Each year, the CSTM conference scientific committee receives over a hundred abstracts to review for presentation the annual conference. The team preparing for the Montreal conference in 2023 brought forward the best in new transfusion medicine knowledge for conference participants and, from those, the top submissions were selected. Each year, the
top submissions are shared in Transfusion Medicine Reviews.
Here is a recap from the
2024 CSTM Conference Abstract Book of those top abstracts.
Isohemagglutinin titres: A comparison of pathogen reduced pooled platelets manufactured with platelet additive solution versus untreated pooled platelets submitted by Melanie Bodnar
Abstract Summary:
Introduction: Limitations in platelet inventory necessitate the use of ABO-incompatible (ABOi) platelets for transfusion with possible risk of an acute hemolytic transfusion reaction due to the presence of high titre (HT) isohemagglutinins (ISO). Pooled platelets psoralen-treated (PPPT) are manufactured following the division of 7 donor buffy coats in a platelet additive solution (PAS). The PAS:plasma ratio of 60:40 provides a dilutional effect on ISO levels. The purpose of this study is to compare the proportion of PPPT that test ISO HT positive versus untreated 4 donor platelet pools without PAS (UPP).
Methods: Component-based ISO titration was performed on 1001 UPP (Nov 8 2022-Feb 8 2023) and 1019 PPPT (Jun 1 2023-Aug 31 2023) followed by testing of 834 additional group O PPPT (Sept 1 2023- Jan 19 2024) to refine the HT rate estimate. All testing was performed at a single laboratory by a manual immediate spin tube method using an aliquot of platelet supernatant diluted 1:50 with saline tested separately against A1 and B cells. Agglutination with either/both A1 and B cell(s) constituted a positive HT result. The proportion of components with HT results were compared for PPPT vs UPP. Statistical analysis was performed using SAS with p-values calculated using the Chi-Square method.
Results: Of 1019 PPPT in PAS, 3 (0.29%) tested HT positive and all were group O. By comparison, 64/1001 (6.4%) UPP were HT positive (p value < 0.0001). The rate of HT positivity by ABO blood group for PPPT vs UPP: Group O 3/559 (0.54%) vs 53/496 (10.6%) (p value < 0.0001); Group A 0/439 (0%) vs 9/468 (1.9%); Group B 0/21 (0%) vs 2/37 (5.4%). For group A and B platelets, the relatively low rate of HT positive events in both UPP and PPPT precluded meaningful statistical comparison. Testing of 834 additional group O PPPT yielded 6 HT positive components for a total of 9/1393 (0.65%) HT positive group O PPPT (99% CI 0.23-1.43%).
Conclusions: Canadian Society for Transfusion Medicine Annual Conference 2024 20 Greater than 99% of pathogen reduced pooled platelets in PAS have low isohemagglutinin titres using a common component-based testing assay. For PPPT, none of the group A or B tested HT positive with 0.65% positivity in group O. The significant reduction in HT positive pooled platelet components with this new manufacturing method confers a greater safety profile when ABO incompatible platelet transfusion cannot be avoided. These findings may impact hospital decisions around inventory management, platelet selection and titre testing.
Monoclonal anti-D induces low efficiency trogocytosis: Implications for the prevention of Hemolytic disease of the fetus and newborn (HDFN) submitted by Yoelys Cryz Leal
Abstract Summary:
Abstract Introduction/Objective: Hemolytic disease of the fetus and newborn (HDFN) is an alloimmune condition provoked by maternal IgG that crosses the placenta and causes fetal red blood cell (RBC) destruction. Donor-derived Rhesus Immune Globulin (RhIG) is the only licensed option available to prevent HDFN through a phenomenon called antibodymediated immune suppression (AMIS). The mechanism as to how RhIG induces AMIS is poorly understood and this has hampered the successful development of monoclonal antibodies to replace RhIG. Our recent murine data suggests that trogocytosis-induced antigen loss could play a central role in AMIS induction. The present work aims to compare the ability of anti-D monoclonal antibody, clinically assessed, to promote in vitro trogocytosis under AMIS conditions compared with RhIg.
Design and Methods: RhD+ human RBCs (RBCs) were fluorescently labeled with PKH67 and sensitized with different concentrations of RhIG (WinRho, SDF) or the IgG1 BRAD5 monoclonal anti-D antibody. Sensitized vs non-sensitized RBCs were incubated with or without THP-1-CD16A macrophages for 30 min and 3 hours. Fluorescent RBCs were recovered, macrophages washed, and remaining RBCs lysed. The ability of BRAD5 vs RhIG to induce RBC membrane fluorescence loss and RBC membrane transfer to the macrophages (ie., trogocytosis) as well as phagocytosis were evaluated. Median fluorescence intensity (MFI) of PKH67 on the RBC recovered, the percentage of PKH67+ macrophages, as well as their PKH67 MFI, were determined by flow cytometry. Confocal cell microscopy to visualize the interaction between macrophages and anti-D sensitized RBCs was performed.
Results: We observed that RBCs sensitized with ≥110 ng/mL of RhIG showed significant phagocytosis while lower concentrations primarily demonstrated significant trogocytosis-driven antigen loss. As the theoretical plasma concentration of anti-D in patients administered RhIG is below 100 ng/mL, our findings indicate that trogocytosis is the probable in vivo mechanism under AMIS conditions. In the case of BRAD5, this antibody, like RhIg, was capable of inducing both phagocytosis and trogocytosis. However, much higher concentrations Canadian Society for Transfusion Medicine Annual Conference 2024 4 of BRAD5 were necessary to achieve a comparable degree of trogocytosis as compared to RhIg.
Conclusions: This work demonstrates that RhIG has the capacity to induce trogocytosis at clinically relevant concentrations, with minimal to no phagocytosis. Conversely, the BRAD5 monoclonal antibody although capable of trogocytosis, was over ten times less efficient than RhIG, mirroring its poorer efficacy in prior clinical studies for preventing RhD alloimmunization.
Implementation of sexual risk behaviour donor screening in Canada submitted by Mindy Goldman
Abstract Summary:
Introduction: In 2022 Canadian Blood Services and Héma-Québec removed the three month deferral for men who have sex with men and adopted gender neutral criteria assessing sexual risk behaviours in all donors. We assessed the impact of these changes on the safety and adequacy of the blood supply, one year post-implementation at Canadian Blood Services and 9 months postimplementation at Héma-Québec.
Methods: All allogeneic donors are asked if they have had a new partner or more than one sexual partner in the last 3 months. Donors answering yes to either question are asked if they had anal sex in the last 3 months; if yes, they are deferred for 3 months. We followed HIV rates before and after the criteria change and interviewed HIV positive donors. We assessed the number of donors answering yes to the new questions and the number deferred by age, gender, and donation status. Data on donors, donations, transmissible disease markers and deferrals were extracted from our epidemiology databases. Source plasma donors were not included. Comparisons were made using the Chi square test.
Results: There were three HIV positive donations out of 990,291 donations pre-implementation and four out of 929,384 post-implementation (0.30/100,000 vs 0.43/100,000, p=0.72). All postimplementation HIV positive donors were male, Canadian Blood Services' donors in Ontario. One was non-compliant with multiple criteria. No risk factors were identified in the other three positive donors, although one had English comprehension difficulties. 2.9% of donors answered yes to a new partner and/or more than one partner; the percentage answering yes to a new partner was higher than more than one partner (2.6% vs 1.2%, p< 0.0001). On implementation, 0.15% of donors were deferred for a new partner and/or more than one partner and anal sex. Deferral rates were highest in first time, younger donors, with similar rates in males and females, and have decreased to 0.06% one year postimplementation.
Conclusions: Implementation of sexual risk behavior donor screening resulted in unchanged HIV rates and a manageable impact on blood availability. Gender-neutral criteria have also simplified screening for trans donors. After over 30 years, we are no longer asking donors about their sexual orientation, increasing the inclusiveness in our donor base.
Towards Safer Transfusion Therapies: The Role of Non-Inflammatory Fcy Receptor 1 Blockade Submitted by Yaima Tundidor Cabado
Abstract Summary:
Introduction: The ongoing need to reduce reliance on intravenous immunoglobulin (IVIg) in treating autoimmune and inflammatory diseases calls for novel, targeted therapeutic strategies. Given the adverse events linked with Fcγ receptor (FcγR) III blockade, this study investigates the therapeutic potential of targeting FcγRI, demonstrated herein to be non-inflammatory, offering a more specific and safer alternative to the generalized action of IVIg.
Objective: This work aims to develop an in vivo anti-FcγRI therapy as a more focused and safer alternative to both IVIg therapy and FcγRIII blockade, with potential implications for improving patient outcomes and quality of life.
Design and Methods: From a phage display library, novel anti-human FcγRI antibodies were selected based on their high affinity and specificity for FcγRI. These antibodies were characterized for their ability to block Fc-FcγRI interactions using a human macrophage cell line and to prevent macrophage-mediated phagocytosis of sensitized red blood cells. The inflammatory nature of anti-FcγRI antibodies, compared to those engaging FcγRIII, was assessed through temperature changes and cytokine responses in FcγRhumanized mice, as well as in C57BL/6 and BALB/c mice, providing a comprehensive safety profile.
Results: We developed five novel anti-human FcγRI antibodies, each demonstrating a significant ability to inhibit FcγRI-mediated phagocytosis in vitro, without eliciting adverse inflammatory responses in vivo. Notably, anti-FcγRI administration did not result in the temperature changes or inflammatory responses observed with anti-FcγRIII, highlighting the non-inflammatory benefits of FcγRI targeting.
Conclusions: Our findings support the development of anti-FcγRI antibodies as a promising, noninflammatory therapeutic approach for transfusion medicine. This strategy not only has the potential to reduce the dependency on IVIg but also offers a safer and more specific method for modulating the immune response in patients.
Abstracts for the 2025 conference are being reviewed now, and we can’t wait to see what we learn this year.