Any intravenously administered fluid can transmit infection, but blood is a uniquely nutritious medium and is seemingly an excellent means for transmitting infection. In fact, any pathogen that is capable of existing in blood can be transmitted in this manner. It is a tribute to modern blood banking procedures that transfusion-transmitted infection is actually quite rare. Blood-borne parasites can be transmitted with transfusion, and a handful of cases of malaria, babesiosis, Chagas' disease, trypanosomiasis, and toxoplasmosis have been reported. The primary means of preventing these infections is through careful screening of donors, especially those who have traveled to areas that are endemic for these diseases [5
]. Syphilis can be transmitted by blood transfusion but no cases have been reported since 1969; it is generally thought that the practice of refrigerating blood, which kills spirochetes within 1–2 days, is responsible for this.
Bacterial contamination is the second most frequently reported cause of blood transfusion-related death after hemolytic reactions, and it accounts for more than 10% of transfusion-associated deaths in the USA [6
]. The Assessment of the Frequency of Blood Component Bacterial Contamination Associated with Transfusion Reaction Study (BaCon), which was implemented by the US Centers for Disease Control and Prevention, was the first study to look at specific characteristics related to bacterial contamination of blood products [7
]. Results from data collected between 1998 and 2000 showed that the risk for transfusion-transmitted bacteremia is 1 in 100,000 units of platelets and 1 in 500,000 units of red blood cells (RBCs), and that the estimated risk for death from bacterial transfusion-transmitted causes is 1 in 500,000 units of platelets and 1 in 8 million units of RBCs. Contamination with Gram-positive bacteria was more common; however, Gram-negative contamination was independently associated with increased risk for death. Rigors, fever, or tachycardia within 4 hours of transfusion were present in at least 75% of the cases, and haziness or discoloration of the blood product was present in 24% of the contaminated units [7
Previous reports of small case series showed that Gram-negative bacteria appeared to be the most common source of blood component contamination. However, as shown by the BaCon study, this is not true and these reports might have been biased by the fact that Gram-negative bacteria are more frequently associated with death and hence are reported more often. Actually, Gram-positive bacteria, including Staphylococcus and Streptococcus spp., as well as Gram-negative bacteria including Escherichia coli, and Serratia, Enterobacter, and Yersinia spp., have all been implicated in blood contamination. In general, if bacteremia or endotoxemia is suspected after transfusion of a unit of blood or platelets, then the remaining blood/platelets in the bag and/or tubing should be examined by stain and cultured. In addition, the recipient's blood should also be cultured.
Unlike bacterial infections, viral infections are not immediately evident. Hepatitis B was once the most serious transfusion risk, but the development many years ago of a sensitive and specific test for hepatitis B has led to a dramatic reduction in the transmission of this infection via transfusion. After the introduction of tests for hepatitis B antigen and antibody, non-A/non-B hepatitis became the most prevalent form of transfusion-transmitted infection. For a period, the risk for developing non-A/non-B hepatitis was estimated to be approximately 7% for recipients of volunteer-donated blood and 28% for recipients of commercial blood [8
]. The availability of increasingly sensitive and specific tests for hepatitis C has greatly reduced this risk as well.
The spread of HIV in the 1980s introduced a new risk for viral infection into the equation for blood transfusion. Again, increasingly sensitive and specific tests have become available, and the absolute risk for acquiring transfusion-associated HIV infection has become quite low, accounting for fewer deaths in the current era than post-transfusion hepatitis. However, the possibility of transfusion-associated HIV is still much more frightening to most patients and many practitioners. Prevention of transfusion-associated HIV infection is accomplished first through careful screening of all potential donors to eliminate those at high risk for having the infection, and second by screening all donated units for antibodies to HIV. It has been estimated that predonation screening is 98% effective in preventing the donation of positive units and that antibody testing is 95% effective, providing a combined effectiveness of approximately 99.9% [10
]. Using these techniques only, between 1985 and 1988 – a time when the overall prevalence of HIV infection in the USA was increasing – post-transfusion HIV infections were reduced by 76%.
The only remaining real risk for acquiring HIV through blood transfusion comes from the small possibility that blood could be donated during the so-called window of sero-negativity between the time when HIV infection occurs and detectable antibodies develop. The average window is estimated to be about 8 weeks [10
]. The incidence of positive units of blood discovered through postdonation screening has been steadily decreasing. The risk for blood being sero-negative but virus-positive is assumed to be proportional to the number of sero-positive units discovered through post-transfusion antibody screening. In one study [11
] conducted at five blood centers across the USA, 2,318,356 units of blood derived from 586,507 donors were tested between 1991 and 1993. In that study, the risk for acquiring an HIV infection from a unit of blood was 1 in 493,000, the risk for hepatitis C was 1 in 103,000, and the risk for hepatitis B was 1 in 63,000. The combined risk for acquiring any type of viral infection was 1 in 34,000, and 88% of that risk was derived from hepatitis B and C.
Current risks with improved, more sensitive tests are considered to be even lower (Table ). Busch and colleagues [12
] reported that risk estimates are now based on mathematical models. These model-based estimates indicate that the current risk for HIV is 1 in 1,800,000, for hepatitis C it is 1 in 1,600,000, and for hepatitis B it is 1 in 220,000. Using the newest nucleic acid technology screening techniques, the window during which infection is not detectable in a donated unit of blood has decreased to 11 days for HIV and 8–10 days for hepatitis C virus [12
]. The risk for a fatal hemolytic transfusion reaction is estimated to be 1 in 100,000 [13
]. Thus, it can be seen that after transfusion the risk for death from hepatitis B or C, or from a hemolytic transfusion reaction, is greater than the risk for dying from transfusion-associated HIV.
Infectious transmission risks with blood transfusion
One of the most recent potential infectious agents in blood transfusion to be proposed is the prion agent of the new variant Creutzfeldt–Jakob disease (nvCJD). To date, no evidence of transfusion-mediated transmission of classic CJD has been found. However, the disease has been transmitted through corneal transplants, human growth hormone derived from human pituitary glands, dura mater transplants, and inadequately sterilized depth electrodes used in the brain during the work-up and treatment of epilepsy. Because experience with nvCJD is so limited and because it appears to have previously unreported modes of transmission, some authorities have enacted precautionary donor exclusion regulations [14
] and some countries have even changed their practice to universal leukoreduction [16
More recently, transfusion-transmitted West Nile Virus was confirmed within the USA. Since screening began in June 2003, 163 highly reactive units were removed from a total of 1.1 million units screened during a 2-month period. The investigations into West Nile Virus transmission, as well as the fast implementation of a screening test and preventive strategies, are all examples of the significant advances in blood transfusion medicine and highlight the need for a multidisciplinary approach to prevent transfusion-mediated infectious complications [17
On the whole, transfusion is a very safe treatment modality. For those patients and physicians who wish to keep the risk for transfusion-associated infection to a minimum, the primary response should be to limit unnecessary transfusion. Another response has been to increase donation of autologous blood for transfusion. Although the practice of autologous blood donation appears to have reached a plateau over the past 10 years, analysis of transfusion practices in the USA has revealed that the number of autologous units donated increased more than 30-fold from 1980 to 1992 [1