Page 1935 - Hematology_ Basic Principles and Practice ( PDFDrive )

C H A P T E R 112

CLINICAL CONSIDERATIONS IN PLATELET

TRANSFUSION THERAPY

Richard M. Kaufman

PLATELET COLLECTION AND MANUFACTURING platelet unit. Thus, alloimmunization is not platelet dose dependent,
and simply providing leukoreduced platelet units prevents most cases
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Platelet components are either prepared from whole blood donations of immune-mediated platelet refractoriness. When platelet refracto-
(platelet concentrates) or, more commonly, are collected by apheresis riness does occur, it is often in multiparous women, who were
(single donor platelets). In the United States, whole blood-derived initially sensitized to foreign (paternal) HLA antigens in previous
platelet concentrates are made using the platelet-rich plasma (PRP) pregnancies. 5
method. First, a whole blood unit is separated by gentle centrifuga-
tion (slow spin) into red blood cells (RBCs) and PRP. The PRP is
then centrifuged a second time (hard spin) to isolate one platelet PROPHYLACTIC PLATELET TRANSFUSION
concentrate plus one unit of plasma. Each platelet concentrate con-
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tains approximately 5.5 × 10 platelets suspended in a plasma volume Most platelet units are transfused to prevent bleeding in nonbleeding
of approximately 50 mL. In Europe and Canada, the alternate buffy patients, rather than to treat active bleeding. Before 1960, platelet
coat method is used to produce platelet concentrates. Platelets are transfusions were not widely available, and death from hemorrhage
stored at room temperature under continuous gentle agitation for up was common among patients with leukemia who received chemo-
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to 5 days. To prepare an adult dose of platelets for transfusion, four therapy. In 1962, Gaydos and colleagues published a seminal study
to six platelet concentrates are pooled together. demonstrating a relationship between platelet count and likelihood
Apheresis platelet units are collected from a single platelet donor of bleeding. After this study was published, prophylactic platelet
by continuous flow centrifugation using an automated device. A high transfusion rapidly became standard practice. Notably, based on their
volume of whole blood is processed through the machine, and the data, no specific platelet transfusion trigger was suggested by the
platelets are retained in a sterile collection bag. According to AABB authors. Regardless, a platelet count of 20,000/µL was widely adopted
(formerly, the American Association of Blood Banks) standards, at the time as the standard prophylactic platelet transfusion trigger.
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an apheresis platelet unit should contain a minimum of 3 × 10 Later studies suggested that a lower transfusion trigger would be
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platelets, a dose that is approximately equivalent to five pooled as effective as a trigger of 20,000/µL. Slichter and Harker, for
platelet concentrates. Current devices allow many different combina- instance, performed RBC radiolabeling studies in thrombocytopenic
tions of blood products to be collected during a single apheresis patients who were not receiving platelet transfusions. They demon-
donation, such as 1 unit of platelets plus 1 unit of RBCs. Apheresis strated that only patients with platelet counts below 5000/µL had
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platelet units generally contain less than 1 × 10 white blood cells significantly elevated fecal RBC loss. Years later, several clinical
(WBCs) per unit; thus, they meet the current AABB definition for studies directly challenged the 20,000/µL trigger. Platelet transfusion
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leukoreduced blood products (<5 × 10 WBCs/unit). Although triggers of 10,000/µL versus 20,000/µL were compared directly in
apheresis platelets cost more to produce than whole blood-derived three randomized prospective studies of patients with acute
platelet concentrates, they have become increasingly popular. In the leukemia. 8–10 These studies, as well as a nonrandomized prospective
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United States in 2011, approximately 2 million therapeutic doses trial, did not show an increased incidence of bleeding when a trigger
of platelets were provided as apheresis platelets, and only 200,000 of 10,000/µL is used. Most recently, the Platelet Dosing (PLADO)
equivalent doses were administered as whole blood-derived platelet trial demonstrated that the risk of bleeding among patients with
concentrates. 2 hypoproliferative thrombocytopenia only increased at platelet counts
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Apheresis platelets provide limited advantages over whole blood- below 6000/µL. As shown in Fig. 112.1, the risk of spontaneous
derived platelet concentrates. Radiolabeling studies indicate that bleeding was equivalent between platelet counts of 6000/µL and
apheresis platelets circulate longer in vivo than pooled concentrates, 80,000/µL.
most likely reflecting gentler handling and less platelet activation Severe hemorrhage in the setting of therapy-related hypoprolif-
during collection. Recipients of apheresis platelets are exposed to erative thrombocytopenia is now quite rare. Given the substantial
fewer donors per transfusion (1 donor versus 4–6 as with a pool of changes in both chemotherapy and the supportive care of patients
platelet concentrates), so in principle, apheresis platelets should pose with hematologic malignancy that have occurred over the past several
a lower risk of viral transmission than whole blood-derived platelets. decades, two randomized controlled trials recently examined whether
However, given that the per-unit transfusion-transmission risks for routine platelet prophylaxis still provides a clinical benefit. In the
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HIV and hepatitis C virus have been reduced to less than 1 per study by Wandt and colleagues, patients receiving chemotherapy
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1,000,000, the viral safety advantage of apheresis platelets over whole or undergoing autologous hematopoietic stem cell transplantation
blood-derived platelets is marginal. Data from surveillance culture (HSCT) were randomly assigned to receive platelet transfusions
studies suggest that apheresis platelets may be less likely than platelet only when bleeding occurred, or standard prophylactic platelet
concentrates to become contaminated with bacteria. At one time, it transfusions for a morning platelet count at or below 10,000/µL.
was predicted that apheresis platelets would be less likely than pooled Grade 2 or higher bleeding occurred in 42% of patients receiving
concentrates to provoke platelet alloimmunization by virtue of expos- therapeutic platelet transfusions only, versus 19% in patients receiv-
ing recipients to fewer unique donor human leukocyte antigens ing platelet prophylaxis (p < .001). There were significantly more
(HLAs). This hypothesis was not confirmed empirically, however. intracerebral hemorrhages in the no-prophylaxis group (7% versus
Although they express surface HLA class I antigens, platelets appear 2%, p = .01), and there were two deaths due to bleeding in the
to be rather poor immunogens. HLA alloimmunization to platelets no-prophylaxis group compared with zero in the prophylaxis group.
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primarily appears to be triggered by contaminating WBCs within a In the Trial of Prophylactic Platelets, a similar population of patients
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