Written by: Mediware Consulting and Analytics on Monday, August 13, 2012 Posted in: Blood Management

CA-Transfusion-Infections-GraphEvery medical intervention has an inherent risk.  Blood transfusion is no exception. Physicians must know the risks versus benefits of therapeutic modalities for each specific patient treated.

Unfortunately, disproportionate emphasis is sometimes placed on the risks and potential infectious complications of transfusion, in part due to transfusion transmitted HIV in the 1980′s.  Today, the primary transfusion transmitted risk is bacteria, not HIV or other viruses as many still fear, thanks to an all volunteer blood supply, robust infectious disease testing, advanced manufacturing practices (employing continuous Good Manufacturing Practices – cGMP), and the FDA’s layers of safety.  Currently, the top risks of transfusion are non-infectious (TRALI, TACO, hemolytic transfusion reactions). Blood is so safe, that many activities considered ‘safe’ by the general population are in fact less safe. The annual risk of death due to a variety of causes is listed in the chart above.

The prevalence of the known infectious agents in collected blood has also been decreasing as a result of moving to volunteer donors, more stringent donor selection requirements, evolving collection, processing, and testing technologies, increasingly sensitive assays, and improved laboratory testing procedures.  For example, in 1999 donor centers adopted new automated Polymerase Chain Reaction-like testing called NAT (Nucleic Acid Amplification Technology) for increased sensitivity in detecting early Human Immunodeficiency Virus and Hepatitis C Virus; West Nile Virus and Hepatitis B Virus were added later.

Bacterial contamination is still a serious risk of transfusion despite sterile technique, bacterial detection (implemented 2003-4), defined sampling techniques and timing, and diversion pouches.  Platelets are stored at room temperature, giving bacteria ample opportunity to grow during storage.  It is estimated that approximately 1 in 5000 apheresis platelets are bacterially contaminated.   The residual risk is thought mainly due to bacteria that enter logarithmic growth in the bag only after the initial sampling 24 hours after collection.  It is frequently noted that the risk may be higher due to under-recognition and under-reporting. Gram-positive skin saphrophytes account for most of the organisms seen, however serious and fatal reactions occur due to occult donor Gram-negative organism (E coli, Klebsiella sp, P rettgeri, Serratia sp) bacteremia.  Red blood cells are refrigerated and less often associated with adverse outcomes due to bacterial contamination, although septic (1:500,000) and fatal (1:10,000,000) reactions are seen.  Microorganisms isolated from RBCs include Staphylococcus epidermidis, Serratia liquifaciens, Pseudomona sp, and Yersinia enterocolitica.

The actual rates of viral transfusion-transmitted infection are so low counting cases is no longer an acceptable method of measurement.  The residual risk of transfusion-associated infection is determined by mathematical models based on estimates of donors giving blood during the “window period.” The infectious window extends from a few days after the virus infects a person, during which there is rapid viral multiplication, until the earliest time that the screening test can detect its presence; if blood is collected during this period, it is presumed infectious.  The overall residual risk of acquiring any infection following a transfusion is less than 1/100,000-200,000 per component transfused; while the risk of death due to a transfusion-transmitted infection is less than 1:1,000,000.  The current estimated risk of viral transfusion transmission is listed in the table.

Infectious agent routinely tested by NAT by
US blood centers

Estimated residual risk
per component transfused

Human Immunodeficiency Virus


Hepatitis C Virus


Hepatitis B Virus


West Nile Virus

at least 11 cases reported
in US since July 2003

The ultimate safety of any medical intervention relies on the diligence of the entire healthcare community.  Blood transfusion is no different.  Today, the residual risk of transfusion is very small but not zero.  The first transfusions were associated with 50% mortality due to hemolytic transfusion reactions.  Hemolytic reactions still occur (9/30 transfusion-related fatalities reported to FDA in FY2011), largely due to human errors in the hospital at order, sample collection, testing, patient identification, or administration.  It has been estimated that even today 1:14,000 units transfused goes to the wrong patient and 1:38,000 transfusions are ABO incompatible.

Fortunately, blood centers have implemented systems and tests to minimize product associated risks, while hospitals serious about appropriate blood management are adopting strategies to maximize the chances that the right blood component will be administered to the right patient in the right dose at the right time for the right reasons. The cliché still bears repeating, the United States blood supply is the safest it has ever been.


  1. Blundell J. Observations on the transfusion of blood. Lancet 1828;2(ii):321–4.
  2. Carson JL, et al. Red Blood Cell Transfusion: A clinical practice guideline from the AABB. Ann Intern Med 2012;157:49-58.
  3. Center for Biologics Evaluation and Research. Blood Products Advisory Committee, 94th Meeting, Gaithersburg, MD, April 1, 2009 (transcript, accessed Aug 2012.  http://www.fda.gov/downloads/AdvisoryCommittee/
  4. Centers for Disease Control. HIV transmission through transfusion — Missouri and Colorado, 2008. MMWR Weekly 2010 Oct 59(41);1335-9.
  5. U.S. Food and Drug Administration. Transfusion/donation fatalities annual report Oct 2010-Sep 2011.
  6. (http://www.fda.gov/biologicsbloodvaccines/safetyavailability accessed Aug 2012).
  7. Fiebig EW, Busch MP. Infectious disease testing. In: Brecher ME (ed.). Technical Manual, 16th ed. Bethesda, Maryland: American Association of Blood Banks, 2008.
  8. Goodnough LT, et al. Transfusion medicine: Looking to the future. Lancet 2003;361(9352):161.
  9. Grimm et al. Blood Bank Safety Practices: mislabeled samples and wrong blood in tube – A Q-Probes analysis of 122 clinical laboratories. Arch Pathol Lab Med. 2010 Aug;134(8):1108-15.
  10. Hillyer CD, et al. Bacterial contamination of blood components: risks, strategies, and regulation: Joint ASH and AABB Educational Session in Transfusion Medicine. Hematology (Am Soc Hematol Educ Program). 2003:575-89.
  11. Klein HG. How safe is blood, really? Biologicals 2010;38:100-04.
  12. Klein HG. Transfusion medicine. In Nabel EG (ed.) ACP Medicine 2011.
  13. Kuenert MJ, et al.  Transfusion-transmitted bacterial infection in the United States, 1998 through 2000. Transfusion 2001;41:1493-9.
  14. Linden et al. Transfusion errors in New York State: Transfusion. 2000;40:1207-13.
  15. Niederhauser C. Reducing the risk of hepatitis B virus transfusion-transmitted infection. J Blood Med 2011;2:91-102.
  16. Stramer SL (ed.) Blood Safety in the new millennium.  American Association of Blood Banks. Bethesda, MD. 2001.
  17. Stramer SL, et al. Blood donation screening for hepatitis B virus markers in the era of nucleic acid testing: are all tests of value? Transfusion 2012;52:440-446.
  18. Strong DM, Katz L. Blood-bank testing for infectious diseases: how safe is blood transfusion? Trends Mol Med. 2002 Jul;8(7):355-8.
  19. Vamvakas EC, Blajchman MA. Transfusion-related mortality: the ongoing risks of allogeneic blood transfusion and the available strategies for their prevention. Blood 2009;113(15):3406–17.
  20. Yomtovian R. Bacterial contamination of blood: Lessons from the past and a road map for the future. Transfusion 2004;44:450-60.