The risk of bacterial growth in units of blood that have warmed to more than 10 degrees C

Most transfusion services discard unopened units of blood that have been returned to the blood bank more than 30 minutes after the issuance or have attained a temperature of more than 10 degrees C. The objective of this study was to learn the prevalence of bacterial growth, if any, in the units of blood that were exposed twice, for six hours each time, to room temperature during their refrigerated storage. All of the 396 units cultured were negative except one red cell unit that grew a Bacillus species, probably B. subtilis. Further studies suggested that the growth of B. subtilis was due to laboratory contamination. The authors concluded that more work is needed to study the bacterial growth and the effect on red cell enzymes in the units of blood that are exposed to room temperature for varying periods or are returned to the blood bank after 30 minutes of issuance. If no adverse effect is noted, the policy of not reissuing such units may need revision so that more units could be salvaged.     

Blood Transfusion,Blood Storage and Immunomodulation

Allogeneic blood transfusion is the most frequent allotransplantation procedure performed on a routine basis with no prior HLA-typing. Roughly 50% of the recipients of unprocessed red cells and platelets become alloimmunized. Evidence also exists for some degree of transfusion-induced immunosuppression. Prior transfusion has been shown to enhance kidney transplant survival and evidence of an increase in tumor recurrence and of infectious complications has also been presented. The presence of donor antigen-presenting cells appears to be a prerequisite for alloimmunization and they must be both viable and capable of presenting a costimulatory signal in order to induce IL-2 secretion and proliferation of responding CD4 T cells. APCs presenting antigen but no costimulatory signal can induce non-responsiveness in CD4 T cells, a possible mechanism of transfusion-induced immunosuppression. APCs in refrigerated blood continue to present antigen but progressively lose their ability to provide costiraulation. By day 14 costimulatory capacity is absent and transfusion of such blood should not alloimmunize but could induce some degree of immunosuppression. Further refrigerated storage in excess of 2 to 3 weeks leads to induction of apoptosis in contaminating leukocytes. We have found that alloantigens expressed on such cells do not appear to be recognized by responder T cells and transfusion of blood stored in excess of 3 weeks should neither alloimmunize nor immunosuppress.     

Red cell transfusion in medicine: Future challenges

Many side-effects of red blood cell transfusion have been described. They include iron-overload, as well as allo- and autoantibody formation against red cells. During storage, erythrocytes undergo complex structural and biochemical changes. It has been suggested that accelerated and/or aberrant forms of the physiological erythrocyte aging process underlie the red cell storage lesion. This storage lesion may contribute to side-effects of transfusion as endothelial damage by release of internal erythrocyte constituents, (pro)inflammatory consequences, hampered microcirculation and oxygen delivery. Understanding the process that determines the fate of red blood cells after transfusion may contribute to the prevention of side-effects after red blood cell transfusion. This should be the focus of research on red blood cell transfusion in clinical transfusion medicine.     

Platelet transfusion in adults: An update

Many patients worldwide receive platelet components (PCs) through the transfusion of diverse types of blood components. PC transfusions are essential for the treatment of central thrombocytopenia of diverse causes, and such treatment is beneficial in patients at risk of severe bleeding. PC transfusions account for almost 10% of all the blood components supplied by blood services, but they are associated with about 3.25 times as many severe reactions (attributable to transfusion) than red blood cell transfusions after stringent in-process leukoreduction to less than 10⁶ residual cells per blood component. PCs are not homogeneous, due to the considerable differences between donors. Furthermore, the modes of PC collection and preparation, the safety precautions taken to limit either the most common (allergic-type reactions and febrile non-hemolytic reactions) or the most severe (bacterial contamination, pulmonary lesions) adverse reactions, and storage and conservation methods can all result in so-called PC “storage lesions”. Some storage lesions affect PC quality, with implications for patient outcome. Good transfusion practices should result in higher levels of platelet recovery and efficacy, and lower complication rates. These practices include a matching of tissue ABH antigens whenever possible, and of platelet HLA (and, to a lesser extent, HPA) antigens in immunization situations. This review provides an overview of all the available information relating to platelet transfusion, from donor and donation to bedside transfusion, and considers the impact of the measures applied to increase transfusion efficacy while improving safety and preventing transfusion inefficacy and refractoriness. It also considers alternatives to platelet component (PC) transfusion.     

Effects of genetic,epigenetic, and environmental factors on alloimmunization to transfused antigens: Current paradigms and future considerations

Transfused red blood cells, platelets, or coagulation factors have the capacity to induce alloantibodies, which once formed, can be a clinical barrier to future transfusion therapy and/or transplantation. Large observational studies over the last 50 years have characterized some of the general properties of transfusion induced alloimmunization, which appear to vary to a considerable extent from what is generally observed for human responses to other immunogens, such as microbial pathogens and vaccines. Transfused cells and factor only induce immune responses in the minority of recipients. There are data to suggest that differences in the unit may play a role. However, there are clearly differences in recipient biology, as once a recipient makes one antibody they are much more likely to make additional antibodies; indeed, recipients have been categorized as “responder” and “non-responder” by the field. Recent mechanistic studies have begun to define potential causes for such differences in alloimmunization from patient to patient, but much progress needs to be made to understand how, why, and in whom alloimmunization occurs. This review gives a general background on immunology in the context of transfusion, summarizes recent progress in the field, and discusses future directions for exploration. Particular attention is paid to the general concept that the human immune system is melded by the wide range of antigens encountered in our environment, and that the effects of such on the immune system may have a profound effect upon response to transfused cells.     

Storage of red blood cell concentrates: Clinical impact

The storage of red blood cells for transfusion purposes induces modifications of biochemical and biological properties. Moreover, these modifications are modulated by the donors’ characteristics and the cell processing. These ex vivo alterations were suspected to decrease the transfusion efficiency and even to induce adverse events. This short article will review the red blood cells storage lesions and the clinical data related to them. In particular, the questions regarding the donors and recipients sex will be discussed.     

CD40 ligand (CD154) involvement in platelet transfusion reactions

Platelet transfusions are commonly used treatments that occasionally lead to adverse reactions. Clinical trials, in vitro and animal studies have been performed to try to understand the causes of such reactions. Multiple studies have shown that the supernatant fraction of platelet concentrates contain prothrombotic and pro-inflammatory mediators. The origin of these mediators was first ascribed to white blood cells contaminating the platelet preparation. However, the accumulation of bioactive mediators after leukoreduction focused attention on platelets themselves during storage. Numerous cytokines, chemokines and prostaglandins are released in stored platelet concentrates. We have focused on a powerful mediator called soluble CD40 ligand (sCD40L, formally known as CD154) as a seminal contributor to adverse reactions. sCD40L can bind and signal the surface receptor, CD40, which is present on various types of human cells including white blood cells, vascular cells and fibroblasts. Downstream results of sCD40L/CD40 signaling include pro-inflammatory cytokine and chemokine production, prothrombotic mediator release, adherence and transmigration of leukocytes to endothelium and other undesirable vascular inflammatory events. Increased plasma levels of sCD40L can be detected in conditions such as myocardial infarction, stroke, unstable angina, high cholesterol, or other cardiovascular conditions. In retrospective studies, correlations were made between increased sCD40L levels of platelet concentrates and adverse transfusion reactions. We hypothesize that transfusion of partially activated, CD40L-expressing platelets along with sCD40L into a recipient with damaged or dysfunctional vascular tissue results in a “double-hit”, thus inciting inflammation and vascular damage in the recipient.     

Erreurs de destinataire de concentrés de globules rouges : méthode d’analyse à partir de déclarations d’incidents de la chaîne transfusionnelle en 2009

ContextAmong the adverse events in the blood transfusion process, transfusion to a “wrong” patient is potentially dangerous, as it can lead to an adverse reaction at least in case of ABO incompatible red cell concentrate.Material and methodsThe “Root Cause Analysis” working party of the National Hemovigilance Commission developed a tool to collect this type of adverse event, and tested it on a sample of 43 cases involving red cell concentrates notified between March, 2009 and February, 2010.ResultsOne hundred and nine failures of a step in the transfusion process were observed, i.e. 2.5 failures per adverse event. Failures may occur early in the process. However, they are mainly found at the time of issuing of the blood component, and further, in the clinical ward. How the failure is eventually detected is not always described when the blood component has been fully transfused, in contrast with the cases where actual transfusion to the wrong patient has been prevented. Knowing the way of failure detection enables an objective approach of the efficacy of the numerous existing safety measures. In this sample, bedside controls (documents check as well as the use of anti-A and anti-B reagents with patient's blood and red cell concentrates) detected the failure in three cases out of 34, which were not detected before, showing an efficacy similar to the administrative control done at reception in the clinical ward.ConclusionThe document, set up to analyse step by step these cases of patient errors, will be used in the future to analyse all similar cases, not only with red cell concentrates, but also with platelet concentrates and fresh frozen plasma, ultimately in order to improve their prevention.     

Mechanisms of severe transfusion reactions.

Serious adverse effects of transfusion may be immunologically or non-immunologically mediated. Currently, bacterial contamination of blood products, particularly platelets, is one of the most significant causes of transfusion-related morbidity and mortality. Septic transfusion reactions can present with clinical symptoms similar to immune-mediated hemolytic transfusion reactions and transfusion-related acute lung injury. Extremely high fever and/or gastrointestinal symptoms, in a transfusion recipient, may be indicative of sepsis. The diagnosis is based upon culturing the same organism from both the patient and the transfused blood component. Numerous organisms have been implicated as the cause of septic transfusion reactions. Due to different storage conditions, gram negative organisms are more often isolated from red blood cell components; gram positive organisms are more often isolated from platelets. Prevention of septic transfusion reactions is primarily dependent on an adequate donor history and meticulous preparation of the donor phlebotomy site. Visual inspection of blood components prior to transfusion is also vital to preventing these reactions. Several methods of detection of bacterial contamination and inactivation of pathogens are currently under active investigation.     

Fiches techniques : aide à l’analyse des effets indésirables receveurs

In order to help the analysis of adverse effects of transfusion, factsheets have been written by working groups of the French agency for the safety of health products ANSM. Each factsheet deals with a blood transfusion side effect and is composed of five parts, including pathophysiological mechanisms, diagnostic criteria, management recommendations, etiologic investigations and rules for filing the notification form to ANSM. Since 2006, 11 factsheets have been published on the French haemovigilance network website. The major characteristics of the two last sheets published “post-transfusion purpura” and “non erythrocyte incompatibility reaction” are presented, followed by the updated card for “allergy”. These factsheets give relevant guidelines allowing better evaluation of recipients’ adverse reactions, particularly their diagnosis, severity and accountability. They also could initiate studies among European and international haemovigilance networks.     

孕妇外周血液中胎儿红细胞的研究进展

研究认为孕妇外周血液循环中出现胎儿红细胞的主要原因是脐动脉和绒毛间隙之间的压力不同造成的。如果绒毛屏障受到破坏时,胎儿的血液就会通过绒毛间隙,进入到母体,最终出现在母体的外周血液循环中。通常可能会有很少量的胎儿红细胞在母体的外周血液循环中出现,这是正常的情况,且没有明显的胎儿和母体不良反应。但是当胎儿进入母体的血量超过一定阈值时,就会引发胎母输血综合征,引起严重的临床症候群。本文主要从胎儿红细胞的来源;现有检测方法;对胎母输血综合征的诊治;与新生儿贫血的相关性;在产前诊断中的价值;及对子痫前期发病预测等临床应用进展方面进行分析总结,为临床诊疗提供依据。     

Red blood cell transfusion strategies.

Although the hemoglobin level of 100 g/L has been used for many years as the allogeneic red blood cell (RBC) transfusion trigger, current evidence indicates that for most patients a more restrictive transfusion strategy is at least as effective as and possibly superior to a liberal transfusion strategy. Moreover, the available data indicate that the use of smaller volumes of allogeneic RBCs may be associated with decreased risk of morbidity and mortality. Thus several recent studies indicate that the use of more restrictive triggers than 100 g/L does not appear to adversely affect patient outcomes. Indeed, the majority of recently published RBC transfusion guidelines recommend a more conservative and cautious approach to allogeneic RBC transfusion practice, primarily to reduce the risk of transfusion-related adverse effects. However, the available transfusion trigger studies do not provide sufficient data to allow the claim that the improved outcomes observed are the sole result of the transfusion strategy used. It is possible that the results are the consequence of effects yet to be defined clearly. Additional studies will be necessary to determine the effects of RBC storage time and the presence of allogeneic leukocytes in allogeneic RBC transfusion practice. Nonetheless, the available data, together with detailed information about alternatives to blood product transfusions, will enable physicians to improve outcomes in transfused patients.     

献血者差异性对红细胞质量影响的研究

临床输注红细胞的质量和安全性有着严格的监管控制。尽管如此,红细胞质量的差异仍然存在,其中的主要原因可能是由于献血者的差异性所致,但在目前输血相关的临床研究中,与献血者有关的差异性对红细胞质量的影响仍不明确。现将献血者差异性对红细胞质量影响的研究进展进行综述。     

Red blood cell homeostasis: recognition of distinct types of damaged homologous red blood cells by a mouse macrophage cell line

The mouse macrophage (M phi) cell line IC-21 preferentially ingests a subpopulation of homologous red blood cells (MRBC) from normal mice. This subpopulation presumably bears the so-called transfusion lesion, a consequence of damage acquired during the drawing and processing of blood. To determine if all damaged MRBC were recognized by a common receptor site on IC-21 M phi, we prepared suspensions of MRBC damaged in vitro by treatment with tannic acid and compared the phagocytic uptake of these cells with those bearing the transfusion lesion. Trypsin treatment of IC-21 M phi rendered them unable to recognize MRBC bearing the transfusion lesion; but it had no effect on the uptake of tannic acid-damaged MRBC, showing that IC-21 M phi have separate recognition sites for these two populations of damaged MRBC.     

Enquête nationale sur les pratiques transfusionnelles pendant la période néonatale en vue de l’élaboration de recommandations selon la méthodologie de la Haute Autorité de santé

Although transfusion practices have changed these last years, the neonatal period remains one period when the transfusion of blood components (in particular in red blood cells concentrates) is frequent, particularly for low birth weight premature babies. It is thus important to know well the pathophysiological characteristics specific to this age of life in order to reduce the risks of transfusion and to allow an optimal effectiveness of this treatment. Various studies on neonatal transfusion show that transfusion practices during the neonatal period are very heterogeneous from a team to another, and even within the same team. Therefore, we wanted to know the practices in France, by addressing a questionnaire to neonatology centres, in collaboration with the French Society Vigilance and Transfusion Therapy and the French Society of Neonatology (SFN). The results obtained confirm the heterogeneity of practices. To follow up on this study, we constituted a working group, in partnership with the SFN, the SFVTT and the EFS, with an aim of proposing good practice recommendations according to the methodology of the French “High Authority for Health”, in order to homogenize at the national level transfusion practices of the new-born baby.     

The Quality of Red Blood Cells

The evolving practice of medicine has required a number of changes in red cell product manufacture to ensure that the final product is more specifically tailored to the needs of the individual patient. As a result of the increasing concern over the risks of transfusion pharmaceutical standards of manufacture are now applied to blood component preparation. Studies have been undertaken to define the optimum method of blood processing, and newer technologies are emerging to allow acquisition of a more consistent dose of red cells in a fashion which may minimize the lesion of collection. Use of high efficiency 3+ generation filter technologies reduces leukokine build up during storage and improves the quality and purity of the stored blood product. The combination of new plasticizers for packaging and improved red cell additive solutions should allow the blood center to supply a more functional red cell with longer storage shelf life. Overall these developments should result in the provision of a more consistent dose of fully functional red cells to the recipient who will be less exposed to the undesirable sequelae of transfusion than previously.     

Laboratory medicine for blood transfusion and transplantation medicine

We discussed the usefulness of routine technologies of laboratory medicine in blood transfusion and transplantation medicine. New parameters that can be measured by automated hematology analyzers have been clinically evaluated and proven to be useful so far. Based on our experience, detection systems for fragmented red cells (FRC), immature platelets (immature platelet function, IPF), and hematopoietic progenitor cells (HPC) are useful for the diagnosis of thrombotic microangiopathy, differential diagnosis of thrombocytopenia, and decision regarding the optimal timing to collect peripheral stem cells, respectively. Moreover, IPF were suggested to be an indicator of the platelet transfusion requirement. The establishment of non invasive assaying technology has been eagerly anticipated. We evaluated a hemoglobin measurement tool, and revealed that it might be applicable in predeposited, autologous blood donation. Some adverse transfusion reactions are related to neutrophil activation. Thus, we investigated the effects of serum from patients and blood donors, in the context of adverse reactions, on adhesion molecule expressions of neutrophils from volunteers using flow-cytometry. This kind of simple technology is expected to be useful in future studies to clarify the mechanisms and prevent adverse reactions.     

Use of whole blood as the routine transfusion product in Africa

In many countries in sub‐Saharan Africa (sSA) whole blood is more commonly available from blood transfusion services than red cell concentrates. Although in recent years, many countries have made significant progress in the implementing component preparation, this has largely been facilitated by external funding support. The large majority of rather than none of the sSA countries are leucocyte‐reducing or irradiating blood for transfusion. Systems for the routine detection of adverse consequences of blood transfusions (haemovigilance) only exist where transfusion safety has been identified as a health priority by the government. As a resource, the availability of blood transfusion in these countries is limited since less than 5 units of blood were donated per 1000 population far below the recommended requirement of 20 units/1000 per year. Young children are the main users of blood for transfusion in these sSA regions, largely due severe anaemia secondary to infection and sickle cell anaemia. Outcomes for children with severe anaemia are poor, even in those receiving a transfusion. Although it has been speculated that this may be due to transfusion‐related cardiac or pulmonary events, available data from observational studies and clinical trials indicate that these are rare complications of transfusion. Evidence from clinical physiology studies including those examining myocardial functions before and after the receipt of whole blood provide reassuring evidence that volume overload is rare and clinical trials reporting outcomes in children receiving whole blood transfusion, including a Phase II trial examining higher volumes, indicate that there is no evidence of cardiac or pulmonary overload events.     

Laboratory hemostatic abnormalities in massively transfused patients given red blood cells and crystalloid.

Most of the literature on massive transfusion concerns whole blood replacement, whereas clinically, packed red blood cells are commonly given. To determine when hemostatic abnormalities occur in patients resuscitated primarily with packed red blood cells and crystalloid, the cases of 39 consecutive patients who were transfused with 10 or more red blood cell units of any kind within 24 hours were reviewed. After transfusion with 20 or more units of red blood cell products of any kind (packed red blood cells, cell-saver units, or whole blood), 75% (3 of 4) of patients had platelet counts less than 50 x 10(9)/L, compared to 0 of 29 patients given less than 20 units (P less than 0.001). After transfusion of 12 units of relatively plasma-free red blood cell products (packed red blood cells or cell-saver units), 100% (8 of 8) of patients had prothrombin time prolonged by more than 1.5 times mid-range of normal, compared to 36% (5 of 14) of patients given less than 12 units (P = 0.012). These data confirm that patients massively transfused with red blood cells of any kind develop significant thrombocytopenia after 20 units. Importantly, probably clinically significant prothrombin time and partial thromboplastin time prolongations occurred consistently after transfusion of 12 units of relatively plasma-free red blood cells in unselected patients at an urban trauma hospital. These data suggest that coagulation factor replacement is necessary in patients who receive 12 or more units of packed red blood cells or cell-saver blood, and platelet replacement is necessary in patients who receive 20 or more units of any red blood cell product. A prospective study is needed to determine whether the expected abnormal clinical bleeding indeed occurs in patients with such laboratory coagulation abnormalities and to determine when plasma transfusion is indicated in patients massively transfused with red blood cells.     

Examination and treatment for dilutional thrombocytopenia

Massive transfusion is defined as transfusion of more than total blood volume within 24 hours. There are several adverse effects associated with massive transfusion, and dilutional thrombocytopenia is known as one of the major adverse effects. Dilutional thrombocytopenia is caused by platelet loss out of the body and platelet dilution with replaced red cells and crystalloids. Volume of blood loss or replaced volume is a good indicator of dilutional thrombocytopenia, and previous reports suggest that severe thrombocytopenia doesn't occur before replaced volume surpasses over one hundred and fifty percent of total blood volume. Recently, an automated blood cell counter has spread and platelet count is available in a short time, even at night. To treat the patient with dilutional thrombocytopenia, platelet count is very helpful to decide when to start platelet transfusion. When platelet count decreases as low as 50,000/mm3, platelet transfusion should be considered. Nowadays, dilutional thrombocytopenia is less frequent complications of massive transfusion than before, because platelet transfusion tends to be performed before platelet count fall to the critical point. Thus, exceeded platelet transfusion might become another problem after massive transfusion.