RESUMEN
Hyperviscosity syndrome (HVS) is defined as the symptomatic presentation of increased blood thickness due to various clinical conditions such as hypergammaglobulinemia. HVS secondary to immunoglobulin (Ig)A multiple myeloma has been infrequently reported. Although the efficiency of IgM or IgG removal by therapeutic plasma exchange (TPE) is well described, the efficiency of IgA removal by TPE is not as well known. Here, we describe a case of HVS due to IgA myeloma in a patient who received 2 TPE treatments, with subsequent symptomatic improvement as well as decrease in IgA and viscosity levels.
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INTRODUCTION: Apheresis practices in the United States (US) have not been comprehensively characterized to date. This study aimed to address this gap by evaluating apheresis therapy through a national survey. METHODS: A multi-institutional survey was conducted between April and July 2023. The survey, comprising 54 questions, focused on institutional demographics, procedures, equipment, staffing, training, and impacts of the Coronavirus Disease 2019 (COVID-19) pandemic. Responses from 22 institutions, primarily academic medical centers, were analyzed. RESULTS: Therapeutic plasma exchange (TPE) was the most common procedure, followed by hematopoietic progenitor cell collection (HPC-A) and red blood cell exchange (RCE). CAR-T cell collections were widespread, with some institutions supporting over 30 protocols concurrently. Most sites used the Spectra Optia Apheresis System, were managed by a transfusion medicine service, and employed internal apheresis providers. Insufficient staffing levels, exacerbated by the COVID-19 pandemic, were common and most often addressed using overtime. DISCUSSION: The survey highlighted the ubiquity of TPE, expanding cellular collections and staffing challenges. The role of apheresis in supporting cellular therapy, particularly in newly developing cell and gene therapies and clinical trials, was evident. Staffing issues during the pandemic emphasized the need for innovative recruitment strategies. CONCLUSION: This nationwide survey provides the most comprehensive analysis to date of apheresis practices in large US academic centers.
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Eliminación de Componentes Sanguíneos , COVID-19 , Intercambio Plasmático , Humanos , Estados Unidos , Eliminación de Componentes Sanguíneos/estadística & datos numéricos , Eliminación de Componentes Sanguíneos/métodos , COVID-19/terapia , COVID-19/epidemiología , Intercambio Plasmático/métodos , Intercambio Plasmático/estadística & datos numéricos , Encuestas y Cuestionarios , SARS-CoV-2 , PandemiasRESUMEN
ABSTRACT: While awaiting confirmatory results, empiric therapy for patients suspected to have immune thrombotic thrombocytopenic purpura (iTTP) provides benefits and also accrues risks and costs. Rapid assays for ADAMTS13 may be able to avoid the cost and risk exposure associated with empiric treatment. We conducted, to our knowledge, the first cost-effectiveness evaluation of testing strategies with rapid vs traditional ADAMTS13 assays in patients with intermediate- to high-risk PLASMIC scores, with and without caplacizumab use. We built a Markov cohort simulation with 4 clinical base-case analyses: (1) intermediate-risk PLASMIC score with caplacizumab; (2) intermediate-risk PLASMIC score without caplacizumab; (3) high-risk PLASMIC score with caplacizumab; and (4) high-risk PLASMIC score without caplacizumab. Each of these evaluated 3 testing strategies: (1) rapid assay (<1-hour turnaround); (2) in-house fluorescence resonance energy transfer (FRET)-based assay (24-hour turnaround); and (3) send-out FRET-based assay (72-hour turnaround). The primary outcome was the incremental net monetary benefit reported over a 3-day time horizon and across accepted willingness-to-pay thresholds in US dollars per quality-adjusted life-year (QALY). While accruing the same amount of QALYs, the rapid assay strategy saved up to $46 820 (95% CI, $41 961-$52 486) per patient tested. No parameter variation changed the outcome. In probabilistic sensitivity analyses, the rapid assay strategy was favored in 100% (3 base cases and scenario analyses) and 99% (1 base-case and scenario analysis) across 100 000 Monte Carlo iterations within each. Rapid ADAMTS13 testing for patients with intermediate- or high-risk PLASMIC scores yields significant per patient cost savings, achieved by reducing the costs associated with unnecessary therapeutic plasma exchange and caplacizumab therapy in patients without iTTP.
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Proteína ADAMTS13 , Análisis Costo-Beneficio , Púrpura Trombocitopénica Trombótica , Anticuerpos de Dominio Único , Humanos , Proteína ADAMTS13/sangre , Púrpura Trombocitopénica Trombótica/diagnóstico , Púrpura Trombocitopénica Trombótica/tratamiento farmacológico , Anticuerpos de Dominio Único/uso terapéutico , Cadenas de MarkovRESUMEN
The current recommended testing algorithm for assessing the alloimmunized pregnancy utilized by many obstetricians in the United States (US) fails to consider the most recent evidence, placing fetuses, and mothers at unnecessary risk of poor outcome or death. This narrative review of the current landscape of fetal red blood cell (RBC) antigen testing evaluates the history of hemolytic disease of the fetus and newborn (HDFN) and how its discovery has continued to influence practices in the US today. We compare current US-based HDFN practice guidelines with those in Europe. We also provide transfusion medicine and hematology perspectives and recommendations addressing the limitations of US practice, particularly regarding paternal RBC antigen testing, and discuss the most valuable alternatives based on decades of data and evidence-based recommendations from Europe.
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Eritroblastosis Fetal , Guías de Práctica Clínica como Asunto , Femenino , Humanos , Recién Nacido , Embarazo , Eritroblastosis Fetal/diagnóstico , Eritroblastosis Fetal/sangre , Eritroblastosis Fetal/prevención & control , Europa (Continente) , Isoanticuerpos/sangre , Isoanticuerpos/inmunología , Medición de Riesgo/métodos , Estados UnidosRESUMEN
The thrombotic risk with haemoglobin C trait (HbAC) or haemoglobin C disease (HbCC) is unclear. However, individuals with HbCC have demonstrated chronic haemolysis, higher blood viscosity and altered rheology when compared to individuals with wild-type haemoglobin (HbAA). These physiological alterations may theoretically translate to increased risk of thrombosis; therefore, a systematic literature review was performed to investigate the possible association between HbAC and/or HbCC and thrombosis. Twenty-two studies met inclusion criteria representing 782 individuals with HbAC (n = 694) or HbCC (n = 88). Fifteen studies described the presence/absence of venous thromboembolism (VTE) in patients with HbAC (n = 685) or HbCC (n = 79), while seven studies described patients with HbAC (n = 9) or HbCC (n = 9) and arterial thrombosis. Most (n = 20) studies were case reports or case series; however, two studies suggested a potential increased VTE risk with HbAC compared to HbAA in (i) all patients (OR 2.2, 95% CI: 0.9-5.5) and in (ii) pregnant individuals (RR 3.7, 95% CI 0.9-16). This review is the largest assessment of patients with HbC trait or disease and thrombosis to date; despite its limitations, the findings suggest HbC may be a predisposing risk factor to thrombosis. Prospective cohort studies are warranted to definitively elucidate the risk of thrombosis in this population.
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Enfermedad de la Hemoglobina C , Hemoglobinopatías , Trombosis , Tromboembolia Venosa , Embarazo , Femenino , Humanos , Hemoglobina C , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología , Estudios Prospectivos , Trombosis/etiología , Factores de RiesgoRESUMEN
The Heidenhain variant of Creutzfeld-Jakob disease (CJD) is a rare form that initially presents with visual disturbances. In early stages, the presentation can mimic neuromyelitis optica spectrum disorders (NMOSD) and lead to unnecessary treatment modalities. Herein, we describe a case of a 66-year-old man who presented with bilateral vision loss and retro-orbital discomfort. In addition to immunosuppressive therapy, he received 4 rounds of therapeutic plasma exchange after his preliminary diagnosis of NMOSD. We were surprised to note that his condition did not show improvement but deteriorated, with severe neurocognitive symptoms. Eventually, CJD was suspected, and real-time quaking-induced conversion (RT-QuIC) was performed. By the time the diagnosis of Heidenhain variant of CJD was confirmed, the patient was discharged to hospice care and died shortly after.
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Síndrome de Creutzfeldt-Jakob , Neuromielitis Óptica , Humanos , Síndrome de Creutzfeldt-Jakob/diagnóstico , Neuromielitis Óptica/diagnóstico , Masculino , Anciano , Diagnóstico Diferencial , Resultado FatalRESUMEN
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.
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Anemia Hemolítica , Eritroblastosis Fetal , Recién Nacido , Humanos , Femenino , Embarazo , Isoanticuerpos , Leche Humana , Placenta , Inmunoglobulina GRESUMEN
Anti-glomerular basement membrane (anti-GBM) disease (formerly known as Goodpasture's syndrome) is a rare autoinflammatory condition that affects the renal and/or pulmonary capillaries. The standard therapeutic regimen for anti-GBM disease involves therapeutic plasma exchange (TPE), cyclophosphamide, and corticosteroids to rapidly remove and inhibit autoantibody production and reduce organ inflammation. Herein we report an 82-year-old female who developed anti-GBM disease but expired despite therapy, secondary to multi-organ failure in the setting of disseminated adenovirus disease. We discuss the utility and potential adverse effect of daily TPE for a protracted course (ie, 10-14 days), the recommended TPE intensity in the 2023 American Society for Apheresis guidelines, updated from every-other-day TPE in the 2019 guidelines, despite no new data. We also highlight the potential for unusual infections to occur in these patients due to the profound immunosuppression, and discuss the importance of balancing immunosuppression to treat the disease with close surveillance of any potential opportunistic infections.
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Infecciones por Adenoviridae , Enfermedad por Anticuerpos Antimembrana Basal Glomerular , Femenino , Humanos , Anciano de 80 o más Años , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/terapia , Intercambio Plasmático , Autoanticuerpos , Inmunosupresores/efectos adversos , Infecciones por Adenoviridae/complicaciones , Infecciones por Adenoviridae/tratamiento farmacológicoRESUMEN
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.
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Anemia Hemolítica Autoinmune , Autoanticuerpos , Masculino , Femenino , Embarazo , Humanos , Anciano , Persona de Mediana Edad , Adulto , Isoanticuerpos , Epítopos , Eritrocitos , Anemia Hemolítica Autoinmune/diagnósticoAsunto(s)
Anemia Hemolítica Autoinmune , Enfermedades Hematológicas , Recién Nacido , Humanos , Autoanticuerpos , Hemólisis , FetoAsunto(s)
Servicios de Laboratorio Clínico , Medicina Transfusional , Embarazo , Femenino , Humanos , Laboratorios Clínicos , IsoanticuerposRESUMEN
Guillain-Barré syndrome (GBS) is an immune-mediated polyradiculoneuropathy and the most common cause of acute flaccid paralysis worldwide. GBS classically presents with acute, progressive, ascending weakness, reduced to absent reflexes, and albuminocytological dissociation on cerebrospinal fluid (CSF) analysis. Botulism is a neurotoxin-mediated acute descending flaccid paralysis with cranial nerve palsies and dysautonomia. Botulism in adults is caused by ingestion/inhalation of botulinum toxin or wound infection with Clostridium botulinum. Both GBS and botulism can rapidly precipitate respiratory failure; thus, prompt diagnosis and treatment are crucial to mitigate poor outcomes. Herein, we describe a case of botulism initially diagnosed as GBS given classic laboratory features, and describe the importance of careful consideration of the most appropriate therapeutic modalities in cases of acute flaccid paralysis, particularly regarding empiric administration of botulinum antitoxin and use of intravenous immune globulin in lieu of plasma exchange for potential GBS to prevent removal of antitoxin.
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Botulismo , Síndrome de Guillain-Barré , Adulto , Humanos , Botulismo/diagnóstico , Botulismo/terapia , Botulismo/etiología , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/terapia , Síndrome de Guillain-Barré/complicaciones , Intercambio Plasmático/efectos adversos , Parálisis/complicaciones , Parálisis/terapiaRESUMEN
Next-generation sequencing (NGS) is used to monitor genetically measurable residual disease (gMRD) following allogeneic stem cell transplantation (aSCT). It is unknown whether an upper limit of chimerism exists such that gMRD NGS testing can be safely forgone. We reviewed 61 patients with acute myeloid leukemia and 24 patients with myelodysplastic syndrome who had at least 1 NGS panel before and after aSCT between 2016 and 2020. Donor chimerism was quantified. Logistic regression characterized which factors predicted gMRD. Receiver operating characteristic (ROC) curves were used to determine the optimal chimerism threshold for which gMRD would not be detected. Data from an additional 22 patients with follow-up NGS testing in 2022 were also analyzed to validate our proposed threshold. A: s expected, donor chimerism was a significant predictor of gMRD (odds ratio, .38; 95% confidence interval, .10 to .62; P = .02). Age, sex, conditioning regimen, presence of a related donor, and diagnosis were not associated with gMRD. A chimerism threshold of 92.5% optimized sensitivity (97.7%) and specificity (95.4%) such that values >92.5% strongly predicted the absence of gMRD (area under the ROC curve [AUC], .986). The validation cohort demonstrated similarly strong predictive capability (AUC, .974) with appropriate sensitivity (100%) and specificity (90.9%). NGS monitoring of gMRD is redundant at chimerism values greater than a more conservative threshold of 92.5% after aSCT.
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Trasplante de Células Madre Hematopoyéticas , Trastornos Mieloproliferativos , Humanos , Quimerismo , Trasplante Homólogo , Neoplasia Residual/diagnóstico , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
Hyperhaemolysis syndrome (HHS), a severe form of delayed haemolytic transfusion reaction most commonly described in patients with sickle cell disease (SCD), involves destruction of both donor and recipient red blood cells (RBCs). As the epidemiology and underlying pathophysiology have yet to be definitively elucidated, recognition can be challenging. We systematically reviewed PubMed and EMBASE to identify all cases of post-transfusion hyperhaemolysis and characterized the epidemiological, clinical and immunohaematological characteristics and treatments of HHS. We identified 51 patients (33 females and 18 males), including 31 patients with SCD (HbSS, HbSC and HbS/ß-thalassaemia). The median haemoglobin nadir (3.9 g/dL) occurred a median of 10 days post-transfusion. 32.6% and 45.7% of patients had a negative indirect anti-globulin test and a negative direct anti-globulin test, respectively. The most common therapies included corticosteroids and intravenous immune globulin. 66.0% of patients received ≥1 supportive transfusion, which was associated with a longer median hospital stay/time to recovery (23 days vs. 15 days; p = 0.015) compared to no supportive transfusion. These findings illustrate that HHS that often results in marked anaemia 10 days post-transfusion is not restricted to patients with haemoglobinopathies, and additional transfused RBCs may be associated with a longer time-to-recovery.
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Anemia de Células Falciformes , Enfermedad de la Hemoglobina SC , Reacción a la Transfusión , Masculino , Femenino , Humanos , Reacción a la Transfusión/complicaciones , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/epidemiología , Anemia de Células Falciformes/terapia , Transfusión Sanguínea/métodos , Eritrocitos , Enfermedad de la Hemoglobina SC/complicaciones , SíndromeRESUMEN
OBJECTIVES: Clinical experts recommend against testing for lupus anticoagulant (LAC) during anticoagulation. METHODS: We quantitated the risk of a single-positive dilute Russell viper venom time (dRVVT) result or partial thromboplastin time-based phospholipid neutralization (PN) result on anticoagulation. RESULTS: Any anticoagulation led to a fourfold greater likelihood of single-positive results, primarily by rivaroxaban (odds ratio [OR]â =â 8.6) and warfarin (ORâ =â 6.6), resulting in a positive dRVVT test with a normal PN test. Heparin and apixaban were twofold more likely to show single-positive results, but enoxaparin did not show significant single positivity. CONCLUSIONS: Our results quantitatively support experts' avoidance of LAC testing during anticoagulation.