Circulating immune complexes involving the ABO system after platelet transfusion

Abstract

Summary. It has been proposed that when ABO unmatched platelets are transfused circulating immune complexes (CIC) may be formed between the patient's soluble ABH antigens and the transfused antibodies. Platelets might then be destroyed by bystander mechanisms or by the binding of CIC to the Fc receptor or to C3 binding membrane proteins on the platelet. An ELISA Clq assay was used to detect CIC in 40 patients with haematological diseases who had received multiple platelet transfusions. A significantly larger number of refractory patients were positive (41%) in the assay than non‐refractory patients (13%) or normal blood donors (0%). The presence of circulating IgG anti‐A was sought in six group A refractory patients who had been transfused with ABO unmatched platelets. To determine whether the IgG anti‐A was monomeric or in high molecular weight complexes, the serum was fractionated by gel exclusion chromatography and fractions were tested for the presence of IgG anti‐A. In all six patients the peak of IgG anti‐A binding occurred in fractions of high molecular weight (200–900 kD). Five out of six patients also demonstrated anti‐A activity in fractions corresponding to monomeric IgG (about 150–180 kD). Fractions containing high molecular weight anti‐A were purified using a protein G column and the eluates were tested for the presence of group A antigen using dot immunoblotting. Group A antigen was associated with the purified IgG anti‐A in 4/5 patients tested. Appropriate transfused and non‐transfused controls had no anti‐A in any fractions. Although not unexpected, these studies demonstrate for the first time that refractory patients receiving ABO unmatched platelets have CIC composed of ABO antigens and their corresponding antibodies present in their serum that circulate for at least several days. It also confirms the hypothesis that some CIC in haematological patients are induced by transfusion.

Platelet Transfusion - the Art and Science of Compromise

“…In one study, it was demonstrated that including 1 non-group O whole blood-derived PLT unit in a pool of 3-4 group O PLTs decreased the titer of, or outright neutralized, the anti-A and anti-B antibodies in the pool [4]. This practice of adding a non-group O whole blood PLT unit in order to decrease the anti-A or anti-B titer should be used with caution as there is a potential for the formation of immune complexes, PLT activation, and an increase in PLT microaggregates which, in small studies, have been implicated in causing adverse clinical outcomes (discussed in more detail below) [26,27]. Another study demonstrated that volume reducing group O apheresis PLTs followed by resuspension in group AB plasma reduced the anti-A and anti-B titers to ≤8 thereby creating a ‘universal donor PLT' [28].…”

“…These complexes form between the solube A and B antigens and the corresponding antibodies in recipient's plasma or that which accompanied the PLTs. ABO immune complexes have been reported to alter PLT function [61] and trigger complement activation and inflammation which has been reported to lead to transfusion reactions and RBC alloimmunization [26,62,63]. ABO immune complex formation was also implicated in higher mortality rates amongst recipients of ABO compatible but not identical plasma recipients [64] and was associated with the development of acute respiratory distress syndrome and sepsis in trauma patients who received ABO compatible but not identical plasma transfusions [65].…”

Allosensitization and the Ventricular Assist Device: Dual Evolution of Technology

“…anti-HLA from pregnancy) antibody responses. Our group has also reported the formation of circulating immune complexes of ABO antigen and their corresponding antibodies in patients who received ABO unmatched platelets [39,40]. We believe that any or all of these phenomena may interfere with immune assays, especially those that use an anti-immunoglobulin (second-step) reagent such as ELISA, and flow or AHG crossmatch.…”

2 Platelet Concentrates

“…In 15-30% of patients HLA class I antibodies are associated with additional HPA antibodies [18,66]. Similar to RBC transfusion, a serological compatibility test can be performed prior to platelet transfusion.…”

“…It is still unresolved whether ABO-incompatible platelet transfusions cause clinically relevant immune modulation [6,7,18,19]. In rare cases acute hemolytic transfusion reactions can occur, caused by isoagglutinins (anti-A and anti-B) in the donor plasma.…”