The accuracy of natriuretic peptides (brain natriuretic peptide and N-terminal pro-brain natriuretic) in the differentiation between transfusion-related acute lung injury and transfusion-related circulatory overload in the critically ill.

BACKGROUND: The diagnostic workup of transfusion-related acute lung injury (TRALI) requires an exclusion of transfusion-associated circulatory overload (TACO). Brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic (NT-pro-BNP) accurately diagnosed TACO in preliminary studies that did not include patients with TRALI. STUDY DESIGN AND METHODS: In this prospective cohort study, two critical care experts blinded to serum levels of BNP and NT-pro-BNP determined the diagnosis of TRALI, TACO, and possible TRALI based on the consensus conference definitions. The accuracy of BNP and NT-pro-BNP was assessed based on the area under the receiver operating curve (AUC). RESULTS: Of 115 patients who developed acute pulmonary edema after transfusion, 34 were identified with TRALI, 31 with possible TRALI, and 50 with TACO. Median BNP was 375 pg per mL (interquartile range [IQR], 123 to 781 pg/mL) in TRALI, 446 pg per mL (IQR, 128 to 743 pg/mL) in possible TRALI, and 559 pg per mL (IQR, 288 to 1348 pg/mL) in TACO patients (p = 0.038). The NT-pro-BNP levels among patients with TRALI, possible TRALI, and TACO differed significantly with a median value of 1559 pg per mL (IQR, 629 to 5114 pg/mL), 2349 pg/mL (IQR, 919 to 4610 pg/mL), and 5197 pg/mL (IQR, 1695 to 15,714 pg/mL; p = 0.004), respectively. The accuracy of BNP and NT-pro-BNP to diagnose TACO was moderate with an AUC of 0.63 (95% confidence interval [CI], 0.51-0.74) and 0.70 (95% CI, 0.59 to 0.80). CONCLUSIONS: Natriuretic peptides are of limited diagnostic value in a differential diagnosis of pulmonary edema after transfusion in the critically ill patients.

Lymphocytic duodenosis and the spectrum of celiac disease.

OBJECTIVES: Celiac disease (CD) is a chronic inflammatory disease of the small bowel that is characterized by increased intraepithelial lymphocytes (IELs) and villous atrophy of the mucosa. It is unclear how often intraepithelial lymphocytosis in the absence of atrophy is a manifestation of gluten sensitive enteropathy. The objective of this study was to identify factors that discriminate patients with CD from those with lymphocytic duodenosis (LD, intraepithelial lymphocytosis without villous atrophy). We compared Class 2 HLA type, presenting symptoms, and serology in patients with LD and CD. METHODS: Retrospective review of 124 systematically assessed patients with LD compared with 454 CD patients with villous atrophy. All patients had duodenal biopsies and Class 2 HLA typing performed. HLA type, symptoms, serology pattern, and response to a gluten-free diet were analyzed using univariate logistic regression modeling, adjusted for age and gender. RESULTS: Half of the (63 (51%)) LD patients lack the Class 2 HLA genotypes encoding DQ2 or DQ8 whereas only 11 (2%) CD patients had neither DQ2 nor DQ8, P<0.001. The genes encoding DQ2 were much more prevalent in CD (91%) than that in LD (37%, P<0.001), however, the rate of carriage of DQ8 did not differ between the two groups (15% vs. 15%, P=0.9). Although diarrhea and weight loss were equally frequent in LD and CD patients, LD patients were less likely to be associated with anemia (P=0.007), malaise (P=0.006), skin disorder (P=0.007), or a family history of CD (P<0.001). The LD subjects were much less likely to have tissue transglutaminase or endomysial antibodies than were CD subjects (12% or 0% vs. 87% and 87%; P<0.001, respectively). CONCLUSIONS: The LD cohort differs significantly in terms of HLA type, serology, and clinical features, suggesting that the majority of patients with LD do not belong in the spectrum of CD.

Transplant glomerulopathy: risk and prognosis related to anti-human leukocyte antigen class II antibody levels.

BACKGROUND: Transplant glomerulopathy (TG) is a histopathologic entity of kidney allografts related to anti-human leukocyte antigen (HLA) antibodies. The goal of this study was to determine the relationships among antibody characteristics (level and specificity), risk for TG, and graft survival. METHODS: The presence and characteristics of anti-HLA antibody were assessed by single antigen beads assays in stored pretransplant sera from 598 kidney recipients with negative T-cell crossmatch. Transplant glomerulopathy was diagnosed by surveillance and clinical biopsies. RESULTS: Thirty-nine percent of patients presented with anti-HLA antibodies pretransplant. Transplant glomerulopathy was diagnosed in 73 patients (12%) during 54+/-19 months of follow-up. The risk of TG increased with higher anti-HLA-II antibody levels (HR=1.890, 95% CI 1.42-2.52; P<0.0001), donor specificity of the antibodies (3.524 [1.67-7.44]; P=0.001), and in patients with history of antibody-mediated rejection (4.985 [2.77-8.97]; P<0.0001, multivariate Cox). Graft survival during the follow-up period was 95% without TG and 62% with TG (P<0.0001). The presence of C4d in peritubular capillaries was an independent risk factor for graft failure after TG diagnosis. Thus, 25% of TG/C4d and 80% of TG/C4d+ grafts failed (P<0.0001). Of interest, higher anti-HLA-II levels were related to the presence of C4d (3.216 [1.376-7.517]; P=0.007). CONCLUSIONS: In T-cell negative crossmatch patients, higher anti-HLA-II antibody levels are related to the increase in the risk of developing TG. Higher antibody levels are also related to the presence of C4d in peritubular capillaries in TG biopsies. Furthermore, the presence of C4d in TG is related to the reduced graft survival.

Predictors of family risk for celiac disease: a population-based study.

BACKGROUND & AIMS: There is an elevated prevalence of celiac disease (CD) in family members (FMs) of CD patients, but most prior studies have been done on selected populations. Our aim was to determine the clinical, serologic, and genetic predictors of CD in FMs of a population-based cohort of index cases. METHODS: Index cases from southeast Minnesota provided contact information for their first-degree relatives. FMs were examined for endomysial antibodies (EMAs), tissue transglutaminase antibodies (tTGAs), and HLA-DQ genotyping. Two questionnaires were applied, Bowel Disease Questionnaire and Short Form Health Survey. Intestinal biopsies were offered if there were any positive autoantibody or seronegative FMs with gastrointestinal symptoms and HLA-DQ at risk for CD. RESULTS: We recruited 111 index cases that had 579 FMs, of whom 344 (59%) were investigated. The average screening rate among families was 65%. A positive tTGA test was found in 47 (14%), 33 with a positive EMA test. CD was diagnosed in 39 (21 males), with an estimated prevalence of 11% (lambda(R) = 16.1). All affected FMs carried the at-risk genotypes. Twenty-one (54%) had "silent" disease, most with severe intestinal villous atrophy. Carrying HLA-DQ2 (odds ratio, 16.1; 95% confidence interval, 2.1-123) and being a sibling (odds ratio, 2.5; 95% confidence interval, 1.1-5.8) are high-risk factors for CD. CONCLUSIONS: CD is more common in first-degree relatives than previously reported in the United States, with siblings having the greatest risk. There is male preponderance of new cases, and many had silent disease despite severe histologic injury. A more proactive case-finding strategy in FMs might improve the diagnostic rate of CD in North America.

Celiac disease autoantibodies in severe autoimmune liver disease and the effect of liver transplantation.

BACKGROUND/AIMS: Celiac disease (CD) is associated with primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis. We investigated the following: (i) the prevalence of tissue transglutaminase antibodies (tTGAs) and endomysial antibodies (EMAs) in end-stage autoimmune liver disease (ESALD), (ii) the correlation among auto-antibodies and the human leucocyte antigen (HLA) haplotype, and (iii) the effect of liver transplantation on antibody kinetics. METHODS: Pretransplantation sera from 488 patients (310 with ESALD, and 178 with non-autoimmune disease) were tested for tTGAs. Positive samples were also tested for EMAs, and retested 6-12 and > or = 24 months post-transplantation. Results were correlated with the HLA type of the recipient. RESULTS: Serological evidence of CD was found in 3% (ESALD) vs. 0.6% (non-autoimmune) of the patients (five-fold increased risk in ESALD). The prevalence of tTGAs (14.2 vs. 5.4%, P=0.0001) and EMAs (4.3 vs. 0.78%, P=0.01) was significantly higher in patients with the HLA-DQ2 or HLA-DQ8 haplotypes. tTGAs and EMAs normalized in 94 and 100%, respectively, without gluten exclusion post-transplantation. Post-transplantation, of the five patients with symptoms of 'classical' CD, three improved. Intestinal lymphoma was diagnosed in another two cases with clinically 'silent' CD. CONCLUSIONS: Patients with ESALD, especially those who are HLA-DQ2 or HLA-DQ8 positive had a high prevalence of CD-associated antibodies. Both tTGAs and EMAs decreased post-transplantation without gluten withdrawal. Immunosuppression may improve symptoms of CD, but might not prevent progression to intestinal lymphoma.

HLA DRB1*13 as a risk factor for type 1 autoimmune hepatitis in North American patients.

Our goal was to determine if HLA DRB1*13 is associated with autoimmune hepatitis in North American patients. Two hundred and ten adults with definite type 1 autoimmune hepatitis were typed by DNA-based techniques, and the frequency of HLA DRB1*13 in patients without DRB1*03 and DRB1*04 was compared to that in 396 patients with eight other chronic liver diseases and 102 normal individuals. HLA DRB1*13 occurred more commonly in the autoimmune patients who lacked DRB1*03 and DRB1*04 than normal subjects who were similarly restricted (56% vs. 27%, P = 0.007). The frequency of HLA DRB1*13 was higher in autoimmune patients without DRB1*03 and DRB1*04 than in patients with other chronic liver diseases who were similarly restricted (59% vs. 32%, P = 0.01). Only patients with primary sclerosing cholangitis had a comparable occurrence of HLA DRB1*13. In conclusion, HLA DRB1*13 may be a genetic risk factor for some white North American patients with type 1 autoimmune hepatitis.

HLA DQ gene dosage and risk and severity of celiac disease.

BACKGROUND & AIMS: Celiac disease (CD) is a chronic inflammatory disorder of the small intestine that is strongly associated with certain HLA molecules encoded by DQA and DQB genes. The aim of this study was to examine the role of DQA and DQB alleles in determining the risk for and the age of onset and severity of CD in an American population. METHODS: High-resolution class 2 HLA genotyping was performed in a population-based sample (n = 84) of southeastern Minnesota residents with CD and a comparable control group (n = 102) to determine the contribution of DQA and DQB alleles to disease risk. Logistic regression modeling was used to examine the relative and absolute risks of CD. RESULTS: Ninety-seven percent of CD patients carried both of the HLA alleles, DQA1*05 and DQB1*02. Those who carried a second allele of DQB1*02 were 5 times more likely to have CD than those with just one (95% confidence interval, 1.4-18.1). The carriage of 2 copies of DQB1*02 did not predict either an earlier age of onset or severity of disease. CONCLUSIONS: Both HLA alleles DQA1*05 and DQB1*02 are associated with a greatly increased risk of CD, although the latter has the greater effect. Carrying 2 copies of DQB1*02 was associated with an even greater risk for disease but did not predict an earlier age of onset and diagnosis or disease severity. Assessing the copy number of the DQB1*02 allele might allow for the stratification of disease risk.

The effect of antithymocyte globulin on anti-human leukocyte antigen antibody detection assays.

BACKGROUND: We evaluated the effect of antithymocyte globulin (ATG) on anti-human leukocyte antigen (HLA) antibody assays. METHODS: We tested sera from six in vivo ATG-treated kidney transplant patients after measuring serum concentrations, as well as six nonsensitized sera with ATG added in vitro. T- and B-cell complement-dependent cytotoxicity (CDC), flow cytometric (FXM), and solid-phase HLA class I and II assays based on antigen-coated microspheres and enzyme-linked immunosorbent assay (ELISA) were studied. Sera were then retested after treatment to remove ATG. RESULTS: We found that ATG affects test results differently depending on whether sera is obtained from in vivo treated patients or added in vitro. In vitro treated sera produced ATG concentration-dependent positive results for T/B CDC, FXM, and flow bead testing for HLA I/II, while the ELISA-based assay was unaffected. In vivo treated sera from ATG-treated patients produced positive test results for T CDC and T/B FXM, while the B-cell CDC crossmatch remained negative. Solid phase assays were minimally affected using in vivo treated sera. After ATG extraction, all tests became negative. CONCLUSION: We conclude that ATG produces positive results in anti-HLA antibody testing, and treatment to remove ATG abolishes this effect. This treatment allows ATG-treated patients to be monitored for anti-HLA antibodies.

Graft vs. host disease after liver transplantation: a new approach is needed.

Graft-vs.-host disease (GVHD) is a rare, serious complication of orthotopic liver transplantation (OLT). We have treated 5 patients to date with GVHD after OLT. A total of 78 patients worldwide have been reported to have experienced this complication. The means by which GVHD after OLT has been managed is guided by experience with the more common GVHD that occurs after stem cell transplantation. However, despite the use of various treatment modalities, the mortality of GVHD after OLT remains high. This case series and review of the literature demonstrates that successful resolution of GVHD after OLT cannot be expected with the use of those modalities that have been tried to date. It is imperative that new treatments be applied to GVHD after OLT in order to improve the prognosis of patients with this diagnosis.

Transfusion-related acute lung injury in the critically ill: prospective nested case-control study.

RATIONALE: Acute lung injury (ALI) that develops 6 hours after transfusion (TRALI) is the leading cause of transfusion-related mortality. Several transfusion characteristics have been postulated as risk factors for TRALI, but the evidence is limited to retrospective studies. OBJECTIVES: To compare patient and transfusion risk factors between patients who do and do not develop ALI. METHODS: In this prospective cohort study, consecutive transfused critically ill patients were closely observed for development of ALI. Donor samples were collected from the transfusion bags. Risk factors were compared between patients who developed ALI after transfusion and transfused control patients, matched by age, sex, and admission diagnosis. MEASUREMENTS AND MAIN RESULTS: Seventy-four of 901 transfused patients developed ALI within 6 hours of transfusion (8%). Compared with transfused control subjects, patients with ALI were more likely to have sepsis (37 vs. 22%, P = 0.016) and a history of chronic alcohol abuse (37 vs. 18%, P = 0.006). When adjusted for patient characteristics, transfusion of plasma from female donors (odds ratio [OR], 5.09; 95% confidence interval [95% CI], 1.37-18.85) rather than male donors (OR, 1.60; 95% CI, 0.76 to 3.37), number of pregnancies among the donors (OR, 1.19; 95% CI, 1.05 to 1.34), number of donor units positive for anti-granulocyte antibodies (OR, 4.85; 95% CI, 1.32-17.86) and anti-HLA class II antibodies (OR, 3.08; 95% CI, 1.15-8.25), and concentration of lysophosphatidylcholine in the donor product (OR, 1.69; 95% CI, 1.10 to 2.59) were associated with the development of ALI. CONCLUSIONS: Both patient and transfusion risk factors determine the probability of ALI after transfusion. Transfusion factors represent attractive targets for the prevention of ALI.

Transfusion from male-only versus female donors in critically ill recipients of high plasma volume components.

OBJECTIVE: To reduce the incidence of transfusion-related acute lung injury (ALI), the American Association of Blood Banks recently recommended rapid implementation of strategies to minimize transfusion of high plasma volume components, fresh frozen plasma and apheresis platelets, from potentially alloimmunized donors, especially females. The objective of this study was to evaluate the effect of transfusing components from male-only vs. female donors on development of ALI, gas exchange, and outcome in critically ill patients. DESIGN: In this retrospective case-control study, we identified patients who received high plasma volume components from male-only donors and compared them with patients matched by severity of illness, postoperative state, and number of transfusions but who received high plasma volume components from female donors. SETTING: Four intensive care units at a tertiary medical center. PATIENTS: Critically ill patients who received >2 units of fresh frozen plasma or apheresis platelets. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: From a database of 3,567 patients who received a total of 46,101 units of fresh frozen plasma and 6,251 units of apheresis platelets, we identified 112 patients who received three or more male-only donor components and 112 matched controls. Baseline characteristics, ALI risk factors, and development of ALI were similar between the two groups. Arterial oxygenation (PaO2/FIO2) worsened after the female (mean difference -52, 95% confidence interval -14 to -91, p = .008) but not after male-only donor product transfusion (mean difference 22, 95% confidence interval -23 to 67, p = .325). Male-only component recipients had more ventilator-free days (median 28 vs. 27, p = .006) and a trend toward lower hospital mortality rates (14% vs. 24%, p = .054). CONCLUSIONS: In critically ill recipients of high plasma volume components, gas exchange worsened significantly after transfusion of female but not male donor components. Prospective studies are needed to evaluate the effect of recommendations by the American Association of Blood Banks on outcome of transfused critically ill patients.

Fresh-frozen plasma and platelet transfusions are associated with development of acute lung injury in critically ill medical patients.

BACKGROUND: Transfusion has long been identified as a risk factor for acute lung injury (ALI)/ARDS. No study has formally evaluated the transfusion of specific blood products as a risk factor for ALI/ARDS in critically ill medical patients. METHOD: In this single-center retrospective cohort study, 841 consecutive critically ill patients were studied for the development of ALI/ARDS. Patients who received blood product transfusions were compared with those who did not, in univariate and multivariate propensity analyses. RESULTS: Two hundred ninety-eight patients (35%) received blood transfusions. Transfused patients were older (mean [+/- SD] age, 67 +/- 17 years vs 62 +/- 19 years; p < 0.001) and had higher acute physiologic and chronic health evaluation (APACHE) III scores (74 +/- 32 vs 58 +/- 23; p < 0.001) than those who had not received transfusions. ALI/ARDS developed more commonly (25% vs 18%; p = 0.025) in patients exposed to transfusion. Seventeen patients received massive RBC transfusions (ie, > 10 U of blood transfused within 24 h), of whom 13 also received fresh-frozen plasma (FFP) and 11 received platelet transfusions. When adjusted for the probability of transfusion and other ALI/ARDS risk factors, any transfusion was associated with the development of ALI/ARDS (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.24 to 3.75). Among those patients receiving individual blood products, ALI/ARDS was more likely to develop in patients who received FFP transfusions (OR, 2.48; 95% CI, 1.29 to 4.74) and platelet transfusions (OR, 3.89; 95% CI, 1.36 to 11.52) than in those who received only RBC transfusions (OR, 1.39; 95% CI, 0.79 to 2.43). CONCLUSION: Transfusion is associated with an increased risk of the development of ALI/ARDS in critically ill medical patients. The risk is higher with transfusions of plasma-rich blood products, FFP, and platelets, than with RBCs.

Acute graft-versus-host disease after liver transplantation diagnosed by fluorescent in situ hybridization testing of skin biopsy specimens.

Acute graft-versus-host disease after orthotopic liver transplantation is an underrecognized entity with a guarded prognosis. We describe a patient who underwent orthotopic liver transplantation with an HLA-matched donor liver. She had an uneventful recovery from operation up until day 36 posttransplantation, when she developed a generalized, erythematous, mostly macular eruption, accompanied by ascites, diarrhea, and fever. The diagnosis of graft-versus-host disease was considered but a drug rash could not be excluded. A polymerase chain reaction-based chimerism assay failed to identify donor DNA in peripheral blood. A confirmatory fluorescent in situ hybridization analysis revealed significant numbers of donor lymphocytes in biopsied skin, with lesser amounts in biopsy specimens from the stomach and colon. Despite immunosuppressive treatment, the patient died of overwhelming sepsis 18 weeks after transplantation. We conclude that early testing of skin biopsy specimens using fluorescent in situ hybridization in sex-mismatched patients with orthotopic liver transplantation can serve as an early diagnostic tool for graft-versus-host disease.

Transfusion-related acute lung injury and pulmonary edema in critically ill patients: a retrospective study.

BACKGROUND: Using the recent Consensus Panel recommendations, we sought to describe the incidence of transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) in critically ill patients. STUDY DESIGN AND METHODS: Consecutive patients at four intensive care units (ICUs) who did not require respiratory support at the time of transfusion were identified with custom electronic surveillance system that prospectively tracks the time of transfusion and onset of respiratory support. Respiratory failure was defined as the onset of noninvasive or invasive ventilator support within 6 hours of transfusion. Experts blinded to specific transfusion factors categorized the cases of pulmonary edema as permeability edema (suspected or possible TRALI) or hydrostatic edema (TACO) according to predefined algorithm. In a nested case-control design, transfusion variables and lung injury risk factors were compared between the TRALI cases and controls matched by age, sex, and admission diagnosis. RESULTS: There were 8902 units transfused in 1351 patients of whom 94 required new respiratory support within 6 hours of transfusion. Among 49 patients with confirmed acute pulmonary edema, experts identified 7 cases with suspected TRALI, 17 patients with possible TRALI, and 25 cases with TACO. The incidence of suspected TRALI was 1 in 1271 units transfused; possible TRALI, 1 in 534 per unit transfused; and TACO, 1 in 356 per unit transfused. When adjusted for sepsis and fluid balance in a stepwise conditional logistic regression analysis, patients who developed acute lung injury (suspected or possible TRALI) received larger amount of plasma (odds ratio 3.4, 95% confidence interval 1.2-10.2, for each liter infused; p = 0.023). CONCLUSION: In the ICU, pulmonary edema frequently occurs after blood transfusion. The association between infusion of plasma and the development of suspected or possible TRALI may have important implications with regards to etiology and prevention of this syndrome.

Clinical and HLA phenotypes of type 1 autoimmune hepatitis in North American patients outside DR3 and DR4.

AIMS: To determine the clinical phenotype and outcome of patients with definite type 1 autoimmune hepatitis, who lack human leukocyte antigen (HLA) DR3 and DR4, and to assess the importance of HLA DR7 and DR13. METHODS: Two hundred and seven adult patients were typed for DR3, DR4, DR7, and DR13 by DNA-based techniques. One hundred and two blood donors constituted a normal population. RESULTS: Twenty-six patients lacked DR3 and DR4 (13%). Treatment failure occurred more commonly in these individuals than in the 68 patients with DR4 (20% vs. 3%, P = 0.03), and relapse after drug withdrawal was less frequent than in the 84 patients with DR3 (55% vs. 87%, P = 0.03). HLA DR13 occurred more often than in those with DR3 (54% vs. 15%, P = 0.0002) or DR4 (54% vs. 12%, P = 0.00005), and it was more frequent than in normal adults (54% vs. 22%, P = 0.003), including those without DR3 or DR4 (54% vs. 27%, P = 0.03). HLA DR7 was not associated with susceptibility or outcome. CONCLUSIONS: White North American patients who lack DR3 and DR4 respond differently to corticosteroid treatment than patients with classical HLA phenotypes. HLA DR13 is common in these adult patients, and it may affect treatment outcome.

Evidence-based red cell transfusion in the critically ill: quality improvement using computerized physician order entry.

OBJECTIVE: The implementation of evidence-based practice poses a significant challenge in the intensive care unit. In this quality improvement intervention we assessed the effect of an institutional protocol and computerized decision support for red cell transfusion in the critically ill. DESIGN: We compared processes of care and outcomes during the two 3-month periods before and after the introduction of a multidisciplinary quality improvement intervention. SETTING: Multidisciplinary intensive care units--medical, surgical, and mixed--in a tertiary academic center. PATIENTS: Consecutive critically ill patients with anemia (hemoglobin of <10 g/dL). INTERVENTION: Using the computerized provider order entry, we developed an evidence-based decision algorithm for red cell transfusion in adult intensive care units. MEASUREMENTS AND MAIN RESULTS: We collected information on demographics, diagnosis, severity of illness, transfusion complications, and laboratory values. The main outcome measures were number of transfusions, proportion of patients who were transfused outside evidence-based indications, transfusion complications, and adjusted hospital mortality. The mean number of red cell transfusions per intensive care unit admission decreased from 1.08 +/- 2.3 units before to 0.86 +/- 2.3 units after the protocol (p<.001). We observed a marked decrease in the percentage of patients receiving inappropriate transfusions (17.7% vs. 4.5%, p< .001). The rate of transfusion complications was also lower in the period after the protocol (6.1% vs. 2.7%, p = .015). In the multivariate analysis, protocol introduction was associated with decreased likelihood of red cell transfusion (odds ratio, 0.43; 95% confidence interval, 0.30 to 0.62). Adjusted hospital mortality did not differ before and after protocol implementation (odds ratio, 1.12; 95% confidence interval, 0.69 to 1.8). CONCLUSIONS: The implementation of an institutional protocol and decision support through a computerized provider order entry effectively decreased inappropriate red cell transfusions.

Transfusion-related acute lung injury (TRALI): clinical presentation, treatment, and prognosis.

The term transfusion-related acute lung injury (TRALI) was coined in 1983 to describe a constellation of clinical and laboratory features seen within 6 hrs of the transfusion of plasma-containing blood products. These products contain antibodies directed to human leukocyte antigens (and subsequently described to nonhuman leukocyte antigens) found on white blood cells. In the intervening 2 decades, other cases not associated with antibodies have been reported as TRALI and an association with passive infusion of lipids accumulated in stored cellular blood products has been made in those cases. This has led to confusion as to what should be considered to constitute TRALI. Therefore, the true incidence of this pulmonary reaction to blood products is currently conjectural at best. Recent consensus development conferences have been held to develop and standardize definitions of TRALI so that epidemiologic and research aspects of this condition can be explored in a scientific manner. These conferences have set out criteria by which TRALI is distinguished from other causes of acute lung injury. This review outlines the widely accepted clinical (mainly pulmonary) features of TRALI, the treatment options, and the excellent long-term prognosis for patients who survive the initial pulmonary insult.