Page 2417 - Williams Hematology ( PDFDrive )

2388 Part XIII: Transfusion Medicine Chapter 139: Preservation and Clinical Use of Platelets 2389

9
increments of 2.6 × 10 /L (p <0.001) and CCIs were less by 1.8 × 10 /L overloaded, or for infants/young children where an adult volume may
9
(p <0.0001), but there was no effect of minor ABO incompatibility on be excessive, volume reduction of platelets before transfusion is a con-
78
these measurements at any time point. Platelet storage duration did sideration. For most children, volume reduction is often unnecessary.
show a progressive decline in platelet increments and CCIs, but the Whenever platelets are concentrated by centrifugation, there is likely
effect was very modest. Importantly, transfusion intervals showed only to be some damage to the platelets, re-suspension is often incomplete,
trivial effects based on transfusion type (AP or rdWBP) and only for and, therefore, this extra processing should only be done if necessary
low-dose platelet transfusions (1.1 × 10 platelets/m ) (p = 0.02), the for patient care. 79
2
11
interval was 3.9 hours less for ABO-major-mismatched transfusions
(p <0.001), and there was no effect of storage duration. Because of the
large number of transfusions, some of the differences between plate- FUTURE ADVANCES IN PLATELET
let products, ABO matching, and storage duration were highly statis- PRODUCTS FOR TRANSFUSION
tically significant. However, for the two most important parameters
for clinicians (e.g., bleeding risk and interval between transfusions), PATHOGEN REDUCTION
there were no important differences based on product transfused, ABO 80,81
65
matching, and storage duration of 5 or fewer days. Even differences in Two methods of pathogen reduction have been evaluated in clinical
platelet increments and CCIs were modest, as confirmed by previous trials. Both systems involve adding an agent—either amotosalen (Inter-
80
81
meta-analysis. 66–68 cept system) or riboflavin (Mirasol system) —to the platelets prior
to exposure to ultraviolet (UV) light. After UV exposure, these agents
prevent replication of RNA and DNA in pathogenic organisms, as well
ADVERSE EVENTS as eliminating the function of contaminating leukocytes. 82,83 Both the
Additional analysis of the PLADO data base showed no differences in Mirasol and Intercept methods produce a reduction in posttransfu-
that
sion autologous radiolabeled platelet recoveries and survivals
84,85
any adverse event based on platelet source, ABO matching, or storage is related to the dose of UV used in the pathogen-reduction process.
86
duration. 69
Recoveries and survivals of 5-day stored pathogen-treated platelets
were reduced by approximately 15 to 25 percent, compared to similarly
MODIFICATIONS TO TRANSFUSED stored nontreated platelets from the same subjects (p <0.05 to <0.01).
The Intercept system has been evaluated in a 645-patient U.S. random-
PLATELETS ized trial comparing treated to control platelets. This technology was
87
approved by the FDA for pathogen reduction of platelet components
LEUKOREDUCTION on December 19, 2014. A limited randomized trial in France involving
There are clear indications for providing leukoreduced platelet products: 110 thrombocytopenic patients documented hemostatic efficacy
42
(1) reduction of platelet alloimmunization, (2) prevention of cytomeg- of Mirasol-treated platelets and similar rates of red cell and platelet
alovirus transmission by transfusion, and (3) reduction in febrile utilization but lower CCIs for patients who received treated compared to
70
88
transfusion reactions. In addition, some studies suggest that white control platelets. However, there were no adverse events following trans-
71
cells that contaminate platelet and red cell transfusions may contribute fusion of the treated platelets, and more studies will likely be needed for
to immunomodulatory effects of transfusion, such as an increased inci- FDA approval. Both technologies have received regulatory approval for
dence of postoperative infections and metastasis formation in cancer their use in Europe.
patients. However, controversy still surrounds whether transfusions Several centers in Europe that have incorporated pathogen reduc-
72
have immunomodulatory effects. 73 tion technology have eliminated γ-irradiation of platelets to prevent
transfusion-associated GVHD. Inactivating leukocytes may also
decrease transfusion-related adverse events such as fever, chills, and
γ-IRRADIATION allergic reactions associated with cytokine release from residual white
γ-Irradiation of platelets is indicated to prevent transfusion-related cells during platelet storage, and it may also reduce rates of platelet allo-
GVHD, which is uniformly fatal. γ-Irradiation with the usual dose of immunization. All of these benefits will mean safer, more cost-effective
74
25 Gy in one study did not affect either posttransfusion platelet survival platelets for transfusion.
or function. However, in a transfusion study in thrombocytopenic
75
patients, γ-irradiation decreased 1-hour posttransfusion increments by EXTENDED PLATELET STORAGE
2.8 × 10 /L and showed an increased hazard ratio of 1.45 for the develop-
9
ment of platelet refractoriness. Furthermore, additional observations The major risk of extended platelet storage at 22°C is bacterial over-
76
from the TRAP demonstrated that γ-irradiation prolonged the dura- growth usually as a consequence of inadequate sterilization of the
tion of HLA alloantibodies in patients who developed these antibodies venipuncture site. Most bacteria have been demonstrated to grow to
89
during the course of their transfusions. Therefore, indiscriminate use confluence by 3 to 5 days. Therefore, once platelets have been stored
77
of γ-irradiation should be avoided. Situations in which γ-irradiation beyond 5 days, there is little increased risk from bacterial overgrowth.
should be performed are: (1) patients receiving allogeneic HSCT and The only remaining issue to allow extended platelet storage will likely be
(2) patients who are severely immunocompromised, usually because of having either a sensitive and specific point of release bacterial assay or
their disease or its treatment (e.g., patients who have Hodgkin or other incorporating a prestorage pathogen reduction process.
lymphomas). 73 The FDA has suggested a hierarchical system for evaluating stored
platelets prior to licensing proceeding from a variety of in vitro assays,
90
to radiolabeled autologous platelet recovery and survival measure-
VOLUME REDUCTION ments in normal subjects, and, finally, depending on the magnitude
For some patients who are receiving large volumes of fluids where con- of the differences in the new product compared to products that are
sideration of intravenous line availability is an issue, who are volume currently licensed, to transfusion trials in thrombocytopenic patients

Kaushansky_chapter 139_p2381-2392.indd 2388 9/18/15 2:23 PM