Distinguishing between transfusion related acute lung ...

1 Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is between transfusion related acute lung injury andtransfusion associated circulatory overloadRobert C. Skeateaand Ted EastlundbPurpose of reviewThe purpose of this review is to provide an overview ofconcepts recently presented in the literature that impact ourunderstanding of transfusion related acute lung injury (TRALI) and transfusion associated circulatory overload(TACO), and how to distinguish between the two findingsAn exceptionally clear review article by Brux and Sachsclarified the two-hit model of TRALI pathogenesis. TheTRALI definition developed at the 2004 consensusconference helped demonstrate that TRALI is likelyunderreported. Brain natriuretic peptide can be useful indistinguishing cardiogenic from noncardiogenic pulmonaryedema.

2 Blood centers are implementing male predominantplasma programs to limit TRALI, and preliminary evidencesuggests that this is a useful and TRALI have emerged as important causes ofposttransfusion morbidity and mortality. As understandingof their pathogenesis improves, incidence, risk factors,differences, and possible preventive interventions arebecoming clearer. There is no sentinel feature thatdistinguishes TRALI from TACO. Developing a thoroughclinical profile including presenting signs and symptoms,fluid status, cardiac status including measurement of brainnatriuretic peptide, and leukocyte antibody testing is thebest strategy currently available to distinguish the overload, diagnosis, TACO, TRALI, transfusionCurr Opin Hematol 14:682 687. 2007 Wolters Kluwer Health | Lippincott Williams & Red Cross, North Central Blood Services, Saint Paul andbDivision ofTransfusion Medicine, Department of Laboratory Medicine and Pathology,University of Minnesota Medical School, Minneapolis, Minnesota, USAC orrespondence to Robert C.

3 Skeate, MD, American Red Cross, North CentralBlood Services, 100 South Robert Street Saint Paul, MN 55107, USATel: +1 651 291 3374; e-mail: Opinion in Hematology2007, 14:682 687 AbbreviationsALIacute lung injuryHLAhuman leukocyte antigenPACpulmonary artery catheterTACO transfusion associated circulatory overloadTRALI transfusion - related acute lung injury 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins1065-6251 IntroductionTransfusion reactions can be difficult to evaluate [1 ].Determining the correct diagnosis is important becausethere are implications for the patient, the donor, and theother products associated with the involved donation [2 ].Pulmonary transfusion reactions can be especially diffi-cult to investigate. The differential diagnosis includesallergic/anaphylactic reactions, transfusion related acutelung injury (TRALI), transfusion associated circulatoryoverload (TACO), bacterial contamination, and hemoly-tic transfusion reaction [3 ].

4 Particularly troublesome isthe scenario wherein the patient presents with acuterespiratory distress due to pulmonary edema, and thetransfusing physician suspects TRALI versus TACO[4 ]. The clinical features are similar, and there are nodiagnostic tests that reliably discriminate. The fact that apatient could have both simultaneously only adds to thecomplexity [5 ,6,7 ]. Yet the therapy and managementof the patient, and the implications for the donor of thetwo different reactions are completely paper will review recent articles in the scientificliterature relevant to diagnosing TRALI and TACO, andto Distinguishing between associated circulatory overloadDespite the fact that circulatory overload has been arecognized complication of transfusion for decades, itstill receives relatively little attention in the scientificliterature [8].

5 There is no universally agreed-upon definition for whatconstitutes TACO [9]. During or within several hours oftransfusion, patients develop respiratory distress, andmay develop orthopnea, cyanosis, tachycardia, and hyper-tension. Rales can be identified on auscultation, and somepatients may have jugular venous distention, an S3 oncardiac auscultation, or lower extremity edema. A chestradiograph can reveal cardiomegaly and interstitial infil-trates, but not all patients with heart failure will havethese abnormalities [10].TACO incidence estimates have ranged from one inapproximately 3000 transfusions to 8% of transfusionsdepending upon patient population and reporting method[5 ,11]. In a recent retrospective review of 8902 transfu-sions in 1351 consecutive ICU patients, TACO was iden-tified in one in 356 transfusions [12 ].

6 Patients at the682 Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is risk for TACO include those younger than 3 andthose older than 60 years of age, particularly those withunderlying cardiac dysfunction [13].The pathogenesis of TACO is felt to be similar to othercauses of acute congestive heart failure: an increase incentral venous pressure and pulmonary blood volumecauses an increase in hydrostatic pressure leading tofluidextravasation into the alveolar space [8].Treatment of TACO starts with discontinuing anyongoing transfusion . Respiratory distress is treated withthe degree of respiratory support needed to maintain thepatient s oxygenation. Diuretics are administered toremove excessfluid. It is common to infuse subsequenttransfusions slowly, but no formal evidence exists thatthis is an effective intervention [9].

7 transfusion related acute lung injuryTRALI is acute lung injury (ALI) that occurs during orfollowing transfusion . It has emerged as the leading causeof transfusion - related fatality reported to the UnitedStates Food and Drug Administration [14].Recently transfused patients present with respiratorydistress, hypoxemia, rales on auscultation, and diffusebilateral infiltrates on chest radiograph. The respiratorydistress can be severe enough to require mechanicalventilation. Other features include hypotension, fever,and transient leukopenia. Treatment is with increasinglyaggressive respiratory support depending on the degreeof respiratory distress. Five to 25% of cases are fatal, butmost patients fully recover within 3 days [15 ,16 ].TRALI results from neutrophil-mediated damage to thepulmonary microvasculature.

8 The current proposedmodel is a two-hit hypothesis wherein a primarystimulus causes neutrophil sequestration in the pulmon-ary capillaries, and a secondary stimulus causes theneutrophils to activate , damaging the endothelial layersuch thatfluid and protein leaks into the alveolar space[17 ]. Neutrophils can befirst primed and subse-quently activated by pro-inflammatory stimuli presenteither in patients with certain disease states, or infusedwith blood exposures that can lead to neutrophil priminginclude surgery, tissue injury , and infection. Pro-inflam-matory stimuli that can be infused with blood productsinclude neutrophil-specific or anti-human leukocyte anti-gen (HLA) antibodies, or bioactive lipids. The require-ment for both priming and activation of neutrophilsexplains why a product from a donor with HLA anti-bodies may induce TRALI in a surgical patient, andcause no clinical reaction in a relatively healthy anemicpatient, even if both patients are positive for the relevantcognate antigens.

9 Neutrophil-specific antibodies appearto be capable of both priming and activating neutrophils,and can cause TRALI in even healthy recipients [17 ].In April of 2004, an international consensus conferencewas convened to develop a definition of TRALI [18].Participants felt that a useful definition of ALI hadalready been proposed [19], and they decided to use thisas the basis for establishing the presence of ALI incandidate TRALI patients. ALI was defined as acuteonset hypoxemia with bilateral infiltrates on chest radio-graph, and with no evidence of circulatory overload [20].Because patients with other risk factors for ALI oftenreceive transfusions, they created a two-tiered definition:TRALI and possible TRALI. TRALI is ALI that occursduring or within 6 h of transfusion , and with no temporalrelationship to an alternative risk factor for ALI (riskfactors for ALI are summarized in [21]).

10 Possible TRALIis used when there is a clear temporal relationship to analternative risk factor for ALI. An important limitation ofthis definition is that patients with circulatory overloadcannot be defined as having ALI or a usable case definition was developed onlyrecently, earlier estimates of the incidence of TRALI have varied widely [18]. The retrospective reviewreferred to earlier [12 ] used the consensus conferencedefinition of TRALI, and the investigators reported aTRALI incidence of one in 1271 units transfused, and apossible TRALI incidence of one in 534 units is a higher incidence than that seen in other studies,but the authors point out that they investigated eachtransfusion event for the possibility of TRALI ratherthan depending on the typical passive reporting conclude that their results suggest that TRALI isan underreported case definition presented above describes a clinicalsyndrome.