Introduction to Blood Management

Written by: Timothy Hannon, MD, MBA

Scope of Blood Component Therapy

Blood products have been a vital and integral part of modern healthcare since the advent of the first blood bank in 1936.  The foundation of the current blood banking industry was laid during WW II, when efficient methods of blood processing, handling and storage were developed to meet the huge war-time demand.  Tremendous advances in blood processing technology and blood screening in the latter half of the 20^th century have resulted in steady increases in blood safety and availability.   The National Blood Data Resource Center estimates that each year 15 million units of whole blood are collected and processed into 24 million blood products, which are then transfused to 4.5 million medical and surgical patients.¹ The development of a safe and readily available blood supply has facilitated the advent of life-saving procedures, such as trauma resuscitation, cardiac surgery, organ transplantation, and chemotherapy.  None of these procedures could have come about, nor could they currently exist, without an efficient collection, distribution, and delivery system for these millions of units of blood products. 

Efficacy of Transfusions

 While blood transfusion therapy has been in common practice since the 1940’s, it wasn’t until 1999 that the first controlled clinical trial of blood transfusions was conducted. The Transfusion Requirements in Critical Care (TRICC) trial was published in the New England Journal of Medicine on February 11th, 1999, and it remains a landmark study in transfusion medicine.² In this study, 838 anemic critically ill patients were prospectively randomized into one of two treatment strategies: transfuse at a hemoglobin level of 10 gm/dL, a very traditional approach to these challenging patients, or transfuse at a hemoglobin level of 7 gm/dL, which was a very radical departure from common practice in 1999. The results of this study were surprising and changed the practice of transfusion medicine because the patients who were transfused at the more liberal “trigger” of 10 gm/dL had substantially worse outcomes than those transfused at the more conservative trigger of 7 gm/dL, particularly cardiopulmonary outcomes such as pulmonary edema, ARDS and myocardial infarction. Further, hospital mortality rates were also higher in those patients transfused more liberally. The conclusion of the authors back in February of 1999 was that “a restrictive strategy of red cell transfusions is at least as effective as and possibly superior to a liberal strategy in critically ill patients, with the possible exception of patients with acute myocardial infarction or unstable angina.” Even the exception to the rule noted by the authors- those patients with acute coronary syndromes (ACS)- have now been shown to also have higher mortality rates when transfused liberally.^3,4,5 The results of the TRICC trial coined the phrase “less is more for transfusions,” a concept whose evidence has grown even stronger over the past decade.

Adverse Effects of Transfusions

 While efficacy studies for blood transfusion are relatively few, there are a growing number of controlled studies have demonstrated a direct relationship between the amount of blood products that patients receive and serious complication rates.  These complications are largely due to the immunosuppressive effects of donor blood and include stepwise increases in infection rates^6-14, ventilator support times, ICU and hospital length of stay^15-21, short term and long term mortality^{12,17,18,22,23} and cancer recurrence rates^24-27.

 These adverse effects become even more concerning in light of the quality management and patient safety implications of improper transfusion decisions and transfusion errors. Owing in large part to a lack of formal training in transfusion medicine for most physicians, the administration of blood products is surrounded by emotions, misconceptions, and myths. In spite of mounting evidence that demonstrates significant harm from unnecessary blood transfusions²⁸, there are several studies that document a generalized lack of compliance with appropriate transfusion guidelines, as well as tremendous variation in transfusion practice between different institutions and among individual physicians within the same institution^29-32.

 With regards to patient safety, transfusion of blood products to the wrong patient (mistransfusion) has become one of the greatest risks to transfused patients.  While improved donor screening has reduced the risk of HIV transmission to less than one in a million transfusions,  mistransfusion still occurs with the alarming frequency of 1:12,000- 19,000 units transfused, with death occurring in 1:600,000- 800,000 transfusions^33,34.  From a medical-legal standpoint, the financial liability of inappropriate transfusions decisions and transfusion errors is substantial, both to the hospital and to individual physicians, and can amount to millions of dollars.

Economics of Transfusions

 Blood costs are increasingly on the minds of hospital administrators and have recently been in the news^35,36.   Although administrators are aware that the cost to purchase blood rises 5- 8% a year, they are often unfamiliar with the total cost of blood transfusion. The total cost of transfuion includes the cost of storing, testing, dispensing and administering blood products within the hospital. Blood is a very resource intensive product, consuming large amounts of med tech and nursing labor, as well as significant amounts of supplies and allocated overhead³⁷. One activity based accounting study looking at cancer patients concluded that the cost to purchase blood represents only 19% of transfusion-related costs, and that the total cost to transfuse a unit of blood (in 2009 dollars) was from $850- $1404³⁸. A recent study used an even more detailed accounting method in a review of the cost of surgical blood transfusions. This study concluded that blood purchase costs represent only 21%- 28% of transfusion-related costs, and that the cost to transfuse a single unit of blood was from $726- $1183³⁹. While these costs are considerable, an additional accounting for the cost of transfusion-related adverse events can more than double the final cost to $2100- $3200 per unit⁴⁰.  These costly transfusion-related adverse events include stepwise increases in infection rates, ventilator support times, ICU and hospital length of stay, short term and long term mortality and cancer recurrence rates⁴¹. It should be evident from the previous discussion that the total cost of transfusing patients is substantially more than just the cost to buy it. The cost of purchasing blood products is merely the tip of the iceberg of total blood costs, when accounting for transfusion-related labor, supplies, overhead and potential adverse effects.

The Rise of Blood Management Programs

Blood is a precious and vital resource that is increasingly scarce and increasingly expensive.  Current evidence supports a more conservative and thoughtful approach to blood component therapy based upon a shifting risk and benefit profile.  However, physicians can be slow in adapting evidence-based practices and hospitals often fail to provide adequate blood utilization oversight and education.  For these reasons, hospitals and hospital systems are increasingly looking to blood management programs as a vehicle to improve safety, quality and stewardship.

 The goal of blood management is to ensure the safe and efficient use of the many resources involved in the complex process of blood component therapy.  These resources extend well beyond blood products and include nursing time, technician time, medical supplies, medical devices, laboratory tests, pharmaceuticals, hospital beds and healthcare dollars.  The cornerstones of blood management programs are the implementation of evidence-based transfusion guidelines to reduce variability in transfusion practice, and the employment of multidisciplinary teams to study, implement and monitor blood management best practices in high risk patient populations.  Our experience with comprehensive blood management programs has demonstrated sustainable reductions in the use of blood products by twenty percent or greater.  This reduction reflects a more efficient utilization of blood and its associated resources, along with improvements in patient safety and the quality of care.

References

1. Report of the US Department of Health and Human Services. The 2009 national blood collection and utilization survey report. Washington, DC: US Department of Health and Human Services, Office of the Assistant Secretary for Health, 2011.
2. Hébert PC, Wells G, Blajchman MA, et al.  A multicenter, randomized, controlled trial of transfusion requirements in critical care. NEJM 1999;340(6):409-68.
3. Rao SV, Jollis JG, Harrington RA, et al. Relationship of blood transfusion and clinical outcomes in patients with acute coronary syndromes. JAMA 2004;292(13):1555-62.
4. Aronson D, Dann EJ, Bonstein L, et al. Impact of red blood cell transfusion on clinical outcomes in patients with acute myocardial infarction. Am J Cardiol 2008; 102: 115-19.
5. Shishebohr MH, Madhwal S, Rajagopal V, et al. Impact of blood transfusions on short-term and long-term mortality in patients with ST-elevation myocardial infarction. J Am Coll Cardiol Intv 2009;2(1):46-53.
6. Agarwal N, Murphy JG, Cayten CG et al. Blood transfusion increases the risk of infection after trauma. Arch Surg 1993;128:171-6.
7. Carson JL, Altman DG, Duff A et al. Risk of bacterial infection associated with allogeneic blood transfusion among patients undergoing hip fracture repair. Transfusion 1999;39:694-700.
8. Claridge JA, Sawyer RG, Schulman AM et al. Blood transfusions correlate with infections in trauma patients in a dose-dependent manner. Am Surg 2002;68:566-72.
9. Leal-Noval SR, Rincon-Ferrari MD, Garcia-Curiel A et al. Transfusion of blood components and postoperative infection in patients undergoing cardiac surgery. Chest 2001;119:1461-8.

1. Triulzi DJ, Vanek K, Ryan DH et al. A clinical and immunologic study of blood transfusion and postoperative bacterial infection in spinal surgery. Transfusion 1992;32:517-24.
2. Houbiers JG, van de Velde CJ, van de Watering LM et al. Transfusion of red cells is associated with increased incidence of bacterial infection after colorectal surgery: a prospective study. Transfusion 1997;37:126-34.
3. Taylor RW, Manganaro L, O'Brien J et al. Impact of allogenic packed red blood cell transfusion on nosocomial infection rates in the critically ill patient. Crit Care Med 2002;30:2249-54.
4. Shorr AF, Duh MS, Kelly KM et al. Red blood cell transfusion and ventilator-associated pneumonia: A potential link? Crit Care Med 2004;32:666-74.
5. Hill GE, Frawley WH, Griffith KE et al. Allogeneic blood transfusion increases the risk of postoperative bacterial infection: a meta-analysis. J Trauma 2003;54:908-14.
6. Moore FA, Moore EE, Sauaia A. Blood transfusion. An independent risk factor for postinjury multiple organ failure. Arch Surg 1997;132:620-4.
7. Malone DL, Dunne J, Tracy JK et al. Blood transfusion, independent of shock severity, is associated with worse outcome in trauma. J Trauma 2003;54:898-905.
8. Vincent JL, Baron JF, Reinhart K et al. Anemia and blood transfusion in critically ill patients. JAMA 2002;288:1499-507.
9. Corwin HL, Gettinger A, Pearl RG et al. The CRIT Study: Anemia and blood transfusion in the critically ill--current clinical practice in the United States. Crit Care Med 2004;32:39-52.
10. Vamvakas EC, Carven JH. RBC transfusion and postoperative length of stay in the hospital or the intensive care unit among patients undergoing coronary artery bypass graft surgery: the effects of confounding factors. Transfusion 2000;40:832-9.
11. Shapiro MJ, Gettinger A, Corwin HL et al. Anemia and blood transfusion in trauma patients admitted to the intensive care unit. J Trauma 2003;55:269-73.
12. Fransen E, Maessen J, Dentener M et al. Impact of blood transfusions on inflammatory mediator release in patients undergoing cardiac surgery. Chest 1999;116:1233-9.
13. Engoren MC, Habib RH, Zacharias A et al. Effect of blood transfusion on long-term survival after cardiac operation. Ann Thorac Surg 2002;74:1180-6.
14. van de Watering LM, Hermans J, Houbiers JG et al. Beneficial effects of leukocyte depletion of transfused blood on postoperative complications in patients undergoing cardiac surgery: a randomized clinical trial. Circulation 1998;97:562-8.
15. Vamvakas EC. Transfusion-associated cancer recurrence and postoperative infection: meta-analysis of randomized, controlled clinical trials. Transfusion 1996;36:175-86.
16. Blumberg N, Heal JM. Effects of transfusion on immune function. Cancer recurrence and infection. Arch Pathol Lab Med 1994;118:371-9.
17. Landers DF, Hill GE, Wong KC et al. Blood transfusion-induced immunomodulation. Anesth Analg 1996;82:187-204.
18. Langley SM, Alexiou C, Bailey DH et al. The influence of perioperative blood transfusion on survival after esophageal resection for carcinoma. Ann Thorac Surg 2002;73:1704-9.
19. Hebert PC, Wells G, Blajchman MA et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care, Canadian Critical Care Trials Group. N Engl J Med 1999;340:409-17.
20. Goodnough LT, Johnston MF, Toy PT. The variability of transfusion practice in coronary artery bypass surgery. Transfusion Medicine Academic Award Group. JAMA 1991;265:86-90.
21. Stover EP, Siegel LC, Body SC et al. Institutional variability in red blood cell conservation practices for coronary artery bypass graft surgery. Institutions of the MultiCenter Study of Perioperative Ischemia Research Group. J Cardiothorac Vasc Anesth 2000;14:171-6.
22. Audet AM, Andrzejwski C, Popovsky MA.  Red blood cell transfusion practices in patients undergoing orthopedic surgery: a multi-institutional analysis. Orthopedics 1998;21:851-8.
23. Poses RM, Berlin JA, Noveck H et al. How you look determines what you find: severity of illness and variation in blood transfusion for hip fracture. Am J Med 1998;105:198-206.
24. Linden JV, Wagner K, Voytovich AE et al. Transfusion errors in New York State: an analysis of 10 years' experience. Transfusion 2000;40:1207-13.
25. Linden JV, Paul B, Dressler KP. A report of 104 transfusion errors in New York State. Transfusion 1992;32:601-6.
26. Tracy D. Blood is big business: why does it cost so much? Orlando Sentinel, April 5, 2010.
27. Annual costs total $1.6 to $6 million per hospital surveyed warranting improved conservation & cost containment strategies. PR Newswire, April 5, 2010.
28. Hannon TJ, Paulson-Gjerde, K. Contemporary economics of transfusions. In: Perioperative Transfusion Medicine (2nd ed), 2005, Spiess BD, editor. Williams & Wilkins: Baltimore.
29. Cremieux PY, Barrett B, Anderson K et al. Cost of outpatient blood transfusion in cancer patients. J Clin Oncol 2000;18:2755-61.
30. Shander A, Hoffmann A, Ozawa S, et al. Activity-based costs of blood transfusion in surgical patients at four hospitals. Transfusion 2010;50:753-65.
31. Boucher BA, Hannon TJ. Blood management: a primer for clinicians. Pharmacotherapy, 2007;27(10):1394-1411.
32. Blumberg N, Kirkley SA, Heal JM. A cost analysis of autologous and allogeneic transfusions in hip replacement surgery. Am J Surg 1996;171:324-30.