Blood transfusion induced changes in cell-mediated lympholysis: to immunize or not to immunize

We have recently observed that the HLA-DR match between recipients and transfusion donors influences the beneficial effect of blood transfusions on allograft survival. To examine the immunologic effects of one-HLA-DR-Ag-matched and completely DR-mismatched transfusions, transfusion-induced changes in cell-mediated lympholysis (CML) were investigated. Blood donor directed CTL activity was measured in vitro before and after blood transfusion in 56 candidates for organ transplantation who received planned HLA-typed blood. We report that blood donor-directed CTL activity increased substantially after a single transfusion mismatched with the recipient for two HLA-DR Ag (p less than 0.0001). A transfusion matched for one HLA-DR Ag did not enhance CTL activity. No correlation was found between CTL reactivity and sharing of HLA class I Ag. The present study supports our previous observation that matching for at least one HLA class II Ag (HLA-DR) between transfusion recipient and blood donor is required if immunization by blood transfusion is to be avoided. These data show that the presence or absence of "autologous" HLA-DR Ag on the leucocytes of the transfusion donor plays a decisive rol whether immunization or immune suppression will ensue.     

Human RBC alloimmunization evaluation after exposure to foreign E antigen of the rhesus system in transfusion

Anti-E alloantibody has been one of the most frequently detected clinically significant alloantibodies in previous studies. Red blood cell (RBC) transfusion is unique in its common intravenous introduction of foreign E antigen and provides a valuable opportunity to study the human immunologic response to intravenous foreign E antigen. Patients exposed to foreign E antigen while receiving RBC transfusions are at risk of forming anti-E alloantibody. Valid estimates of anti-E alloimmunization risk are clinically important, but the forming mechanism of anti-E alloimmunization remains unclear. Here, we screened 516 inpatients at risk of exposure to foreign E antigen while receiving RBC transfusions and monitored the development of anti-E alloantibody for up to two years after left hospital. However, only 2 cases of anti-E alloimmunization were identified in this study. Patients who received RBC transfusion had a very high risk of exposure to foreign E antigen, but the anti-E alloantibody production incidence was very low and few anti-E alloantibodies were produced within 3 to 6 months after RBC transfusion in this study. Further research would contribute to our knowledge of the anti-E alloimmunization mechanism and prevent anti-E development, which would be significantly useful in clinical for transfusions, obstetric management, and the evaluation and management of transfusion reactions in laboratory and institutional resources and cost reduction in healthcare system.     

The use of blood at a large Red Cross center; an evaluation of various aspects of utilization

During the past ten years over 1,000,000 pints of blood have been collected at the Los Angeles Regional Red Cross Blood Center. In addition to the progressive increase in the number of whole blood transfusions there has been a greater use of specific blood elements which results in purposeful and economical hemotherapy. With the increased use of blood there has also been a growing awareness of transfusion reactions and dangers. Serious transfusion complications reported have been due to bacterial contamination, to hemolytic reactions, to homologous serum jaundice, and to a mistake in cross-matching. Surgeons and anesthetists must pay strict attention to the use of blood since anesthesia masks severe hemolytic transfusion reactions. At present there is no way of eliminating the danger of the transmission of virus disease (infectious hepatitis and homologous serum jaundice) in blood transfusions.     

THE USE OF BLOOD AT A LARGE RED CROSS CENTER—An Evaluation of Various Aspects of Utilization

During the past ten years over 1,000,000 pints of blood have been collected at the Los Angeles Regional Red Cross Blood Center.In addition to the progressive increase in the number of whole blood transfusions there has been a greater use of specific blood elements which results in purposeful and economical hemotherapy.With the increased use of blood there has also been a growing awareness of transfusion reactions and dangers. Serious transfusion complications reported have been due to bacterial contamination, to hemolytic reactions, to homologous serum jaundice, and to a mistake in cross-matching.Surgeons and anesthetists must pay strict attention to the use of blood since anesthesia masks severe hemolytic transfusion reactions.At present there is no way of eliminating the danger of the transmission of virus disease (infectious hepatitis and homologous serum jaundice) in blood transfusions.     

Post-Transfusion Hepatitis—A Serious Clinical Problem

Serum hepatitis and infectious hepatitis may have a common pathogen and their few clinical differences the result only of a difference in portal of entry.The risk of serum hepatitis from transfusions derived from prison and Skid Row populations is at least 10 times that from the use of volunteer donors. For every 100 patients receiving a single transfusion, the attack rate is 0.3 per cent when the donor is of the family or volunteer type and 3.2 per cent when the donor is from a prison or Skid Row population.The most practical methods of reducing the hazard of serum hepatitis from blood are to limit the use of blood by giving one transfusion instead of two, two instead of three, etc., and especially by excluding, if possible, all prison and Skid Row donors.It is urged that state and federal control of the quality of blood used for blood transfusions be studied with the possibility that measures may be taken to increase its safety. If it is necessary that blood from prison and Skid Row donors be used to meet the demands, such blood should be labeled as carrying a significantly increased hazard of transmitting serum hepatitis in order that the physician prescribing blood may take the necessary precautions.     

Prevalence of hepatitis A and B infections in multiply transfused thalassaemic patients.

Evidence of hepatitis B virus (HBV) and hepatitis A virus (HAV) infections was south in 148 multiply transfused patients with thalassaemia and in healthy controls (2040 for HBV and 217 for HAV). The prevalence of the HBV surface antigen or antibody to it was significantly higher in patients than in controls and increased with the number of blood transfusions. In contrast, the prevalence of antibody to HAV was significantly lower in patients than in controls and decreased with the number of blood transfusions. These results support the view that blood transfusion does not play any appreciable part in transmitting HAV. Indeed, regular blood transfusion, where donors almost all have HAV antibody, seems to give protection against infection.     

High viscosity plasma expanders: Volume restitution fluids for lowering the transfusion trigger

Hemorheological studies lead to the axiom that high plasma viscosity is detrimental and that it is beneficial to lower blood viscosity, a precept embodied in the practice of hemodilution, where improved perfusion is attributed to the lowering of blood viscosity. Hemodilution is limited by the transfusion trigger, hemoglobin content of blood of about 7-8 g/dl, which indicates when further volume replacements must restore oxygen carrying capacity with red blood cells (RBC). However, oxygen consumption and delivery are not compromised upon passing this landmark. The reduced blood viscosity does not transmit adequate pressure to the capillaries, causing functional capillary density (FCD) to decrease, jeopardizing organ function through the inadequate extraction of products of metabolism from the tissue by the capillaries. Studies in hemorrhagic shock show that survival is primarily determined by the maintenance of FCD and secondarily by tissue oxygenation. FCD is maintained as hematocrit is reduced beyond the transfusion trigger by increasing plasma viscosity, which transmits systemic pressure to the capillaries and induces vasodilatation through the increased shear stress dependent release of vasodilators. Consequently the transfusion trigger is also a "viscosity trigger" indicating when blood and plasma viscosity are too low. In this condition increasing plasma viscosity is beneficial and extends the transfusion trigger reducing the use of blood transfusions.     

Transfusion strategy for patients in therapeutic aplasia. Experience of the Henri Mondor Hospital apropos of 2 successive protocols

Retrospective analysis of two transfusion protocols applied in our institution to the bone marrow transplanted patients was conducted. Granulocyte transfusions should be only proposed as a therapeutic treatment to patients with severe well documented bacterial infection resistant to an adapted antibiotherapy. Leukocyte-depleted blood products reduce the incidence of HLA-immunization but do not influence the frequency of CMV infections. Random single donor platelet concentrates (obtained by cytapheresis) could decrease the incidence of polyspecific HLA-antibodies in comparison with the use of random standard platelet concentrates. The best transfusion protocol should associate leukocyte-depleted blood products with transfusion of prophylactic single donor platelet concentrates. In our institution, this protocol is less expensive than the protocol with prophylactic white blood cell transfusions and has the same cost than other protocols using standard blood products.     

CRITERIA FOR BLOOD TRANSFUSIONS

A review of the use of blood transfusions used in a small community hospital over a two-year period revealed a high incidence of instances in which the clinical record did not show essential need for the procedure. Educational efforts in hospital staff meetings resulted in some improvement in this respect during the two-year period. Of single unit transfusions given during the first year, 80 per cent were deemed to have been nonessential; during the second year, 52 per cent.Methods which will reduce the use of blood except when it is essential are (1) continuation of staff education; (2) providing the staff with accurate methods of measurement of blood volume and of monitoring blood loss; (3) use of a separate blood transfusion chart in the patient''s hospital record; and (4) establishment of a hospital transfusion committee to review the criteria in all cases in which blood is transfused.     

Whole blood transfusion in common marmosets: a clinical evaluation

In veterinary medicine, blood transfusion is commonly performed on companion animals. The common marmoset is a small nonhuman primate with increasing popularity as an animal model in biomedical research. Because of its small whole blood volume, the marmoset is at high risk of exsanguination, and blood transfusion is required to care for life-threatening bleeding. However, few clinical evaluations exist on transfusions for marmosets. This study performed whole blood transfusion with cross-matching on nine marmosets and surveyed the therapeutic effects. Recipients included clinical cases with persistent bleeding, anemia, and coma, as well as animals subjected to postoperative bleeding prophylaxis. Donors were selected from healthy marmosets, including littermates. Cross-match assay before transfusion were all negative, and recipients showed no visible signs of transfusion-related adverse reactions. Whole blood transfusions caused hemostasis and successful recovery in bleeding marmosets, including long-term improvement of anemia cases. Our results indicated that blood transfusion is effective for marmosets with severe anemia and persistent hemorrhage from both non-experimental and surgical causes. Furthermore, DNA sequencing for blood-group classification revealed that all subject marmosets were type A, suggesting that the risk of blood type mismatch may be low in this species.     

Supportive care including growth factors in myelodysplastic syndromes

In spite of recent advances in the treatment of myelodysplastic syndromes (MDS), supportive care remains a very important part of the therapy. Red blood cells transfusions are the most important component of this supportive care. They transiently relieve anemia symptoms and alleviate their effects on quality of life and daily functioning. Platelet transfusion therapy is less frequently needed, at least in low-risk MDS. Dealing with an increased risk of infections linked to neutropenia, mainly by broad spectrum antibiotics, is also needed, more often in advanced stages of [dict: MDS] or when the MDS evolves to acute myeloid leukemia. Chronic red blood cell transfusions expose patients to various side-effects, including blood components intolerance reactions and alloimmunization risks, but also increased frequency of iron overload, a more significant problem in low-risk heavily transfused MDS patients, who have prolonged life expectancy. The use of growth factors is becoming a more and more important part of current supportive care. High-dose erythropoietin is able to reduce or suppress red blood cell transfusions needs in selected subgroups of MDS. The short-term use of granulocyte colony-stimulating factor is also often proposed in infections, although not formally established by prospective trials. Although trials of growth factors with thrombopoeitic activity have been performed with interleukin 11 and are underway with thrombopoeitin, none of them are available for routine use.     

Intrauterine transfusion with red cells and platelets.

Having direct access to the fetoplacental circulation by ultrasound-directed needle puncture has led to therapeutic interventions for fetal anemia and thrombocytopenia. Most cases of red cell alloimmunization associated with fetal anemia are caused by the antibody to the D red cell antigen. The intravascular transfusion of red cells to a hydropic fetus in such cases has notably improved survival. Nonimmune hydrops fetalis due to maternal parvovirus infection has also been treated successfully with the intravascular transfusion of red cells, whereas fetomaternal hemorrhage has not proved amenable to such therapy. Sensitization to the PLA-1 platelet antigen is the most common cause of fetal thrombocytopenia in maternal platelet alloimmunization. Fetal platelet transfusions have not proved to be a practical therapeutic modality for this disorder owing to the short half-life of the platelets. Platelets transfusions to the fetus just before delivery may avert the need for cesarean section in cases of severe thrombocytopenia.     

Haematological, immunological and endocrinological aspects of chronic high frequency blood sampling in rats with replacement by fresh or preserved donor blood

Haematological, immunological and endocrinological aspects of blood transfusions with either freshly collected or preserved donor blood were investigated in chronically cannulated unrestrained rats. Three anticoagulant preservatives were tested: citrate, citrate-dextrose and citrate-phosphate-dextrose-adenine (CPDA-1). Prolactin was used as an indicator of stress in endocrine studies. The repeated collection of 4 ml blood at 2-week intervals did not affect normal blood composition. Whole blood of rats could be stored in citrate, citrate-dextrose or CPDA-1 for 8, 22 or 35 days, respectively. Blood transfusions with fresh or preserved donor blood of F1 (R X U) rats did not affect normal blood composition nor did it induce immunological responses in F1 rats. Frequent blood sampling for several hours at highest rates of 1 sample/min did not affect prolactin secretion when blood volume reduction was replaced by blood transfusions with fresh donor blood. However, compensation with preserved blood affected prolactin secretion significantly. Blood transfusions did not affect health, behaviour, cyclicity or pseudopregnancy. The application of blood transfusion in chronically cannulated rats appeared to be quite simple. Its advantages are the possibility of following individual secretion patterns of blood-bound substances, the repeated use of animals and the reduction of the number of animals.     

Superiority of B locus matching over other HLA matching in renal graft survival.

Graft survival after 348 consecutive first cadaver-donor renal transplants was significantly improved by HLA matching when recipients who had received pretransplant blood transfusions were matched with their kidney donor for two HLA-B locus antigens. No other type of HLA matching significantly improved graft survival in transfused recipients nor did any type of HLA matching in non-transfused recipients. Matching for one HLA-DR antigen had no benefit in transfused recipients. Only two patients received kidneys matched for both DR antigens and only two of those in whom DR matching had been performed had not been transfused. These results indicate that pretransplant blood transfusion and selection of graft recipients predominantly on the basis of HLA-B matching has significantly reduced the renal graft rejection rate in Newcastle upon Tyne over two years. Thus, HLA-B antigen matching should be adopted as the main criterion for kidney sharing between transplant centres.     

Occurrence of hepatitis and hepatitis B surface antigen in adult patients with acute leukemia.

Fifty-eight adult patients with acute leukemia were screened at the onset of the disease for hepatitis B antigen (HBSAg) in the serum, and during the course of the disease for the development of hepatitis B. One patient had a positive test for HBSAg by the radioimmunoassay technique only at the time leukemia was diagnosed; this patient had received transfusions some years before. In six patients icteric hepatitis B developed; five recovered completely and one died of leukemia during the course of hepatitis. All patients in whom hepatitis developed had received transfusions as a part of supportive therapy for leukemia. The hepatitis risk for patients who received transfusions of blood found to be negative for HBSAg by counterimmunoelectrophoresis was 0.26 percent per unit of blood administered.     

Clinical use of blood,blood components and blood products.

The goal of modern transfusion therapy is to provide appropriate replacement therapy with blood components as opposed to whole blood for patients with specific hematologic deficiencies. A prerequisite of component therapy is, therefore, correct identification of the deficiency. Appropriate use of components avoids many of the hazards associated with the use of whole blood, and at the same time makes maximal use of this valuable resource. Blood components separated from whole blood soon after collection and appropriately stored can, in combination, provide all the factors present in fresh whole blood. Red cell concentrates prepared from multiple packs have a hematocrit of approximately 70%. They may be stored for up to 3 weeks at 4 degrees C and are recommended for most situations requiring red cell transfusions. Platelet concentrates, which can be stored for up to 72 hours at 22 degrees C, may be used for thrombocytopenic patients. Fresh frozen plasma, stored plasma, cryoprecipitated factor VIII, factor VIII concentrate and factor IX complex concentrate are available for the proper treatment of patients with hemorrhagic disorders due to coagulation factor deficiencies. Similarly, albumin and immune serum globulin are available for their oncotic and antibody properties respectively. Thus, the availability and appropriate use of the various blood products allows not only optimal transfusion therapy for each patient, but also fuller utilization of national blood resources.     

The Efficacy and Cost-Effectiveness of Cell Saver Use in Instrumented Posterior Correction and Fusion Surgery for Scoliosis in School-Aged Children and Adolescents

Posterior spinal instrumentation and fusion surgery in school-aged children and adolescents is associated with the potential for massive intraoperative blood loss, which requires significant allogeneic blood transfusion. Until now, the intraoperative use of the cell saver has been extensively adopted; however, its efficacy and cost-effectiveness have not been well established. Therefore, the aim of this study is to determine the efficacy and cost-effectiveness of intraoperative cell saver use. This study was a single-center, retrospective study of 247 school-aged and adolescent patients who underwent posterior spinal instrumentation and fusion surgery between August 2007 and June 2013. A cell saver was used intraoperatively in 67 patients and was not used in 180 patients. Matched case-control pairs were selected using a propensity score to balance potential confounders in baseline characteristics. Allogeneic red blood cell (RBC) and plasma transfusions as well as blood transfusion costs were analyzed. The propensity score matching produced 60 matched pairs. Compared to the control group, the cell saver group had significantly fewer intraoperative allogeneic RBC transfusions (P = 0.012). However, when the combined postoperative and total perioperative periods were evaluated for the use of allogeneic RBC transfusion, no significant differences were observed between the two groups (P = 0.813 and P = 0.101, respectively). With regard to the total cost of perioperative transfusion of all blood products (RBC and plasma), costs for the control group were slightly lower than those of the cell saver group, but this variance did not reach statistical significance (P = 0.095). The use of the cell saver in posterior spinal instrumentation and fusion surgery in school-aged children and adolescents was able to decrease the amount of intraoperative allogeneic RBC transfusion but failed to decrease total perioperative allogeneic RBC transfusion. Moreover, the use of the cell saver was not cost-effective.     

Comparison of immune responsiveness in mice after single or multiple donor-specific transfusions

Immune responsiveness was compared in B6AF1 mice after one, two, three, or four donor-specific DBA/2 blood transfusions (DST). Ten days after the last transfusion, the spleen cells of transfused mice were assayed for direct lymphocyte-mediated cytotoxicity, for the ability to respond in mixed lymphocyte culture (MLC) and cell-mediated lymphocytotoxic (CML) assays to DBA/2 and C3H/He antigens, and for the ability to inhibit the MLC and CML response of normal B6AF1 to DBA/2 and C3H/He antigens. Immune responsiveness was also tested in B6AF1 2 to 80 days after a single DBA/2 DST. The MLC response of transfused mice was specifically suppressed to the blood donor after both single and multiple transfusions. The CML response to DBA/2 was suppressed after a single DST, but returned to normal after multiple transfusions. Spleen cells from transfused mice did not inhibit the MLC response of normal B6AF1 mice to DBA/2 or C3H/He antigens after one or two transfusions regardless of time tested, but were able to inhibit the response to both stimulators after three or more transfusions. The MLC response remained specifically suppressed to the blood donor for as long as 80 days after a single DST, while the CML response was suppressed up to 50 days after transfusion, but had returned to normal by 80 days.     

Evaluation of red blood cell transfusion practices with the use of preset criteria.

OBJECTIVE: To assess current red blood cell (RBC) transfusion practices and to determine the potential impact of implementing recently published guidelines on RBC transfusion from the American College of Physicians (ACP). DESIGN: Medical chart review. SETTING: A 219-bed teaching hospital in Kingston, Ont. PARTICIPANTS: All patients over 12 years of age who received RBC transfusions in March 1992. MAIN OUTCOME MEASURES: Need for transfusion according to the ACP guidelines and the number of blood units ordered for each transfusion. RESULTS: A total of 55 patients received 170 RBC units. According to the ACP guidelines 94 (55.3%) of the units were judged unnecessary. The departments of Surgery and Internal Medicine did not differ significantly in the number of unnecessary units (56.4% v. 52.8%). Among the surgical subspecialties, unnecessary transfusion was most common in the orthopedics service (73.5%, p < 0.05). Blood was most frequently ordered 2 units at a time (51.8% of units). Transfusion in normovolemic, hemodynamically stable patients with anemia and unnecessary multiple-unit transfusions were the most common violations of the ACP guidelines. CONCLUSIONS: According to the ACP guidelines, there was significant unnecessary blood use in the hospital surveyed. The guidelines provide a useful framework for assessing transfusion practices but may require further refinement to apply to a broader spectrum of clinical settings.     

Impact of vCJD on blood supply.

Variant Creutzfeldt-Jakob disease (vCJD) is an at present inevitably lethal neurodegenerative disease which can only be diagnosed definitely post mortem. The majority of the approximately 200 victims to date have resided in the UK where most contaminated beef materials entered the food chain. Three cases in the UK demonstrated that vCJD can be transmitted by blood transfusion. Since BSE and vCJD have spread to several countries outside the UK, it appears advisable that specific risk assessments be carried out in different countries and geographic areas. This review explains the approach adopted by Germany in assessing the risk and considering precautionary measures. A fundamental premise is that the feeding chain of cattle and the food chain have been successfully and permanently cleared from contaminated material. This raises the question of whether transmissions via blood transfusions could have the potential to perpetuate vCJD in mankind. A model calculation based on actual population data showed, however, that this would not be the case. Moreover, an exclusion of transfusion recipients from blood donation would add very little to the safety of blood transfusions, but would have a considerable impact on blood supply. Therefore, an exclusion of transfusion recipients was not recommended in Germany.