Erythrocyte T-antigen activation in children: Patient characteristics and the hemolytic risk of transfusion.

BACKGROUND: T-antigen activation usually occurs upon red blood cell (RBC) membrane cryptantigen exposure due to bacterial enzymes. Although uncommon, the condition is probably underrecognized. There is concern about hemolysis after plasma and plasma-containing platelet transfusions due to naturally occurring anti-T antibody in healthy blood donors. However, experts have debated the extent and severity of clinical hemolysis due to anti-T. PROCEDURE: We retrospectively identified patients who tested positive for polyagglutination with Arachis hypogea and Glycine max lectins from 2008 to 2019. The records of the patients were reviewed to determine clinical symptoms, laboratory evidence of hemolysis, need for transfusion, and clinical outcomes. RESULTS: Ten patients were identified. At diagnosis, all were anemic and four had thrombocytopenia. Severe Streptococcus pneumoniae infection affected seven patients; one died. Seven of 10 patients (70%) had laboratory evidence of hemolysis. Peripheral blood smear findings in six patients included RBC agglutination and changes suggesting hemolysis (spherocytes and schistocytes), but three had unremarkable RBC morphology. Four patients required plasma or platelet transfusions; all survived to discharge. CONCLUSIONS: T-antigen activation is a rare entity. Most patients diagnosed at our hospital had hemolytic anemia and severe pneumococcal infection. Hemoglobin decreased after plasma and platelet transfusions in all patients assessed, but these transfusions were necessary to support treatment. RBCs were given to maintain appropriate hemoglobin levels.

Identification of red blood cell antibodies in maternal breast milk implicated in prolonged hemolytic disease of the fetus and newborn.

BACKGROUND: Alloantibodies against more than 50 non-ABO blood group antigens have been implicated in hemolytic disease of the fetus and newborn (HDFN) and are expected to wane within weeks after delivery. Persistent anemia leads to the hypothesis of continued exposure to red blood cell (RBC) alloantibodies via breast milk, which has been shown in a murine model and suggested in rare case reports. CASE REPORT: We report three cases of prolonged HDFN in two neonates with anti-D HDFN and one with anti-Jka HDFN. Patient 1 demonstrated 4+ anti-D serologic testing beyond 2 months; therefore, antibody testing was performed on maternal breast milk. METHODS: Maternal serum samples were tested for the presence of unexpected antibodies using standard Ortho gel card and 37 °C 60 minutes with anti-human globulin (AHG) tube saline methods. Antibody titrations were performed using the standard 37 °C 60 minutes to AHG tube saline method. Fresh breast milk samples were tested using the standard 37 °C 60 minutes to AHG tube saline method for both unexpected antibodies and titration study. Fresh breast milk from an O-positive, antibody-negative donor was used as control for any reactivity that may have been due to milk solids or proteins alone. RESULTS: Using a known methodology applied in a novel way to test breast milk for RBC alloantibodies, antibodies against fetal RBCs were identified in the maternal breast milk of three patients. CONCLUSION: Maternal RBC alloantibodies are present in breast milk and may be clinically significant in patients with prolonged recovery from HDFN.

High-dose intravenous immunoglobulin is strongly associated with hemolytic anemia in patients with Kawasaki disease.

BACKGROUND: Hemolysis is a reported side effect of intravenous immunoglobulin (IVIG) therapy in adults, but pediatric data are scarce. We determined the frequency of IVIG-associated hemolysis in patients with Kawasaki disease (KD) and characterized risk factors for hemolysis. We hypothesized that hemolysis is more common in children with KD than adults with other disorders, and hemolysis risk is related to IVIG dose and degree of inflammation. STUDY DESIGN AND METHODS: This was an 8-year, single-center, retrospective cohort study. A total of 419 KD patients were identified; 123 had pre- and post-treatment complete blood counts allowing for assessment of anemia. Hemolytic anemia was defined as decrease in hemoglobin after IVIG greater than 1 g/dL with immunohematologic or biochemical studies supporting hemolysis. RESULTS: 123 patients were stratified as having hemolysis (n = 18, 15%) or nonhemolysis (n = 105, 85%). Patients with hemolysis were more likely to have complete versus incomplete KD (65% vs. 39%, p = 0.04) and refractory versus nonrefractory course (78% vs. 16%, p < 0.001). Patients receiving 4 g/kg versus 2 g/kg IVIG were more likely to hemolyze (89% vs. 34%, p < 0.001). Patients with hemolysis had mostly non-O blood group (94%), positive direct antiglobulin tests (89%), and positive eluates (72%). Two-thirds of patients with hemolysis required RBC transfusion. CONCLUSIONS: Hemolysis occurred in 15% of KD patients evaluated for anemia and is strongly associated with high-dose (4 g/kg) IVIG. KD patients receiving high-dose IVIG should have close hematologic monitoring to identify hemolysis.

Intravenous immunoglobulin-related hemolysis in patients treated for Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is an idiopathic, multisystem disorder characterized by vasculitis of arteries, veins, and capillaries, affecting pediatric patients, and is the leading cause of acquired heart disease in childhood. The mainstays of therapy for KD are high-dose intravenous immunoglobulin (IVIG) and aspirin, which are thought to prevent or modify the most serious cardiac sequelae. A well-documented complication of high-dose IVIG infusion in adults is hemolytic anemia due to passive transfer of anti-A and anti-B. Risk factors for hemolysis in another case series included patient blood group (group A, B, or AB), a high cumulative dose of IVIG, and concomitant inflammation documented by one or more markers like ferritin, fibrinogen, erythrocyte sedimentation rate, or C-reactive protein. STUDY DESIGN AND METHODS: A 3-year retrospective case review of patients previously recognized with apparent IVIG-related hemolytic anemia identified by standard blood bank testing was performed at a tertiary care pediatric hospital. RESULTS: Five patients were identified with severe anemia each requiring RBC transfusion for anemia. All five patients demonstrated a positive direct antiglobulin testing. Four of five patients had anti-A, anti-B, and/or anti-A1 with elution assays. All patients had signs of extravascular hemolysis with reticulocytosis, spherocytosis, and other hemolysis markers. One child died. CONCLUSION: Our cases represent dose-dependent hemolysis caused by IVIG in association with severe anemia requiring transfusion with an average yearly incidence rate of 0.36%. Hemolysis is an underrecognized complication of IVIG administration. KD patients are at greater risk for anemia because of their lower baseline hemoglobin concentration, underlying acute inflammation, and oxygen requirements during acute illness.

RH genotyping in a sickle cell disease patient contributing to hematopoietic stem cell transplantation donor selection and management.

African individuals harbor molecular RH variants, which permit alloantibody formation to high-prevalence Rh antigens after transfusions. Genotyping identifies such RH variants, which are often missed by serologic blood group typing. Comprehensive molecular blood group analysis using 3 genotyping platforms, nucleotide sequencing, and serologic evaluation was performed on a 7-year-old African male with sickle cell disease who developed an "e-like" antibody shortly after initiating monthly red blood cell (RBC) transfusions for silent stroke. Genotyping of the RH variant predicted a severe shortage of compatible RBCs for long-term transfusion support, which contributed to the decision for hematopoetic stem cell transplantation. RH genotyping confirmed the RH variant in the human leukocyte antigen-matched sibling donor. The patient's (C)ce(s) type 1 haplotype occurs in up to 11% of African American sickle cell disease patients; however, haplotype-matched RBCs were serologically incompatible. This case documents that blood unit selection should be based on genotype rather than one matching haplotype.