A historical perspective on blood transfusions was published in 1998 by Rossi et al.¹ William Harvey first described the circulatory system in 1628 in his book, Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus (An Anatomical Exercise on the Motion of the Heart and Blood in Animals). The first recorded blood transfusion in a human was performed by Jean Baptiste Denis in Paris on June 15, 1667. Denis transfused the blood of a lamb to a 15-year-old boy. The first reports of human-to-human blood transfusion began emerging in the early 19th century. These transfusions predated the recognition of different blood groups and were confounded by difficulty with collection, storage, and administration of blood. Not surprisingly, the outcomes of these bold treatments were indifferent at best. It was not until Karl Landsteiner identified the A, B, and C (later renamed O) blood groups in 1900 that we began to understand the importance of immunohematology. Ottenberg introduced compatibility testing in 1907. The Rh system was discovered in 1939 and by the 1940s, collection and storage of donor blood, along with reliable compatibility testing, had rendered blood transfusion almost routine, and apparently safe. However, in 1943, Beeson described posttransfusion hepatitis and by 1962, it became apparent that there was an association between paid blood donors and posttransfusion hepatitis. In 1983, the first report of the acquired immune deficiency syndrome (AIDS) transmission associated with transfusion (in an infant) was published. Hepatitis and AIDS are not alone, and transmission of bacterial and
viral disease remains a risk of transfusion. Recently, there has been concern about the transmission of variant Creutzfeldt-Jakob Disease (CJD) from contaminated blood, and at least two case reports serve to justify this concern.²,³

The broadest classification of transfusion reactions includes all the complications of blood transfusion. Infectious, immunologic, and nonimmunologic reactions occur with variable frequencies. Table 35.1 shows a simple classification of transfusion reactions.

Ever since the link between transfusion and the transmission of AIDS was reported in 1983, the medical community and the lay public have both been increasingly concerned with the risk of transmission of diseases by “tainted” blood. Viruses, bacteria, parasites, and prions can all be transmitted by transfusion of contaminated blood. Fortunately, advances in screening of donors, including testing of donor blood as well as behavioral risk factor screening of donors, have reduced the incidence of major transmissible viral infections.⁴ The risks of infectious complications will vary to some extent, depending on the donor population and prevalence of infection, as well as local screening practices. The risk of transfusion-transmitted infection will never be eliminated, but with high levels of vigilance, effective screening, and a rigorous surveillance program, the risk can be reduced dramatically.

Transmissions of viruses responsible for hepatitis and AIDS have long been recognized as risks of blood transfusion. The cost of transmission of these diseases in the past is incalculable. Blood collection and distribution authorities, including governmental agencies, all over the world have been held responsible for the many cases of virus transmission that could have been avoided. This has led to many large compensation claims, and a great deal of media attention has been given to this phenomenon. The human cost to patients who have received contaminated blood and contracted these diseases is enormous. Although blood transfusion will never be a zero-risk intervention, much attention has been focused on reducing the risk of transmission of infectious diseases, in particular viral diseases. Human immunodeficiency virus (HIV) is only one of many viruses that have been implicated in transfusion-transmitted infections. Table 35.2 lists the viruses that are considered potential contaminants of blood products, and can potentially lead to transmittable diseases.

With the HIV in particular, huge strides have been made to reduce the risk of transfusion. It is estimated that if a patient receives a transfusion with HIV-contaminated blood, the risk of that patient becoming infected is in the order of 90%. Advances in screening and testing of the donor population have reduced the risk of transmission of HIV to an unlikely possibility. Donor blood is routinely tested for antibodies to HIV-1 and HIV-2. Recently, nucleic acid testing has been implemented. The window
of time between a donor becoming potentially infected and demonstrating nucleic acid testing-detectable HIV nucleic acids is 13 days. Before this, the window for the antibody testing alone was approximately 22 days.

The estimated risks for transmission of viral disease per blood component transfused are calculated mathematically using input variables such as the virus’ incidence in the donor population, as well as the window of time of the current screening techniques to identify the disease.

The current estimates⁵ of transmission risk of some viral diseases from blood transfusion are listed in Table 35.3.

CMV transmission in particular, is associated with transfusion of leukocytes; hence, leukodepleted RBCs and platelet units are less likely to be a vehicle for its transmission. Blood products that do not contain cellular components do not transmit CMV; FFP and cryoprecipitate are safe in this regard. CMV infection is an undesirable outcome in immunocompromised patients, and patients at greatest risk should receive only leukodepleted blood from CMV seronegative donors. These patients include the following:

Severe acute respiratory syndrome (SARS) is caused by the highly contagious coronavirus, SARS-CoV. This virus can be detected in the blood of affected patients, and, although there are yet no reports of SARS transmission by transfusion of infected blood, screening of at-risk donors could reduce the risk of transmission of this disease by blood transfusion.⁷

Other viruses less frequently implicated in the transmission of disease from blood transfusion include the parvovirus B19 and the human herpesvirus 8. Although both of these viruses have been detected in donor blood, the risk of symptomatic transfusion transmission is estimated as extremely low to virtually nonexistent.⁸

The most common infectious complication of blood transfusion is the bacterial contamination of platelet components, which occurs with a frequency of 1:2,000.⁴ The incidence of sepsis is between 1:2,500 and 1:12,000 pooled platelet transfusions.⁵

Bacterial contamination of RBC components is less common, as erythrocytes are stored at colder temperatures. It is estimated that sepsis from contaminated RBC transfusion occurs with a frequency of 1:500,000 per component transfused,⁴ with a mortality rate of <1:1,000,000.⁵ Given the relatively low frequency of sepsis, the associated mortality is very high. Approximately 10% of deaths associated with transfusion are attributed to bacterial sepsis. Commonly transmitted bacteria include gram-negative species, including Yersinia enterocolitica, Pseudomonas, Klebsiella pneumoniae, and Serratia marcescens.⁵ These organisms are implicated because they can grow and multiply at 4°C, the temperature at which RBCs are commonly stored. The endotoxins released by these organisms are responsible for the clinical spectrum of sepsis, which they cause. Less commonly gram-positive organisms, including Staphylococcus aureus, Staphylococcus epidermidis, Bacillus cereus, and other skin surface organisms are implicated. These organisms have been cultured from platelets stored at room temperature.

Donor blood may become contaminated by inadequate skin preparation at the time of blood collection, prior contamination of the collection equipment, or by donor bacteremia at the time of collection. The clinical presentation of bacterial infection from transfusion includes fever and rigors soon after initiation of transfusion, as well as tachycardia, hypotension, and even circulatory collapse. Bacterial sepsis from contaminated blood is not usually associated with hemolysis and hemoglobinuria, and can therefore be distinguished from hemolytic transfusion reactions (HTRs). Successful treatment and outcome requires early diagnosis and appropriate treatment with antimicrobial agents. Bacterial sepsis is a very serious complication of transfusion; virtually all deaths associated with transfusion-transmitted infection are the result of bacterial sepsis.⁹

The transmission of syphilis (Treponema pallidum) is very rare. All donated blood is screened with serologic tests for syphilis; this measure, combined with storage of blood at 4°C, has virtually eliminated this disease as a risk of transfusion.

The spirochete, Borrelia burgdorferi, is the causative agent of Lyme disease. This organism can survive in platelets and stored RBCs. The theoretical possibility exists that Lyme disease could be transmitted by blood transfusion, although this appears to be most unlikely.

The transmission of parasites is rare, but will also be influenced by donor and recipient demographic factors, including prevalence of parasites in the donor population.

Malaria is the most commonly recognized culprit, with a risk of 1:4,000,000⁵ and is caused by the Plasmodium species, typically Plasmodium falciparum. In areas where malaria is endemic, transfusion-related transmission is much more common. The plasmodium organism exists within the erythrocytes of infected individuals, and can therefore be transmitted by RBC transfusion or by transfusion of platelets that contain RBCs. Donors who have recently traveled to areas where malaria is endemic should be temporarily excluded from the donor pool.

Babesiosis is the second most commonly transmitted parasitic disease in North America, and is caused by the organism, Bebesia microti. Chagas disease, ehrlichiosis, leishmaniasis, toxoplasmosis, and microfiliariasis are all rare, with the risk of clinical disease low in most recipients. The appropriate screening of donors, including recent travel history, will reduce the risks of transmitting these diseases. Splenectomized and otherwise immunocompromised patients are at greater risk of developing disease from transfusions contaminated with parasites.

CJD is a human prion disease of uncertain origin, but is thought to be caused by mutations of a prion protein gene and is recognized as a hereditary condition. CJD is a progressive fatal disease, characterized by seizures, incoordination, and dementia. Iatrogenic transmission of CJD can occur and is associated with the administration of human pituitary hormones, human dura mater grafts, and other tissues found within or close to the central nervous system of affected donors. There is no evidence that blood transfusion is a means of transmission for CJD.

Variant Creutzfeldt-Jakob disease (vCJD) is caused by infection with the prion, which causes bovine spongiform encephalopathy. It is thought that this primarily bovine prion (which causes mad cow disease) can enter the food
chain through ingestion of contaminated meat products. It is likely that the time from infection with this particular prion to the onset of symptoms may be many years or even decades. Whereas CJD is not associated with blood transfusion, vCJD may well be. In at least one patient in the United Kingdom who died from vCJD, there is strong suggestive evidence that vCJD was transmitted by transfusion of contaminated blood products;³ another report of preclinical vCJD was likely to have been transmitted by blood transfusion.²

As of yet, there is no screening test for vCJD, and diagnosis is usually confirmed at autopsy. Because of the long latency period between infection and the development of symptoms, it is difficult to estimate accurately the number of donors contaminated with vCJD and the exact risk of transmission and subsequent development of this disease. It is possible, although there is no conclusive evidence, that universal leukodepletion may reduce the risk of transmission of vCJD.