Page 1938 - Hematology_ Basic Principles and Practice ( PDFDrive )

1718 Part XI Transfusion Medicine

Platelet units contain a small number of contaminating RBCs. In the TABLE
case of whole blood-derived platelet concentrates, approximately 0.3 112.1 Causes of Refractoriness to Platelet Transfusion
to 0.5 mL RBCs may be present. In contrast, current apheresis
platelets contain far fewer RBCs (≈0.0002 to 0.0007 mL per unit). Nonimmune
When possible, D-negative platelet units are given to D-negative Fever
recipients. However, inventory constraints often force blood banks to Sepsis
issue D-positive platelet products to D-negative recipients. Transfu- Drug associated
sion of such units is associated with a low but nonzero risk of sensi- Active bleeding
tization and formation of anti-D. D sensitization can be prevented Splenomegaly
by administering Rh immune globulin, as is done to prevent fetoma- Disseminated intravascular coagulation
ternal Rh sensitization in D-negative mothers of D-positive children. Venoocclusive disease
The risk of sensitization is very low among D-negative immunocom- Immune
promised patients transfused with D-positive platelets (e.g., HSCT Anti-HLA antibodies
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patients). In this setting, the value of Rh immune globulin (RhIG) Anti-HPA antibodies
prophylaxis appears to be low. ABO mismatch
Drug-dependent antibodies
PLATELET REFRACTORINESS HLA, Human leukocyte antigen; HPA, human platelet antigen.

Causes of Refractoriness to Platelet Transfusion

Platelet refractoriness is defined as an inappropriately low platelet Detection of Antiplatelet Antibodies
increment after repeated platelet transfusions. It can be caused by
nonimmune or immune factors (Table 112.1). The most commonly The most commonly used methods for detection of anti-HPA anti-
reported nonimmune causes of platelet refractoriness include fever, bodies are solid-phase assays using purified platelet antigens for
sepsis, bleeding, splenomegaly, and disseminated intravascular coagu- detection of antibody specificity. However, testing for anti-HPA
lation. In a small subset of cases, platelet refractoriness is immune antibodies is not typically performed in the workup of platelet refrac-
mediated. Platelets express HLA class I antigens, ABO antigens, and tory patients, mainly because the importance of these antibodies in
several platelet-specific antigens. Any of these molecules may poten- causing clinical refractoriness is not well established.
tially serve as an immune stimulus in a transfusion recipient. Whereas
antibodies directed against HLA molecules are responsible for most
cases of immune-mediated platelet refractoriness, antibodies to the Prevention of Alloimmunization
human platelet antigens (anti-HPA) are less frequently implicated.
Although they express HLA class I antigens, platelets themselves are
fairly weak immunogens. It has been shown that contaminating
Diagnosis of Platelet Refractoriness leukocytes in platelet products are primarily responsible for stimulat-
ing HLA antibody formation in platelet transfusion recipients. Thus
Because fewer than half of all platelet-refractory patients have demon- removing WBCs from blood products (leukoreduction) is an essential
strable anti-HLA or antiplatelet antibodies, evaluation of both an means of preventing alloimmunization and subsequent platelet
immediate response to platelet transfusion and an 18- to 24-hour refractoriness. The definitive study showing this was the Trial to
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posttransfusion platelet survival is needed to help establish the cause Reduce Alloimmunization to Platelets (TRAP study) that compared
of platelet refractoriness. Platelet counts obtained from 10 minutes alloimmunization rates in 530 newly diagnosed patients with acute
to 1 hour after transfusion that repeatedly fail to demonstrate a myeloid leukemia randomized to receive unmodified, pooled platelet
corrected count increment of more than 5000/µL usually indicate concentrates (control); filtered, pooled platelet concentrates (F-PC);
immune-mediated platelet refractoriness. If the 10-minute to 1-hour filtered single-donor apheresis platelets (F-AP); or UV-B-irradiated
posttransfusion platelet count shows a reasonable increment but the pooled platelet concentrates (UVB-PC). Anti-HLA antibodies were
platelet count falls back to baseline by 18 to 24 hours, a nonimmune detected in 45% of control participants compared with 17% to 21%
mechanism of refractoriness may be presumed (see Table 112.1). In of patients receiving modified platelets. A total of 13% of control
cases of suspected immune-mediated refractoriness, HLA antibody group patients became platelet refractory versus only 3% in the F-PC
screening (panel reactive antibody [PRA]) provides valuable support- group, 4% in the F-AP group, and 5% in the UVB-PC group.
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ing evidence that allosensitization has occurred. A patient with a
PRA greater than 70% may be considered to be “severely immunized”
and a good candidate for HLA-matched platelets (below). Management of Platelet-Refractory Patients
When platelet refractoriness has been demonstrated, several strategies
Detection of Anti-Human Leukocyte Antigen Antibodies may facilitate achieving therapeutic platelet increments in vivo (Table
112.2). A trial of ABO-matched, fresh (1–2 days old) platelets may
Several assays are available to detect the presence of anti-HLA class I be helpful. In cases of immune-mediated refractoriness, a trial of
antibodies in the serum of alloimmunized patients. Years ago, the HLA-matched platelets, antigen-negative platelets, or cross-matched
most commonly used test was the lymphocytotoxicity assay (LCA). platelets should be considered. The basic principles for selection of
The results of the LCA correlate well with the response to platelet HLA-matched platelets are outlined in Table 112.3. In most cases,
transfusion. However, this assay does not detect anti-HLA antibodies alloimmune refractory patients will show some degree of response to
that do not activate complement. The anti-HLA antibodies can also HLA-matched platelets. Because of the high degree of polymorphism
be detected using an HLA-specific solid-phase enzyme-linked immu- of the HLA loci, it is often not possible to find perfect HLA-A and
nosorbent assay, glycoprotein-specific monoclonal antibody-specific HLA-B locus matches, leading to the use of platelets mismatched at
immobilization of platelet antigens, or flow cytometric detection of one or more loci (Table 112.4). In general, transfusion of grade A- or
antibody binding to beads coated with purified HLA antigens. The BU-matched platelets can result in an increase in platelet count that
flow cytometry-based methodology has significantly improved sensi- is superior to platelet increment obtained using either cross matched
tivity over LCA and, similar to solid-phase assays, it can detect both platelets or platelets with different degrees of HLA mismatching (BX,
complement-fixing and noncomplement-fixing antibodies. C, or D). An additional step that may help in finding compatible