what is the difference between blood and chicken soup? maureane hoffman, md, phd professor of...
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What Is the Difference Between Blood and Chicken Soup?Maureane Hoffman, MD, PhDProfessor of Pathology and ImmunologyDuke UniversityDirector, Blood Bank and Hematology LaboratoriesDurham VA Medical CenterDurham, North Carolina
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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.
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Blood CAN Cause Harm
• Infectious diseases
• Complications resulting from misidentification or clerical error
• Transfusion-related acute lung injury
• Bacterial contamination
• Immunomodulation
• Unknown mechanism
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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.
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Blood CAN Cause Harm
• Infectious diseases
• Complications resulting from misidentification or clerical error
• Transfusion-related acute lung injury
• Bacterial contamination
• Immunomodulation
• Unknown mechanism
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Summary of Transfusion Errors2000-2003
0 5 10 15 20 25
Misidentified on issue/transfusion
Units transfused/not ordered
Mislabeled crossmatch sample
No crossmatch but transfused
Wrong ABO FFP transfused
Technical error
Computer related error
Contra-indicated medication
Transfused but not indicated
Patient refused but transfused
Medication administered with blood
FFP = fresh frozen plasma.Data on file, US Department of Veterans Affairs.
No. of Cases
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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
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Blood CAN Cause Harm
• Infectious diseases
• Complications resulting from misidentification or clerical error
• Transfusion-related acute lung injury
• Bacterial contamination
• Immunomodulation
• Unknown mechanism
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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.
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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.
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Blood CAN Cause Harm
• Infectious diseases
• Complications resulting from misidentification or clerical error
• Transfusion-related acute lung injury
• Bacterial contamination
• Immunomodulation
• Unknown mechanism
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Blood CAN Cause Harm
• Infectious diseases
• Complications resulting from misidentification or clerical error
• Transfusion-related acute lung injury
• Bacterial contamination
• Immunomodulation
• Unknown mechanism
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Blood CAN Cause Harm
• Infectious diseases
• Complications resulting from misidentification or clerical error
• Transfusion-related acute lung injury
• Bacterial contamination
• Immunomodulation
• Unknown mechanism
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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.
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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.
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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.
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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.
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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
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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.
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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.
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… 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.
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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
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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.
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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.
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The Decision to Transfuse Is a Clinical Judgment That Considers
1. Patient’s cardiopulmonary reserve (cardiopulmonary disease,
hemodynamic indexes, affected by drugs and anesthetics)
2. Rate and magnitude of blood loss (actual and anticipated)
3. Oxygen consumption (affected by body temperature, drugs,
sepsis, muscular activity)
4. Atherosclerotic disease (cerebrovascular, cardiovascular,
peripheral, renal)
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Thus….
RBC transfusion trigger should be Hb/HCT at which risks of
reduced oxygen-carrying capacity exceed risks of transfusion
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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.
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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.
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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.
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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.
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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.
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Alternatives to Transfusion
• Increase RBC production
• Local measures
• Save patient’s own blood
• Prohemostatic agents
Goodnough LT, et al. Transfusion. 2003;43:668-676.
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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