Potential impact of complement regulator deficiencies on hemolytic reactions due to minor ABO-mismatched transfusions

Abstract

Key Points• An in vitro model shows that hemolysis could be due to the presence of a subclinical PNH clone causing a negative C3b/d DAT.• Changes to decayaccelerating factor and membrane inhibitor of reactive lysis may lead to overt hemolysis after minor mismatched transfusions.Minor ABO-mismatched transfusions are a common occurrence, although infrequent transfusion reactions occur. We sought to investigate the regulation of complement

Fatal acute hemolytic transfusion reaction due to anti‐B from a platelet apheresis unit stored in platelet additive solution

“…Hematopoietic stem cell transplantation with a different blood type has been proposed as a potential risk factor for isohemagglutinins targeting RBCs for hemolysis, given the lack of endothelial ABO antigens in transplants between ABO‐mismatched donors and recipients. Although the described patient had previously undergone a hematopoietic stem cell transplant, the donor was also blood group B. Complement regulator deficiencies have been described in patients with some types of acute leukemias and have also been described in some transfusion recipients to contribute to hemolytic reactions . Further, recipient secretor status and recipient ABO zygosity have been suggested to potentially impact the risk of isohemagglutinin‐mediated hemolysis; donor secretor status may also impact isohemagglutinin titer .…”

SCAR: The high‐prevalence antigen 013.008 in the Scianna blood group system

“…The ability of anti‐SCAR to activate complement was evaluated as previously described 29 . Following incubation of 50 μL of a 5% suspension of SC:8 red cells with 200 μL of patientʼs serum in a saline IAT for 30 minutes at 37°C, the anti‐SCAR sensitized red cells were washed and resuspended in 200 μL of fresh AB serum for 30 minutes at 37°C 29 .…”

Complement activating ABO IgM/IgG act synergistically to cause erythrophagocytosis: implications among minor ABO incompatible platelet transfusions

“…(Table 1). [18] Seven patient sera had IgM titers ≤ 64, and 3 sera had IgM titers ≥ 128 (H3 = 128, H4 = 256, and H5 = 128). Patient sera (H1-H5) had high IgG titers > 1024, while H6-H10 had low IgG titers ≤ 128.…”

“…Complement activation of anti-A sera was evaluated at a dilution of 1:100 (vol:vol) according to the previously published protocol. [18] Briefly, a 5% Group A1 + RBC suspension was incubated at 37 °C Representative donor plasma and patient sera from each cluster (n = 12, highlighted in Data was analyzed using CellQuest Pro software (BD Biosciences, Franklin Lakes, NJ, USA). Increase in fluorescence in the FL1 channel (517 nm) was recorded as a positive signal for phagocytosis (Fig.…”

“…The following samples were evaluated in this study: 1) plasma from a single Group O donor that caused extravascular hemolysis in a Group A patient of a minor ABO incompatible apheresis platelet transfusion (EH-PT), 2) random Group O plasma (n = 30) from healthy blood donors, and 3) selected Group O sera (n = 10) from outpatients being evaluated for possible ABO incompatible kidney transplantation. The plasma from healthy donors had known IgM/IgG anti-A titers, some with the ability to activate complement as previously published [18]. The serum samples had known IgG anti-A titers and demonstrated anti-A hemolysis at low titer when tested with freshly clotted serum.…”