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Blood donor and component management strategies to prevent transfusion-related acute lung injury (TRALI).

OBJECTIVE: Discuss the pros and cons of using donor and blood product-management strategies to prevent transfusion-related acute lung injury (TRALI). DATA SOURCE: A review of the literature was performed. RESULTS: Despite therapeutic advances in pulmonary and critical care medicine, TRALI is now considered to be one of the leading causes of transfusion-associated mortality, and thus determining how to prevent TRALI is extremely important. Donor and product-management strategies to prevent this life-threatening condition have been suggested, but because of gaps in our understanding of TRALI, blood-bankers do not know how beneficial these interventions will be, nor the amount of potential harm-such as decreasing the availability of blood-that could arise if they were implemented. This article discusses the advantages and disadvantages of the various preventive measures that have been described in the literature. CONCLUSIONS: Preventing TRALI poses a difficult challenge for blood-banking experts, because it is unknown which measures will be effective in decreasing the incidence of TRALI and which could have significant drawbacks. Only additional research into TRALI prevention will provide the answers on how to best protect patients from this potentially fatal reaction.

Blood Donors↗

Transfusion in the intensive care unit.

OBJECTIVE: To summarize the incidences of anemia and blood transfusions in critically ill patients, assess their comparative risks and benefits, and briefly speculate on the possible effects of leukoreduction and blood storage on the need to reevaluate transfusion triggers. DESIGN: A review of the current literature was performed. RESULTS: Anemia is common in intensive care unit patients and is associated with increased mortality. Some 20-53% of intensive care unit patients will receive a blood transfusion during their stay, and these have also been associated with worse outcomes. Leukoreduction may limit some of the infectious and immunomodulatory risks associated with blood transfusion. CONCLUSIONS: Data on the risks and benefits of blood transfusion are conflicting, and with recent changes in blood transfusion practice, including the widespread introduction of leukoreduction, it is time to reevaluate our transfusion triggers.

Anemia↗

Effect of blood temperature on the efficacy of systemic leucodepletion during cardiopulmonary bypass: a prospective randomized clinical study.

The authors examined the effect of blood temperature within the cardiopulmonary bypass (CPB) circuit on the efficacy of an arterial line filter. Eighty patients undergoing elective, primary coronary artery bypass grafting under CPB were prospectively randomized in two equal groups. Blood temperature was kept at 35 degrees C in the first group and reduced to 28 degrees C in the second group. Twenty patients in each group had an arterial line LG6 filter attached onto CPB circuit. The other 20 patients in each group (controls) had a non-leukocyte-depleting filter. Blood samples (10 ml) were taken before CPB, at 5 minutes on CPB, at 30 minutes on CPB, 5 minutes after aortic clamp removal, and 6 hours postoperatively. Leucocytes were counted under light microscopy. Activated leucocytes were identified using nitroblue tetrazolium staining. Patients undergoing leucodepletion had significantly lower total and activated leukocyte counts than control patients in both groups (p < 0.05). Patients having a leukocyte-depleting filter at a CPB temperature of 35 degrees C had significantly lower total leukocyte counts (p < 0.05) than those having a leukocyte-depleting filter at a CPB temperature of 28 degrees C (p < 0.05). However, there were not statistically significant differences in the activated leukocyte counts between the two leucodepleted groups (p > 0.05). This study shows that warm blood temperature within the CPB circuit has a positive effect on the overall leucodepleting efficacy of the LG6 filter. Activated leucocytes, however, seem to be depleted at similar rates irrespective of the blood temperature in the CPB circuit.

Aged↗

Can we safely restrict transfusion in trauma patients?

PURPOSE OF REVIEW: Transfusion of red blood cells in the trauma patient can be lifesaving. The question is how much and when? It is important to weigh the risks and benefits of red blood cell transfusions, as well alternatives to transfusion as these products are not benign. RECENT FINDINGS: We explore the evidence, and provide the rationale for current and future red blood cell transfusion strategies within a framework of prehospital and hospital care of the trauma patient. We also describe how red blood cell transfusion trends are changing in trauma, discuss alternatives to red blood cell transfusion and present evidence from randomized controlled trials that support a lower transfusion trigger. SUMMARY: Optimal transfusion practice and use of alternatives in trauma is a rapidly expanding and important area of research. Strong clinical evidence derived by future randomized controlled trials in the area of transfusion triggers as well as transfusion alternatives is required to determine their roles in clinical practice.

Blood Substitutes↗

Efficacy of Epstein-Barr virus removal by leukoreduction of red blood cells.

BACKGROUND: Epstein-Barr virus (EBV) infection results in life-long carriage of latent virus in B lymphocytes in the majority of the adult population, including blood donors. The removal of EBV from red blood cell (RBC) components by leukoreduction was assessed. STUDY DESIGN AND METHODS: Sixteen randomly selected fresh AS-5 units were leukoreduced by filtration. B lymphocytes from preleukoreduction specimens and mononuclear cells (MNCs) from postleukoreduction specimens were assayed for EBV DNA with sensitive real-time polymerase chain reaction (PCR). RESULTS: EBV genomes were detected in CD19+ B cells in 14 of 16 preleukoreduced RBC units. EBV genomic copy number in the units ranged from 0.18 to 96.84 per 10(5) B lymphocytes representing approximately 135 to 72,630 total EBV genomes per bag. Leukoreduction rendered all but one unit EBV-negative by PCR. The lone PCR-positive unit after leukoreduction amplified 1.2 EBV genome copies from MNCs recovered from the entire unit of leukoreduced RBCs; this unit had the highest EBV viral load before leukoreduction (72,630 EBV genomes). CONCLUSIONS: These results indicate that a 4-log reduction of EBV genomic copy number can be achieved with leukoreduction of RBC units and renders most RBC units EBV-negative by sensitive PCR.

Antigens, CD19↗

Molecular evidence of tumour cell removal from salvaged blood after irradiation and leucocyte depletion.

Intra-operative autologous blood recovery offers many advantages. However, blood salvage during cancer surgery is of limited use due to the potential presence of circulating tumour cells. It was the aim of this study to show that intra-operative salvage blood can be freed of cells and cellular DNA after leucoreduction by filtration and irradiation of washed blood. Known amounts of tissue culture derived from carcinoma, melanoma and osteosarcoma were added to whole blood bags. This mixture was then submitted to washing, leucoreduction and irradiation. Samples were studied stepwise in relation to the integrity and size of DNA by the polymerase chain reaction (PCR). After filtration and irradiation, PCR targeting the beta-globin gene (268 bp amplicon) was negative. Our results were corroborated by studying plasma samples added with tumoural cells. Using PCR methodology, we showed the absence of DNA from cells in experimentally contaminated blood and plasma bags after filtration and irradiation. This experimental study is an effort to ensure the safety of intra-operative autologous transfusion.

Blood Cells↗

Implementation of a strategy to prevent TRALI in a regional blood centre.

Transfusion-related acute lung injury (TRALI) can be a life-threatening complication of transfusion and it is probably underdiagnosed. Human leucocyte antigen (HLA) and granulocyte antibodies are thought to play a major role, but preventive measures are difficult to implement. In our regional blood centre, we implemented a preventive strategy avoiding donor deferral. Previously, pregnant apheresis donors were screened for HLA antibodies, and those with positive results were assigned to a plasma-only protocol. Plasma from these donors and from all previously pregnant whole blood donors was diverted for protein fractionation. Plasma-poor red blood cells (in additive solution, buffy coat removed) and platelets (pools with additive solution) were prepared. Prestorage leucodepletion was also applied. We found HLA antibodies in 18.1% of previously pregnant apheresis donors, and our strategy caused a 6.0% loss of apheresis platelets, a 4.8% increase of apheresis fresh frozen plasma (FFP) and a 7.8% loss of transfusable apheresis FFP. The effect on FFP from whole blood donors could be compensated. The platelet preparation method reduced the mean volume of plasma from each donor to 24.4 mL. Fifteen months after the start of our strategy, no cases of TRALI have been reported. Our experience shows that a practical strategy to prevent TRALI is feasible.

Adolescent↗

Pall eBDS: an enhanced bacterial detection system for screening platelet concentrates.

Bacterial contamination of blood components remains a significant problem in transfusion medicine. The Pall enhanced bacterial detection system (Pall eBDS) detects the presence of bacteria in leucodepleted platelet concentrates by measuring the reduction of oxygen in the sample, due to aerobic bacterial growth. Pooled platelet concentrates were spiked at 10 cfu mL(-1) with 10 organisms (one species per bag). Pall eBDS pouches were inoculated with the spiked platelet concentrates. After 24 and 30 h of incubation, the oxygen level was measured. A further set of pouches were taken from the inoculated platelet concentrates at 24 h. Incubation and reading intervals were as for the initial set of pouches. A sensitivity study was also performed comparing the Pall eBDS with the BacT/ALERT system. Spiking at 10 cfu mL(-1) and immediately sampling into Pall eBDS pouches resulted in 97.6 and 100% detection after an incubation period of 24 and 30 h, respectively. After 24 h of incubation of the spiked platelet concentrates and then sampling into Pall eBDS pouches, 99.1% detection was obtained after incubation for both 24 and 30 h. The sensitivity of the Pall eBDS and BacT/ALERT is similar and in the order of 1 cfu mL(-1). Implementation of either BacT/ALERT or Pall eBDS for routine screening of platelet concentrates has the potential to further increase the safety of the blood supply.

Bacteria, Aerobic↗

Pre-storage leucocyte depletion and transfusion reaction rates in cancer patients.

Passenger leucocytes transfused with allogenic blood are responsible for potential adverse effects. The impact of pre-storage leucodepletion (in-line filtration) of all whole blood units on transfusion reaction rate among patients suffering from cancer was retrospectively studied, comparing all reactions following red blood cell (RBC) transfusions during 2 years of pre-storage vs. 2 years of selective (bedside) leucodepletion. During selective leucodepletion, 5165 RBC units - of which 2745 were bedside filtered units- were transfused to 866 patients. Twenty-eight reactions were recorded: 22 (15 in the bedside group) febrile non-haemolytic transfusion reactions (FNHTR) and six allergic reactions (five in the bedside group). The overall percentage of reactions was 0.54 (0.76 for bedside) and 0.42 for FNHTR (0.54 for bedside). During pre-storage leucodepletion, 4116 RBC units were transfused to 841 patients. Eleven reactions were recorded: four FNHTR and seven allergic reactions (urticaria). The percentage of reactions for transfused RBC units was 0.26 (0.09 for FNHTR). Comparison between pre-storage filtration and bedside filtration with regard to FNHTR showed an odds ratio of 2.80 (95% confidence interval = 0.83-14.87) for bedside filtration. The study suggests that, for transfused patients affected by cancer, pre-storage leucodepletion is more effective than selective (bedside) filtration in reducing the incidence of transfusion reactions (FNHTR).

Adolescent↗

Cost-effectiveness of leucocyte-depleted erythrocyte transfusion in cardiac valve surgery.

Cost-effectiveness of leucodepleted erythrocytes (LD) over buffy-coat-depleted packed cells (PC) is estimated from the primary dataset of a recently reported randomized clinical trial involving valve surgery (+/-CABG) patients. Data on the patient level of 474 adult patients who were randomized double-blind to LD or PC were used in order to calculate the healthcare costs and longevity per patient. The incremental cost-effectiveness ratio (ICER) in net costs per life-year gained was established from the healthcare perspective. Bootstrapping and cost-effectiveness acceptability curves were used in order to determine the confidence interval (CI) of the ICER. The longevity of patients in the PC and LD group was 10.6 and 11.4 years, respectively. Relative to PC, LD yielded an estimated 0.8 (95% CI = -0.27 to 1.84) life-year in the baseline. Adjusted for age and sex differences, health gains for LD are 0.4 life-year gained (95% CI = -0.67 to 1.44). Healthcare costs per patient averaged 10163 US dollars per patient in the PC group and 9949 US dollars in the LD group. Average cost-savings were 214 US dollars (95% CI = -1536 to 1964) per patient. Acceptability curves constructed from bootstrap simulations showed a probability of being cost-saving of 59% for universal leucodepletion from the healthcare perspective. The probability of adopting leucodepletion regardless of the costs reaches 92.7%. LD in patients receiving four or more transfusions showed the highest cost-savings and health gains. Leucodepletion of erythrocytes is a cost-saving strategy in cardiac valve (+/-CABG) patients. However, probablistic analysis failed to show a significant difference with buffy-coat-depleted PC.

Aged↗

Prestorage leucoreduction improves several in vitro red cell storage parameters following gamma irradiation.

Gamma irradiation (GI) can prevent transfusion-associated graft-vs.-host disease, result in a small decrement in 24-h in vivo red blood cell (RBC) recovery and in a minor loss of maintenance of several in vitro parameters during routine storage. Results from studies by Davey et al. (Transfusion 1995, 35, 55S) demonstrated that the decrement in 24-h recovery was not observed if units were first leucoreduced (LR), suggesting that RBC damage on leucocytes from GI was secondary to the effects of irradiation . In this study, we further investigated how leucoreduction affected eight in vitro storage parameters of gamma-irradiated units by using a matched sample study design. Leucoreduction significantly reduced (P < 0.05) the deleterious effect of GI on adenosine triphosphate glucose levels, haemolysis and mean corpuscular volume (MCV) for AS-3 units and significantly decreased (P < 0.05) the deleterious effect of GI on glucose levels, haemolysis and MCV for AS-1 units. Leucoreduction did not influence (P >> 0.5) the enhanced potassium release associated with GI. Some, but not all, the observed RBC damage caused by GI appears to be secondary to the effect of irradiation on leucocytes. Based on the in vivo survival studies of Davey et al. and the results of this study, there is justification to consider performing additional survival studies to support extended storage of LR gamma-irradiated RBC.

Adenosine Triphosphate↗

Effect of combined T- and B-cell depletion of allogeneic HLA-mismatched bone marrow graft on the magnitude and kinetics of Epstein-Barr virus load in the peripheral blood of bone marrow transplant recipients.

Recipients of T-cell-depleted bone marrow (BM) transplants (BMT) frequently develop Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disease (PTLD) preceded by a rapid and prominent increase of EBV load in the peripheral blood. The level of this increase positively correlates with the incidence of PTLD. Using a semiquantitative PCR assay we compared the blood levels of EBV-DNA in patients transplanted with either T-cell or T- and B-cell-depleted human leukocyte antigen (HLA)-mismatched BM grafts. Combined T- and B-cell depletion correlated with significantly lower maximal levels of EBV load, which were reached with slower kinetics. These data indicate that B-cell depletion of BM can be used for prophylaxis of PTLD in BM transplant recipients and can affect the long-term balance between EBV and its host.

Acute Disease↗

Effects of extended storage of whole blood before leucocyte depletion on coagulation factors in plasma.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the quality of leucocyte-depleted plasma produced from leucocyte-depleted whole blood, stored for different periods of times before filtration through polyurethane filters. MATERIALS AND METHODS: Whole blood was collected, from 48 voluntary donors, into quadruple blood bag sets with integrated whole-blood filters, and stored at room temperature for 1, 2, 6, or 18 h before filtration. Five samples were taken: one directly from the donor; one immediately after collection; one before and one after filtration; and one from plasma units before freezing. All samples were analysed for the following parameters: prothrombin time; activated partial thromboplastin time; prothrombin fragments F1+2; fibrinogen; factors VIII, XI and XII; von Willebrand factor antigen; ristocetin cofactor activity; collagen-binding capacity; multimers; and complement C3a-desArg. RESULTS: Different whole-blood storage times before filtration did not have a significant effect on the stability of coagulation factors. The activity of all investigated coagulation factors in plasma was generally above 90 U/dl, even after 18 h of storage of whole blood before filtration. von Willebrand factor multimeric distribution remained stable throughout the process. However, activation of complement did occur during storage. CONCLUSIONS: Leucodepleted plasma originating from leucodepleted whole blood maintains a satisfactory level of coagulation factors, even after the storage of whole blood for 18 h at room temperature before filtration.

Adult↗

Influence of blood prestorage conditions and white blood cell filtration on the bacterial load of blood deliberately inoculated with Gram-positive and Gram-negative pathogens.

BACKGROUND AND OBJECTIVES: Currently, the bacterial contamination of blood constitutes one of the major infectious risks of transfusion. The aim of this study was to evaluate the bactericidal effect of blood on various bacterial species and to determine the influence of prestorage conditions and white blood cell (WBC) filtration on the reduction of the bacterial load in isolated red blood cells (RBCs). MATERIALS AND METHODS: The growth kinetics of eight different species of bacteria were studied at 20 degrees C in deliberately contaminated RBC units. Further experiments evaluated the effect of prestorage conditions and WBC filtration on the viability of two model bacteria (Klebsiella oxytoca and Staphylococcus epidermidis) in comparison to previous results obtained with Yersinia enterocolitica. RESULTS: For bacteria susceptible to the bactericidal effect of blood (mainly Gram-negative rods), a reduction of the bacterial load was obtained within 2 h of prestorage at 20 degrees C. When the prestorage period was prolonged beyond 3 h at 20 degrees C, rapid growth was observed with some Enterobacteriaceae. Whereas WBC filtration reduced dramatically the viability of Y. enterocolitica, it had only a minimal effect on the viability of S. epidermidis and K. oxytoca. However, the two latter species of bacteria did not survive prolonged storage at 4 degrees C. CONCLUSIONS: Experiments conducted under realistic conditions are needed to determine whether it would be worthwhile recommending the rapid storage of RBCs at 4 degrees C after WBC reduction of the blood product.

Bacteriological Techniques↗

Leucodepletion leads to component-like storage stability of whole blood--suggesting its homologous use?

BACKGROUND AND OBJECTIVES: Leucodepleted whole blood (LWB) is already widely used for autologous donations and could also be appropriate for certain instances of allogeneic transfusion provided that storage quality can be preserved at component-like levels. MATERIALS AND METHODS: Sixteen units of whole blood (WB), donated by healthy volunteers into CPDA-1 according to German guidelines, were leucofiltered prestorage and stored for up to 49 days. Unfiltered WB in CPDA-1 (UFWB, n=16) and filtered red blood cells in SAGM (RCC, n=14) served as controls. Several haematological, biochemical and coagulatory quality parameters were determined at designated time-points during storage. RESULTS: Apart from significant differences (P<0.05) in haematocrit (56.2+/-3.6 vs. 37.9+/-3.9%), and in the plasma concentrations of free haemoglobin (93.1+/-37.8 vs. 57.8+/-24.3 g/dl), K+ (38.9+/-5.3 vs. 31.5+/-4.3 mm) and ATP (2.7+/-0.2 vs. 1.6+/-0.4 micromol/g haemoglobin), with higher levels detected in RCC, no remarkable differences (P>0.05) were observed regarding haemolysis (0.23+/-0.07% vs. 0.31+/-0.13) and pH value (6.63+/-0.03 vs. 6.62+/-0.02) between RCC and LWB at the end of storage. Lack of leucodepletion manifested in significantly (P<0.05) higher rates of haemolysis (0.44+/-0.21%), free haemoglobin (89.6+/-43.5 g/dl) and lower pH values (6.56+/-0.04). During 42 days of LWB storage, sufficient amounts (% of the initial mean value) were observed with stable (factor XI, 97.5+/-15.0) and labile (factor V, 92.9+/-18.0; factor VIII, 69.2+/-17.1) clotting factors and inhibitors (antithrombin III 88.9+/-9.5), without any signs of activated coagulation. CONCLUSIONS: Our data indicate that the quality of LWB is comparable to that of components during 42 days of storage. Thus, LWB could be an interesting option for using to facilitate and economize the blood supply, especially for surgical or trauma patients.

Blood Coagulation Factors↗