Donor Leukocytes:
A Transfusion Risk May Remain Even After Leukoreduction
The presence of viable donor leukocytes in donated blood has long been
recognized as a source of risk for recipients. Transfusion-associated
graft-versus-host disease (TA-GVHD) caused by proliferation of donor T-cells
in the recipient may carry a mortality rate as high as 84%. In addition,
cytokines released by leukocytes during unit storage can cause febrile
non-hemolytic transfusion reactions (FNHTR) [45].
Finally, leukocytes can also harbor latent viruses such as CMV and HTLV
[46].
Current Safeguards
Gamma irradiation is a common treatment option used to inactivate donor
leukocytes and reduce the incidence of TA-GVHD. Leukoreduction is another
standard tool for reducing risk to recipients, and leukofiltered units
contain a much reduced number of white cells. However, any residual
leukocytes may still be capable of proliferation, leading to theories
that gamma irradiation is still indicated for blood products intended
for patients at risk of GVHD [47].
Benefits of the INTERCEPT Blood System
During the INTERCEPT Blood System pathogen inactivation process, leukocytes
are also inactivated preventing both leukocyte replication and
cytokine production.
| |
Leuko-reduction |
Gamma-
irradiation |
INTERCEPT
Blood System |
| Mechanism |
Filters out leukocytes |
Irradiation damages the genetic material of pathogens |
Amotosalen molecule crosslinks the
genetic material of both leukocytes and pathogens that may be present
and inhibits cellular function and replication |
| Effectiveness |
Residual leukocytes may still be present after leukoreduction |
Introduces one nucleic acid strand break every ~37,000
base pairs
|
Introduces a nucleic acid crosslink
every ~83-89 base pairs* |
| Post-Transfusion Complications |
Live donor leukocytes can cause GvHD and FNHTR |
Irradiated leukocytes are still able to produce cytokines
[48]; FNHTR may still occur
|
Inactivated leukocytes reduce the
probability of both GvHD and FNHTR |
| Additional Information |
Does not address the problem of cell-free
pathogens; does not alter cytokine levels at time of filtration; CMV
transmission still possible in immuno-
compromised patients [49] |
Does not address the problem of pathogens; gamma doses
used to inactivate leukocytes are not intended to be virucidal, and
CMV may be recovered from infected host cells [50]
|
Also effective against a broad spectrum
of pathogens, including cell-associated CMV |
| * Approved product claims – see leukocyte inactivation information in
technical data sheets for INTERCEPT Platelets and INTERCEPT Plasma. |
|