Transfusion-Related Acute Lung Injury

1. Transfusion-Related Acute Lung Injury Melanie F. Clemens, CRNA, MSN Brooklyn VA Medical Center

2. Objectives • Discuss the incidence of TRALI • Review the proposed pathophysiology of TRALI • Discuss the proposed risk factors associated with TRALI • Review the clinical presentation & diagnosis of TRALI • Review the treatment of TRALI • Discuss the clinical impact of TRALI

3. Disclosures

4. Clinical Relevance • TRALI • 1 in 5,000 units* • 1 in 625 patients* • Bacterial Contamination Related Sepsis • 1 in 25,000 platelets • 1 in 250,000 PRBCs • Hepatitis C • 1 in 1,935,000 transfusions • Hepatitis B • 1 in 205,000 transfusions • HIV • 1 in 2,135,000 transfusions

5. Clinical Relevance http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/ReportaProblem/TransfusionDonationFatalities

6. Presentation • Within 6 hours of transfusion • Symptoms • Dyspnea • Cyanosis • Hypoxemia • Pulmonary edema • Hypotension • Decreased lung compliance • Fever • Chills • Cough • Tachycardia • Frothy sputum • Absence of other clinical indicators of fluid overload

7. Pathophysiology • Antibody Hypothesis • Human leukocyte antigen (HLA) • Class I & class II • Human neutrophil antigen (HNA) • Biologic Response Modifiers • Not antibody mediated • Two-Hit Hypothesis • 2 events • Opportunistic Sachs 2011

8. Pathophysiology • Antibody mediated lung injury • 70% of TRALI cases • 85%-90% component based • 5%-10% recipient based • HLA & HNA antibody formation • Pregnancy • Transplantation • Transfusion • Antibodies target WBCs • Pulmonary microvascular infiltration & damage Dennison 2008

9. Pathophysiology • Biologic Response Modifiers • Accumulate in stored blood • Activate & prime neutrophils • Independent of antibodies • Lower morbidity & mortality http://online.wsj.com/article/SB10001424052748703939404574567771148801570.html

10. Pathophysiology • Two-Hit Theory • First event • System activation • Pulmonary endothelium • Primed neutrophils • Second event • Transfusion • Opportunistic • Threshold Sachs 2011

11. Risk Factors • Product related risk factors Triulzi 2009

12. Risk Factors • Recipient related risk factors Sachs 2011

13. Diagnosis • Unrecognized • TRALI vs. TACO http://www.arabanesthesia.com/2011/03/association-between-intraoperative.html

14. Diagnosis • Transfusion-Related Cardiac Overload (TACO) • Similar presentation to TRALI • Jugular venous distension • Hypertension • Elevated pulmonary artery occlusion or central venous pressures* • Prompt improvement of symptoms with diuresis • Pulmonary edema/plasma protein concentration ratio <0.65 • ≥50% increase in post transfusion BNP levels

15. Presentation • Within 6 hours of transfusion • Symptoms • Dyspnea • Cyanosis • Hypoxemia • Pulmonary edema • Hypotension • Decreased lung compliance • Fever • Chills • Cough • Tachycardia • Frothy sputum • Absence of other clinical indicators of fluid overload

16. Diagnosis http://jama.ama-assn.org/content/287/15/1968.full Gilliss et al. 2011

17. Diagnosis Gajic et al. 2006

18. Diagnosis Skeate et al. 2007

19. Treatment • Differential diagnosis • Stop the suspected product • Supportive • Intubation & mechanical ventilation • Fluids • Vasopressors • 5%-20% mortality rate • Retain the transfused products http://web.squ.edu.om

20. Clinical Impact • Prevention • Limit unnecessary transfusions • Donor limitations • Leukocyte reduction • Washing cellular components • Pooled products • Product testing • Using freshest available products www.ag.ndsu.edu

21. Clinical Impact • Alternatives to transfusion • Crystalloids • Colloids • Conservative transfusion thresholds • Risk stratification • Concentrated fibrinogen/Factor VII • Vitamin K

22. Questions

23. References • Curtis, Brian. McFarland, Janice. (2006). Mechanisms of Transfusion-Related Acute Lung Injury. Critical Care Medicine, 34, S118-S123. • Dennison, Carol. (2008). Transfusion-Related Acute Lung Injury-A Clinical Challenge. Dimensions of Critical Care Nursing, 27, 1-7. • Gajic, Ognjen. Gropper, Michael. Hubmayr, Rolf. (2006). Pulmonary Edema After Transfusion: How to Differential Transfusion-Associated Circulatory Overload from Transfusion-Related Acute Lung Injury. Critical Care Medicine, 34, S109-S113.

24. References • Gillis, Brian. Looney, Mark. Gropper, Michael. (2011). Reducing Noninfectious Risks of Blood Transfusion. Anesthesiology, 115, 635-649. • Kopko, Patricia. (2010). Transfusion-Related Acute Lung Injury. Journal of Infusion Nursing, 33, 32-37. • Looney, Mark. Gillis, Brian. Matthay, Michael. (2010). Pathophysiology of Transfusion-Related Acute Lung Injury. Current Opinion in Hematology, 17, 418-423. • Mair, D. Hirschler, Nora. Eastlund, Ted. (2006). Blood Donor and Component Management Strategies to Prevent Transfusion- Related Acute Lung Injury. Critical Care Medicine, 34, S137- S143.

25. References • Moore, S. (2006). Transfusion-Related Acute Lung Injury: Clinical Presentation, Treatment, and Prognosis. Critical Care Medicine, 34, S114-S117. • Sachs, Ulrich. (2011). Recent Insights into the Mechanic of Transfusion-Related Acute Lung Injury. Current Opinion in Hematology, 18, 436-442. • Skeate, Robert. Eastlund, Ted. (2007). Distinguishing Between Transfusion-Related Acute Lung Injury and Transfusion- Associated Circulatory Overload. Current Opinion in Hematology, 14, 682-687.

26. References • Triulzi, Darrell. (2009). Transfusion-Related Acute Lung Injury: Current Concepts for the Clinician. Anesthesia and Analgesia, 108, 770-776. • Vlaar, Alexander. Binnekade, Jan. Prins, David. Van Stein, Danielle. Hofstra, Jorrit. Schultz, Marcus. Juffermans, Nicole. (2010). Risk Factors and Outcome of Transfusion- Related Acute Lung Injury in the Critically Ill: A Nested Case- Control Study. Critical Care Medicine, 38, 771-778. • Federal Drug Administration (2010). Fatalities Reported to FDA Following Blood Collection and Transfusion. Annual Summary for Fiscal Year 2010. www.fda.org