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).

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)

[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.

[The role of human recombinant erythropoietin in oncologic surgery]. / Ruolo dell'eritropoietina umana ricombinante rHuEPO nella chirurgia oncologica.

Anemia is common in cancer patients, especially in those with more advanced stages of progressive tumor growth, the frequency varying on type of cancer, stage and chemotherapy or radiation therapy used. The pathophysiology is multifactorial. However the most common anemia is the anemia whose features are similar to those seen in other chronic diseases (anemia of chronic disease--ACD). The pathophysiological mechanisms are: a mild decrease in red blood cells survival, a decreased re-utilization of bone marrow iron stores and an inadequate erythropoietin response to the degree of anemia. When anemia cannot be corrected through the administration of hematinics and anemia is severe enough to significantly restrict physical activity and quality of life, blood transfusion is requested. It has been reported that the percentage of patients requiring transfusion ranges from 20 to 50%. The transfusion of allogeneic blood exposes the recipient to immunological and infectious risks. There is evidence that allogeneic blood transfusions can have immunologic consequences and some argue that these immune changes can adversely affect the prognosis in cancer patient. Although this is still controversial, until it can be shown that blood transfusion is not harmful in the long term to patients with cancer, it seems reasonable to avoid it whenever possible. Recently the availability of recombinant DNA technology permitted large scale production of recombinant human erythropoietin (rHuEPO). To date several clinical trials employed rHuEPO in anemic cancer patients with various solid tumors both on and off chemotherapy. All these studies have reported a significantly increase in Hct than placebo in more than 50% of the treated patients. The problem of correcting anemia and of blood transfusion is even more important when cancer patients become candidate to major surgery. In such situation, the transfusion of a consistent number of units is generally required to cover the surgical blood loss. The use of homologous blood in surgery can be substantially reduced by the introduction of autologous blood transfusion (ABT) programmes in association with rHuEPO. A number of experimental and clinical studies on the effects of rHuEPO on AB donation and on erythropoiesis in the peri-operative period have demonstrated that it resulted to be effective in stimulating erythropoiesis, with a consequent increase in the volume of red cells produced during the course of treatment and in the number of units predeposited. It was also effective in correcting anemia induced by collection of blood units. The efficacy of rHuEPO in increasing the volume of autologous blood the patient can predeposit before surgery has been demonstrated also in patients with ACD and cancer. No significant adverse effects of rHuEPO administration have been reported in any of the studies published to date. It can be concluded that rHuEPO therapy may be safe and effective in selected surgical patients, in stimulating erythropoiesis, in expanding the circulating RBCs mass, in increasing the volume of AB that can be collected pre-operatively and, consequently, in reducing the exposure to homologous blood. Therapy with rHuEPO may prove to be a useful addition to existing strategies of blood conservation to minimize exposure to HB.

Practical methods to improve transfusion safety by using novel blood unit and patient identification systems.

Human error is a leading cause of transfusion-associated death. Many of these events are associated with a failure to comply with established unit-recipient identification protocols. Although several dedicated systems designed to minimize this problem are currently available, none of them have been sufficiently challenged by the various conditions that exist in diverse clinical settings. However, data available for computer-based recognition procedures and for a disposable blood bag combination lock, which precludes access to the blood before it is properly identified, are encouraging.

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.

Epoetin alfa increases the volume of autologous blood donated by patients scheduled to undergo orthopedic surgery.

In patients scheduled to undergo major orthopedic surgery, predonation of autologous blood (AB) has emerged as a means of avoiding subsequent exposure to allogeneic blood. However, patients with a baseline hematocrit (Hct) less than 40% may not be able to donate sufficient AB to fully meet their requirements. In female patients with a baseline Hct < or = 39%, epoetin alfa (300 to 600 IU/kg twice weekly for 3 weeks) significantly increased the amount of AB donated prior to elective orthopedic surgery and significantly reduced allogeneic blood requirements in comparison with placebo. Iron availability was a critical factor in determining the response to epoetin alfa. In these patients, parenteral supplementation with iron saccharate significantly increased the amount of AB donated and the volume of red blood cells (RBCs) collected in comparison with oral iron alone. Parenteral iron supplementation, therefore, ensures that sufficient iron is available to meet the demands of epoetin alfa-accelerated erythropoiesis in patients enrolled in an AB donation program.

Epoetin alfa for autologous blood donation in patients with rheumatoid arthritis and concomitant anemia.

In patients scheduled for major orthopedic surgery, the presence of anemia can preclude the donation of sufficient autologous blood (AB) to meet transfusion requirements. Although a number of studies have investigated the use of epoetin alfa (in conjunction with parenteral iron supplementation) to facilitate AB donation and reduce exposure to allogeneic blood in this patient population, the optimum treatment regimen and route of administration has yet to be defined. In rheumatoid arthritis (RA) patients with a low predonation hematocrit (Hct; < or = 39%), intravenous (i.v.) treatment with epoetin alfa 300 IU/kg twice weekly for 3 weeks was the optimum dosage for facilitation of AB donation and minimization of the decrease in Hct prior to elective orthopedic surgery. However, the subcutaneous (s.c.) route of epoetin alfa administration may allow lower dosages of epoetin alfa to be used. Indeed, epoetin alfa 100 IU/kg s.c. twice weekly for 3 weeks (in conjunction with a single i.v. bolus of 200 IU/ kg at the first s.c. dose) was as effective as 300 IU/kg i.v. administered according to the same schedule. The number of AB units collected, total red blood cell (RBC) volume donated, and peak proportion of reticulocytes were similar regardless of the route of administration. Both treatment groups were associated with a significant reduction in allogeneic blood exposure compared with historical controls. Findings consistent to all of these studies were that epoetin alfa was well tolerated, and that i.v. iron supplementation was necessary to maximize its beneficial effects.

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.

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.

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 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.

[HLA typing in a neonate with posttransfusional graft vs host disease (PT-GVHD)]. / Tipizzazione HLA in un neonato affetto da "graft versus host disease" post trasfusionale (PT-GVHD).

The authors report a case of post-transfusion-graft-versus-host disease (PT-GVHD) in a premature infant after parental blood donation. This disease seems to be due to the transfusion of immunocompetent T lymphocytes into an immunodeficient recipient or into an immunocompetent host who shares an HLA haplotype with HLA-homozygous blood donors (i.e. relatives or members of inbred populations) and who is therefore unable to reject the graft cells. The results of HLA typing of the patient and his family demonstrated that the infant was identical with his father for HLA class II antigens (DR, DQ) and, concerning HLA class I, he had in common the remaining paternal haplotype (A29, B44). Prevention of this disease, performed by gamma irradiation of blood components before transfusion, appears to be effective in most cases.

[Consensus conference. Saving blood: which are still the doubts and the problems?]. / Consensus conference. Risparmiare sangue: quali ancora i dubbi e i problemi?

The consensus conference on blood saving has allowed us to formulate some interesting guidelines. The autologous and homologous transfusion require the patient's consent. For volemic replacement crystalloid solutions are used for phlebotomies below 10-15%, and colloid solutions for those greater than 10-15% of the blood mass. Severe isovolemic hemodilution (Ht < 20%) necessitates the reduction of the dosage of some drugs. A limit of Hb around 9 g/dl after phlebotomy may be acceptable in the absence of cerebral and coronary vascular disease. Phlebotomies are therefore possible also when the Hb values are 10 g/dl (Ht 30%). Hb values around 7 g/dl in the late postoperative period (from day 3 to 6) may be accepted only if well tolerated. The blood salvaged during surgery and at the beginning of the postoperative phase must always be centrifugated, washed and microfiltered. Subsequently, in the first 8 hours it is possible to reinfuse red cells after sedimentation and microfiltration. The techniques of predeposit, hemodilution and recovery are valid especially if associated with careful control of postoperative bleeding by means of aspiration under controlled pressure (at minimum negative values and sometimes positive ones), monitoring of blood loss from drainage and application of elastic compression bandages.

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.