Leukocytereduced Blood Components

There are three main indications for using red blood cell and platelet components that are leukocyte-reduced: (1) to decrease or prevent the occurrence of febrile, nonhemolytic transfusion reactions, (2) to reduce the incidence of HLA alloimmunization, and (3) to prevent or reduce the risk of transfusion-transmitted

Leukocytosis Algorithm
Figure 104.1 Algorithm for evaluation of platelet refractoriness

cytomegalovirus (TT-CMV) infection.22,23 Other clinical uses of leukocyte-reduced blood components, such as reducing transfusion-related immunomodulation, or reducing other transfusion-transmitted infections (e.g., EBV, HHV-8, HTLV-I/II, etc.), should be considered experimental until additional studies are performed. Leukocyte reduction has not been shown to prevent transfusion-associated GVHD (TA-GVHD; see below).3637

A unit of whole blood contains approximately >1-10 X 109 white blood cells.10 Leukocyte reduction can be performed during or shortly after collection (prestorage leukocyte reduction), in the laboratory prior to issuing of the blood component (poststorage leukocyte reduction), or at the bedside. The first two methods are preferable, as bedside leukocyte reduction lacks proper quality control measures to achieve uniform leukocyte reduction.38 Red blood cells and platelets (pooled platelets and apheresis platelets) are considered to be leukocyte-reduced if the residual leukocyte count is <5 X 106. In addition to the use of specialized filters to achieve leukocyte reduction, apheresis platelets can also be considered leukocyte-reduced if the residual leukocyte count is < 5 X 106 at the time of collection.

Some blood centers in the United States, as well as a number of countries, have promoted and instituted universal leukocyte reduction of all blood components for all patients.

Leukocyte reduction for febrile, nonhemolytic transfusion reactions

Febrile, nonhemolytic (FNH) transfusion reaction is one of the most frequent adverse reactions related to transfusion.39 In addition to a rise in temperature (>1°C), FNH transfusion reactions can be associated with chills, rigors, headaches, nausea, and/or vomit-ing.39 Symptoms typically appear during the transfusion, but may not manifest until 1-2 h later. Usually, FNH transfusion reactions are not life-threatening, but can be associated with increased patient discomfort requiring the administration of additional medications. In addition, fever can also be a manifestation of more severe transfusion reactions (e.g., hemolytic transfusion reactions or bacterial contamination).

Leukocyte reduction for the prevention of FNH reactions is more effective in the case of red blood cell transfusions and less effective for platelet transfusions.39-42 FNH transfusion reactions can have multiple causes related to both recipient and donor factors, but in the case of platelets, the release of inflammatory cytokines by leukocytes during storage probably accounts for the majority of reactions. Prestorage leukocyte reduction helps to further decrease the incidence of platelet-related FNH reactions by decreasing the passive accumulation of cytokines released by white cells. IL-1a is one of the primary cytokines felt to be responsible for FNH reactions following platelet transfusion. TNFa, IL-6, and IL-8 have also been shown to accumulate in plasma during platelet storage, but the role played by these cytokines in contributing to FNH reactions is unclear.39'43

There is suggestive evidence that some severe hypotensive reactions following the transfusion of leukocyte-reduced blood components may be related to the infusion of bradykinin.3943 It is speculated that bradykinin is generated during the filtration process when certain leukocyte-depletion filters are used. These hypotensive reactions may be enhanced if the recipient, or the donor, is taking angiotensin converting enzyme (ACE) inhibitor medications.3943

HLA alloimmunization and leukocyte reduction

A number of studies have been performed that demonstrate the efficacy of leukocyte reduction to prevent HLA alloimmunization.3244-48 As platelets have HLA class I antigens, leukocyte reduction has been shown to decrease the incidence of refractoriness to platelet transfusion (see above). There does not appear to be any significant effect of leukocyte reduction on the incidence of platelet refractoriness secondary to platelet-specific antibody. All patients who are potential candidates for stem cell transplantation should receive leukocyte-reduced blood transfusions to minimize the formation of HLA antibodies. In our institution, as in many others, all patients with hematologic and solid tumor malignancies routinely receive leukocyte-reduced blood products from the time of initial diagnosis.

CMV "safe" blood components and leukocyte reduction

Transfusion-transmitted CMV (TT-CMV) infection was first described in 1966. The incidence of CMV seroposi-tivity in the blood donor population ranges from 60% to 80% or higher, depending on the geographic area. Prior to the advent of current leukocyte-reduction filters, providing CMV "safe" blood products required the collection of blood from CMV-seronegative blood donors. However, despite seronegativity, some donors may still be able to transmit CMV (approximately 4% of seronegative blood products are associated with a risk of TT-CMV), and maintaining a separate inventory of CMV-seronegative blood is problematical.49'50 Some blood centers no longer routinely test blood donors for CMV.

Following primary infection, CMV remains latent in various white blood cell populations, but periodic viral shedding and/or reactivation of infection may occur. Sites of latency include CD34+ hematopoietic progenitor (stem) cells, CD33+ progenitor cells, monocytes (macrophages), and probably granulocytes. Monocytes appear to be one of the primary sites of CMV latency.50-53 In healthy, CMV-seropositive blood donors, approximately 0.004-0.12% of peripheral blood mononuclear cells are latently infected.52 Over the years, a growing number of studies have demonstrated the efficacy of leukocyte reduction in making blood components CMV "safe" for the prevention of

TT-CMV in hematologic and stem cell transplant patients.51-60 However, some studies question the efficacy of leukocyte reduction in preventing TT-CMV.61 Improved methods to monitor and detect CMV antigen-emia and infection in the immunosuppressed patient have led to early detection and treatment of infec-tion.6263 In addition, emerging data indicates that other factors, such as the seropositive stem cell transplant recipient, the degree of immunosuppression, and the stage of acute GVHD put the recipient at greater risk for CMV infection/disease because of reactivation of latent virus, rather than through the acquisition of new infection through blood transfusion.64-66

While specific data is lacking, a number of institutions have used leukocyte reduction as the sole method for providing CMV-safe blood components. The only cellular blood component that cannot be leukocyte-reduced is granulocytes. If CMV status of the donor is important in those rare instances when gran-ulocyte transfusions are considered for the infected patient with a hematologic malignancy, consideration should be given to test the donor for CMV (see below).

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