Febrile non-hemolytic transfusion reactions (FNHTR) 16-17 This complication is defined as a rise in temperature by one degree Celsius, or more during or within 24 hours of the completion of the transfusion. Flu-like symptoms of chills, cold sensation, rigors (shaking) and, in some cases, headache and nausea are also present. These reactions are estimated to occur in approximately three to seven percent of patients receiving red blood cell transfusions and are more common -- twenty to thirty percent -- in platelet transfusions. On occasion, fevers can approach 40 degrees Celsius (or 104 degrees Fahrenheit). FNHTR causes discomfort and necessitates the use of medication.

FREQUENCY OF WHITE BLOOD CELL ASSOCIATED ADVERSE TRANSFUSION REACTIONS
Red Cells	0.5 - 6%
Platelets	20% - 30%

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Alloimmunization and platelet refractoriness 18-23 Refractoriness to platelet transfusions that accompanies alloimmunization is one of the most serious and difficult to manage of all transfusion therapy hazards. It occurs when a patient receives blood from another person that contains leukocytes. The body reacts to the leukocytes and creates antibodies against them. This immune response, called alloimmunization, can cause patients to become refractory (resistant) to subsequent platelet transfusions. This means that they do not respond or benefit from the transfusion, increasing the risk of spontaneous bleeding from the patient. Approximately 50 percent of patients undergoing multiple blood transfusions become alloimmunized and are refractory to platelet transfusions. Refractory patients require platelets matched to their specific type. This can be a problem in that a sufficient number of matched platelets may not be available for continuous support and can result in a time and cost-intensive process. Patients receiving leukocyte reduced blood products are at a much lower risk for refractoriness to platelet transfusion than are recipients of blood that is not leukocyte reduced. The use of leukocyte reduced blood components from the patient’s first transfusion greatly minimizes the risk of alloimmunization leading to this reaction.

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Transfusion-associated viruses 11-15 Transfused leukocytes serve as reservoirs for several blood-borne viruses that can be transmitted to patients through transfusions. Most of these viruses belong to the herpes virus groups and exist primarily as latent or inactive infections in the leukocytes of individuals who carry the disease but do not have symptoms. In addition to screening the blood of donors, the use of leukocyte reduction can be the first line of defense against the transmission of many of these life-threatening viruses. Leukocytes in stored blood components serve no therapeutic benefit to transfusion recipients. Cytomegalovirus (CMV) is one of the viruses that resides in leukocytes. In certain patient populations, CMV infection can cause fever, hepatitis, pneumonia and severe brain damage, and can ultimately lead to death. In North America, fifty percent or more of the adult population has been exposed to this virus, making transfusion-transmitted CMV a high risk. Transfusion-associated CMV infections are a major cause of morbidity and mortality in many patient populations. The costs of managing patients with CMV, the second highest of all infectious disease in 1985, along with direct hospital costs estimated at one billion dollars. Today, the costs of treating CMV infection have substantially increased due to the prevalence in people with AIDS. Until recently, the use of CMV screening of donor blood has been the primary strategy to provide blood to critical patient populations. Today, more and more health care practitioners are filtering blood because there is sufficient evidence to conclude that leukocyte reduction of red blood cells and platelets to 5 x 106 leukocytes per unit or below reduces the incidence of CMV transmission by these components. This eases blood supply problems and makes CMV-safe units available to more patients. In addition to CMV, there are other concerns in the medical community. Other leukocyte-associated viruses include Epstein-Barr (EBV), Human Herpes Virus type 6, HTLV-I and HTLV-II. Infectious mononucleosis, caused by EBV, leads to malaise, fatigue, headache and chills, followed by high fever and sore throat. Human Herpes Virus type 6 causes a disease that is common in infants and is characterized by high fever and transient rash. HTLV-I and II were discovered in the early 1980’s as the first retroviruses in humans. HTLV-I causes a type of adult leukemia and is associated with other types of diseases; no disease has yet been associated with HTLV-II. These viruses pose some risks to all patients but are a particular concern in patients with weakened immune systems. There may be potential for leukocyte reduction to prevent transmission of these leukocyte-associated viruses as well. Viruses such as HIV are found both in the leukocytes and in the plasma. There is no evidence that leukocyte reduction will prevent the transmission of HIV. For people who are already HIV positive, the risks associated with allogeneic blood transfusions containing leukocytes may be much greater than for the average patient. Transfused leukocytes may activate latent virus leading to replication of the virus in the recipient’s blood, causing the disease to spread rapidly and the immune system to weaken.

WHITE BLOOD CELL ASSOCIATED VIRUSES
	Risk per three unit transfusion episode
Cytomegalovirus (CMV)	*
Epstein-Barr Virus (EBV)	1:333,333 14
Human Herpes Virus Type 8 (HHV-8)	NA
Human T-Lymphotrophic Virus Type I & II (HTLV I & II)	1:23,333 14
HIV (leukocyte and plasma associated)	1:226,667 15
* Approximately 50% of blood donors have antibodies to CMV. Asymptomatic infections in transfusion recipients have been reported at 9%. 16 Infection and adverse consequence risk is greater in immune compromised transfusion recipients.

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Immunosuppression 1-10 Blood transfusions suppress the recipient’s immune system. This transfusion risk is called immunomodulation and appears, strong associates, to be caused by the presence of donor leukocytes in the transfused product. Immunosuppression may lead to life-threatening events, such as multiple organ failure, increased risk of infection after surgery and/or diminished prospect of cure in patients with certain malignancies. There is increasing evidence that allogeneic blood transfusions have a major impact on the immune system of patients undergoing surgery who require transfusion. Transfusion-associated immune suppression results in increased incidence of infection in transfused patients after trauma and surgery. Animal as well as clinical studies have shown that leukocyte reduction by filtration of blood components reduces transfusion associated immunosuppression expressed as a reduction in postoperative infection rates. Figure 1. Leukocyte Reduced Blood Decreases Complications In Surgery

Figure 1 illustrates the significant reduction in postoperative infectious complications, in colorectal surgery patients, when leukocyte reduced blood is used compared with non-leukocyte reduced blood in three conditions: Wound infection Reoperation Pneumonia Adapted from Jensen et al 6

Figure 2. Mortality Rates are Lower When Leukocyte Reduced Blood Is Used
	Figure 2 illustrates leukocyte reduction results in a significant reduction of the mortality in patients undergoing cardiac surgery. Adapted from van de Watering et al 8

Other clinical studies recently reported the use of leukocyte reduced blood components along with other leukocyte reduction techniques contributed to reducing the length of stay by one day for cardiac surgery patients in the low mortality risk category.

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