Kleinman, Steven

AbstractBackgroundConsensus definitions for transfusion‐related acute lung injury (TRALI) and transfusion‐associated circulatory overload (TACO) have recently been revised; however, pulmonary transfusion reactions remain difficult to diagnose. We hypothesized that N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) levels could have utility in the identification and classification of pulmonary transfusion reactions.Study design and methodsWe performed a secondary analysis of a case‐control study of pulmonary transfusion reactions at four academic hospitals. We evaluated clinical data and measured NT‐proBNP levels prior to and following transfusion in patients with TACO (n = 160), transfused acute respiratory distress syndrome (ARDS) [n = 51], TRALI [n = 12], TACO/TRALI [n = 7], and controls [n = 335]. We used Wilcoxon Rank‐Sum tests to compare NT‐proBNP levels, and classification and regression tree (CART) algorithms to produce a ranking of covariates in order of relative importance for differentiating TACO from transfused controls.ResultsPre‐transfusion NT‐proBNP levels were elevated in cases of transfused ARDS and TACO (both P < .001) but not TRALI (P = .31) or TACO/TRALI (P = .23) compared to transfused controls. Pre‐transfusion NT‐proBNP levels were higher in cases of transfused ARDS or TRALI with a diagnosis of sepsis compared to those without (P < .05 for both). CART analyses resulted in similar differentiation of patients with TACO from transfused controls for models utilizing either NT‐proBNP levels (AUC 0.83) or echocardiogram results (AUC 0.80).ConclusionsNT‐proBNP levels may have utility in the classification of pulmonary transfusion reactions. Prospective studies are needed to test the predictive utility of pre‐transfusion NT‐proBNP in conjunction with other clinical factors in identifying patients at risk of pulmonary transfusion reactions.

Abstract Background: Use of direct-acting oral anticoagulants (DOAC) is increasingly common among patients with atrial fibrillation and venous thromboembolic disease. Differences in the mechanisms of action as compared to warfarin could impact transfusion patterns and clinical outcomes in patients, especially for those presenting with major hemorrhage. The management of patients taking these newer medications and corresponding outcomes are relevant to optimizing clinical decision making in situations of major hemorrhage. Methods: We tested the hypothesis that inpatient all-cause mortality among patients presenting with major hemorrhage differs based on the home-administered anticoagulant medication class (DOAC versus warfarin). A cohort of patients presenting to twelve US hospitals from 2013 to 2016 was identified using the Recipient Epidemiology and Donor Evaluation Study (REDS)-III Recipient Database. Primary ICD diagnosis codes, issued blood products, laboratory data, and early mortality events were used in the application of the International Society on Thrombosis and Hemostasis definition of major hemorrhage. Exposure status was defined as a record of home-administered DOAC (apixaban, dabigatran, edoxaban, or rivaroxaban; exposed) or warfarin (non-exposed). Patients with multiple encounters and those transferred into or out of network were excluded from the analysis. Proportional hazards regression was used to compare all-cause mortality and hospital length of stay. We then repeated the analysis using a cohort matched on propensity scores to account for confounding by age, gender, concurrent aspirin and anti-platelet use, liver and renal dysfunction, cancer, CHA2DS2-VASc score, traumatic injury, and hospital. We then repeated the propensity score matched analysis stratified by anatomic location of bleed and traumatic injury. Results: More than 1.5 million hospitalizations were screened for eligibility. Exclusion of minors, outpatients, hospitalizations without a medication of interest, absence of major hemorrhage, multiple hospitalizations, and hospital transfers resulted in 3,731 patients available for the unadjusted analysis. Inpatient all-cause mortality was lower among DOAC users when the entire cohort was considered (HR = 0.60, 95%CI 0.45 - 0.80, p=0.0005). Implementation of propensity score matching to account for confounding abrogated this difference (HR=0.84, 95%CI 0.58 - 1.22, p=0.36). Time to hospital discharge was shorter for DOAC users (HR = 1.17, 95%CI 1.05 - 1.30, p=0.0034). Transfusion patterns were similar by medication, except for plasma transfusion occurring in 42% of warfarin encounters and 11% of DOAC encounters. Vitamin K was administered in 63% of warfarin encounters, whereas specific DOAC reversal agents were largely unavailable during the analysis period [used in 5 (1%) DOAC encounters]. There were no statistically significant differences in inpatient all-cause mortality in the stratified analysis (warfarin as reference): HR = 0.69 (95%CI 0.31 - 1.55) for traumatic head injuries; HR = 1.10 (95%CI 0.62 - 1.95) for non-traumatic head injuries; HR = 0.62 (95%CI 0.20 - 1.94) for traumatic, non-head injuries; and HR = 0.69 (95%CI 0.29 - 1.63) for non-traumatic, non-head injuries. Conclusions: Analysis of a population taking oral anticoagulation and presenting with major hemorrhage showed that transfusion of plasma was more commonly employed to treat major hemorrhage among warfarin users than DOAC users. Inpatient all-cause mortality was lower among DOAC users in the overall cohort; however, accounting for potential confounding factors using propensity score matching abrogated this difference. Hospital length of stay was shorter for DOAC users compared to warfarin users. Stratification by location of bleed and traumatic injury did not alter these findings. Less plasma use and a shorter length of hospitalization in this study, combined with no observable difference in inpatient all-cause mortality, suggests that outcomes following major hemorrhage are at least no different for DOAC users as compared to warfarin users. Disclosures Mast: Novo Nordisk: Research Funding. Kor:NIH: Consultancy; NIH: Research Funding; UpToDate: Patents & Royalties; CSL Behring: Honoraria.

BACKGROUNDTransfusion‐related acute lung injury (TRALI) is a serious complication of blood transfusion and is among the leading causes of transfusion‐related morbidity and mortality in most developed countries. In the past decade, the pathophysiology of this potentially life‐threatening syndrome has been increasingly elucidated, large cohort studies have identified associated patient conditions and transfusion risk factors, and preventive strategies have been successfully implemented. These new insights provide a rationale for updating the 2004 consensus definition of TRALI.STUDY DESIGN AND METHODSAn international expert panel used the Delphi methodology to develop a redefinition of TRALI by modifying and updating the 2004 definition. Additionally, the panel reviewed issues related to TRALI nomenclature, patient conditions associated with acute respiratory distress syndrome (ARDS) and TRALI, TRALI pathophysiology, and standardization of reporting of TRALI cases.RESULTSIn the redefinition, the term “possible TRALI” has been dropped. The terminology of TRALI Type I (without an ARDS risk factor) and TRALI Type II (with an ARDS risk factor or with mild existing ARDS) is proposed. Cases with an ARDS risk factor that meet ARDS diagnostic criteria and where respiratory deterioration over the 12 hours before transfusion implicates the risk factor as causative should be classified as ARDS. TRALI remains a clinical diagnosis and does not require detection of cognate white blood cell antibodies.CONCLUSIONSClinicians should report all cases of posttransfusion pulmonary edema to the transfusion service so that further investigation can allow for classification of such cases as TRALI (Type I or Type II), ARDS, transfusion‐associated circulatory overload (TACO), or TRALI or TACO cannot distinguish or an alternate diagnosis.

Objectives: Transfusion-associated circulatory overload is characterized by hydrostatic pulmonary edema following blood transfusion. Restrictive transfusion practice may affect the occurrence and severity of transfusion-associated circulatory overload in critically ill patients. We sought to examine contemporary risk factors and outcomes for transfusion-associated circulatory overload. Design: Case-control study. Setting: Four tertiary care hospitals. Patients: We prospectively enrolled 200 patients with transfusion-associated circulatory overload identified by active surveillance and 405 controls matched by transfusion intensity. Interventions: None. Measurements and Main Results: Among 20,845 transfused patients who received 128,263 blood components from May 2015 until July 2016, transfusion-associated circulatory overload incidence was one case per 100 transfused patients. In addition to cardiovascular comorbidities, multivariable analysis identified the following independent predictors of transfusion-associated circulatory overload: acute kidney injury, emergency surgery, pretransfusion diuretic use, and plasma transfusion—the latter especially in females. Compared with matched controls, transfusion-associated circulatory overload cases were more likely to require mechanical ventilation (71% vs 49%; p < 0.001), experienced longer intensive care and hospital lengths of stay following transfusion, and had higher mortality (21% vs 11%; p = 0.02) even after adjustment for other potentially confounding variables. Conclusions: Despite restrictive transfusion practice, transfusion-associated circulatory overload remains a frequent complication of transfusion and is an independent risk factor for in-hospital morbidity and mortality. In addition to cardiovascular and renal risk factors, plasma transfusion was associated with transfusion-associated circulatory overload after controlling for other covariates. Additional research is needed to examine the benefit of reduced erythrocyte or plasma exposure in patients at high risk for transfusion-associated circulatory overload.

BackgroundThe concordance of haemovigilance criteria developed for surveillance of transfusion‐associated circulatory overload (TACO) with its clinical diagnosis has not been assessed. In a pilot study to evaluate an electronic screening algorithm, we sought to examine TACO incidence and application of haemovigilance criteria in patients with post‐transfusion pulmonary oedema.Study Design and MethodsFrom June to September 2014, all transfused adult inpatients at four academic hospitals were screened with an algorithm identifying chest radiographs ordered within 12 h of blood component release. Patients with post‐transfusion pulmonary oedema underwent case adjudication by an expert panel. TACO incidence was calculated, and clinical characteristics were compared with other causes of post‐transfusion pulmonary oedema.ResultsAmong 4932 transfused patients, there were 3412 algorithm alerts, 50 cases of TACO and 47 other causes of pulmonary oedema. TACO incidence was 1 case per 100 patients transfused. TACO classification based on two sets of haemovigilance criteria (National Healthcare Safety Network and proposed revised International Society for Blood Transfusion) was concordant with expert panel diagnosis in 57% and 54% of reviewed cases, respectively. Although the majority of clinical parameters did not differentiate expert panel adjudicated TACO from other cases, improved oxygenation within 24 h of transfusion did (P = 0·01).ConclusionsThe incidence of TACO was similar to that observed in prior studies utilizing active surveillance. Case classification by haemovigilance criteria was frequently discordant with clinical diagnoses of TACO in patients with post‐transfusion pulmonary oedema. Improvements in oxygenation within 24 h of transfusion merit further evaluation in the diagnosis of TACO.