Acomplex issue commonly faced by the blood

Transcription

1 HOW DO I...? How do we investigate and manage donors associated with a suspected case of transfusion-related acute lung injury Leon Su and Hany Kamel Acomplex issue commonly faced by the blood collection facility is how to best investigate and manage donors involved in a suspected case of transfusion-related acute lung injury (TRALI). To date, there is no detailed or uniform approach to managing donors associated with a suspected case of TRALI, although useful guidelines have been published by the AABB. 1 Further complicating the issue is our incomplete understanding of TRALI. Current knowledge on TRALI suggests that the cause of TRALI may be multifactorial and that there are immune and possibly separate or combined nonimmune mediated mechanisms that can result in TRALI. 2-4 Of the cases reported, it is estimated that the majority (approx. 89%) have an immune-mediated component, where human leukocyte antigen (HLA) or neutrophil antibodies have been identified in the donor. 4-6 There is also data from the American Red Cross between 2003 and 2005 that shows 71 percent of all probable TRALI cases that resulted in a fatality involved female donors that were antibody-positive. 7 The result is that workups for suspected cases of TRALI predominantly focus on identifying donors with antibodies as they are believed to be the donors at highest risk for causing severe TRALI reactions. Although there are good data to suggest which donors may be at highest risk for causing severe TRALI, there is sparse guidance available on how to investigate and manage donors involved in a suspected case of TRALI. In particular, little is known regarding what data are important to collect, which donors to test, and what to do with test results. In an attempt to provide a detailed approach ABBREVIATIONS: BNP = B-type natriuretic peptide; TACO = transfusion-associated circulatory overload. From Blood Systems, and United Blood Services of Arizona, Scottsdale, Arizona. Address reprint requests to: Leon Su, MD, Blood Systems, 6210 E. Oak Street, Scottsdale, AZ 85257; lsu@ bloodsystems.org. Received for publication April 9, 2007; accepted April 9, doi: /j x TRANSFUSION 2007;47: to donor management in suspected cases of TRALI, we have developed a strategy that details the handling of these cases beginning from the moment we are made aware of a case up to deciding which donors to defer. Different approaches to evaluating donors in a suspected case of TRALI have been published, all with good merit. 6,8,9,13 For the most part, these strategies may differ in details, but they are built on the same common principles. Our approach represents an alternative way to think about and handle these cases. The overall design reflects a strong effort to balance blood safety with the need to control rising costs and avoid needless s. OUR APPROACH All suspected cases of TRALI reported to our blood centers are investigated in the steps outlined below. Upon completion of the investigation, a letter describing the outcome of the investigation is sent to the reporting facility. Letters are also sent to any donor requiring as a result of a TRALI investigation. The investigative process is divided into four general steps. COLLECT CLINICAL INFORMATION Regulatory oversight on the management of adverse reactions due to blood transfusion requires that unexpected adverse events suspected to be related to an attribute of a donor or a unit be reported to the collecting facility. 10,11 To that end, suspected TRALI reactions are reported to our blood centers from the hospital transfusion service via a standardized adverse reaction form. This form is geared toward capturing details relevant to a suspected TRALI or bacterial contamination investigation. Information of interest includes the type and label of the units involved and the time and date the blood products were transfused. In addition, a clinical description of the adverse reaction and a timeline of the events leading up to and after the transfusion reaction are captured on the form. Once the form is received, any in date cocomponents linked to donors associated with the adverse reaction are traced and quarantined. These components are kept quarantined until the investigation is complete TRANSFUSION Volume 47, July 2007

2 MANAGING DONORS WITH SUSPECTED TRALI If a blood component marked for retrieval has already been transfused, the recipients are investigated for any potential transfusion reactions. After review of the adverse reaction form, the first step we take is to ask the hospital blood bank to assist in the investigation. The blood bank staff can help gather additional documentation such as the hospital s own transfusion reaction workup and any pertinent patient records such as progress notes or laboratory results from the day of the reaction. Additionally, the blood bank staff can assist in obtaining a recipient sample for HLA and/or neutrophil antigen typing. If an associated blood component was not entirely transfused and returned to the blood bank, a request can be made for the blood component to be returned to the blood center. In some situations, these blood components may be suitable for HLA and/or neutrophil antibody testing. In general, the focus of our investigation is to gather clinical information as it pertains to the recommended definition of TRALI set forth by the National Heart, Lung, and Blood Institute (NHLBI) working group on TRALI 12 and the Canadian consensus conference panel. 13 To best accomplish this, we make every effort to discuss the adverse event with the clinician reporting the transfusion reaction. This is an important step in the data collection process because many details about the reaction are often not captured in the documentation reported to the hospital blood bank. Discussion of the event with the clinician also serves as an opportunity to learn more about the patient s overall medical condition. Details that we try to capture when speaking with the clinician include, but are not limited to, the indications for transfusion, the admitting diagnosis, the hospital course, and the presence or absence of other medical conditions that may cause acute lung injury. If other conditions that can cause acute lung injury are present in the recipient, then these conditions are fully evaluated for history, date and/or time of onset, current status, and treatment. For instance, we are justifiably more suspicious about TRALI in the setting of a patient with a stable pneumonia who has completed antibiotic treatment than in the setting of a newly diagnosed pneumonia that has not completed treatment, continues to evolve, and is temporally related to the acute lung injury. It is not uncommon for both scenarios above to be captured as history of pneumonia in the documentation received by the blood center despite being markedly differently; such an example underscores the importance of speaking with the clinician for all TRALI investigations. After a thorough medical background is obtained, attention is shifted to investigating details commonly associated with the diagnosis of TRALI. If it has not already been documented, it is important to inquire about the presence or absence of signs and symptoms such as dyspnea, fever, hypotension, tachypnea, and/or tachycardia at the time of the adverse reaction. When documenting evidence of hypoxia, it is helpful to not only know the patient s oxygen saturation at the time of reaction, but to also inquire about the oxygen requirement and whether or not the patient required ventilatory support. If available, arterial blood gas values are useful in assessing the degree of hypoxia and for calculating PaO 2/FiO 2 ratios. If the reaction is recent and a chest X-ray has not been performed, talking with the clinician can serve as a reminder to obtain a chest X-ray. Finally, we will ask whether the patient experienced a transient decrease in WBC count at the time of reaction; such an observation has been noted previously in reported cases of TRALI. 14 Equally important in trying to fit the adverse reaction to a diagnosis of TRALI is to rule out transfusionassociated circulatory overload (TACO) as a cause of the adverse reaction. To do so, we will inquire about the patient s cardiac history, any physical signs suggestive of volume overload, the patient s input and output volume, pulmonary wedge pressure if known, central venous pressure if known, any recent echocardiogram results, and any past episodes of acute circulatory overload. A B-type natriuretic peptide (BNP) level can be very helpful in predicting the presence or absence of TACO. A recent prospective study evaluating the use of a BNP level in the emergency diagnosis of heart failure judged an elevated result of more than 100 pg per ml to be the optimal cutoff level for the diagnosis of congestive heart failure. 15 The same study also showed a negative predictive value of 96 percent for levels of less than 50 pg per ml. In a separate study, application of a BNP level as a diagnostic marker for TACO with a cutoff of 100 pg per ml or a posttransfusion-topretransfusion ratio of at least 1.5 yielded a sensitivity of 89 percent and a specificity of 81 percent, further demonstrating the usefulness of BNP as an adjunct marker in identifying TACO. 16 Perhaps of even greater utility in the diagnosis of TACO is the use of atrial natriuretic peptide, a marker not commonly used for congestive heart failure but may be superior to BNP given its rapid release and shorter t 1/2, which correlates more closely with the kinetics of an acute volume overload. 17 The final step we take in collecting clinical information is to gather information on the treatment and clinical course after the adverse reaction. Questions of interest include what medications and/or interventions were administered to the patient and what was their response to treatment. A rapid response to therapy such as diuretics is helpful to know and suggestive of TACO over TRALI. Knowing the time course to resolution is also helpful information given that the typical time course for TRALI ranges from 48 to 96 hours, with most cases resolving within 72 hours of onset. 2,8 Finally, because TRALI is a clinical diagnosis by exclusion, it is always helpful to ask the clinician his or her opinion on what they think has caused the patient s adverse reaction. Such information Volume 47, July 2007 TRANSFUSION 1119

3 SU AND KAMEL is helpful to take into consideration when deciding on how to best classify the reaction. CLASSIFY THE REACTION All our cases are classified based on the existing definition of TRALI as recommended by the Canadian consensus conference panel. 13 This classification is important because the use of a widely accepted definition facilitates the comparison of TRALI incidence reported from different hospitals and different blood collection facilities. Thus, cases that qualify as TRALI or possible TRALI are labeled as such. In some cases, required criteria may be missing to make a diagnosis of TRALI or possible TRALI. For instance, a frontal chest radiograph may not have been performed but there may be other clinical evidence to suggest pulmonary edema such as frothy sputum or frothy endotracheal aspirate from the patient. In such cases, a decision may still be made to label the reaction as TRALI or possible TRALI, even if the adverse event does not exactly meet the recommended criteria. Any substitution in criteria is properly documented with the case so that differences are clear when cases are compared across different institutions. For the purposes of donor investigation and management, cases that qualify as possible TRALI and cases that do not meet the criteria of TRALI or possible TRALI are further subclassified (Table 1). The idea behind subclassification is that not all cases that fall into the above categories should be investigated and managed in the same way. Cases of possible TRALI are further subdivided clinically into cases that are likely to be TRALI, equivocal for TRALI, and unlikely to be TRALI. In our experience, such breakdown is necessary given the wide clinical spectrum of cases that meet the criteria for possible TRALI. This distinction is made at the time of classification because these subcategories play a role in which donors we test and how we ultimately manage our donors. Cases that we typically classify as likely to be TRALI are cases where there is consensus among the clinicians, hospital transfusion service medical director, and the blood center physician that despite the presence of an alternative risk factor for acute lung injury, the overall clinical impression is that Category TRALI Possible TRALI TABLE 1. Classifying the Reaction Subcategory Possible TRALI or TACO TACO Not TRALI Likely to be TRALI Equivocal for TRALI Unlikely to be TRALI Likely to be TRALI Equivocal for TRALI Unlikely to be TRALI TRALI is the most likely cause of the symptoms. These cases get managed in the same way as TRALI cases. In equivocal cases, it is unclear from the clinical information available whether the adverse event is the result of TRALI or if it is due to an alternative risk factor. There may be a discrepancy in medical opinion between the clinician, the hospital transfusion service medical director, and the blood center physician regarding the cause of the adverse event. Other times, cases will fall into this category because there is simply not enough clinical information available to make a definitive decision one way or the other. Although we try to avoid putting cases into this category, the reality is that there are cases that best fit into an equivocal category. Donors involved in these cases are investigated if they are later discovered to be at high risk for causing TRALI by history. Cases that get subclassified as unlikely to be TRALI are cases that despite meeting the clinical criteria for possible TRALI, the clinical impression by all is that another risk factor is the more likely cause of the acute lung injury. Nonetheless, these cases are reported to the blood center just to rule out TRALI. In some cases, there is the misconception that HLA and/or neutrophil antibody testing is diagnostic for TRALI and a request will come to the blood center to test donors to rule out TRALI. In other cases, the reporting transfusion service may not have experience with TRALI and are reporting the case simply for a second opinion. No case is ever classified as unlikely to be TRALI until the case is discussed with the clinician and the hospital transfusion service medical director. If after discussion there is consensus that TRALI is unlikely, then the case is managed in the same way we manage cases that are determined not to be TRALI. A recognized limitation of the Canadian consensus conference definition is the exclusion of circulatory overload from the category of possible TRALI; by definition cases with evidence suggestive of circulatory overload are not classified as TRALI or possible TRALI. Yet, one cannot exclude the possibility that TRALI and circulatory overload can occur together. 17 As a result, cases where circulatory overload is in the differential but otherwise the case would fit the category for possible TRALI are classified in a category called possible TRALI or TACO. Like possible TRALI, the category of possible TRALI or TACO can also be further subdivided into cases that are likely to be TRALI, equivocal for TRALI, and unlikely to be TRALI. If TACO is the likely cause of the reaction and the reaction does not meet other criteria to suggest possible TRALI, then the case is labeled as TACO only. All other cases that do not meet any of the criteria above are classified as not TRALI. Similar to cases that are unlikely to be TRALI, any suspected case of TRALI that eventually gets classified as not TRALI is discussed with the hospital transfusion service to ensure that there is agreement in the classification. Once we have placed the adverse reaction into a diagnostic 1120 TRANSFUSION Volume 47, July 2007

4 MANAGING DONORS WITH SUSPECTED TRALI category, we then proceed to determine whether donors need to be tested. DECISION TO TEST The decision to test for HLA and/or neutrophil antibodies in associated donors is done for the purposes of donor management. We try to avoid performing HLA and/or neutrophil antibody testing to confirm or rule out TRALI because TRALI is currently defined as a clinical diagnosis by exclusion. In addition, there are two caveats to HLA and/or neutrophil antibody testing that prevent it from being a useful diagnostic test for TRALI. The first is that it is generally recognized that not all HLA and/or neutrophil antibodies will cause a TRALI reaction in a recipient. 3,18 An antibody-antigen match is consistent with a diagnosis of antibody-mediated TRALI but its presence alone does not make a diagnosis of TRALI. The second is that not all cases of TRALI are believed to be antibody-mediated; hence if an antibody is not found in an associated donor, it does not follow that TRALI has not occurred. The first step in deciding which donors to test is to identify all donors whose blood products were transfused within 6 hours of the adverse event. Donors whose blood products were transfused outside of the 6-hour window are removed from investigation. The remaining donors are considered associated donors to the case. They are contacted and asked the following questions: Have you ever received a blood transfusion or received a human-derived tissue graft? Female donors only: Have you ever been pregnant or had a miscarriage or an abortion? A yes answer to either question places the donor at high risk for causing TRALI in a recipient. The high risk for these donors is based on the increased likelihood of having HLA and/or neutrophil antibodies due to a history of being exposed to a foreign antigen. It is estimated that HLA alloimmunization can occur in the reported range of 8 to 40 percent in parous women, with increasing percentages associated with increasing number of pregnancies. 3,4,19 Alloimmunization to neutrophil-specific antigens is estimated at approximately 2 percent of parous women. 4,20 Less is known about the percentages of alloimmunization in patients with a history of transfusion and/or tissue graft. An ongoing REDS II (The Retrovirus Epidemiology in Donors II) study examining HLA and leukocyte antibody prevalence (LAPS) in blood donors will eventually shed more light in this area and provide better guidance in identifying those donors at high risk. A high-risk status may also be given to donors who were previously associated with a suspected TRALI case. If a donor was previously flagged with being associated with a TRALI, possible TRALI, or possible TRALI or TACO, the previous case is reviewed. Depending on the degree of association and the likelihood of TRALI in the previous case and in the present case, the donor may be assigned a high-risk status. For example, if donors were previously associated with a case likely for TRALI but they were not tested, we would consider assigning the donors a high-risk status at the time of the second hit. In contrast, if a donor was previously 1 of 14 associated donors and an implicated donor had already been identified in the previous case, we would consider the first hit to be less relevant and would not assign a high-risk status to the donor at second hit. Once all high-risk donors are identified, we combine this information with our classification of the adverse reaction and test donors according to Table 2. In general, if a case is clinically TRALI or likely to be TRALI, we will test all donors regardless of their risk status if the number of associated donors to a case is fewer than or equal to four donors. The four is an arbitrary number and was chosen as a suitable cutoff that considers cost containment while maintaining a reasonable turnaround time for investigation. If there are more than four donors associated with a case, we will first begin by only testing those at high risk. If an implicated donor (i.e., match between donor antibody and recipient antigen) is found, we will finish testing the high-risk donors and we will not perform any further testing on donors not at high risk. If no implicated donor is found in the high-risk group, we will then proceed to test all remaining donors regardless of risk status. Equivocal cases are managed differently than cases that are TRALI or likely to be TRALI. In equivocal cases, the uncertainty of the clinical case places less of a concern that any associated donor would be at great risk of causing a future TRALI event. Therefore, only donors that are assigned a high-risk status are tested. If no high-risk donors are implicated, no further testing is performed on remaining donors. For cases that are not likely to be TRALI or do not qualify for TRALI, no donor testing is performed. If new TABLE 2. When to test for HLA and/or neutrophil antibodies Category or subcategory Not more than four donors More than four donors TRALI or likely to be TRALI Test all Test high-risk donors first. If implicated donor found, no further donor testing. If no implicated donor found, test remaining donors. Equivocal for TRALI Test high-risk donors only Test high-risk donors only Not TRALI or TACO or unlikely to be TRALI No test No test Volume 47, July 2007 TRANSFUSION 1121

5 SU AND KAMEL information becomes available to suggest that TRALI is more likely, the case can be reviewed and reclassified. Otherwise, once a case is designated not likely to be TRALI or not TRALI, the investigation is complete and no further action is taken on the associated donors. Overall, for all cases a letter will be written to the reporting hospital to summarize the outcome of the investigation. Again, any case that does not result in testing is discussed with the hospital transfusion service to ensure that all parties agree with the course of action. Recipient antibody testing is not typically performed in our investigations. We limit our testing to donors because the majority of antibody-mediated TRALI cases involve a donor antibody directed to a recipient antigen. Nevertheless, collecting data on recipient antibodies may contribute to a better understanding of TRALI. Thus, we may perform antibody testing in recipients when there is academic interest or if requested by the hospital transfusion service, particularly in cases clinically classified as TRALI and donor antibody testing is negative. DONOR MANAGEMENT Upon completion of donor testing, donor s are managed according to the clinical classification and the outcome of the donor testing, if performed (Table 3). According to Table 3, donors will be indefinitely deferred if there is an HLA and/or neutrophil antibody-antigen (cognate) match. A cognate match is assumed if the antibody is directed to a high-frequency antigen or if multiple antibodies are identified and broad specificity is present (i.e., for HLA antibodies, panel reactive antibodies 99% is reported). In such cases, we will forego recipient antigen testing. A donor will also be indefinitely deferred if the antibody identified is a neutrophil antibody directed against human neutrophil antigen-3a (HNA-3a) (5b), with or without a match with the recipient. The reasoning behind deferring all donors with HNA-3a (5b) regardless of clinical classification or recipient data stems from multiple reports in the literature that suggest these antibodies may be more commonly associated with severe or fatal cases of TRALI. 2,18,21 In addition, the HNA-3a (5b) antigen is known to be a high-frequency antigen (97% Caucasian), 3 suggesting a high likelihood of an antibody match in subsequent transfusions. In cases where an antibody is identified in a donor but the recipient data are either not available or there is no match, the donor is deferred from donating high-plasmavolume components. They remain eligible to give whole blood and double red blood cell donations. We currently do not produce platelets from whole blood, and plasma derived from whole blood would be sent for fractionation. If the clinical classification is TRALI or likely to be TRALI and the donor is the only donor associated with the case, consideration may be made to defer the donor indefi- TABLE 3. Donor management HLA and/or neutrophil antibody with specificity HLA and/or neutrophil antibody Donor did not return for testing Donor not tested based on algorithm HLA and/or neutrophil antibody negative Weak with no apparent antigen specificity With specificity, no recipient data No antibodyantigen match Cognate match* Neutrophil antibody HNA-3a (5b) until tested Clinical category or subcategory TRALI or likely to be TRALI, and consider indefinite if single case, and if single case, and consider indefinite if single case, and if single case low-plasma-volume components only, and consider indefinite if single donor involved in case low-plasmavolume components only, and consider indefinite if single donor involved in case Flag donor, indefinite until tested if status unknown low-plasmavolume components only low-plasmavolume components only Equivocal for TRALI * Cognate match assumed for antibodies to high frequency antigens and multiple antibodies with broad specificity. No is necessary if another donor associated with the same case has been implicated TRANSFUSION Volume 47, July 2007

6 MANAGING DONORS WITH SUSPECTED TRALI nitely. In such cases, we will consider the strength of the diagnosis for TRALI, whether the blood product was a high-plasma-volume product, and the time between when the blood product was given to the time the reaction occurred. Donors deferred from donating high-plasmavolume components will be flagged in their donor record with the clinical classification and the resulting type. Donors with HLA and/or neutrophil antibodies that are reported as weak with no apparent antigen specificity, regardless of isotype (i.e., immunoglobulin G [IgG] and/or IgM), are currently treated the same as donors who have no detectable antibody. Some of these antibodies may be false-positive, particularly if the donor is not classified as high risk. Others may be true HLA and/or neutrophil antibodies; however, with a nonspecific and weak pattern of reactivity, the clinical significance is unknown. Until more is known about these antibodies, we will continue to manage these donors the same as donors with no antibodies and donors we do not choose to test; this includes flagging the donor s record and placing no restrictions on future blood donations. Of note, our current TRALI risk reduction measures at United Blood Services restricts production of transfusable plasma in donors who answer yes to TRALI high-risk questions. These risk questions have only recently been incorporated into our donor history questionnaire. As a result, if a donor is identified as high risk by history and they are found to have a weak antibody with no apparent antigen specificity, the donor s future blood donations will still be blocked from production into transfusable plasma. In the event the donor does not return for testing, the donor is placed on indefinite until tested if the clinical case is classified as TRALI or likely to be TRALI. If the case is an equivocal case for TRALI, the donor will only be indefinitely deferred if he or she is considered high risk or if his or her risk status is unknown. Donors who we know are not at high risk but do not return for testing will not be deferred but accordingly flagged in their donor record. SUMMARY Overall, there are several components that we believe are critical for the successful investigation of a suspected case of TRALI. One is verbal communication with the hospital transfusion service and the clinicians taking care of the patient, the importance of which can not be overstated. Data that may be missed or understated on a form are often made clear when questions are asked directly to the clinician. Additionally, communication with the clinical staff improves TRALI education and awareness and streamlines the reporting of future suspected TRALI cases. In short, verbal communication with the hospital transfusion service and clinical staff facilitates a timely and thorough investigation. It also ensures the capture of vital information that assists in the clinical diagnosis and donor management of suspected TRALI cases. Equally important is a clinical classification that is consistent with what other institutions are using to document cases of TRALI. To better understand TRALI, larger case numbers need to be analyzed and studied, and only through consistent reporting and classification can this be accomplished. We currently rely on the working definition recommended by the Canadian consensus conference panel for TRALI and possible TRALI. We have made some modifications to the Canadian consensus conference panel for our classifications, but these modifications are for the purposes of donor management only. As long as complete documentation is maintained, the use of these modifications should not affect our ability to share data with other institutions that do not use similar modifications. Despite our best efforts to establish a consistent and effective way to manage suspected TRALI cases, the management of donors associated with TRALI remains a difficult task given that TRALI remains an incompletely understood reaction. Contributing to the problem is the inconsistent recognition and reporting of TRALI that continues to occur from the bedside to the collecting facility, an issue that ultimately hampers the blood centers ability to recognize and prevent potential TRALI reactions. There is great promise that reporting of suspected TRALI events will improve significantly once the AABB s efforts to establish a US hemovigilance system come to fruition. We expect that these efforts will have similar success to programs already established internationally. A US hemovigilance system will make great strides in improving data collection and may provide new insight into additional risk factors for TRALI in donors. The approach described has been in place for United Blood Services since 2006 and thus far has been effective at providing a consistent framework to our TRALI investigations. Over the past several years, we have investigated approximately 30 to 40 suspected cases of TRALI per year. In 2007, we have had 10 TRALI investigations to date, of which 2 were classified as TRALI or likely to be TRALI. Since implementation of our new approach, donor testing has been reduced from previous years; this is a result of more selective donor testing under the newly designed algorithm. In the past, only donors with antibody to HNA-3a (5b) were deferred. Now, with the criteria for donor expanded, implementation of this protocol has resulted in the of more donors. Our approach represents only one of many potential ways to handle donors associated with TRALI. To what degree a donor is truly at risk for causing TRALI is not well known and thus accounts for the variability in possible strategies. Nevertheless, our current approach represents what we believe to be an effective and judicious strategy Volume 47, July 2007 TRANSFUSION 1123

7 SU AND KAMEL for deferring those donors at highest risk of causing severe or fatal TRALI based on our current understanding of TRALI. As we learn more about TRALI through basic science and improved data collection and reporting, we expect our management of suspected TRALI cases to continue to evolve. ACKNOWLEDGMENTS We are grateful to the physicians affiliated with Blood Systems Research Institute, Blood Centers of the Pacific, Inland Northwest Blood Center, and United Blood Services for their discussion and input into our management of TRALI cases. REFERENCES 1. Mintz PD, Lipton KS. Transfusion-related lung injury [monograph on the Internet]. Association Bulletin Bethesda: American Association of Blood Banks; 2005 Aug Silliman C, Ambruso D, Boshkov L. Transfusion-related acute lung injury. Blood 2005;105: Curtis B, McFarland J. Mechanisms of transfusion-related acute lung injury (TRALI): anti-leukocyte antibodies. Crit Care Med 2006;34(Suppl):S118-S Triulzi D. Transfusion-related acute lung injury: an update. Hematology Am Soc Hematol Educ Program 2006: Popovsky M, Moore SB. Diagnostic and pathogenic considerations in transfusion-related acute lung injury. Transfusion 1985;25: Webert K, Blajchman M. Transfusion-related acute lung injury. Transfus Med Rev 2003;17: Eder A, Herron R, Strupp A, et al. Transfusion-related acute lung injury surveillance ( ) and the potential impact of the selective use of plasma from male donors in the American Red Cross. Transfusion 2007;47: Popovsky M, Chaplin H, Moore S. Transfusion-related acute lung injury: a neglected, serious complication of hemotherapy. Transfusion 1992;32: Kopko PM, Popovsky MA, MacKenzie MR, Paglieroni TG, Muto KN, Holland PV. HLA class II antibodies in transfusion-related acute lung injury. Transfusion 2001; 41: Adverse reaction file, 21 C.F.R. Sect (2002). 11. Standards for Blood Banks and Transfusion Services. 24th ed. Bethesda: American Association of Blood Banks; p Toy P, Popovsky M, Abraham E, et al. Transfusion-related acute lung injury: definition and review. Crit Care Med 2005;33: Kleinman S, Caulfield T, Chan P, et al. Toward an understanding of transfusion-related acute lung injury: statement of a consensus panel. Transfusion 2004;44: Nakagawa M, Toy P. Acute and transient decrease in neutrophil count in transfusion-related acute lung injury: cases at one hospital. Transfusion 2004;44: Maisel A, Krishnaswamy P, Nowak R, et al. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med 2002;347: Zhou L, Giacherio D, Cooling L, Davenport RD. Use of B-natriuretic peptide as a diagnostic marker in the differential diagnosis of transfusion-associated circulatory overload. Transfusion 2005;45: Fiebig E, Wu A, Krombacj J, Tang J, Nguyen KA, Toy P. Transfusion-related acute lung injury and transfusionassociated circulatory overload: mutually exclusive or coexisting entities? Transfusion 2007;47: Kopko PM, Marshall CS, MacKenzie MR, Holland PV, Popovsky MA. Transfusion-related acute lung injury: report of a clinical look-back investigation. JAMA 2002;287: Densmore T, Goodnough L, Ali S, et al. Prevalence of HLA sensitization in female apheresis donors. Transfusion 1999; 39: Clay M, Kline W, McCullough J. The frequency of granulocyte specific antibodies in postpartum sera and a family study of the 6B antigen. Transfusion 1984;24: Davoren A, Curtis BR, Shulman IA, et al. TRALI due to granulocyte-agglutinating human neutrophil antigen-3a (5b): alloantibodies in donor plasma: a report of 2 fatalities. Transfusion 2003;43: TRANSFUSION Volume 47, July 2007