What Is the Difference Between Blood and Chicken Soup? Maureane Hoffman, MD, PhD Professor of Pathology and Immunology Duke University Director, Blood Bank and Hematology Laboratories Durham VA Medical Center Durham, North Carolina

80 million units donated worldwide yearly1 Transfusion Facts 80 million units donated worldwide yearly1 12.5 million units transfused each year in the United States2 A blood transfusion is the most intimate possible contact with a stranger 1. World Health Organization. Available at www.who.int/bloodsafety/en/Blood_Transfusion_Safety.pdf; 2. Goodnough LT, et al. N Engl J Med. 1999;340:438-447.

Blood CAN Cause Harm Infectious diseases Complications resulting from misidentification or clerical error Transfusion-related acute lung injury Bacterial contamination Immunomodulation Unknown mechanism

Infectious Diseases Human immunodeficiency virus risk: 1:2.3 million1 Hepatitis C risk: 1:1.8 million1 Hepatitis B: 78,000 new infections annually, United States2  Risk of transmission through transfusion of 1 unit of blood, 1:58,000-1:149,0003 Other viral diseases4,5  West Nile: 2539-9862 cases in United States between 2002 and 20064  Cytomegalovirus: 40%-100% of US population shows prior exposure by serology5 Malaria: 300-500 million cases worldwide6 Chagas disease: 1 million new cases annually*6 Prions6 *In humans, confined to South and Central America and Mexico. 1. Busch MP, et al. Transfusion. 2005;45:254-264; 2. Centers for Disease Control and Prevention. Available at: www.cdc.gov/vaccine/pubs/pinkbook/downloads/hepb.pdf. Accessed March 3, 2008; 3. Goodnough LT, et al. Lancet. 2003;361:161-169; 4. Centers for Disease Control and Prevention. Available at: www.cdc.gov/ncidod/dvbid/westnile/surv&controlCaseCount. Accessed March 3, 2008; 5. Taylor GH. Am Fam Physician. 2003;67:519-524, 526; 6. Snyder EL, et al. Hematology. 2001;433-442.

Blood CAN Cause Harm Infectious diseases Complications resulting from misidentification or clerical error Transfusion-related acute lung injury Bacterial contamination Immunomodulation Unknown mechanism

Summary of Transfusion Errors 2000-2003 No. of Cases FFP = fresh frozen plasma. Data on file, US Department of Veterans Affairs.

Patient Identification Is Critical Identify at time of phlebotomy  Ask patient his/her name  Verify identity with wrist band  Label tube at bedside Identify at time of transfusion  Two people must identify patient and verify match to label on blood product If there are ANY discrepancies when blood sample and paperwork arrive at blood bank  It is 40 times more likely that the wrong patient’s blood is in the tube than if all identifying information is complete and matches

Blood CAN Cause Harm Infectious diseases Complications resulting from misidentification or clerical error Transfusion-related acute lung injury Bacterial contamination Immunomodulation Unknown mechanism

Transfusion-Related Acute Lung Injury (TRALI) New acute pulmonary insufficiency occurring during or within 6 hours after transfusion1 Incidence estimated at 1:5000 to 1:100,000 transfusions1 Most common with FFP and RBC1 Usually resolves within 96 hours with supportive care2 RBC = red blood cells. 1. Toy P, et al. Best Pract Res Clin Anaesthesiol. 2007;21:183-193; 2. Mariani SM. Medscape Gen Med. 2003;5.

Three Hypotheses for TRALI Antigranulocyte antibodies in donor's plasma (or, less commonly, recipient's plasma) Biologically active substances in transfused blood “2-hit" hypothesis  Recipient granulocytes are primed in vivo, then transfused antibodies "activate" granulocytes Toy P, et al. Best Pract Res Clin Anaesthesiol. 2007;21:183-193.

Blood CAN Cause Harm Infectious diseases Complications resulting from misidentification or clerical error Transfusion-related acute lung injury Bacterial contamination Immunomodulation Unknown mechanism

Blood CAN Cause Harm Infectious diseases Complications resulting from misidentification or clerical error Transfusion-related acute lung injury Bacterial contamination Immunomodulation Unknown mechanism

Blood CAN Cause Harm Infectious diseases Complications resulting from misidentification or clerical error Transfusion-related acute lung injury Bacterial contamination Immunomodulation Unknown mechanism

Transfusion Has Deleterious Effects via Mechanisms We Do Not Understand A number of studies have found that patients who are on liberal transfusion strategies do WORSE (more morbidity and mortality) than do patients on restrictive transfusion strategies Corwin HL, et al. N Engl J Med. 2007;356:1667-1669. Hébert PC, et al. Crit Care Med. 2001;29:227-234. Raghavan M, et al. Chest. 2005;127:295-307.

Transfusion Requirements in Critical Care (TRICC) Prospective, randomized trial that supports causal link between blood transfusion and adverse outcomes among critically ill patients Hébert PC, et al. N Engl J Med. 1999;340:409-417.

TRICC, cont’d 838 patients randomized to liberal (threshold Hb = 10 g/dL) or restrictive (Hb = 7 g/dL) transfusion strategy Cardiac and pulmonary complications increased significantly, and trend existed toward increased mortality in liberal-strategy group (23.3% vs 18.7% in restrictive- strategy group) Mortality was also significantly increased in younger (<55 years), less-sick patients in liberal-strategy group Hb = hemoglobin. Hébert PC, et al. N Engl J Med. 1999;340:409-417.

Nonetheless.… Subgroup analysis of patients (N=257) with cardiac disease showed trend (P=0.3) toward increased survival in liberal-strategy group, in spite of increased incidence of pulmonary complications and multiorgan failure Hébert PC, et al. Crit Care Med. 2001;29:227-234.

Subsequent Studies: Transfusion Also a Risk Factor for Patients With Cardiovascular Disease Rao SV, et al. Relationship of blood transfusion and clinical outcomes in patients with acute coronary syndromes. JAMA. 2004;292:1555-1562 Yang X, et al. The implications of blood transfusions for patients with non–ST-segment elevation acute coronary syndromes. Results from the CRUSADE National Quality Improvement Initiative. J Am Coll Cardiol. 2005;46:1490-1495 Published in 2008 Koch CG, et al. Duration of red-cell storage and complications after cardiac surgery. N Engl J Med. 2008;358:1229-1239

Cardiac Surgery Patients Also Did Worse With Transfusion Retrospective cohort study utilizing database of adult cardiac surgery patients (N=8598) No benefit from transfusion for HCT as low as 21% for patients undergoing cardiac surgery Risk of death within 30 days of surgery almost 6 times greater for patients who received blood Patients receiving transfusions more likely to experience infections and ischemic complications HCT = hematocrit. Murphy GJ. et al. Circulation. 2007;116:2544-2552.

Effects Are Long-Lasting…. Cohort study of 10,289 patients who underwent coronary artery bypass grafting (CABG) between 1995 and 2002 Transfusion of as little as 1 U RBC associated with decreased 10-year survival after CABG procedure Koch CG, et al. Ann Thorac Surg. 2006;81:1650-1657.

… and There Is Little Evidence of Benefit for Cardiac Surgery Patients Ischemic complications (myocardial infarction, neurologic and renal injury) were not decreased with blood transfusion regardless of patient’s nadir HCT or comorbidities Thus, we want to be sure patient really needs transfusion before we give blood products Murphy GJ, et al. Circulation. 2007;116: 2544-2552.

Indications for Transfusion RBC for inadequate oxygen-carrying capacity Plasma for inadequate clotting factor activity Cryoprecipitate for fibrinogen and factor VIII/ von Willebrand factor Platelets for inadequate platelet function

Recommendations Transfusion is rarely indicated when Hb is >10 g/dL and is almost always indicated when Hb is <6 g/dL, especially when anemia is acute 6-10 g/dL: decision to transfuse should be based on patient’s risk for complications of inadequate oxygenation Ferraris VA, et al. Ann Thorac Surg. 2007;83(suppl 1):S27-S86.

Recommendations Threshold Hb of 7 g/dL has been suggested for postoperative cardiac surgery patients Ferraris VA, et al. Ann Thorac Surg. 2007;83(suppl 1):S27-S86.

The Decision to Transfuse Is a Clinical Judgment That Considers Patient’s cardiopulmonary reserve (cardiopulmonary disease, hemodynamic indexes, affected by drugs and anesthetics) Rate and magnitude of blood loss (actual and anticipated) Oxygen consumption (affected by body temperature, drugs, sepsis, muscular activity) Atherosclerotic disease (cerebrovascular, cardiovascular, peripheral, renal)

Thus…. RBC transfusion trigger should be Hb/HCT at which risks of reduced oxygen-carrying capacity exceed risks of transfusion

Platelet Concentrates Prophylactic platelet transfusion not indicated unless platelet count is <10,000/µL Platelet count of 50,000/µL is generally adequate for hemostasis during/following minor procedures Platelet count of 100,000/µL is generally adequate for hemostasis during/following major procedures Mintz PD, ed. Transfusion Therapy: Clinical Principles and Practice. 2nd ed. Bethesda, MD: American Association of Blood Banks; 2004.

Give FFP if clotting tests are prolonged AND patient is bleeding Fresh Frozen Plasma Give FFP if clotting tests are prolonged AND patient is bleeding We don’t really know what PT and PTT are sufficient for adequate hemostasis, and normal PT and PTT do not guarantee against bleeding PT = prothrombin time; PTT = partial prothrombin time.

Alternatives to Transfusion Increase RBC production  Iron supplementation  Erythropoietin Local measures Save patient’s own blood Prohemostatic agents Network for Advancement for Transfusion Alternatives is useful: http://www.nataonline.com/ Goodnough LT, et al. Transfusion. 2003;43:668-676.

Alternatives to Transfusion Increase RBC production Local measures  Tourniquet  Embolization  Fibrin glue/topical thrombin Save patient’s own blood Prohemostatic agents Goodnough LT, et al. Transfusion. 2003;43:668-676.

Alternatives to Transfusion Increase RBC production Local measures Save patient’s own blood  Autologous transfusions  Hemodilution  Cell saver Prohemostatic agents Society for the Advancement of Blood Management is useful: http://www.sabm.org/ Goodnough LT, et al. Transfusion. 2003;43:668-676.

Alternatives to Transfusion Increase RBC production Local measures Save patient’s own blood Prohemostatic agents Goodnough LT, et al. Transfusion. 2003;43:668-676.

Take-Home Messages Blood transfusion can be bad for your patients Don’t transfuse unless you are sure that the patient really needs it There are alternatives to transfusion that should be considered seriously for all types of medical and surgical patients