Warm autoimmune hemolytic anemia with anti-Jka specificity following babesiosis masquerading as a delayed hemolytic transfusion reaction.

BACKGROUND: Warm autoimmune hemolytic anemia (WAIHA) is characterized by the development of autoantibodies that react with red blood cells (RBCs) optimally at physiologic temperature, classically resulting in a positive direct antiglobulin test (DAT) for IgG and a panreactive eluate. Babesiosis has been described as a potentiator of WAIHA, and all cases have shown classic blood bank findings. Only rare reports have described autoantibodies, both secondary to babesiosis and overall, with specificity for Kidd antigens. METHODS: Antibody detection and identification were performed using IgG-specific column agglutination technology. Jka antigen phenotyping was assessed using monoclonal reagents and genotypic analysis was performed at an immunohematology reference laboratory. DATs were performed via standard tube methods. The elution was performed using the ELUclear glycine acid red cell elution kit. RESULTS: We report a case of WAIHA induced by Babesia microti infection with an autoantibody with Jka specificity, originally believed to be a delayed hemolytic transfusion reaction, given the detection of an RBC antibody in close proximity to numerous RBC transfusions. Determination of autoantibody status with anti-Jka -like reactivity was only confirmed after Kidd antigen genotyping predicted expression of the Jka antigen. DISCUSSION: Healthcare providers should be cognizant of the potential for babesiosis-induced WAIHA, particularly in individuals who continue to hemolyze despite undetectable parasitemia. Furthermore, this case highlights the possibility for warm autoantibodies to demonstrate Kidd antigen specificity. Though Kidd antigen variants are rare, antigen genotyping may be beneficial, particularly in the context of recent RBC transfusions, which typically preclude accurate serological phenotypic assessment.

Alloimmunization following antigen-negative red blood cell transfusion.

BACKGROUND: Red blood cell (RBC) alloimmunization can occur secondary to transfusion or pregnancy. It is observed most frequently among patients with hemoglobinopathies and myeloid neoplasms. Although previous antigen exposure is generally required for alloimmunization, some alloantibodies may develop naturally without prior exposure. Other alloantibodies may become evanescent, only to reemerge at a detectable titer following a stimulatory event. In a minute fraction of cases, 'non-naturally occurring' alloantibodies may appear without a known antigenic stimulus. METHODS AND MATERIALS: All testing (antibody detection tests and identification, antigen phenotyping, and crossmatching) was performed using the same method and reagents, but occurred at two hospitals within the Yale New Haven Hospital delivery network, and was performed by technologists utilizing different instruments and reagent lots. RESULTS: We present two cases of seemingly de novo alloimmunization (anti-E and anti-K), and one case of re-emergence of a known, previously evanescent alloantibody (anti-K) following transfusion of RBCs that were antigen-negative for the corresponding antibodies. CONCLUSION: While the exact mechanism underlying the development and/or re-emergence of RBC alloantibodies in the absence of antigenic stimulation remains unclear, these cases highlight this unusual phenomenon, underscoring the general immunogenicity, as well as the potential consequences, of RBC transfusion and reiterates the importance of concluding an alloantibody specificity, even in the absence of known transfusion of RBCs with a particular antigen.

Passive transfer of alloantibodies through breast milk as a mediator of hemolytic anemia.

BACKGROUND: Hemolytic disease of the fetus and newborn (HDFN) is characterized by destruction of fetal/neonatal red blood cells (RBCs) secondary to maternally derived antibodies, which are typically thought to be passively acquired via placental transfer. Few cases have examined the possibility of HDFN mediated by maternal antibodies passively transferred via breast milk. METHODS: We describe two cases of persistent HDFN in infants potentially mediated by passively acquired antibodies via maternal breast milk. We discuss supporting and refuting evidence that may account for this possibility and describe testing methodology illustrating how maternal alloantibodies can be detected in breast milk. RESULTS: In both cases, anti-D antibodies were detected in maternal breast milk. One patient experienced a significant decrease in anti-D plasma titer from 64 to 4 dilutions following 2 weeks of breastfeeding cessation. The other patient experienced a resolution of anemia without breastfeeding cessation. CONCLUSION: There is a paucity of data regarding the lifespan of passively acquired RBC antibodies in neonatal circulation, with significant variation noted between passively acquired IgG based on studies utilizing intravenous immunoglobulin compared to studies of maternally-acquired antiviral IgG antibodies. While our data do not definitively implicate passive transfer of alloantibodies in breast milk as a mediator of HDFN, they do illustrate the need for further investigation into the mechanisms and kinetics of passively acquired antibodies in neonatal circulation.

Therapeutic plasma exchange for peripheral neuropathy associated with trisulfated heparan disaccharide IgM antibodies: A case series of 17 patients.

BACKGROUND: Small fiber neuropathy (SFN) can be associated with autoantibodies, including those of IgM class with specificity for the trisulfated heparan disaccharide (TS-HDS) antigen. We hypothesized that, as an IgM autoantibody-mediated disorder, TS-HDS-associated SFN symptoms may be reduced with therapeutic plasma exchange (TPE). STUDY METHODS: This was an observational analysis of all patients referred for TPE from 2018 to 2020 following laboratory confirmation of SFN with TS-HDS autoantibodies; a loading course of 3 to 5 procedures over 2 weeks was completed, with some patients returning for monthly procedures. The following data were collected: demographics, symptoms and duration, TS-HDS levels, skin biopsy results, reported responses to TPE, and TPE-associated adverse events. RESULTS: Of the 17 subjects, 12 (71%) were female and the mean age was 57.5 years (range 27-94). The most common reported symptom was lower extremity paresthesia (88% of subjects). The mean number of TPE procedures completed per subject was 9 (range 3-18), with 71% (12/17) reporting symptomatic improvement or slowed disease progression. About 15% of procedures were associated with an adverse event, with vasovagal reactions being the most common; 53% of patients had at least one adverse event. CONCLUSIONS: Given a reported symptomatic response rate of more than 70%, TPE may be a treatment option for individuals with autoimmune-mediated SFN associated with increased titers of TS-HDS IgM autoantibodies. Since TPE-associated adverse events appear common in this population, close monitoring during procedures is warranted.

Passive anti-C acquired in the setting of Rh immune globulin administration following Rh mismatched apheresis platelet transfusion: A case series.

Rh immune globulin (RhIG) may be administered to Rh(D)-negative recipients of Rh(D)-positive platelet (PLT) transfusions to mitigate anti-D alloantibody formation. We report a series of seven patients in which anti-C was detected as a result of RhIG administered as immunoprophylaxis following Rh-mismatched apheresis PLT transfusion, persisting for a range of 27 to 167 days post-RhIG. The passively transferred anti-C antibodies created complexities for subsequent transfusion support. Based on these challenges, in combination with emerging evidence supporting an extremely low anti-D alloimmunization risk following Rh-mismatched apheresis PLTs, we have changed our practice and now limit RhIG immunoprophylaxis in this setting to women of reproductive age. In summary, the blood bank and apheresis communities should be aware that passive transfer of non-D antibodies is possible following RhIG administration. This phenomenon represents a compelling reason to consider the risk/benefit ratio of RhIG and to limit its use to situations in which it is clinically necessary.

State of the Evidence: Drug Removal via Apheresis.

Therapeutic apheresis refers to a diversity of procedures in which specific hematologic components (e.g., plasma, erythrocytes, leukocytes, etc.) with pathological associations are removed from circulation (with possible replacement) in order to treat a variety of disease processes. As pharmacologic agents also circulate with these components, their removal is sometimes incidental, or in the scenario of drug toxicity, a therapeutic goal. The corpus of published manuscripts on this subject has grown immensely over the past few decades; however, the breadth of diseases, methods, and drugs that co-exist in this space make it challenging to generate generalizable evidence regarding drug removal via apheresis. This review discusses factors worth considering when interpreting literature-reported data on drug removal by apheresis with examples from several notable studies and highlights topics in need of evidential improvement and growth as our palette of therapeutic agents continues to expand.

Incidental Discovery of a Patient with the Bombay Phenotype.

Bombay phenotype, an exceptionally rare blood type in individuals outside of Southeast Asia, occurs in approximately 1 in 1,000,000 individuals in Europe. This blood phenotype is characterized by the absence of the H antigen on red blood cells (RBCs) and in secretions. As the H antigen is the structure on which the ABO system is built, individuals lacking this antigen are unable to produce A or B antigens and appear as type O on routine ABO phenotyping. H deficiency does not cause ill effect; however, these individuals produce an anti-H alloantibody capable of causing severe acute hemolytic transfusion reactions when exposed to RBCs that express the H antigen. In this case study, we highlight the incidental discovery of a patient with Bombay phenotype in a North American hospital system, expected test results, the immunologic and genetic basis underlying the Bombay and para-Bombay phenotypes, and methods to ensure availability of compatible blood.

Warm autoantibodies mimicking alloantibodies: Three cases of autoantibodies with unusual antigenic specificity.

OBJECTIVES: We describe 3 cases of red blood cell (RBC) autoantibodies with unusual apparent antigenic specificity and discuss the testing methodology and implications of these findings. METHODS: All immunohematologic testing, including ABO and RhD typing, antibody detection and identification, RBC antigen phenotyping and genotyping, direct antiglobulin tests, and elution studies were performed using standardized and validated methods and reagents. RESULTS: Three patients were found to have autoantibodies, which were originally presumed to be alloantibodies. Case 1 was a 60-year-old man with autoanti-Jka following babesiosis; case 2 was a 79-year-old woman with an autoanti-f; and case 3 was a 28-year-old pregnant woman with an autoanti-S. Cases 1 and 2 required RBC transfusions, which were performed with Jka-negative and f-positive RBC units, respectively. No transfusion reactions were reported, and the hemoglobin responded appropriately in both cases. CONCLUSIONS: These 3 cases complement the minimal literature regarding warm autoantibodies with unusual antigenic specificity and their potential to mediate clinically significant hemolysis. There are only rare reports of warm autoantibodies with specificity for non-Rh antigens, and prior authors have suggested that autoantibodies with mimicking specificity are usually detected only serologically; in contrast, 2 of the 3 patients herein experienced autoimmune hemolytic anemia.

Pediatric Hemovigilance and Adverse Transfusion Reactions.

Some types of transfusion reactions occur more frequently in the pediatric than the adult population. Allergic reactions are the most common, followed by nonhemolytic transfusion reactions; male children seem most susceptible to such reactions. Platelets are often implicated and pulmonary reactions are understudied in children. Clinical sequelae in neonates, such as bronchopulmonary dysplasia/chronic lung disease and intraventricular hemorrhage, have received increasing attention in relation to transfusion. There is a need to better understand the pathophysiology of transfusion reactions in neonatal and pediatric populations so preventive strategies can be undertaken. There is also a need for robust hemovigilance systems.