Bendix, Brenda J.

Abstract Our facility changed antibody screening methods from a gel microcolumn–based test (ID-Micro Typing System Gel Test; Ortho Clinical Diagnostics, Inc., Raritan, NJ) to an automated solid-phase test (Galileo/Capture-R Ready-Screen [I and II], Immucor, Inc., Norcross, GA). To determine whether detection rates for commonly encountered clinically significant red blood cell antibodies differed as a consequence of this change, preimplementation and postimplementation antibody identification records were retrospectively reviewed. A statistically significant difference in the percentage of positive screening tests during the gel microcolumn testing period (73,903 total screens, 1.56% confirmed positive) versus the solid-phase screening period (80,242 total screens, 1.81% confirmed positive; p < 0.0002) was observed. The number of antibodies to K identified was significantly lower with solid phase than with gel (27% decrease; p = 0.004). It is unknown whether there is a statistical difference in delayed or hemolytic transfusion reaction rates as this was not evaluated. Immunohematology 2013;29:101–04.

Abstract Abstract 4332 Background: Hemolytic anemia caused by the passive transfer of isoagglutinins, typically anti-A or anti-B antibodies, is a rare and likely under-recognized complication of intravenous immunoglobulin (IVIG) therapy. The Immunohematology Reference Laboratory at Mayo Clinic Rochester has detected 12 cases of passively acquired isoagglutinins following IVIG administration during the first seven months of this calendar year (January-July 2011). This frequency of detection is much higher than that seen over the three prior calendar years, when only two cases were detected. Given this “cluster” of isoagglutinin detection, we analyzed these 12 cases to determine the clinical significance of this finding as well as characteristics of resulting cases of hemolytic anemia. Materials/Methods: Charts of patients identified as having passively acquired isoagglutinins following IVIG therapy were analyzed for evidence of a significant drop in hemoglobin (defined as >1 g/dL) as well as evidence of hemolysis (elevated lactate dehydrogenase, reticulocytosis, spherocytosis, decreased haptoglobin, indirect hyperbilirubinemia, hemoglobinemia and hemoglobinuria). Cases with a >1 g/dL drop in hemoglobin and two or more of the above findings consistent with hemolysis were considered “confirmed” cases. Those with passively acquired isoagglutinins but without evidence of hemolysis or with an alternative explanation for anemia were considered “asymptomatic”, and cases without a full hemolytic evaluation but still clinically suspicious were categorized as “suspected” cases. Results: Passively acquired isoagglutinins were detected in 11 patients following 12 separate treatments with IVIG (one patient had antibodies noted after two separate treatment episodes >3 weeks apart). Four of these 12 cases were categorized as “confirmed” cases, five as “suspected” and three as “asymptomatic”. The indication for IVIG use was a neurologic disorder in three of the four confirmed cases, with immune thrombocytopenic purpura (ITP) being the indication in the other case. In suspected cases, ITP was the indication in four of the five cases, with the fifth patient carrying a diagnosis of Kawasaki’s disease. During the 7 month period reviewed, 250 unique patients were treated with IVIG, meaning 1.6% of patients (4/250) had confirmed IVIG-associated hemolytic anemia and another 1.6% (4 patients; 5 events) had suspected hemolytic anemia during this period. The mean decrease in hemoglobin was 4.1 g/dL in confirmed cases (range 1.3–7.1 g/dL) and 2.7 g/dL in suspected cases (range 1.7–4.2 g/dL). Eight of nine patients reviewed had blood type A positive; the other was B positive. The median time from initiation of therapy to hemoglobin nadir was eight days in confirmed and three days in suspected cases. The mean dose of IVIG administered in confirmed cases was 300 g (range 180–400 g) and was 162 g (range 50–300 g) in suspected cases. Red cell transfusion was required in three of the four confirmed cases. Privigen™ was the IVIG product utilized in all four confirmed and the first three suspected cases. After removal of Privigen™ from the Mayo Clinic formulary given concerns regarding these cases, two suspected cases of IVIG-associated hemolytic anemia occurred with Gamunex-C™, including one in a patient who previously suffered confirmed hemolysis after receipt of Privigen™. Conclusions: Hemolytic anemia is a rare complication of therapy with IVIG. The rate of hemolytic anemia following IVIG administration over the evaluated period is consistent with previous reports, but it should be noted that these cases were detected without the aid of an active surveillance policy, indicating the actual rate of hemolytic anemia associated with IVIG use was likely greater than that detected by this review. Our series suggests that those with blood type A may be at increased risk for this complication; further work is ongoing to better define risk factors for development of this potentially significant complication of IVIG therapy. Disclosures: Off Label Use: IVIG use in various off-label indications.

Abstract Background: Little data exists on the incidence rate of transfusion reactions and red cell antibody formation following allogeneic (allo) hematopoietic progenitor cell transplant (HPCT) recipients. Study Design and Methods: Consecutive related and unrelated Allogeneic HPCTs from 2006 to 2013 were retrospectively reviewed regardless of graft source. Allo HPCT recipients were analyzed as a whole as well as divided into ABO compatibility groups of identical, minor mismatch, and major/bidirectional mismatch. Transfusions, transfusion reactions and antibodies were analyzed for the first year post-transplant while survival was recorded throughout the available follow-up period. Results: During the study period, 573 patients ranging in age from 0.6 to 72 years underwent first allo HPCT for various malignant and non-malignant etiologies: 278 acute leukemias, 89 lymphomas, 40 multiple myelomas, 134 other hematologic malignancies, 32 non-neoplastic etiologies. Of these, 52% underwent myeloablative conditioning and 48% reduced intensity conditioning. Transfusion reactions were reported in 93 of the 573 allo HPCT recipients. The incidence rate of transfusion reactions per 10,000 transfusion episodes was 45.54 in the ABO identical, 61.28 in the minor mismatch, and 29.95 in the major mismatch groups (p=0.04). The most common reaction type reported in all groups was allergic followed by febrile non-hemolytic, transfusion associated circulatory overload, and delayed hemolytic or serologic reactions. No acute hemolytic, transfusion related acute lung injury (TRALI), post transfusion purpura, transfusion associated graft-versus-host disease, or transfusion associated sepsis reactions were reported. A total of 43 unique patients(7.5%) developed new antibodies post-transplant: 16 allo HPCT recipients developed clinically significant antibodies, 17 developed clinically insignificant antibodies, and 17 developed auto antibodies post-transplant. Including those patients with pre-transplant antibodies the overall prevalence of red blood cell antibodies was 14.5%. See Table 1 for incidence rate for forming new rbc antibodies post-transplant. Table 1. New RBC Antibody Formation Incidence Rate Post-Transplant ABO Compatibility Group Clinically Significant Antibody Incidence /10,000 RBC Transfusions Clinically Insignificant Antibody Incidence/ 10,000 RBC Transfusions, Auto Antibody Incidence/10,000 RBC Transfusions Total Antibody Incidence/10,000 RBC Transfusions Identical 39.33 16.85 39.33 95.51 Minor Mismatch 35.87 57.39 43.04 136.30 Major Mismatch 8.34 16.67 8.34 33.35 A statistically significant difference (p=0.001) was seen in total antibody incidence when comparing the ABO compatibility groups. The most common, clinically significant allo antibodies formed were Anti-E, Anti-Jka, Anti-A1, Anti-K, Anti-D, and Anti-C. Survival of allo HPCT recipients as a whole was not statistically different for those who formed new rbc antibodies post-transplant following adjustment for ABO compatibility, age at transplant, diagnosis, graft source, and pre-transplant rbc infusions (p=0.068). Allo HPCT recipients that formed new rbc antibodies were not shown to have prolonged engraftment. Engraftment, neutrophils (ANC) and platelets (PLT), were not statistically different (p=0.34 ANC; p=0.20 PLT) when comparing all allo HPCT recipients to those who formed a new rbc antibody. Conclusion: Transfusion reaction and rbc antibody incidence rates were higher in the ABO minor mismatch when compared to the ABO identical and ABO major mismatch groups. The reaction etiology (predominantly antibody mediated) and the formation of new antibodies indicates a surprisingly active humoral immune system. The overall prevalence of antibody formation is likely affected by high exposure to transfusions. Development of a new rbc antibody did not affect engraftment or survival outcomes. Disclosures No relevant conflicts of interest to declare.

BackgroundThe cold agglutinin (CAGG) titer is offered at our institution to aid in diagnosing cold agglutinin disease (CAD). Our goal was to create a seasonally adjusted reference range using prospective samples and compare it to a reference range generated retrospectively.Study Design and MethodsProspective CAGG titer testing was performed on healthy blood donors. Retrospective electronic analysis was performed on patients in two groups defined by current and historical testing methods. Blood donor testing was performed in January and July to determine if seasonal variation existed. Retrospective patients with conditions associated with CAD were excluded from analysis. Additional prospective CAGG testing using reference range program volunteers was performed to verify blood donor and patient result differences.ResultsTiters from the blood donor and patient cohorts had no age association (p > 0.44). Titers from those same cohorts did not show winter/summer variation (p > 0.11). No sex association was found with titer reference ranges in the blood donor and historical patient cohort. A sex association was found with titers in the current method patient cohort (male 64 to 512 and female ≤64; p < 0.0001). Blood donor CAGG titer lower 95% reference range was not more than 4 while historical and current patient cohorts ranges were not more than 32 and not more than 64, respectively. Reference range volunteers confirmed the narrow reference range in healthy individuals when compared to patients and blood donors.ConclusionProspective blood donor CAGG titers were lower than retrospective patient cohorts. This may be due to blood donors representing a healthier population than the patient cohorts.