfusion techniques. Autotransfusion techniques available include ABD predeposit, normovolaemic haemodilution and perioperative salvage. ABD predeposit may be limited by the delay in the natural erythropoietic response to allow recovery of red cells collected. Together with adequate iron support, epoetin alfa accelerates recovery of the Hct and increases the tolerated blood loss. The availability and judicious use of these blood conservation strategies provide for both effective and cost-conscious blood transfusion strategies.

[Blood transfusion in oncologic surgery: the role of recombinant human erythropoietin (rHuEPO)]. / La trasfusione di sangue nella chirurgia oncologica: ruolo della eritropoietina ricombinante umana (rHuEPO).

Anemia is common in cancer patients. The pathophysiology is multifactorial, however the most common cause is the anemia of chronic diseases (ACD). In 20-50% of cancer patients, anemia restricts physical activity and quality of life and requires transfusion support. The percentage of patients necessitating transfusion dramatically increases when patients require surgery. The traditional belief that blood transfusion is an effective and safe therapy has been challenged by a heightened awareness of the infectious and immunologic risks associated with allogeneic blood administration. In cancer patients transfusion-induced immunomodulation may have the potential to significantly increase postoperative infections and cancer recurrence so that it seems reasonable to minimize allogeneic blood exposure. Several strategies have been adopted to reduce allogeneic transfusion in surgical patients, however to properly select the appropriate blood conservation strategies the blood transfusion requirements for each patient should be defined. Allogeneic blood transfusion in surgery can be reduced by the introduction of autologous blood (AB) programmes and by the use of rHuEPO, alone or in association with AB techniques. AB donation is currently a standard of care for elective surgical patients but its efficacy is limited by anemia that prevents the donation of the optimal number of AB units. rHuEPO has been shown to significantly increase the volume of AB that anemic patients can predeposit or, used perisurgically, to expand the circulating RBCs mass before surgery. Moreover clinical trials employed rHuEPO in anemic cancer patients with various solid tumors both on and off chemotherapy reporting a significantly increase in Hct in more than 50% of the treated patients. Recently different studies have shown the efficacy of rHuEPO in increasing the volume of AB also in patients with ACD and cancer, thus proving to be a useful addition to existing strategies of blood conservation to minimize exposure to allogeneic blood in surgical cancer patients.

Autotransfusion program: integrated use of different techniques.

A successful autologous program should enroll all appropriate patients, conserve homologous blood and minimise the exposure to the risks of donor blood. A program of autotransfusion and proper use of blood has been implemented since 1980 with the objectives to include all eligible patients and to transfuse autologous blood only. The following strategies were adopted: critical review of transfusion indications; control of overtransfusion; avoidance of waste; systematic and integrated use of all autotransfusion techniques currently available. Results in 1992 in elective surgery: 98% enrollment, 75% blood conservation. Exposure to homologous blood was completely avoided in 53% of the cases.

One-year use of the Bloodloc system in an orthopedic institute.

UNLABELLED: Human error in patient or specimen identification due to fatigue, stress and lack of attention by technologists, nurses, interns, and physicians, can cause routinely safety procedures to be circumvented. Clerical errors may occur during the specimen collection, the issue of blood unit and the transfusion of blood. The introduction in an increasing number of hospital of preoperative autologous blood donation programs further increases the chance of error, because a single patient can predeposit multiple units of blood. In this cases there is a greater commitment not only to transfuse any blood unit that is ABO compatible but to transfuse the specific units the patient previously donated for his own use. Human error has been recognized as a significant cause of transfusion-associated fatalities. The persistence of the frequency and type of errors observed in spite of extensive efforts to eradicate them, suggests that errors are inevitable as long as large number of repetitive procedures are performed unless major system changes are adopted. A system (Bloodloc System) that physically prevents the possibility of error was adopted since January 1993 and cuncurrently a quality improvement program (QI) was implemented specifically designed to monitor: 1. the absence of the code on the blood samples, 2. the blood bank error in setting the Bloodloc, 3. the misidentification of blood samples, 4. any attempt to transfuse the wrong blood unit, 5. any attempt to transfuse, the wrong patients. RESULTS: 4895 blood units (2469 autologous and 2426 allogeneic units) were transfused to 1478 patients (849 predeposited an average of 3.3 +/- 2.0 units). The methodological errors (absence of three-letter code on the patient's specimen tube, wrong transcription of the code on the blood sample, wrong setting of the Bloodloc in the blood bank)--41 cases--were limited at the first four months of implementation of the system. In the same period however have been reported 3 potentially fatal errors which have been avoided by the Bloodloc. Two cases of misidentification of blood samples at the moment of the specimen collection, and one attempt to transfuse the wrong units to the wrong patients. CONCLUSIONS: The Bloodloc system is effective in preventing potential transfusion-associated fatalities caused by units or recipients misidentification.

Transfusion risks and limitations.

The safety of the blood transfusion therapy has dramatically increased over the last few years because of improvements in donor screening, testing of donated blood and pre-transfusion tests. However blood transfusion can never be seen as a risk free procedure. The risks to which the patients receiving blood are exposed are infectious, immunologic and other non infectious, non immunologic hazards. Transmission of viral, bacterial and protozoal infections is probably the greatest concern associated with allogeneic blood transfusion. While the risk of transmitting viruses is now very small, there is an increasing concern regarding bacterial contamination of donated blood. Among immunological sequelae, beside alloimmunization, are fever and chills, allergic and acute hemolytic reactions, the last being the currently most important cause of deaths associated with blood transfusion. Moreover allogeneic blood transfusion may lead to immunosuppression, which may increase the risk of infection and cancer recurrence. Other non infective pulmonary edema and physical and biochemical alterations (such as hypothermia, electrolyte and acid base disturbances).

The potential role of oxygen-carrying products in autologous blood transfusion protocols.

For surgical patients transfusion of autologous blood (AB) is the most useful of measures to reduce patient's exposure to homologous blood (HB). In our Institute an autotransfusion program was started in 1982 utilizing all the autotransfusion techniques currently available. The integrated use of the techniques offered to the majority of the patients the possibility of receiving AB (98% of the elective surgery patients) and a consistent conservation of HB has been achieved (60-70%). However 42% are still exposed to some HB. Critical parameters that render the patients unable to fulfill the anticipated transfusion needs with the current AB transfusion techniques are: the patient's ability to predonate sufficient AB prior to surgery and the amount of blood transfused intraoperatively that in turn depends on different "transfusion trigger". In our Institute over 50% of all the blood units are transfused the day of operation (60% being AB, 40% HB) and 50% postoperatively (only 33% being AB). For this reason, a clinical application for the oxygen-carrying products can be the replacement of the blood lost during, or immediately after the operation permitting the surgeon to operate safely at a lower Hct levels, thereby delaying the transfusion of blood and saving the AB obtained.

Epoetin alfa in low hematocrit patients to facilitate autologous blood donation in total hip replacement: a randomized, double-blind, placebo-controlled, dose-ranging study.

We investigated the safety and efficacy of preoperative epoetin alfa used in conjunction with preoperative autologous blood donation (PAD) in 40 anemic orthopedic surgical patients undergoing hip replacement surgery [hematocrit (Hct)

Autologous blood pre-deposit and cell salvage in orthopedic surgery.

A successful autologous blood program should enrol all appropriate patients, conserve homologous blood and minimize the exposure to the risks of donor blood. A program of autotransfusion and proper use of blood has been implemented since 1980 with the objectives of including all eligible patients and to transfuse autologous blood only. The following strategies were adopted: critical review of transfusion indications; control of over-transfusion; avoidance of waste; systematic and integrated use of all autotransfusion techniques currently available. Results in 1992 in elective surgery: 98% enrolment, 75% blood conservation. Exposure to homologous blood was completely avoided in 53% of the cases.

Use of erythropoietin to increase the volume of autologous blood donated by orthopedic patients.

For patients who donate blood for autologous use and undergo major orthopedic surgery, low basal hematocrit (Hct) is the major cause of allogeneic blood exposure. To determine whether recombinant human erythropoietin (rHuEPO) could increase autologous blood procurement and reduce allogeneic blood exposure, a prospective randomized study was conducted in 50 women undergoing total hip replacement who had basal Hct < 40 percent (0.40). Patients were randomly placed in three groups: those receiving placebo, those receiving 300 U of rHuEPO per kg, and those receiving 600 U of rHuEPO per kg every 3 to 4 days for 21 days. Oral iron (125-270 mg/day) was given; in the last 24 patients, 100 mg of iron saccharate was administered intravenously at each donation. At each visit, 350 mL of blood was collected if Hct was > or = 34 percent (0.34). Patients receiving rHuEPO donated a greater amount of blood for autologous use than did patients in the placebo group (4.5 +/- 1.1 vs. 2.8 +/- 0.6 units; p < 0.05) and received a significantly lower amount of allogeneic blood (1.2 +/- 1.4 vs. 0.4 +/- 0.8 units; p < 0.05). No difference between the effects of the two doses of rHuEPO was observed. Iron support was a critical factor in the efficacy of treatment. No untoward effects were observed. The rHuEPO emerged as a safe and effective treatment, with adequate iron support, by which to increase preoperative deposit of autologous blood and to reduce exposure to allogeneic blood for patients with low basal Hct.

Bedside transfusion errors: analysis of 2 years' use of a system to monitor and prevent transfusion errors.

Clerical errors occurring during specimen collection, issue and transfusion of blood are the most common cause of AB0 incompatible transfusions. 40-50% of the transfusion fatalities result from errors in properly identifying the patient or the blood components. The frequency and type of errors observed, despite the implementation of measures to prevent them, suggests that errors are inevitable unless major changes in procedures are adopted. A fail-safe system, which physically prevents the possibility of error, was adopted in January 1993 and concurrently a quality improvement program was implemented to monitor any transfusion errors. Up to December 1994, 10,995 blood units (5,057 autologous and 5,938 allogeneic) were transfused to 3,231 patients. Seventy-one methodological errors(1/155 units) were observed, half of which were concentrated during the first 4 months of introducing the system. However the system detected and avoided four potentially fatal errors (1/2,748 units). Two cases involved the interchanging of recipient sample tubes, 1 case was due to patient misidentification and the other involved misidentification of blood units. In conclusion the system is effective in detecting otherwise undiscovered errors in transfusion practice and can prevent potential transfusion-associated fatalities caused by misidentification of blood units or recipients.

Comparison between intravenous and subcutaneous recombinant human erythropoietin (Epoetin alfa) administration in presurgical autologous blood donation in anemic rheumatoid arthritis patients undergoing major orthopedic surgery.

BACKGROUND AND OBJECTIVES: Intravenous (i.v.) Recombinant erythropoietin (Epoetin alfa) is effective in allowing autologous blood donation in patients unable to donate because of anemia. We undertook this open pilot study in order to asses whether a low subcutaneous (s.c.) dose of Epoetin alfa would prove as effective and well tolerated as the higher i.v. dose. Such a move would also decrease costs. MATERIALS AND METHODS: A total Epoetin alfa s.c. dose of 800 IU/kg was compared with a total i.v. dose of 1,800 IU/kg. Twenty-two rheumatoid arthritis patients, unable to donate because of hemoglobin (Hb) < 11 g/dl, received 300 IU/kg of IV Epoetin alfa twice weekly for 3 weeks (11 patients), or 100 IU/kg of s.c. Epoetin alfa twice weekly for 3 weeks plus an i.v. bolus of 200 IU/kg of Epoetin alfa at the first visit (11 patients). At each visit, all patients received 100 mg of i.v. iron saccharate and when the hematocrit (hct) > or = 34%, 350 ml of autologous blood (AB) were collected. RESULTS: No significant differences were observed between the 2 groups of treated patients in terms of units of AB collected (2.6 +/- 0.6 vs. 2.5 +/- 0.5 units for i.v. and s.c. groups, respectively), ml of RBC produced during the study period (291 +/- 99 vs. 337 +/- 65 ml for the i.v. and s.c. groups, respectively), or in the degree of reduced exposure to allogeneic blood in comparison with the control group. CONCLUSIONS: Lower dose of Epoetin alfa (reduced by 56%), supplemented by i.v. iron, is as effective and well tolerated as higher doses administered i.v., supplemented by i.v. iron.

Use of recombinant human erythropoietin to assist autologous blood donation by anemic rheumatoid arthritis patients undergoing major orthopedic surgery.

BACKGROUND: In rheumatoid arthritis (RA) patients undergoing orthopedic surgery, anemia is the major factor in the use of allogeneic blood. STUDY DESIGN AND METHODS: To determine whether recombinant human erythropoietin (rHuEPO) could allow preoperative autologous blood procurement and reduce allogeneic blood exposure, 11 RA patients who were unable preoperatively to deposit blood for autologous use because of their anemia (baseline hematocrit < 34% [0.34]) and who were scheduled for primary total hip replacement or total knee replacement were treated intravenously with 300 U per kg of rHuEPO in combination with intravenous iron saccharate (100 mg), given twice weekly for 3 weeks. The transfusion treatment was compared with that in 12 control patients with comparable baseline hematologic values who underwent the same operation. RESULTS: Control patients could not preoperatively deposit any blood for autologous use, while all but one of the rHuEPO-treated patients deposited 2 or more units (mean, 2.6 +/- 0.6; range, 2-4) (p < 0.001). The control group received more allogeneic units (2.6 +/- 1.6 vs. 0.8 +/- 0.8) (p = 0.009). Moreover, 50 percent of the rHuEPO-treated patients, as compared with 8 percent of controls, completely avoided allogeneic transfusion. CONCLUSION: Recombinant human erythropoietin is safe and effective in stimulating erythropoiesis, allowing preoperative donation of blood for autologous use, and reducing exposure to allogeneic blood for RA patients who are unable preoperatively to deposit blood because of anemia.