The effects of leukodepletion on the generation and removal of microvesicles and prion protein in blood components

Krailadsiri, Pranee; Seghatchian, Jerard; MacGregor, Ian; Drummond, Olive; Perrin, Rachel M.; Spring, Frances A.; Prescott, R. J.; Williamson, Lorna M.; Prowse, C. V.; Anstee, David J.; Turner, Marc

doi:10.1111/j.1537-2995.2006.00737.x

Cited by 30 publications

(21 citation statements)

References 17 publications

(26 reference statements)

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“…This may complicate understanding the process of identifying the relationship between the infectious agent and cell targets. It is also possible that mechanisms such as release of membrane fractions during processing [42] or shedding/transit by plasma membrane-derived microvesicles [43], [44] may also contribute to the dissemination of infectivity in blood. It will be critical to understand how prion infectivity associates with particular blood components, and may identify new targets for diagnostics, therapeutics and allow for more refined risk reduction strategies.…”

Section: Discussionmentioning

confidence: 99%

All Clinically-Relevant Blood Components Transmit Prion Disease following a Single Blood Transfusion: A Sheep Model of vCJD

et al. 2011

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Variant CJD (vCJD) is an incurable, infectious human disease, likely arising from the consumption of BSE-contaminated meat products. Whilst the epidemic appears to be waning, there is much concern that vCJD infection may be perpetuated in humans by the transfusion of contaminated blood products. Since 2004, several cases of transfusion-associated vCJD transmission have been reported and linked to blood collected from pre-clinically affected donors. Using an animal model in which the disease manifested resembles that of humans affected with vCJD, we examined which blood components used in human medicine are likely to pose the greatest risk of transmitting vCJD via transfusion. We collected two full units of blood from BSE-infected donor animals during the pre-clinical phase of infection. Using methods employed by transfusion services we prepared red cell concentrates, plasma and platelets units (including leucoreduced equivalents). Following transfusion, we showed that all components contain sufficient levels of infectivity to cause disease following only a single transfusion and also that leucoreduction did not prevent disease transmission. These data suggest that all blood components are vectors for prion disease transmission, and highlight the importance of multiple control measures to minimise the risk of human to human transmission of vCJD by blood transfusion.

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Section: Discussionmentioning

confidence: 99%

All Clinically-Relevant Blood Components Transmit Prion Disease following a Single Blood Transfusion: A Sheep Model of vCJD

et al. 2011

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“…Removing approximately 99.9% of the donor WBCs and platelets in RBC concentrates before transfusion can prevent 90% or more of class HLA 1 allosensitizations [71]. Leukoreduction also removes apoptotic WBCs and platelets that accumulate during blood storage [54,72]. Some of the clinical benefits that have been realized worldwide by leukoreduction are significant reduction of a number of transfusion adverse events.…”

Section: Blood Product Manipulationsmentioning

confidence: 99%

Transfusion immunomodulation from a clinical perspective: an update

Refaai

Blumberg

2013

Expert Review of Hematology

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Accumulated evidence demonstrates that allogeneic blood transfusions have clinically significant effects on the recipient's immune system. This transfusion immunomodulation effect is associated with an increased rate of cancer recurrence (uncertain causality) and post-operative infection (established causality). The exact mechanisms of transfusion immunomodulation are still unknown. Data suggests that transfusion immunomodulation is a biologic effect strongly associated with the infusion of allogeneic leukocytes. Soluble mediators that accumulate in transfused red cells and platelets during storage are also possible causes of post-transfusion complications. Some approaches can mitigate these effects. Most important is adopting more conservative transfusion practices. Leukoreduction (proven) and plasma depletion (proposed) are other methods to significantly reduce transfusion immunomodulation and its clinical sequela.

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“…Finally, since MV express phosphatidylserine on their surface, it may be possible to eliminate them from the PB using absorption columns containing Annexin-V matrix. Another important anti-MPdirected strategy would be to avoid transfusions of outdated platelets, 90,91 particularly in cancer patients and those suffering from cardiovascular disorders.…”

Section: Modulation Of MV Secretionmentioning

confidence: 99%

Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication

et al. 2006

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The effects of leukodepletion on the generation and removal of microvesicles and prion protein in blood components

Abstract: These findings suggest no detrimental effects of LD processes in terms of generation of MVs or PrP(c) release.

Cited by 30 publications

References 17 publications

All Clinically-Relevant Blood Components Transmit Prion Disease following a Single Blood Transfusion: A Sheep Model of vCJD

All Clinically-Relevant Blood Components Transmit Prion Disease following a Single Blood Transfusion: A Sheep Model of vCJD

Transfusion immunomodulation from a clinical perspective: an update

Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication

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