Leukoreduction of Blood Products

Leukocytes (white blood cells [WBCs]) remain in red blood cell (RBC) and platelet (PLT) components after simple component preparation. Residual leukocytes have the potential to cause harmful effects in the transfusion recipient including febrile nonhemolytic transfusion reactions (FNHTRs), HLA alloimmunization, and transmission of cytomegalovirus (CMV). Other possible effects include transmission of other leukocyte-associated herpesviruses and transfusion-related immunomodulation (TRIM). The likelihood of these effects depend on the number in each component, storage temperature, and recipient clinical status including previous and latent infection with the viruses above, and their immune status. Thus, leukoreduction significantly decreases their incidence.

Before the 1980s, it was recognized that residual leukocytes could be removed by washing components or by some membrane and fiber “filter” methods. These later methods were further developed into “filter leukoreduction.” Filter leukoreduction that is performed within 24 hours of collection is termed prestorage leukoreduction, whereas leukoreduction performed after 24 hours, typically just before the product is issued, is termed poststorage leukoreduction. Currently, there are a variety of leukoreduction filters, which remove 3 logs of WBCs. These filters use a combination of barrier filtration (i.e., pore size) and cell adhesion to decrease leukocyte content. Some filters are PLT sparing, which is used to make leukoreduced whole blood, while RBC filters usually also remove PLTs. The RBC product from non-PLT sparing filters will lack PLTs or PLT-derived cytokines. In addition, leukofiltration of RBCs from hemoglobin AS (sickle trait) patients is often less effective secondary to reduced RBC deformability leading to clogging or decreasing the area of the filter. Apheresis-derived PLTs are leukoreduced by the apheresis devices, known as “process leukoreduction.” Because of the clear clinical benefit with minimum cost, most blood products are leukoreduced in developed nations.

Definitive Indications

Decreasing Incidence of Febrile Nonhemolytic Transfusion Reactions

The frequency of FNHTRs is significantly decreased (75%–95%) when prestorage leukoreduced products are transfused. There are two mechanisms by which leukocytes in transfused units contribute to FHNTRs. The first mechanism involves leukocyte-derived cytokines and is most commonly associated with PLT products. Leukocyte-derived cytokines (e.g., interleukins [IL-1, IL-6, IL-8] and tumor necrosis factor α [TNF-α]) accumulate in the supernatant during room temperature storage of PLT products. Unlike prestorage leukoreduction, poststorage leukoreduction will be ineffective in addressing this accumulation of cytokines. The second mechanism involves WBC antibodies and is most commonly associated with RBC products. Anti-HLA and anti-HNA antibodies in the transfusion recipient’s plasma directed toward the transfused WBCs lead to an antigen–antibody complex, resulting in the release of endotoxin, which results in fever and other symptoms (see Chapter 61 ).

Decreasing Incidence of HLA Alloimmunization

Leukoreduction of RBCs and PLTs has been shown to decrease the incidence of HLA alloantibody formation in transfusion recipients. This is of primary importance in patients who require ongoing PLT transfusion support, as anti-HLA antibodies can lead to PLT refractoriness by binding to the corresponding antigens (major histocompatibility complex) on transfused PLTs. The TRAP study in 1997 assessed reduction in HLA alloimmunization and PLT refractoriness by randomized controlled trial in patients with acute leukemia; in addition, a number of smaller studies had previously addressed the same issue. In aggregate, metaanalysis of these studies showed a relative risk reduction of HLA immunization of approximately one-third for patients with acute leukemia or other hematologic malignancies not previously sensitized to HLAs. These data are then extrapolated to other patient populations. For example, because HLA immunization can contribute to rejection of an organ graft and thus difficulty finding a compatible organ and/or undergoing transplantation, many transfusion physicians recommend leukoreduced cellular products for potential solid organ transplant recipients.

Decreasing Cytomegalovirus Transmission

Blood donors in an active viremia phase (CMV DNA detectable in plasma) appear to be most likely to transmit CMV to a recipient. However, latent CMV can reactivate on transfusion and infect the naïve recipient. Because current leukoreduction filters achieve a 3 log reduction in WBCs in a cellular blood product, leukoreduction substantially decreases the inoculum of latent CMV genomes a recipient receives. Accordingly, transmission by blood transfusion is substantially decreased by leukoreduction (from as high as 30% in susceptible patients to 0%–2.5%). Data indicate that leukoreduced blood has rates of CMV transmission as low as seronegative products (which still have a risk of CMV transmission). However, in patient populations such as fetuses requiring intrauterine transfusion, where monitoring for CMV viremia is not possible, some suggest that these patients may benefit from CMV seronegative products (see Chapter 44 ).

Potential Indications

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