Risks and Indications for RBCs Transfusions David Stroncek, MD Chief, Laboratory Services Section Department of Transfusion Medicine, Clinical Center, NIH, Bethesda, Maryland

Adverse Effects of RBC Transfusions Viral Infections Hepatitis B Hepatitis C HIV HTLV I and II West Nile Virus CMV

Risk of Transfusion-Transmitted Infections 2002 USA Canada 2 HBV1:205,0001:153,000 HCV1:1,935,0001:2,300,000 HIV1:2,135,0001:7,800,000 HTLV1:2,993,0001:4,300, Dodd RY et al. Transfusion. 2002;42: O'Brien SF et al.Transfusion. 2007;47:316-25

Adverse Effects of RBC Transfusions Other pathogens Bacteria Malaria Chagas Babesia

Adverse Effects of RBC Transfusions Hemolytic Transfusion Reactions ABO (wrong unit of blood) Antibodies to other RBC antigens (delayed hemolytic transfusion reactions) Leukocyte antibody mediated problems Alloimmunization (refractory to platelet transfusions) Febrile reactions (antibody in transfusion recipient) Transfusion related acute lung injury (TRALI) (antibody in blood donor)

Adverse Effects of RBC Transfusions Other Fluid overload Anaphylaxis Urticaria GVHD Immune modulation

Transfusion Fatalities Reported to the FDA (FY 2004 to 2006)

Function of RBCs Oxygen Transport Delivery of oxygen from lungs to tissues Oxygen transport is dependent on Hematocrit Cardiac output Oxygen extraction

Normovolemic Amenia As hematocrit falls Blood viscosity decreases Cardiac output increases (  Stroke volume,  pulse) Delivery of O 2  O 2 extraction  Consumption of O 2 remains constant

Limits of Compensation At very low hemoglobin levels (approximately 4 g/dL) O 2 delivery does not meet demand Anerobic metabolism  lactic acidosis  cardiac arrest

Indications for RBC transfusions 1940s Recommended that surgery patients have a hemoglobin of 8 to 10 g/dL Led to a general rule of hemoglobin > 10 g/dL of surgery patients 1980s Development of invasive monitoring techniques lead to a better understanding of oxygen delivery and consumption Lower hemoglobin levels could be tolerated

Hemoglobin and Hematocrit Levels in Healthy Adults Hemoglobin (g/dL) Hematocrit (%) Mean-2SDMean-2SD Female Male Hematology: Basic Principles and Practice. Elsevier 2005

Transfusion Trigger: Multicenter, Randomized Control Study of ICU Patients Transfusion Strategy Hb Trigger Maintenance Level Conservative7.0 g/dL7.0 to 9.0 g/dL Liberal10.0 g/dL10.0 to 12.0 g/dL Herbert PC et al. N Engl J Med. 1999;340:

Transfusion Trigger: Multicenter, Randomized Control Study of ICU Patients 30-day mortalityP Restrictive18.7%0.11 Liberal23.3% Less acutely ill 30-day mortalityP Restrictive8.7%0.03 Liberal16.1% Cardiac disease patient 30-day mortalityP Restrictive20.5%0.69 Liberal22.9% Herbert PC et al. N Engl J Med. 1999;340:

Restrictive vs Liberal Transfusion in Other Conditions No difference Pediatric ICU patients 7.0 g/dL vs 9.5 g/dL Lacroix J, et al. N Engl J Med. 2007:356; Moderate to severe head injury 7.0 g/dL vs 10.0 g/dL McIntyre LA et al. Neutrocrit Care 2006;5:4-9 Possible difference Cardiovascular disease 7.0 g/dL vs 10.0 g/dL Liberal transfusions may be better in patients with acute myocardial infarction and unstable angina Hebert PC et al. Crit Care Med. 2001;29:

Optimal Hematocrit? Laboratory and mathematical model Maximize delivery of oxygen O 2 delivery is proportional to hematocrit and blood flow rate. As hematocrit increases viscosity increases and flow rate decrease Optimal hematocrit is approximately 35% Crowell JW and Smith EE. J Appl Physiol 1967;22: Clinical Risks associated with increasing the hemoglobin/hematocrit justify the clinical benefits

Conclusions Although RBCs are much safer than 20 years ago, transfusion practices have become more restrictive The transfusion threshold at most institutions is a hemoglobin of 7 to 8 g/dL for most patients Higher thresholds are used for specific patients

Disclaimer The views expressed are those of the presenter and do not necessarily represent the position of the National Institutes of Health or the Department of Health and Human Services.