Background: Daratumumab (Dara), an anti-CD38 monoclonal antibody for hematologic malignancies, interferes with routine blood bank testing, specifically affecting the antibody screen and identification panels. In 2016, the AABB recommended performing a baseline phenotype or genotype before a patient (Pt) begins taking anti-CD38 to avoid this interference and potential problems with transfusion. The objective of this study was to assess red blood cell (RBC) utilization and subsequent incidence of alloimmunization to the transfused RBCs in patients receiving Dara. Methods and Materials:We monitored 244 patients taking Dara to determine their red blood cell transfusions and incidence of clinically significant antibody formation before and following administration of Dara. Poisson generalized estimating equations with log link were used comparing the post-Dara incidence and prevalence to those prior, with significance defined as p < .05. Results:From September 1, 2015 to December 22, 2018, 244 patients on Dara were identified, of which 145 patients (59.4%) received a red blood cell transfusion. Antibody screens were performed on 97 of the 145 patients at least 2 weeks following RBC transfusion. Four of the total transfused patients (2.8% total, 4.1% patients with follow-up antibody screen testing) formed new clinically significant alloantibodies, which was not significantly different from Asare's hematologic incidence (p = .98/p = .49).Conclusions: This study showed our patients on Dara did not form alloantibodies following RBC transfusion at a higher incidence than similar patient populations.

Background Primary cold agglutinin disease (CAD) is a monoclonal antibody (M‐protein) and complement‐mediated chronic hemolytic disease process. Antibody glycosylation can play a role in both antibody half‐life and complement fixation. Recently, M‐protein light chain (LC) glycosylation has been shown to be associated with AL amyloidosis. We hypothesized that M‐protein LC glycosylation is also associated with cold agglutinin (CA) titers and CA‐mediated hemolysis. Study Design and Methods A cross‐sectional study of patients undergoing CA titer evaluation underwent mass spectrometric analysis for M‐proteins and M‐protein LC glycosylation. A subset of serum samples also underwent evaluation for the ability to trigger cold hemolysis in vitro. M‐protein and M‐protein LC glycosylation rates were compared across CA titer groups, clinical diagnosis, direct antiglobulin testing (DAT) results, and cold in vitro hemolysis rates. Results Both M‐protein and M‐protein LC glycosylation rates significantly differed across CA titer groups with the highest rates in those with elevated CA titers. M‐protein LC glycosylation occurred almost exclusively on IgM kappa M‐proteins and was significantly associated with positive DAT results and a clinical diagnosis of CAD. Cold in vitro hemolysis was demonstrated in two patients who both had a CA titer of more than 512 but there was no significant association with CA titer group or M‐protein LC glycosylation status. Conclusion M‐protein LC glycosylation is significantly associated with higher CA titer levels. Given the role that antibody glycosylation can play in antibody half‐life and complement fixation, further studies are needed to clarify the effects of LC glycosylation within the context of CAD.

Introduction: Patients with sickle cell disease (SCD) have repeated episodes of red blood cell (RBC) sickling and microvascular occlusion that manifest as pain crises, acute chest syndrome, and chronic hemolysis. These clinical sequelae usually increase during pregnancy. Given the racial distribution of SCD, patients with SCD are also more likely to have rarer RBC antigen genotypes than RBC donor populations. We present the management and clinical outcome of a 21-year-old pregnant woman with SCD and an RHD*39 (RhD[S103P], G-negative) variant. Case Presentation: Ms. S is B positive with a reported history of anti-D, anti-C, and anti-E alloantibodies (anti-G testing unknown). Genetic testing revealed both an RHD*39 and homozygous partial RHCE*ceVS.02 genotype. Absorption/elution testing confirmed the presence of anti-G, anti-C, and anti-E alloantibodies but could not definitively determine the presence/absence of an anti-D alloantibody. Ms. S desired to undergo elective pregnancy termination and the need for postprocedural RhD immunoglobulin (RhIG) was posed. Given that only the G antigen site is changed in an RHD*39 genotype and the potential risk of RhIG triggering a hyperhemolytic episode in an SCD patient, RhIG was not administered. There were no procedural complications. Follow-up testing at 10 weeks showed no increase in RBC alloantibody strength. Discussion/Conclusion: Ms. S represents a rare RHD*39 and partial RHCE*ceVS.02 genotype which did not further alloimmunize in the absence of RhIG administration. Her case also highlights the importance of routine anti-G alloantibody testing in women of childbearing age with apparent anti-D and anti-C alloantibodies.

Background The two major types of cold autoimmune hemolytic anemias are cold agglutinin disease (CAD) and paroxysmal cold hemoglobinuria (PCH). In CAD, the cold agglutinin is usually IgM with anti-I specificity. In PCH, the Donath-Landsteiner (DL) antibody is a cold reacting IgG with anti-P specificity. In this study, we describe the clinical and serological characteristics of patients with autoimmune hemolytic anemia positive for both cold agglutinin and DL antibodies. Methods On review of our immunohematology reference laboratory database, we identified patients over a 16-year period (January 2000- March 2016) with the following: i) age ≥18 years, ii) hemoglobin (Hb) &lt;12g/dL, iii) positive direct antiglobulin test (DAT) with hemolysis (increased lactate dehydrogenase/low serum haptoglobin/ elevated indirect bilirubin), and iv) tested for both CAD and DL antibodies. We classified the patients into 3 cohorts. Cohort 1 included patients positive for both cold agglutinin (titer ≥1:64) and DL antibodies. Cohort 2 consisted of patients with DL antibody but no cold agglutinin (titer &lt;1:64), while Cohort 3 was comprised of patients with cold agglutinin but no DL antibody. We evaluated the clinical response based on the GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) criteria (Barcellini W, et al . Blood 2014) defined as i) complete (CR): hemoglobin ≥12 g/dL with normalization of at least one previously abnormal hemolytic marker; ii) partial (PR): hemoglobin 10-12 g/dL with hemolysis; or iii) none (NR): if any of the above criteria were not met. Results Seven patients had cold autoimmune hemolytic anemia with concomitant cold agglutinin and DL antibodies (Cohort 1). The clinical and serological characteristics are described in table 1. The median age at diagnosis was 68 years (range: 59-78) and the median hemoglobin at onset was 10.3 g/dL (range: 8.2-10.6). Six had red cell agglutination in the blood smear. Two patients had a recent history of infection (1 with Mycoplasma pneumoniae and 1 with upper respiratory tract infection). The median follow-up was 4.8 months (range: 1.0-166.4). Five patients received steroid/other immunosuppressants and two were managed conservatively. The clinical response to treatment was CR in 28.6% patients, PR in 42.9%, and NR in 14.3%. In comparison, Cohort 2 had a 20% CR, 20% PR and 40% NR, while Cohort 3 had a 50% CR, 25% PR and 25% NR, respectively. Conclusion Our study is the first series describing patients with cold autoimmune hemolytic anemia with concomitant cold agglutinin and DL antibodies. In terms of clinical response, patients with negative DL antibodies and cold agglutinin titers &gt;1:64 had better response (50% CR, Cohort 3) to immunosuppressants compared to patients with positive DL antibody (20-30% CR, Cohorts 1 and 2). Large scale studies may be warranted to determine the treatment strategies among patients with concomitant DL and high cold agglutinin titers. Disclosures Kay: Agios: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Research Funding; Tolero Corporation: Research Funding; Gilead: Research Funding. Winters: Fresenius Kabi USA: Consultancy; Eliaz Therapeutics Inc: Membership on an entity's Board of Directors or advisory committees; Sanofi Inc: Other: Moderated opinion leader's forum; Wiley Blackwell: Employment; Regional Health Inc: Consultancy; Mayo Clinic: Employment; Grifols International SA: Consultancy.