what is the difference between blood and chicken soup? maureane hoffman, md, phd professor of...

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