RESUMEN
Aplastic anemia is a rare disease with a large differential diagnosis, including neoplastic origin as well as congenital bone marrow failure syndromes. Investigations must be quick and precise. Treatment depends on the patient's age and consists of immunosuppression treatment or allogeneic bone marrow transplantation. Because of the risk of progression to other hematological diseases, a close specialized follow-up is recommended.
L'anémie aplasique est une maladie rare avec un diagnostic différentiel large, comprenant des maladies d'origine néoplasique ainsi que les syndromes d'insuffisance médullaire congénitale. Les investigations doivent être rapides et précises. Le traitement dépend de l'âge du patient et consiste en une immunosuppression plus ou moins sévère ou une allogreffe de moelle osseuse. En raison du risque d'évolution vers d'autres maladies hématologiques, un suivi spécialisé rapproché est préconisé.
Asunto(s)
Anemia Aplásica , Humanos , Anemia Aplásica/diagnóstico , Anemia Aplásica/terapia , Diagnóstico Diferencial , Trasplante de Médula Ósea/métodos , Inmunosupresores/uso terapéuticoRESUMEN
During one of the worst global health crises, millions of people were vaccinated against SARS-CoV-2. In rare cases, new onset systemic inflammatory diseases were reported with temporal coincidence to the vaccination. We describe a case of severe Eosinophilic Granulomatosis with Polyangiitis (EGPA) in a young asthmatic woman, occurring after a second dose of the mRNA-1273 vaccine. She presented with multisystem EGPA with cardiac and central nervous system involvement, complicated by secondary immune thrombocytopenia (ITP). We review the reported cases of EGPA coinciding with SARS-CoV-2 mRNA vaccination. All potentially vaccine-related EGPA cases reported so far occurred within 14 days from immunization. EGPA is very rare with an incidence of 1:1,000,000 inhabitants, and the number of reported post-vaccination EGPA cases lies within the expected incidence rate for the period. While we cannot prove a causal relationship between the vaccine and EGPA onset, the temporal relationship with the vaccine immune stimulation is intriguing, in a disease occurring almost always in adults with asthma and/or chronic rhinosinusitis and driven by an aberrant Th2 lymphocyte activation with hypereosinophilia; nevertheless, cases of inflammatory diseases (IMIDs) emerging in the context of vaccination remain rare and the benefits of preventing severe COVID presentations with SARS-CoV-2 mRNA vaccines remain unquestionable.
RESUMEN
BACKGROUND: About 1%-5% of acquired haemophilia A cases affect mothers in the postpartum setting. AIMS: This study delineates the characteristics of this disease, specific to the postpartum setting, notably relapse in subsequent pregnancies. METHODS: Report of two cases and literature study (1946-2019), yielding 73 articles describing 174 cases (total 176 cases). RESULTS: Patients were aged 29.9 years (17-41) and 69% primigravidae. Diagnosis was made at a median of 60 days after delivery (range 0-308). Bleeding types were obstetrical (43.4%), cutaneous (41.3%), and muscular (36.7%). In >90% of the cases, FVIII at diagnosis was <1% (range 0%-8%). FVIII inhibitor was documented in 75.4% cases (median titre of 20 BU/ml, range 1-621). Haemostatic treatment was necessary in 57.1% using fresh frozen plasma (16%), factor concentrate (27.6%) and/or bypassing agents (37.4%). Immunosuppressive treatment was administered in 90.8%, mostly steroids (85.3%), alone or combined with immunosuppressants (27%). Rituximab was used mostly as a second line treatment. Only 24 patients (13.6%) had documented subsequent pregnancies and 6 (22.2%) suffered haemophilia recurrence during pregnancy. CONCLUSION: This study allows better definition of: (1) clinical and laboratory characteristics of postpartum acquired haemophilia, (2) response to therapy, and (3) the risk of relapse for subsequent pregnancies.
Asunto(s)
Hemofilia A , Hemostáticos , Factor VIII , Femenino , Hemofilia A/diagnóstico , Hemofilia A/tratamiento farmacológico , Hemofilia A/epidemiología , Humanos , Periodo Posparto , Embarazo , RecurrenciaAsunto(s)
Vasos Sanguíneos/metabolismo , Sobrecarga de Hierro/patología , Hierro/metabolismo , Metales Pesados/metabolismo , Anciano de 80 o más Años , Anemia Sideroblástica/etiología , Anemia Sideroblástica/patología , Anemia Sideroblástica/terapia , Arteriosclerosis/etiología , Arteriosclerosis/metabolismo , Arteriosclerosis/patología , Biopsia , Transfusión Sanguínea , Vasos Sanguíneos/patología , Médula Ósea/metabolismo , Médula Ósea/patología , Deferasirox/uso terapéutico , Femenino , Humanos , Sobrecarga de Hierro/diagnóstico , Sobrecarga de Hierro/tratamiento farmacológico , Sobrecarga de Hierro/etiología , Enfermedades Mielodisplásicas-Mieloproliferativas/complicaciones , Enfermedades Mielodisplásicas-Mieloproliferativas/patología , Enfermedades Mielodisplásicas-Mieloproliferativas/terapia , Trombocitosis/etiología , Trombocitosis/patología , Trombocitosis/terapia , Reacción a la Transfusión/complicaciones , Reacción a la Transfusión/tratamiento farmacológico , Reacción a la Transfusión/patología , Insuficiencia del TratamientoRESUMEN
This original report describes the management of a pregnant woman with congenital erythrocytosis (Chuvash polycythaemia) and reviews the scarce data available in the literature. Therapy consisted of low-dose aspirin and phlebotomies to maintain haematocrit <50% while monitoring iron stores to avoid severe deficiency detrimental to the foetus. Despite normal initial foetal growth, the pregnancy was complicated by preterm birth due to chorioamnionitis. The placenta showed no signs of thrombotic events. The published reports cover 13 pregnancies in 8 patients, showing 1 first-trimester miscarriage, 5 infants with intrauterine growth restriction and/or preterm birth and 1 maternal thrombotic event. These cases were managed with phlebotomies, low-dose aspirin and/or low-molecular-weight heparin, although inconsistently.
Asunto(s)
Policitemia/congénito , Adulto , Aspirina/uso terapéutico , Femenino , Ferritinas/análisis , Heparina de Bajo-Peso-Molecular/uso terapéutico , Homocigoto , Humanos , Hierro/administración & dosificación , Policitemia/diagnóstico , Policitemia/tratamiento farmacológico , Polimorfismo de Nucleótido Simple , Embarazo , Nacimiento Prematuro , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/genéticaRESUMEN
Improved treatments are needed for hemophilia A and B, bleeding disorders affecting 400 000 people worldwide. We investigated whether targeting protein S could promote hemostasis in hemophilia by rebalancing coagulation. Protein S (PS) is an anticoagulant acting as cofactor for activated protein C and tissue factor pathway inhibitor (TFPI). This dual role makes PS a key regulator of thrombin generation. Here, we report that targeting PS rebalances coagulation in hemophilia. PS gene targeting in hemophilic mice protected them against bleeding, especially when intra-articular. Mechanistically, these mice displayed increased thrombin generation, resistance to activated protein C and TFPI, and improved fibrin network. Blocking PS in plasma of hemophilia patients normalized in vitro thrombin generation. Both PS and TFPIα were detected in hemophilic mice joints. PS and TFPI expression was stronger in the joints of hemophilia A patients than in those of hemophilia B patients when receiving on-demand therapy, for example, during a bleeding episode. In contrast, PS and TFPI expression was decreased in hemophilia A patients receiving prophylaxis with coagulation factor concentrates, comparable to osteoarthritis patients. These results establish PS inhibition as both controller of coagulation and potential therapeutic target in hemophilia. The murine PS silencing RNA approach that we successfully used in hemophilic mice might constitute a new therapeutic concept for hemophilic patients.
Asunto(s)
Coagulación Sanguínea , Proteínas Portadoras , Hemofilia A , Hemorragia , Animales , Proteínas de Unión al Calcio , Proteínas Portadoras/antagonistas & inhibidores , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Fibrina/genética , Fibrina/metabolismo , Silenciador del Gen , Hemofilia A/sangre , Hemofilia A/genética , Hemofilia A/terapia , Hemorragia/genética , Hemorragia/metabolismo , Hemorragia/patología , Hemorragia/prevención & control , Humanos , Ratones , Ratones Noqueados , Trombina/genética , Trombina/metabolismoRESUMEN
The objective of this work was to develop and validate a set of clinical criteria for the classification of patients affected by periodic fevers. Patients with inherited periodic fevers (familial Mediterranean fever (FMF); mevalonate kinase deficiency (MKD); tumour necrosis factor receptor-associated periodic fever syndrome (TRAPS); cryopyrin-associated periodic syndromes (CAPS)) enrolled in the Eurofever Registry up until March 2013 were evaluated. Patients with periodic fever, aphthosis, pharyngitis and adenitis (PFAPA) syndrome were used as negative controls. For each genetic disease, patients were considered to be 'gold standard' on the basis of the presence of a confirmatory genetic analysis. Clinical criteria were formulated on the basis of univariate and multivariate analysis in an initial group of patients (training set) and validated in an independent set of patients (validation set). A total of 1215 consecutive patients with periodic fevers were identified, and 518 gold standard patients (291 FMF, 74 MKD, 86 TRAPS, 67 CAPS) and 199 patients with PFAPA as disease controls were evaluated. The univariate and multivariate analyses identified a number of clinical variables that correlated independently with each disease, and four provisional classification scores were created. Cut-off values of the classification scores were chosen using receiver operating characteristic curve analysis as those giving the highest sensitivity and specificity. The classification scores were then tested in an independent set of patients (validation set) with an area under the curve of 0.98 for FMF, 0.95 for TRAPS, 0.96 for MKD, and 0.99 for CAPS. In conclusion, evidence-based provisional clinical criteria with high sensitivity and specificity for the clinical classification of patients with inherited periodic fevers have been developed.