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.

The cadaver kidney transplantation programme of Milano. Immunological report.

A retrospective investigation was carried out to evaluate the infuence of HLA (A, B) matching, blood transfusions, and preexistence of lymphocytotoxic antibodies on the outcome of the cadaver kidney graft: only non-NIH standard antibodies were considered, since patients with NIH standard antibodies do not undergo transplantation in the programme of Milano. It was found that (1) about one-half the patients with transplants had antibodies in their pretransplant serum. The preexistence of antibodies directed against B lymphocytes had an unfavourable effect on the graft survival; (2) the graft did particularly well in the nonimmunized patients who had been previously transfused; the graft survival was about 80% at 3 years in these patients; and (3) the HLA (A, B) match influenced the graft survival only in patients with antibodies.

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.

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.

[Hashimoto's thyroiditis and HLA in Caucasian Italians]. / Tiroidite di Hashimoto e HLA in caucasici italiani.

Sixty cases of goitrous Hashimoto's thyroiditis were observed at the first diagnosis. For 18 of the cases, the diagnosis was made only on the basis of cytological examination since antithyroid antibodies were always negative. To determine if seronegative or seropositive forms constituted a particular genetically determined subgroup, we evaluated whether such peculiarities were related to specific HLA haplotype. Analysis of HLA antigens showed in the seropositive a significant increase in the frequency of HLA-B51 and HLA-A2, a significant decrease in the frequency of HLA-A1 and HLA-DR1. In seronegative cases no increase was found in the frequency of HLA-A-B-DR antigens, but they showed a strong positive association with HLA-DQ3. Our results show that association of Hashimoto's thyroiditis with HLA antigens was different in seronegative and seropositive subgroup. This finding would seem to support the hypothesis that in a few subjects the entire immune process develops exclusively within the involved organ and this process would be genetically determined.

Blood transfusion and kidney transplantation: effect of small doses of blood on kidney graft function and survival.

A controlled clinical trial was started to evaluate whether small doses of blood given pretransplant determine a transfusion effect while reducing the risk of antibody production. For this purpose, 65 consecutive never transfused patients suffering from end-stage renal failure were assigned to one of two groups: the first group was transfused with 1 unit of packed red cells (containing a mean of 2350 x 10(6) leukocytes, 900 x 10(6) mononuclear cells) 3 times at 15-day intervals. The second group received one transfusion of about 30 ml of blood adjusted to contain 100 x 10(6) mononuclear cells. While no definitive conclusions are still possible, preliminary data indicate the following: (1) three small transfusions are capable of immunizing the recipient, but lymphocytotoxic antibodies tend to disappear rapidly; (2) in vitro lymphocyte response to lectins of patients receiving small transfusions is not significantly different from that of patients receiving standard transfusions; (3) the two groups of patients differ significantly as far as the T4+ /T8+ cell ratio is concerned: in fact while a decrease of the ratio is observed after standard transfusions, small transfusions determine an increase of the ratio, mainly due to a decrease in the number of T8+ cells; and (4) the clinical course and survival of the graft is worse in patients treated with small transfusions than in those treated with standard transfusions.

[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.

[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.

[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.