Transfusion Reactions: What? How? What now? Part II

Transcription

1 Transfusion Reactions: What? How? What now? Part II Margo Rollins, MD Assistant Professor of Pathology Emory University SOM Assistant Medical Director for Tissue, Transfusion & Apheresis Children s Healthcare of Atlanta Immucor Webinar Series July 2018

2 Disclosures None

3 Objectives Define and categorize transfusion reactions Describe clinical manifestations of specific transfusion reactions Discuss patient evaluation and management when transfusion reaction is suspected

4 Introduction DDx of any untoward clinical event should always consider adverse sequelae of transfusion, even when transfusion occurred weeks earlier No pathognomonic S/Sx that differentiates a transfusion reaction from other potential medical problems Vigilance- during and after transfusion Transfusion reactions are common, BUT uncommonly fatal FDA receives ~40 reports/yr of fatalities attributable to transfusion Savage, W

5 Introduction Transfusion reactions may be defined by case type, timing, severity, and imputability (the causal relationship of a reaction to transfusion) Other classification schemes differentiate reactions by mechanism Immunologic/non-immunologic Type of blood component Savage, W

6 Background NHSN Biovigilance Component Hemovigilance Module Surveillance Protocol v2.4

7 Timing and manifestations of transfusion reactions

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9 Transfusion-related acute lung injury The leading cause of transfusion-related death reported to the FDA , 41% (72 of 176) of reported fatalities to the FDA were due to TRALI (Fatalities reported to FDA following blood collection and transfusion. Accessed September 2, 2015.) ~ 1/10,000 transfusions is complicated by TRALI (Toy P., Gajic O., Bacchetti P., et al: Transfusion-related acute lung injury: incidence and risk factors. Blood 2012; 119: pp ) Symptoms Mild dyspnea severe noncardiogenic pulmonary edema Patients require O2 support (many require mechanical ventilation) Develops within 6 hrs of starting a transfusion (typically within 2 hrs) (Goldman M., Webert K.E., Arnold D.M., et al: Proceedings of a consensus conference: towards an understanding of TRALI. Transfus Med Rev 2005; 19: pp. 2-31). Pulmonary edema is non-cardiogenic classically no in cardiopulmonary pressures. Chills Fever Hypotension Because TRALI is hard to distinguish from fluid overload without CVPs, it is not straightforward to diagnose

10 TRALI- 2 Hit Event 1st hit- underlying clinical condition sequestration and priming of neutrophils in the lung tissue 2nd hit- transfusion of blood products containing anti-hla or anti-human neutrophil antigen (HNA) antibodies activate neutrophils in the lung parenchyma (Vlaar A.P., and Juffermans N.P.: Transfusion-related acute lung injury: a clinical review. Lancet 2013; 382: pp ; Peters A.L., van Hezel M.E., Juffermans N.P., et al: Pathogenesis of non-antibody mediated transfusion-related acute lung injury from bench to bedside. Blood Rev 2015; 29: pp ) Previously pregnant women make anti-hna and anti-hla antibodies (Endres R.O., Kleinman S.H., Carrick D.M., et al: Identification of specificities of antibodies against human leukocyte antigens in blood donors. Transfusion 2010; 50: pp ) Removal of female donors from the plasma pool ~50% reduction in TRALI(Toy P., Gajic O., Bacchetti P., et al: Transfusion-related acute lung injury: incidence and risk factors. Blood 2012; 119: pp ; Endres R.O., Kleinman S.H., Carrick D.M., et al: Identification of specificities of antibodies against human leukocyte antigens in blood donors. Transfusion 2010; 50: pp ) Other antibody-independent mechanisms of TRALI Aged blood products accumulated bioactive lipids/ soluble mediators (CD40 L) that hamper chemokine scavenging ability of RBCs (2 nd hit) (Khan S.Y., Kelher M.R., Heal J.M., et al: Soluble CD40 ligand accumulates in stored blood components, primes neutrophils through CD40, and is a potential cofactor in the development of transfusion-related acute lung injury. Blood 2006; 108: pp ) Lysophosphatidyl choline accumulation during storage neutrophil priming substance (Silliman C.C., Fung Y.L., Ball J.B., et al: Transfusion-related acute lung injury (TRALI): current concepts and misconceptions. Blood Rev 2009; 23: pp )

11 TRALI- Management HLA/HNA reactions are usually donor specific and should not recur with a different donor Treatment is supportive Glucocorticoids and diuretics have not been established to help (a positive fluid balance is a risk factor for TRALI) (Toy P., Gajic O., Bacchetti P., et al: Transfusion-related acute lung injury: incidence and risk factors. Blood 2012; 119: pp ). Donors clearly implicated in TRALI reactions should be permanently deferred from blood donation

12 Transfusion-associated circulatory overload Hydrostatic transudate accumulation in the lungs Consider in pts who develop sudden signs of fluid overload during transfusion including but not limited to: Dyspnea Jugular venous distention Tachycardia Congestive heart failure At risk pts: compromised cardiopulmonary status R/L sided heart failure (infants, elderly, pts with renal/heart failure)

13 TACO- Management Vastly underreported (Raval JS, Mazepa MA, Russell SL, et al. Passive reporting greatly underestimates the rate of transfusion-associated circulatory overload after platelet transfusion. Vox Sang 2015;108: ) ~1/100 transfusions If TACO is suspected, the transfusion should be stopped diuretics For concerning pts: Divide the product into aliquots for separate transfusions Infusions in adults 3 ml/kg/hr (Pediatrics pts max 5ml/kg/hr) The initial stages of TACO may be difficult to distinguish from other transfusion related reaction N-terminal pro-brain natriuretic peptide (NT-pro-BNP) NT-pro-BNP is at least 50% higher after transfusion than pretransfusion levels NT-pro-BNP is sensitive and specific for TACO (Tobian AA, Sokoll LJ, Tisch DJ, et al. N-terminal pro-brain natriuretic peptide is a useful diagnostic marker for transfusion-associated circulatory overload. Transfusion 2008;48: ; 74. Zhou L, Giacherio D, Cooling L, et al. Use of B-natriuretic peptide as a diagnostic marker in the differential diagnosis of transfusion-associated circulatory overload. Transfusion 2005;45: )

14 Transfusion-associated graft versus host disease Immunologically competent lymphocytes are introduced into a host who cannot inactivate the donor lymphocytes The immunocompetent donor lymphocytes engraft host HLA is presented to donor lymphocytes activated lymphocytes attack host tissues : 2 fatalities were reported to the FDA ( UCM pdf. Accessed September 2, 2015.) Occurs after transfusion of non-irradiated cellular blood components Much higher fatality rate than HSCT-related GVHD Donor lymphocytes recipient BM aplasia in addition to typical liver, gut, and skin manifestations of acute GVHD In GVHD after BMT, the BM is of donor origin, and BM aplasia does not occur. > 90% of cases are fatal 2/2 recipient BM aplasia

15 TA-GVHD Management Presentation 8-10 days after transfusion Marked pancytopenia, gut, skin, and liver (GVHD Ohto H, Anderson KC. Survey of transfusionassociated graft-versus-host disease in immunocompetent recipients. Transfus Med Rev 1996;10:31 43.) S/Sx: N/V, anorexia, fever, diarrhea, liver dysfunction, and erythroderma Pts often die of infection and hemorrhage (3-4wks) NO EFFECTIVE TX (possible exception of BMT) Haplo-identical directed donor units of blood posttransfusion GVHD even in immunocompetent recipients, when donor and recipient share HLA types (Kopolovic I, Ostro J, Tsubota H, et al. A systematic review of transfusion-associated graft-versus-host disease. Blood 2015; 126: ) Using irradiated blood (2500 cgy) is recommended (pt receive directed blood transfusions from their relatives) Leukocyte-reduction filters SHOULD NOT be used as prophylaxis

16 Post-Transfusion Purpura RARE ~1/100,000 transfusions Sudden onset, self-limited thrombocytopenia 5-10 days s/p transfusion; resolved in 14 days Pts lacking a specific platelet antigen (usually HPA-1a (GPIIIa, CD61)) (Metcalfe P. Platelet antigens and antibody detection. Vox Sang 2004;87(Suppl 1):82 6.) H/o sensitization with prior transfusions or pregnancies (~85% of cases occur in women) After re-exposure with transfusion develop Abs against the PLT-specific antigen they are lacking but which is present on donor PLTs These PLT Abs often have a high titer and can fix complement, destroying the pt s own PLTs through indiscriminant adsorption of the antigen or immune complexes on their own PLTs

17 PTP- Management Severe thrombocytopenia (<10,000/mL) can distinguish PTP from heparin-induced thrombocytopenia Consider if platelet refractoriness persists despite transfusion of HLA-matched PLTs Treatment options IVIg Plasma exchange Steroids Splenectomy Pts with acute bleeding PLT-specific antigen negative PLTs Random donor PLTs severe inflammatory reactions

18 Additional Resources Delaney, M., et al. (2016). "Transfusion reactions: prevention, diagnosis, and treatment. The Lancet 388(10061): Savage, W. J. (2016). Transfusion Reactions. Hematology/Oncology Clinics of North America. Volume 30, Issue 3, Pages NHSN Biovigilance Component Hemovigilance Module Surveillance Protocol v

19 Thank You