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Chapter 112 Clinical Considerations in Platelet Transfusion Therapy 1717

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might cause clinically significant damage in a vulnerable vital struc- colleagues demonstrated that the plasma component of platelet
ture such as the brain. units, rather than the cellular component, causes most reactions.
Cytokines that accumulate during product storage have been impli-
cated. Allergic transfusion reactions are the second most-common
ADVERSE EFFECTS OF PLATELET TRANSFUSION type of adverse event associated with platelet transfusion. Allergic
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reactions to blood products occur when the recipient has a preexisting
Infectious Risks allergy to a plasma protein component. Allergic reactions range from
mild, uncomplicated urticarial reactions (most common) to full-
Platelets are associated with essentially the same range of infectious blown anaphylaxis. Platelet Additive Solution (PAS) platelet units are
pathogens as other blood components, but septic transfusion reac- those in which a preservative solution replaces most of the residual
tions caused by bacterially contaminated units comprise a unique risk plasma. Using PAS platelets has been shown to reduce the risk of
of platelet transfusion. Over time, improvements in donor screening allergic reactions. 25
virtually eliminated the risk of transfusion transmission of hepatitis
B virus, hepatitis C virus, and HIV. The risk of septic transfusion
reactions remained fairly constant over this same time period, so ABO and Hemolytic Reactions to Platelets
eventually, platelet bacterial contamination became, by default, the
most frequent infectious risk of transfusion. Unlike other blood Whenever possible, platelet units are assigned so as to match the
components, which are stored either refrigerated or frozen, platelets donor plasma with recipient RBC type. For example, a type A patient
are stored at room temperature. The reason is that if platelets are would ordinarily receive type A or AB platelets, which do not contain
refrigerated before transfusion, they are cleared rapidly from the anti-A antibody. When platelet inventories are constrained, however,
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recipient’s circulation. Although room temperature storage allows it is common for blood banks to issue ABO-incompatible platelets.
transfused platelets to circulate in vivo, it has the downside of pro- For example, a type A patient might receive type O platelets, contain-
moting bacterial growth. Because of this risk, platelet storage is ing anti-A. The passive transfusion of donor anti-A or anti-B to a
ordinarily limited to only 5 days, making platelet inventory manage- patient usually does not cause adverse sequellae. Rarely, however,
ment extremely challenging. hemolysis may be observed. Most often, this occurs with units from
In the 1990s, numerous studies demonstrated that contaminating type O donors, who occasionally have high titer anti-A, anti-B, or
bacteria, usually representing skin flora from the donor, could be anti-A,B antibody. In a typical type O adult, the titer of circulating
cultured out of approximately 1 of 3000 platelet units. Clinically anti-A is on the order of 128 to 256. Some donors, however, have
apparent septic transfusion reactions were thought to occur after anti-A titers of 10,000 or higher. Recipients of products from donors
approximately 1 of 25,000 platelet transfusions, although there is with high-titer anti-A (and less frequently, anti-B) rarely do have
considerable uncertainty around this point estimate. In response to clinically apparent hemolysis, and a small number of fatalities have
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the issue, AABB developed the following standard: been reported. This is considered to be a low-risk event, but it may
be on the rise in the United States because of the increased number
5.1.5.1 The blood bank or transfusion service shall have methods to of single-donor apheresis platelet units used. One strategy to deal
limit and detect or inactivate bacteria in all platelet components. with this issue is to measure the anti-A/B titer on all platelet donors;
Standard 5.6.2 applies [skin disinfection]. 1 components exceeding a threshold titer are assigned to type-specific
recipients. An alternate strategy is to reduce the load of plasma in a
How this standard is being met varies by facility. Many blood collec- platelet unit before transfusing the unit to a non–ABO-identical
tion centers have begun routinely culturing platelet units using an recipient, either by washing or concentrating the unit, or by using a
automated culture system. The BacT/ALERT system (BioMerieux), PAS unit (above.)
used by many centers, works by continuously monitoring for bacte-
rial production of CO 2 within culture bottles. Platelet units are
sampled on the day after collection. The samples are cultured for a Transfusion-Related Acute Lung Injury
period of time, typically 24 hours, and if the cultures fail to produce
abnormal levels of CO 2 , the product is released into inventory. Transfusion-related acute lung injury (TRALI) is an acute respiratory
Overall, culture-based bacterial screening appears to have decreased, distress syndrome associated with the transfusion of any plasma-
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but not eliminated, the risk of septic reactions. Rapid, point-of-issue containing blood component, including platelets. Most cases of
tests that can be used to test the sterility of a platelet unit just before TRALI appear to be precipitated by the passive transfusion of donor
issue have also been developed, but are not widely used due to issues anti-HLA or (less commonly) anti-neutrophil antibody. It is believed
of logistics and cost. Reducing the bacterial risk further may ulti- that products containing higher volumes of plasma such as fresh-
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mately require alternative approaches, such as pathogen reduction. frozen plasma (FFP) and apheresis platelets carry a higher risk of
Pathogen inactivation systems, using photoactivated reagents such as TRALI. Approximately one-third of female blood donors have circu-
amotosalen or riboflavin plus ultraviolet (UV) light, can provide up lating anti-HLA antibody because of prior sensitization during
to 6 logs of killing of spiked virus or bacteria within 1 unit of pregnancy. To help mitigate against the risk of TRALI, many coun-
platelets. Such systems have been used in Europe and elsewhere, and tries, including the United States, now produce FFP from the blood
in 2015, a pathogen reduction system for platelets and plasma was of male donors only. Although this strategy has been relatively easy
licensed for use in the U.S. 22 to apply to FFP production, female platelet donors are still needed
to ensure an adequate platelet supply. A variety of strategies are being
Allergic and Febrile Nonhemolytic implemented to screen female platelet donors for anti-HLA antibody
and to defer women who are antibody positive.
Transfusion Reactions

The typical RBC unit contains approximately 20 mL of plasma. D Sensitization
Platelet units contain far more plasma, approximately 200 mL on
average. There are multiple potential adverse effects associated with The Rh(D) antigen is the most immunogenic RBC protein antigen.
this large plasma content. Indeed, in the PLADO trial, higher platelet More than 80% of individuals who are D-negative will form anti-D
doses were associated with significantly increased risk of transfusion- after a single D-positive RBC transfusion. Anti-D is associated with
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related adverse events. Febrile nonhemolytic reactions, defined as both hemolytic transfusion reactions and hemolytic disease of the
an increase in temperature of more than 1°C, are the most common fetus and newborn. For this reason, it is standard practice to provide
reactions seen after platelet transfusion. In a classic study, Heddle and D-negative individuals exclusively with D-negative RBC units.