Relationship of HLA and platelet‐reactive antibodies in alloimmunized patients refractory to platelet therapy

Abstract

Platelet crossmatching assays have been used to predict the outcome of platelet transfusions in alloimmunized patients by detecting antibodies against platelets. The transfusion failure of HLA-matched platelets predicted by platelet crossmatching may be related to HLA antibodies undetected by lymphocytotoxicity but detected by platelet immunoglobulin-binding assays or platelet-specific antibodies (both antibodies defined here as platelet-reactive antibodies). To differentiate platelet-reactive antibodies from lymphocytotoxic HLA antibodies, we used HLA characterized lymphocytes in parallel with platelets from individuals to form separate frozen panels. Sera from 10 allosensitized patients were studied in the lymphocyte panel by lymphocytotoxicity and in the platelet panel by enzyme-linked immunoassay (ELISA). By comparing pattern and percent wells reacting in each panel, lymphocytotoxic HLA antibodies and antibodies reactive with platelets in ELISA were detected separately. In all 10 allosensitized patients, platelet-associated antibodies were present and 7 had additional lymphocytotoxic HLA antibodies. Using this double parallel panel technique, we found platelet-reactive antibodies important in platelet alloimmunization, unrecognized by lymphocytotoxicity. These data indicate platelet-crossmatching be solely used in the selection of platelets for allosensitized patients.

Intravascular and total body platelet equilibrium in healthy volunteers and in thrombocytopenic patients transfused with single donor platelets

“…Refractoriness is often used to indicate a poor response 1 hr post-platelet infusion [2,7,10]. However, we and others defined refractoriness as repeated inadequate 1-hr post-transfusion increments on successive days or successive transfusions [27,30]. One incident with a poor response may result from 5-day stored platelets or ABO mismatch rather than more se-vere conditions such as alloimmunization, splenomegaly, sepsis, etc., that truly cause poor responses to more than one platelet transfusion [31,32].…”

Specificities of anti‐platelet antibodies in multitransfused patients with haemato‐oncological disorders

“…7% of patients with no history of prior immunization, develop HLA antibodies if transfused with leucocyte-depleted blood products. HLA antibodies can be detected in 25-70% of patients, who have received nonleucocyte-depleted blood products (Dutcher et al, 1981;Brubaker & Romine, 1987;Slichter, 1990). In all these investigations the presence of HLA antibodies was determined by the reactivity of sera against leucocyte antigens inferring their reactivity against platelets.…”

Incidence and specificity of HLA antibodies in multitransfused patients with acquired aplastic anemia

“…Similar effects are achieved by infusing ABH and Class I–compatible PLTs, 31,35 , 36 or by neutralizing antibody with intravenous immunoglobulin 37 . PLT cross‐matching is advocated as a more pragmatic way to detect antibodies to both HLA and HPA 38‐40 . The specificities associated with anti‐HLA in patients with PLT transfusion refractoriness tend to conform to the so called “public” antigens shared by “cross‐reactive groups” (CREGs) of the HLA Class I alleles 32,41 …”