Transfusion Reactions: What? How? What now? Part II Margo Rollins, - - PDF document

11/13/2018 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

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Disclosures

• None

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Objectives

• Define and categorize transfusion reactions
• Describe clinical manifestations of specific

transfusion reactions

• Discuss patient evaluation and management

when transfusion reaction is suspected

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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. 2016.

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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. 2016.

Background

https://patientsafety.aabb.org/ NHSN Biovigilance Component Hemovigilance Module Surveillance Protocol v2.4 www.cdc.gov/nhsn

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Timing and manifestations of transfusion reactions

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Transfusion-related acute lung injury

• The leading cause of transfusion‐related death reported to

the FDA

– 2010‐2014, 41% (72 of 176) of reported fatalities to the FDA were due to TRALI (Fatalities reported to FDA following blood collection and transfusion.

http://www.fda.gov/downloads/BiologicsBloodVaccines/SafetyAvailability/ReportaProblem/TransfusionDonationFatalities/UCM459461.pdf. 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. 1757‐1767)

• 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

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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. 984‐994; 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. 51‐61)

– 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. 1749‐1760)

– 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. 1757‐

1767; 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. 1749‐1760)
• Other antibody‐independent mechanisms of TRALI

– Aged blood products accumulated bioactive lipids/ soluble mediators (CD40 L) that hamper chemokine scavenging ability of RBCs (2nd 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. 2455‐2462)

– 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. 245‐255)

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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. 1757‐1767).

– Donors clearly implicated in TRALI reactions should be permanently deferred from blood donation

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Transfusion-associated circulatory

• verload
• Hydrostatic transudate accumulation in the lungs
• Consider in pts who develop sudden signs of fluid
• verload 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)

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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;108:387–92.)

– ~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
• ther transfusion related reaction N‐terminal pro‐brain

natriuretic peptide (NT‐pro‐BNP)

– NT‐pro‐BNP is at least 50% higher after transfusion than pre‐ transfusion 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;48:1143–50; 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;45:1056–63.)

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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

• 2010‐2014: 2 fatalities were reported to the FDA

(http://www.fda.gov/downloads/BiologicsBloodVaccines/SafetyAvailability/ReportaProblem/TransfusionDonationFatalities/ UCM459461.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

• ccur.

– > 90% of cases are fatal 2/2 recipient BM aplasia

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TA-GVHD Management

• Presentation

– 8‐10 days after transfusion – Marked pancytopenia, gut, skin, and liver (GVHD Ohto H, Anderson KC. Survey of transfusion‐

associated 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 post‐

transfusion 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; 126:406–14.)

• Using irradiated blood (2500 cGy) is recommended (pt receive

directed blood transfusions from their relatives)

• Leukocyte‐reduction filters SHOULD NOT be used as

prophylaxis

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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%

• f 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

• f the antigen or immune complexes on their own PLTs

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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

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Additional Resources

• Delaney, M., et al. (2016). "Transfusion reactions: prevention,

diagnosis, and treatment“. The Lancet 388(10061): 2825‐ 2836.

• Savage, W. J. (2016). “Transfusion Reactions”.

Hematology/Oncology Clinics of North America. Volume 30, Issue 3, Pages 619‐634.

• NHSN Biovigilance Component Hemovigilance Module

Surveillance Protocol v2.4 www.cdc.gov/nhsn

• http://www.aabb.org/research/hemovigilance
• http://www.bbguy.org/

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Thank You