RESUMEN
BACKGROUND: Allogeneic platelet (PLT) infusion is a strategy to raise Factor V (FV) levels in patients with congenital FV deficiency. However, since FV is labile in vitro, we hypothesized that FV activity could be low in PLT units. STUDY DESIGN AND METHODS: FV activity was tested using a prothrombin time-based platform in the supernatant and platelet lysate (PL) of apheresis PLT units (16 units stored in PLT additive solution with acetate and phosphate [PAS-C] and 10 units stored in plasma only), on post-collection days 3-6. Statistical analysis was performed using Student's t test (P < .05). RESULTS: FV activity was severely diminished in PAS-C PLTs (N = 16) supernatant (3.70% ± 1.02%) and PL (3.26% ± 1.02%). FV activity in plasma-only PLTs (N = 10) was lower in both supernatant (44.55% ± 6.46%) and lysate (39.67% ± 6.33%) relative to normal plasma levels, but both were significantly higher (P < .0001) compared to PAS-C PLTs. In a separate set of experiments, FV activity in PAS-C PLTs examined serially over storage time (N = 3 for these experiments) showed that FV levels were reduced by day 3 and not significantly different by day 5 of storage (Day 3 supernatant 5.03% ± 1.41%; Day 5 supernatant: 3.10% ± 0.57%; P = .2; Day 3 lysate: 3.89% ± 1.03%; Day 5 lysate: 2.61% ± 0.41%; P = .4). CONCLUSION: Plasma should be considered over PLTs as first-line therapy for non-complex FV deficiency-associated hemorrhage. If PLTs are considered for transfusion, plasma-only PLT units should be preferentially utilized, as PAS-C PLT have near-absent FV activity.
Asunto(s)
Plaquetas/química , Deficiencia del Factor V/terapia , Factor V/análisis , Transfusión de Plaquetas , Plaquetoferesis , Transfusión de Componentes Sanguíneos , Medios de Cultivo Condicionados/química , Gránulos Citoplasmáticos/química , Deficiencia del Factor V/sangre , Deficiencia del Factor V/complicaciones , Hemorragia/etiología , Hemorragia/prevención & control , Humanos , Plasma , Tiempo de ProtrombinaRESUMEN
BACKGROUND: People living with sickle cell disease (SCD) are prone to red blood cell (RBC) alloimmunization. We hypothesized that subjects with alloantibodies (responders) would have differences in circulating T-follicular helper (Tfh)-like cells compared to subjects without alloantibodies (non-responders). MATERIALS AND METHODS: Peripheral blood mononuclear cells were collected from 28 subjects, including those with SCD and controls. Circulating CD4 T-cell subsets were first evaluated at baseline. CD4 T-cell subsets were also evaluated after naïve CD4 T-cells were differentiated into Tfh-like cells following in vitro culture with CD3/CD28 beads, IL-7, IL-12, and Activin A. Transfusion and alloantibody histories were extracted from the electronic medical record. RESULTS: Non-responders had a lower percentage of CD45RA negative Tmemory cells than responders or controls (p<0.05). Notably, there were no differences in circulating Tfh-like cells between any group. However, naïve CD4 T-cells from subjects with SCD were more likely to express CXCR5 after in vitro culture than cells from controls. After culture, CXCR5 expressing cells from responders were more likely to express PD1 and ICOS (16.43 %, sd. 20.23) compared to non-responders (3.69 %, s.d. 3.09) or controls (2.78 %, s.d. 2.04). DISCUSSION: The tendency for naïve CD4 T-cells from responders to differentiate into Tfh-like cells after in vitro culture may suggest these cells are prepared to assist B-cells with antibody production regardless of antigen specificity. Further studies are needed, but it is possible that these results may explain why some responders form RBC alloantibodies with multiple specificities, in addition to RBC autoantibodies and HLA alloantibodies.
Asunto(s)
Anemia de Células Falciformes/inmunología , Transfusión de Eritrocitos/métodos , Subgrupos de Linfocitos T/inmunología , Medicina Transfusional/métodos , Adulto , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: Despite the clinical significance of red blood cell (RBC) alloantibodies, there are currently no laboratory tests available to predict which patients may be at risk of antibody formation after transfusion exposure. Given their phagocytic and inflammatory functions, we hypothesized that differences in circulating monocytes may play a role in alloimmunization. STUDY DESIGN AND METHODS: Forty-two adults with sickle cell disease (SCD) were recruited, with data extracted from the electronic medical record and peripheral blood analyzed by flow cytometry for total monocytes, monocyte subsets (CD14 high/CD16 low+ classical monocytes, CD14 high/CD16 high+ intermediate monocytes, and CD14 intermediate/CD16 high+ non-classical/inflammatory monocytes), and FcγR1 (CD64) expression. Thirteen "non-responder" patients (non-alloimmunized patients with documented RBC transfusion at the study institution) were compared to 20 alloimmunized "responder" patients, who had a total of 44 RBC alloantibodies identified. RESULTS: There were no significant differences in the percentages of total monocytes, monocyte subsets, or measured cytokines between non-responders and responders. However, non-responders had higher CD64 expression on classical monocytes (MFI mean 3424 ± standard deviation 1141) compared to responders (MFI mean 2285 ± 1501), p = 0.029, and on intermediate monocytes (MFI mean 3720 ± 1191) compared to responders (MFI mean 2497 ± 1640), p = 0.033. CONCLUSIONS: Monocytes and the inflammatory milieu increasingly are being appreciated to play a role in some complications of SCD. The differences in FcγR1 expression on monocyte subsets noted between responders and non-responders, which cannot be directly explained by the serum cytokines evaluated, warrant further investigation.
Asunto(s)
Anemia de Células Falciformes/inmunología , Eritrocitos/inmunología , Isoanticuerpos/inmunología , Monocitos/inmunología , Receptores de IgG/análisis , Adulto , Anciano , Anciano de 80 o más Años , Autoanticuerpos/sangre , Antígeno CD11b/análisis , Citocinas/sangre , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE OF REVIEW: The aim of this study was to summarize the basic epidemiology, pathophysiology and management of delayed serologic and delayed haemolytic transfusion reactions (DHTRs), as well as recent developments in our understanding of these adverse events. RECENT FINDINGS: Several studies have identified risk factors for DHTRs, including high alloantibody evanescence rates among both general patient groups and those with sickle cell disease (SCD). Antibody detection is also hampered by the phenomenon of transfusion record fragmentation. There have also been enhancements in understanding of what may contribute to the more severe, hyperhaemolytic nature of DHTRs in SCD, including data regarding 'suicidal red blood cell death' and immune dysregulation amongst transfusion recipients with SCD. With growing recognition and study of hyperhaemolytic DHTRs, there have been improvements in management strategies for this entity, including a multitude of reports on using novel immunosuppressive agents for preventing or treating such reactions. SUMMARY: Delayed serologic and haemolytic reactions remain important and highly relevant transfusion-associated adverse events. Future directions include further unravelling the basic mechanisms, which underlie DHTRs and developing evidence-based approaches for treating these reactions. Implementing practical preventive strategies is also a priority.
Asunto(s)
Anemia de Células Falciformes , Transfusión Sanguínea , Hemólisis , Inmunosupresores/uso terapéutico , Anemia de Células Falciformes/fisiopatología , Anemia de Células Falciformes/prevención & control , Anemia de Células Falciformes/terapia , HumanosAsunto(s)
Vacuna BNT162/uso terapéutico , Babesiosis/complicaciones , COVID-19/complicaciones , Leucemia Mieloide Aguda/complicaciones , Anciano de 80 o más Años , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Atovacuona/administración & dosificación , Azitromicina/administración & dosificación , Babesiosis/tratamiento farmacológico , Babesiosis/parasitología , Babesiosis/patología , COVID-19/patología , Fiebre/etiología , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Masculino , Parasitemia/etiología , Inducción de Remisión , SARS-CoV-2 , Esplenectomía , Tratamiento Farmacológico de COVID-19RESUMEN
Red blood cell (RBC) alloimmunization is a serious complication of transfusion or pregnancy. Despite the widespread use of Rh immune globulin to prevent pregnancy associated anti-D alloimmunization, its mechanism of action remains elusive. We have previously described a murine model in which immunoprophylaxis with polyclonal anti-KEL sera prevents alloimmunization in wild-type recipients transfused with transgenic murine RBCs expressing the human KEL glycoprotein. To investigate the mechanism of action, we have now evaluated the outcome of immunoprophylaxis treatment in mice lacking Fcγ receptors (FcγRs), complement (C3), both, or none. Whereas polyclonal anti-KEL sera completely prevented alloimmunization in wild-type and single-knockout (KO) mice lacking FcγRs or C3, double-KO mice lacking both FcγRs and C3 became alloimmunized despite immunoprophylaxis. Rapid clearance of essentially all transfused RBCs with detectable KEL glycoprotein antigen occurred within 24 hours in wild-type and single-KO recipients treated with immunoprophylaxis, with the transfused RBCs remaining in circulation having minimal KEL glycoprotein antigen detectable by flow cytometry or western blot. In contrast, transfused RBCs with the KEL glycoprotein antigen fully intact continued to circulate for days in double-KO mice despite treatment with immunoprophylaxis. Further, in vitro phagocytosis assays showed no consumption of opsonized murine RBCs by double-KO splenocytes. Taken in combination, our data suggest that modulation of the KEL antigen (and potentially RBC clearance) by redundant recipient pathways involving both FcγRs and C3 may be critical to the mechanism of action of polyclonal anti-KEL immunoprophylaxis. These findings could have implications for the development of immunoprophylaxis programs in humans.
Asunto(s)
Antígenos/metabolismo , Inmunización , Glicoproteínas de Membrana/inmunología , Metaloendopeptidasas/inmunología , Animales , Anticuerpos Antiidiotipos/metabolismo , Transfusión Sanguínea , Western Blotting , Complemento C3/metabolismo , Cruzamientos Genéticos , Eritrocitos/metabolismo , Humanos , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Opsoninas/metabolismo , Fagocitosis , Receptores Inmunológicos/metabolismo , Bazo/citologíaRESUMEN
In patients suspected to have myelodysplastic syndrome (MDS), especially in those patients without cytogenetic abnormalities or blast excess, accurate morphologic review by an expert hematopathologist and meticulous exclusion of other secondary causes of myelodysplasia are vital to establish the diagnosis. Errors in diagnosis can lead to dangerous consequences such as the administration of hypomethylating agents, lenalidomide, or even the use of intensive chemotherapy or allogeneic hematopoietic cell transplantation in patients who do not have an underlying MDS or even a malignant hematopoietic process. Additionally, beyond the possible harm and lack of efficacy of such therapies if the diagnosis of MDS is erroneous, the secondary myelodysplasia and resultant cytopenias are not likely to resolve unless the underlying etiology is identified and addressed. Discriminating a malignant process such as MDS from non-malignant secondary myelodysplasia can be quite challenging, and community hematologists/oncologists should consider referral to specialized physicians (both clinical experts and experienced hematopathologists) if there is any doubt regarding the diagnosis. In this article, we present a representative case series of patients from our own practice who posed diagnostic dilemmas and propose a systematic approach for assessment for secondary causes of myelodysplasia.
Asunto(s)
Neoplasias Hematológicas/diagnóstico , Síndromes Mielodisplásicos/diagnóstico , Adulto , Diagnóstico Diferencial , Femenino , Neoplasias Hematológicas/terapia , Humanos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/terapiaAsunto(s)
Basófilos/patología , Citometría de Flujo/métodos , Trastornos Leucocíticos/patología , Proteínas de Neoplasias/genética , Anciano , Basófilos/metabolismo , Humanos , Hibridación Fluorescente in Situ , Trastornos Leucocíticos/genética , Trastornos Leucocíticos/metabolismo , Masculino , Proteínas de Neoplasias/metabolismo , PronósticoAsunto(s)
Transfusión de Plaquetas , Rayos Ultravioleta , Plaquetas , Transfusión Sanguínea , Ficusina , HumanosRESUMEN
Identification of hemoglobinopathies in pediatric patients can be challenging and has important implications for the patient, as well as family members. Laboratory identification of uncommon hemoglobin (Hb) variants can pose a significant problem. Although many Hb variants can be largely identified using conventional electrophoresis and HPLC, confirmatory Hb DNA analysis may be necessary. This report provides an example of a pediatric patient with a complex heterozygous Hb by electrophoresis and HPLC, which necessitated identification by DNA analysis. Clinical and laboratory scenarios warranting Hb DNA analysis are additionally discussed.
Asunto(s)
Anemia/complicaciones , Hemoglobinopatías/diagnóstico , Hemoglobinas Anormales/análisis , Adolescente , Cromatografía Líquida de Alta Presión , Femenino , Pruebas Hematológicas , Hemoglobinopatías/etiología , Hemoglobinas Anormales/genética , Humanos , PronósticoAsunto(s)
Insuficiencia Suprarrenal , Hemorragia , Leucemia Mieloide Aguda , Insuficiencia Suprarrenal/diagnóstico por imagen , Insuficiencia Suprarrenal/metabolismo , Insuficiencia Suprarrenal/patología , Anciano , Femenino , Hemorragia/diagnóstico por imagen , Hemorragia/metabolismo , Hemorragia/patología , Humanos , Leucemia Mieloide Aguda/diagnóstico por imagen , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologíaRESUMEN
The proliferation of new molecular technologies in recent years has greatly advanced our knowledge of the genetics that underlie hematologic cancers. Particularly, with the advent and wide-implementation of next-generation sequencing (NGS), a host of somatic (and some germline) gene mutations have been identified as significant in the classification, prognostication, and treatment of the spectrum of myeloid neoplasms. These driver and disease modifier mutations now play a prominent role in the updated international diagnostic guidelines of acute myeloid leukemia (AML), myelodysplastic syndromes/neoplasms (MDS), and myeloproliferative neoplasms (MPN). As high-throughput technologies such as NGS increasingly become standard in the genetic evaluation of myeloid disorders, it is critical that clinicians understand the clinical relevance of these mutations in order to further personalize patient care. In this review we discuss some of the most essential somatic and cytogenetic findings.
Asunto(s)
Neoplasias Hematológicas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Trastornos Mieloproliferativos , Humanos , Trastornos Mieloproliferativos/diagnóstico , Trastornos Mieloproliferativos/genética , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Mutación , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/genéticaRESUMEN
Sequencing technology, particularly next-generation sequencing, has highlighted the importance of gene mutations in myelodysplastic syndromes (MDSs). Mutations affecting DNA methylation, chromatin modification, RNA splicing, cohesin complex, and other pathways are present in most MDS cases and often have prognostic and clinical implications. Updated international diagnostic guidelines as well as the new International Prognostic Scoring System-Molecular incorporate molecular data into the diagnosis and prognostication of MDS. With whole-genome sequencing predicted to become the future standard of genetic evaluation, it is likely that MDS diagnosis and management will become increasingly personalized based on an individual's clinical and genomic profile.
Asunto(s)
Metilación de ADN , Síndromes Mielodisplásicos , Humanos , Mutación , Pronóstico , Empalme del ARN , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/genéticaRESUMEN
The genetic underpinnings of myeloid neoplasms are becoming increasingly well understood. The accessibility to sequencing technology, in particular next-generation sequencing (NGS), has highlighted the importance of gene mutations in myelodysplastic syndromes (MDS) in conjunction with traditional cytogenetics. With the relatively recent influx of molecular information to complement known cytogenetic abnormalities, the diagnosis, classification, and prognosis of MDS and acute myeloid leukemia (AML) have been increasingly refined, which has also led to therapeutic advancements. It has been shown that TP53 mutations have a significant impact in cases of MDS, as well as AML, and have led to TP53-defined myeloid disease. TP53 mutations are also now incorporated into prognostic scoring systems, as patients have been shown to have aggressive disease and poor outcomes. With the increased understanding of the importance of TP53 disruption in myeloid neoplasia, it is likely that the critical role of TP53 will continue to be highlighted by an individual's disease classification and personalized therapeutic management.
Asunto(s)
Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Humanos , Mutación , Aberraciones Cromosómicas , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Pronóstico , Proteína p53 Supresora de Tumor/genéticaRESUMEN
CONTEXT.: The World Health Organization Classification of Tumours: Female Genital Tract Tumors, 5th edition, published in September 2020, comes 6 years after the 4th edition, and reflects the monumental leaps made in knowledge about the biology of gynecological tumors. Major changes include revised criteria for the assignment of the site of origin of ovarian and fallopian tube tumors, a revision in the classification of squamous and glandular lesions of the lower genital tract based on human papillomavirus association, and an entire chapter devoted to genetic tumor syndromes. This article highlights the changes in the 5th edition relative to the 4th edition, with a focus on areas of value to routine clinical practice. OBJECTIVE.: To provide a comprehensive update on the World Health Organization classification of gynecological tumors, highlighting in particular updated diagnostic criteria and terminology. DATA SOURCES.: The 4th and 5th editions of the World Health Organization Classification of Tumours. CONCLUSIONS.: The World Health Organization has made several changes in the 5th edition of the update on female genital tumors. Awareness of the changes is needed for pathologists' translation into contemporary practice.
Asunto(s)
Neoplasias de los Genitales Femeninos , Femenino , Humanos , Neoplasias de los Genitales Femeninos/diagnóstico , Organización Mundial de la Salud , LibrosRESUMEN
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.