Asunto(s)
Proteínas de Neoplasias/antagonistas & inhibidores , Nivolumab , Neoplasias Pancreáticas , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Púrpura Trombocitopénica , Femenino , Humanos , Megacariocitos/metabolismo , Megacariocitos/patología , Persona de Mediana Edad , Nivolumab/administración & dosificación , Nivolumab/efectos adversos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Púrpura Trombocitopénica/inducido químicamente , Púrpura Trombocitopénica/metabolismo , Púrpura Trombocitopénica/patologíaRESUMEN
Association of pure red-cell aplasia with thymoma is well documented. However, acquired amegakaryocytic thrombocytopenia (AAMT) has been rarely associated with thymoma with only five reported cases in literature. We report a patient with thymoma complicated by pure red cell aplasia (PRCA) and AAMT who progressed to develop aplastic anemia (AA). The patient was refractory to 10-months of immunosuppressive therapy with cyclosporine, prednisone, and antithymocyte globulin. She was eventually treated with allogeneic stem cell transplantation (allo-SCT). On Day +323 the patient continues to be transfusion-independent. This case illustrates how in patients with thymoma and AAMT may herald development of AA. This is also the first report of a patient with AAMT progressing to thymoma-associated AA being successfully treated with allo-SCT. The successful outcome suggests allo-SCT as a feasible option similar to other AA patients.
Asunto(s)
Anemia Aplásica/terapia , Enfermedades de la Médula Ósea/terapia , Trasplante de Células Madre Hematopoyéticas , Púrpura Trombocitopénica/terapia , Aplasia Pura de Células Rojas/terapia , Timoma/terapia , Neoplasias del Timo/terapia , Anemia Aplásica/patología , Suero Antilinfocítico/administración & dosificación , Enfermedades de la Médula Ósea/patología , Ciclosporina/administración & dosificación , Femenino , Humanos , Terapia de Inmunosupresión , Persona de Mediana Edad , Prednisolona/administración & dosificación , Púrpura Trombocitopénica/patología , Aplasia Pura de Células Rojas/patología , Timoma/patología , Neoplasias del Timo/patologíaRESUMEN
Acquired pure red cell aplasia and acquired amegakaryocytic thrombocytopenic purpura are rare in children. Similarly, clonal expansion of T-cell large granular lymphocytes is infrequently seen in pediatrics. Lipopolysaccharide-responsive beige-like anchor (LRBA) protein deficiency is a recently described immunodeficiency syndrome that has been associated with inflammatory bowel disease and autoimmune phenomena such as Evans syndrome. Here, we describe a patient with LRBA deficiency who developed acquired pure red cell aplasia and acquired amegakaryocytic thrombocytopenic purpura associated with expansion of clonal T-cell large granular lymphocytes. This has not been described in the literature previously and adds to the knowledge on the spectrum of manifestations of LRBA deficiency.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/deficiencia , Aplasia Pura de Células Rojas , Linfocitos T , Adolescente , Enfermedades de la Médula Ósea/complicaciones , Enfermedades de la Médula Ósea/genética , Enfermedades de la Médula Ósea/metabolismo , Enfermedades de la Médula Ósea/patología , Humanos , Masculino , Púrpura Trombocitopénica/complicaciones , Púrpura Trombocitopénica/genética , Púrpura Trombocitopénica/metabolismo , Púrpura Trombocitopénica/patología , Aplasia Pura de Células Rojas/complicaciones , Aplasia Pura de Células Rojas/genética , Aplasia Pura de Células Rojas/metabolismo , Aplasia Pura de Células Rojas/patología , Linfocitos T/metabolismo , Linfocitos T/patologíaRESUMEN
Acquired amegakaryocytic thrombocytopenia (AAT), a rare entity characterized by severe thrombocytopenia and the absence of megakaryocytes in the bone marrow, may mimic or precede the diagnosis of aplastic anemia (AA). Here, we describe a patient who presented with apparent Epstein-Barr virus (EBV)-associated immune thrombocytopenia resistant to several lines of therapies, which was in fact a form of AAT with some features of AA. He eventually responded to therapy with eltrombopag, cyclosporine A (CSA), and antithymocyte globulin (ATG) and recovered completely. EBV infection is known to cause a variety of benign and malignant hematologic disorders, including bone marrow failure. However, to the best of our knowledge, this is the first case report of EBV-associated AAT. Treatment options for AAT are still not well defined, and even response to eltrombopag together with CSA and ATG does not always imply successful therapy. The natural history of EBV infection may well be sufficient to explain unexpected eventual recovery.
Asunto(s)
Anemia Aplásica/diagnóstico , Anemia Aplásica/etiología , Enfermedades de la Médula Ósea/etiología , Enfermedades de la Médula Ósea/patología , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/virología , Herpesvirus Humano 4 , Púrpura Trombocitopénica/etiología , Púrpura Trombocitopénica/patología , Adulto , Anemia Aplásica/metabolismo , Biomarcadores , Médula Ósea/patología , Enfermedades de la Médula Ósea/metabolismo , Progresión de la Enfermedad , Humanos , Inmunohistoquímica , Masculino , Púrpura Trombocitopénica/metabolismoRESUMEN
We report the first case of a patient with hepatitis C virus (HCV) infection and idiopathic thrombocytopenic purpura (ITP), who later developed acquired amegakaryocytic thrombocytopenia (AAMT), with autoantibodies to the thrombopoietin (TPO) receptor (c-Mpl). A 64-year-old woman, with chronic hepatitis C, developed severe thrombocytopenia and was diagnosed with ITP. She died of liver failure. Autopsy revealed cirrhosis and liver carcinoma. In the bone marrow, a marked reduction in the number of megakaryocytes was observed, while other cell lineages were preserved. Therefore, she was diagnosed with AAMT. Additionally, autoantibodies to c-Mpl were detected in her serum. Autoantibodies to c-Mpl are one of the causes of AAMT, acting through inhibition of TPO function, megakaryocytic maturation, and platelet formation. HCV infection induces several autoantibodies. HCV infection might also induce autoantibodies to c-Mpl, resulting in the development of AAMT. This mechanism may be one of the causes of thrombocytopenia in patients with HCV infection.
Asunto(s)
Autoanticuerpos/sangre , Enfermedades de la Médula Ósea/diagnóstico , Hepatitis C Crónica/inmunología , Fallo Hepático/sangre , Púrpura Trombocitopénica Idiopática/diagnóstico , Púrpura Trombocitopénica/diagnóstico , Autoanticuerpos/inmunología , Médula Ósea/patología , Células de la Médula Ósea/patología , Enfermedades de la Médula Ósea/sangre , Enfermedades de la Médula Ósea/inmunología , Enfermedades de la Médula Ósea/patología , Diagnóstico Diferencial , Resultado Fatal , Femenino , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/sangre , Hepatitis C Crónica/virología , Humanos , Hígado/inmunología , Hígado/patología , Fallo Hepático/etiología , Fallo Hepático/inmunología , Fallo Hepático/patología , Megacariocitos/patología , Persona de Mediana Edad , Púrpura Trombocitopénica/sangre , Púrpura Trombocitopénica/inmunología , Púrpura Trombocitopénica/patología , Púrpura Trombocitopénica Idiopática/sangre , Receptores de Trombopoyetina/inmunología , Trombopoyetina/metabolismoRESUMEN
Acquired amegakaryocytic thrombocytopenic purpura is a very rare condition characterized by severe thrombocytopenia linked to the reduction or disappearance of megakaryocytes in the bone marrow. It may be primary idiopathic or secondary to many pathological conditions including hematologic disorders. We report the case of a 24-year-old patient admitted for haemorrhagic syndrome caused by immunological thrombocytopenic purpura. The diagnosis was acquired amegakaryocytosis after the failure of corticotherapy and the performance of myelography. The patient was treated with ciclosporin with rapid progression to acute myeloblastic leukemia. The progression of acquired amegakaryocytosis to acute leukemia is reported but it is generally not so rapid and above all it is preceded by myelodysplastic syndrome or medullary aplasia. This study highlights the importance of a close follow-up of these pathologies with a benign-like appearance.
Asunto(s)
Leucemia Mieloide Aguda/diagnóstico , Megacariocitos/patología , Púrpura Trombocitopénica/diagnóstico , Ciclosporina/administración & dosificación , Progresión de la Enfermedad , Humanos , Inmunosupresores/administración & dosificación , Leucemia Mieloide Aguda/patología , Masculino , Mielografía/métodos , Púrpura Trombocitopénica/etiología , Púrpura Trombocitopénica/patología , Adulto JovenAsunto(s)
Carbamazepina/efectos adversos , Genotipo , Polimorfismo de Nucleótido Simple , Púrpura Trombocitopénica , Carbamazepina/administración & dosificación , Niño , Femenino , Humanos , Púrpura Trombocitopénica/sangre , Púrpura Trombocitopénica/inducido químicamente , Púrpura Trombocitopénica/genética , Púrpura Trombocitopénica/patologíaAsunto(s)
Plaquetas/patología , Proteínas Motoras Moleculares/genética , Mutación , Cadenas Pesadas de Miosina/genética , Púrpura Trombocitopénica , Receptores Fc/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Trombocitopenia , Trombopoyetina/administración & dosificación , Adulto , Femenino , Humanos , Púrpura Trombocitopénica/tratamiento farmacológico , Púrpura Trombocitopénica/genética , Púrpura Trombocitopénica/patología , Trombocitopenia/tratamiento farmacológico , Trombocitopenia/genética , Trombocitopenia/patologíaRESUMEN
Nucleoside reverse transcriptase inhibitors (NRTIs)/nucleotide reverse transcriptase inhibitors are key components of combination antiretroviral therapy for HIV infection. First-generation NRTIs are associated with mitochondrial toxicity in patients, mainly due to inhibition of human DNA polymerase γ (hDNA polγ) that manifests as adverse events such as lipodystrophy, lactic acidosis, myopathy, cardiomyopathy, or nephropathy in patients. In chronic nonclinical studies in rodents and nonrodents, eukaryotic (host) mitochondrial toxicity manifests as some drug-specific toxicities similar to human toxicity. BMS-986001, a novel thymidine analog with minimal hDNA polγ inhibition, has demonstrated antiretroviral activity in early clinical studies. The primary toxicity of BMS-986001 in rats and monkeys is bone marrow dyserythropoiesis with associated decreases in red blood cell mass. Additionally, at high doses, severe platelet reductions accompanied by cutaneous petechiae began during weeks 8 and 11 in 3 of 60 monkeys in chronic toxicity studies. In a 6-month study, platelet reductions required euthanasia of the 2 affected monkeys (300 mg/kg/d) at week 14, but with dose reduction (200 mg/kg/d) remaining monkeys had no platelet changes. One affected monkey (200 mg/kg/d) in a 9-month study completed dosing and its platelet counts recovered during a 1-month recovery. Formation of platelet-bound immunoglobulin in the presence of BMS-986001, together with rapid and complete platelet recovery in the absence of BMS-986001, suggested that platelet decreases in monkeys may be immune mediated. No findings indicative of mitochondrial toxicity were observed in rats or monkeys given BMS-986001, suggesting an improved safety profile compared to marketed NRTI or tenofovir disoproxil fumarate.
Asunto(s)
Anemia Macrocítica/inducido químicamente , Fármacos Anti-VIH/efectos adversos , Drogas en Investigación/efectos adversos , Púrpura Trombocitopénica/inducido químicamente , Inhibidores de la Transcriptasa Inversa/efectos adversos , Timidina/análogos & derivados , Anemia Macrocítica/sangre , Anemia Macrocítica/metabolismo , Anemia Macrocítica/patología , Animales , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/sangre , Fármacos Anti-VIH/metabolismo , Biotransformación , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Drogas en Investigación/administración & dosificación , Drogas en Investigación/metabolismo , Eritropoyesis/efectos de los fármacos , Femenino , VIH-1/efectos de los fármacos , VIH-1/crecimiento & desarrollo , Semivida , Macaca fascicularis , Masculino , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/patología , Púrpura Trombocitopénica/inmunología , Púrpura Trombocitopénica/metabolismo , Púrpura Trombocitopénica/patología , Distribución Aleatoria , Ratas Sprague-Dawley , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Inhibidores de la Transcriptasa Inversa/sangre , Inhibidores de la Transcriptasa Inversa/metabolismo , Análisis de Supervivencia , Timidina/administración & dosificación , Timidina/efectos adversos , Timidina/sangre , Timidina/metabolismo , Pruebas de Toxicidad Crónica , ToxicocinéticaRESUMEN
Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare, autosomal recessive disorder induced by mutations of the gene coding for thrombopoietin (TPO) receptor (c-MPL) despite high levels of serum TPO. Patients initially present with isolated thrombocytopenia that subsequently progresses into pancytopenia. Although the mechanisms leading to aplasia are unknown, the age of onset has been reported to depend on the severity of the c-MPL functional defect. The primary treatment for CAMT is bone marrow transplantation. This report describes a newborn girl who presented to us with symptoms of sepsis but septic profile came negative except thrombocytopenia. Bone marrow biopsy was done for thrombocytopenia which revealed amegakaryocytic thrombocytopenia. She was given prednisolone.
Asunto(s)
Mutación , Pancitopenia/patología , Receptores de Trombopoyetina/genética , Trombocitopenia/patología , Trombocitopenia/terapia , Antineoplásicos/uso terapéutico , Biopsia , Médula Ósea/patología , Trasplante de Médula Ósea , Síndromes Congénitos de Insuficiencia de la Médula Ósea , Femenino , Humanos , Recién Nacido , Pancitopenia/complicaciones , Pancitopenia/genética , Prednisolona/uso terapéutico , Púrpura Trombocitopénica/complicaciones , Púrpura Trombocitopénica/genética , Púrpura Trombocitopénica/patología , Sepsis/etiología , Trombocitopenia/genética , Resultado del TratamientoRESUMEN
La purpura trombocitopénica inmunitaria y las trombocitopenias secundarias representan condiciones patológicas graves cuyo tratamiento plantea diversos grados de dificultad. La aproximación terapéutica convencional ha sido la administración de esteroides, la esplenectomía y el uso de inmunoglobulina intravenosa u otros tipos de anticuerpos (e.g., anti-D). La mejor comprensión de la fisiología y fisiopatología de la trombopoyesis aunado a los avances en biología molecular ha permitido el desarrollo de una nueva aproximación terapéutica, la aplicación de las trombopoyetinas sintéticas o no inmunogénicas. Dentro de este grupo resaltan dos compuestos: el romiplostin (una proteína de fusión) y el eltrombopag (un compuesto sintético de bajo peso molecular). Ambas se encuentran disponibles comercialmente. Los estudios clínicos indican que estos medicamentos tienen un efecto satisfactorio en el tratamiento de las trombocitopenias, particularmente en los casos refractarios a los tratamientos convencionales.
Immune thrombocytopenic purpura and the secondary thrombocytopenias are conditions potentially severe with diverse degrees of treatment difficulties. Steroids administration, splenectomy and the use of intravenous immunoglobulin and other antibodies (e.g., anti-D) had been the conventional therapy. The better understanding of the thrombopoiesis physiology and physiopathology togetter with the biology advances have permitted the development of a new terapheutic approach: the use of synthetic or nonimmunogenic thrombopoietines. Among this group highlights composites: romiplostim (a fusion protein) and eltrombopag (a synthetic composite with low molecular wheigt). Both are already available and produce a satisfactory effect particularly in nonrespondent cases to the conventional treatment.
Asunto(s)
Humanos , Masculino , Adulto , Femenino , Anticuerpos/farmacología , Esteroides/administración & dosificación , Globulina Inmune rho(D)/administración & dosificación , Púrpura Trombocitopénica/patología , Púrpura Trombocitopénica/terapia , Trombopoyesis/fisiología , Trombopoyesis/inmunología , Vacunas Sintéticas/administración & dosificación , Anemia/terapia , Biología Molecular/métodos , Hematopoyesis/inmunología , Preparaciones Farmacéuticas , Recuento de Plaquetas/métodos , Desarrollo TecnológicoRESUMEN
Reactive thrombocytosis occurs in response to infection, trauma, or surgery. Splenectomy alone accounts for 19% of all possible causes of extreme thrombocytosis. We performed thrombocytapheresis in a young lady with chronic idiopathic thrombocytopenic purpura (ITP) who developed postsplenectomy reactive thrombocytosis. Her post splenectomy platelet count was 227 × 10(6)/ml which elevated to 1623 × 10(6)/ml on the 7th postoperative day. A single thrombocytapheresis procedure reduced her platelet to 403 × 10(6)/ml. She was discharged on the 10th postoperative day and then maintained a count of 204-238 × 10(6)/ml with aspirin. Thrombocytapheresis reduces the platelet count rapidly in thrombocytosis and prevents patients from having thrombotic events. However, such procedures should be performed very meticulously to ensure patient safety.
Asunto(s)
Plaquetoferesis , Complicaciones Posoperatorias/terapia , Púrpura Trombocitopénica/cirugía , Esplenectomía/efectos adversos , Trombocitosis/terapia , Adulto , Femenino , Humanos , Complicaciones Posoperatorias/etiología , Púrpura Trombocitopénica/patología , Trombocitosis/etiología , Factores de TiempoRESUMEN
Laboratory testing for immune-mediated thrombocytopenias involves identification and classification of antibodies present in patient sera or attached to patient platelets. This article summarizes the available types of platelet antibody testing and applications in disorders such as neonatal alloimmune thrombocytopenia, post-transfusion purpura, multiple platelet transfusion refractoriness, immune thrombocytopenia, and drug-induced thrombocytopenia.
Asunto(s)
Autoanticuerpos/aislamiento & purificación , Púrpura Trombocitopénica/diagnóstico , Trombocitopenia Neonatal Aloinmune/diagnóstico , Trombocitopenia/diagnóstico , Autoanticuerpos/sangre , Autoanticuerpos/clasificación , Plaquetas/inmunología , Plaquetas/patología , Humanos , Inmunoensayo , Recién Nacido , Transfusión de Plaquetas , Púrpura Trombocitopénica/inmunología , Púrpura Trombocitopénica/patología , Quinina/efectos adversos , Sulfonamidas/efectos adversos , Trombocitopenia/inducido químicamente , Trombocitopenia/inmunología , Trombocitopenia/patología , Trombocitopenia Neonatal Aloinmune/inmunología , Trombocitopenia Neonatal Aloinmune/patologíaRESUMEN
AIM: To perform a dynamic study of beta-endorphin, hypoxia-inducible factor-1alpha (HIF-1alpha), and cytokines in hematologic patients. SUBJECTS AND METHODS: Fifty-nine patients with different types of acute leukemia (AL), 30 with anaplastic anemia (AA), 24 with thrombocytopenic purpura, and 20 healthy volunteers were examined during their 40-day stay at 3200 m above sea level. beta-Endorphin and HIF-la were measured by a sandwich-type enzyme immunoassay using the Abcam antibodies. Cytokines (interleukin (IL)-2, IL-6, and tumor necrosis factor-alpha) were estimated by enzyme immunoassay applying the Pro Con kits (Saint Petersburg). RESULTS: Serum beta-endorphin concentrations were 1.5-2-fold above the normal values in the majority of patients with AL. The patients with initial leukocytosis at onset of disease were noted to have elevated white blood cell beta-endorphin concentrations up to 85.9 +/- 22.4 pg/ml; moreover, during chemotherapy this index increased about two times (170.74 +/- 33.8 pg/ml). There was a direct correlation between the concentrations of beta-endorphin and HIF-1alpha (r = 0.9) and an inverse correlation between the levels of IL-6 and beta-endorphin (r = -0.7). On ascending to 3200 m, under the conditions of hypoxic hypoxia the patients with AA or idiopathic thrombocytopenic purpura showed a considerable increase in serum beta-endorphin concentrations, mainly in the acute period of being at high altitudes. CONCLUSION: Stress factors (tumor, use of cytostatics, pain, anemia, hypoxia, high environment temperature) stimulate the elaboration of beta-endorphin, particularly in the white blood cells of patients with AL during chemotherapy. The highest elevation in the index was seen during acute adaptation to hypoxic hypoxia.
Asunto(s)
Anemia Aplásica/patología , Leucemia/patología , Púrpura Trombocitopénica/patología , betaendorfina/metabolismo , Enfermedad Aguda , Altitud , Antineoplásicos/uso terapéutico , Estudios de Casos y Controles , Humanos , Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Técnicas para Inmunoenzimas , Interleucina-2/metabolismo , Interleucina-6/metabolismo , Leucemia/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
We report a patient with a diagnosis of systemic lupus erythematosus who concurrently developed a syndrome of thrombotic microangiopathy that resembled thrombotic thrombocytopenic purpura. The patient underwent plasma exchange and immunosuppressive therapy for months before clinical improvement was finally achieved through bilateral nephrectomy. Ultimately, our patient died of disseminated aspergillosis from prolonged immunosuppression. We believe that recognition of bilateral nephrectomy as a potential treatment earlier in her course would have spared her this unfortunate demise. We hope that this review of current literature will help the reader to consider bilateral nephrectomy in patients with refractory systemic lupus erythematosus with clinical overlap of thrombotic microangiopathy resembling thrombotic thrombocytopenic purpura.
Asunto(s)
Nefritis Lúpica/cirugía , Nefrectomía , Púrpura Trombocitopénica/cirugía , Microangiopatías Trombóticas/cirugía , Aspergilosis/etiología , Biopsia , Diagnóstico Diferencial , Resultado Fatal , Femenino , Humanos , Inmunosupresores/uso terapéutico , Nefritis Lúpica/patología , Persona de Mediana Edad , Intercambio Plasmático , Complicaciones Posoperatorias , Púrpura Trombocitopénica/patología , Sepsis/etiología , Microangiopatías Trombóticas/patologíaRESUMEN
A 6-year-old girl, who had received corticosteroid and cyclosporine on the diagnosis of interstitial pneumonitis related to juvenile dermatomyositis, developed severe thrombocytopenia. Her thrombocytopenia was resistant to repeated intravenous immunoglobulin administration and methylprednisolone pulse therapy. After additional treatment with mycophenolate mofetil (MMF), instead of cyclosporine, the thrombocytopenia improved, facilitating a reduction in the dose of corticosteroid without exacerbation of the interstitial pneumonitis. We propose MMF as effective option in the treatment of immune thrombocytopenic purpura with autoimmune disease.
Asunto(s)
Dermatomiositis/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Ácido Micofenólico/análogos & derivados , Púrpura Trombocitopénica/tratamiento farmacológico , Niño , Ciclosporina/uso terapéutico , Dermatomiositis/complicaciones , Dermatomiositis/patología , Quimioterapia Combinada , Femenino , Glucocorticoides/uso terapéutico , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/patología , Metilprednisolona/uso terapéutico , Ácido Micofenólico/uso terapéutico , Quimioterapia por Pulso , Púrpura Trombocitopénica/complicaciones , Púrpura Trombocitopénica/patología , Insuficiencia del TratamientoRESUMEN
Seven patients with chronic refractory immune thrombocytopenic purpura (ITP) received adipose tissue-derived mesenchymal stem cells (AMSC) from haplo-identical family donors. The AMSC dose was 2.0×10(6)/kg. No side effects were noted after the AMSC infusions. Overall responses were reached in all patients and sustained response rate was 57.1% (4/7). The serum levels of transforming growth factor ß1 (TGF-ß1), interleukin (IL)-4, and IL-10 were significantly elevated, whereas those of interferon-γ (IFN-γ) and IL-2 were significantly decreased after AMSC administration, compared with those in the patients with active ITP. During follow-up, the cytokine profiles in patients maintaining sustained response remained stable compared with the post-treatment level, but IFN-γ and IL-2 levels were significantly increased, and those of TGF-ß1, IL-4, and IL-10 were significantly reduced again in relapsed patients. AMSC therapy seems to represent reasonable salvage treatment in severe, chronic refractory ITP by causing a shift in the Th1/Th2 cytokine balance to the same levels as normal controls.
Asunto(s)
Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/metabolismo , Púrpura Trombocitopénica/terapia , Adulto , Enfermedad Crónica/terapia , Femenino , Estudios de Seguimiento , Humanos , Interferón gamma/sangre , Interleucina-10/sangre , Interleucina-2/sangre , Interleucina-4/sangre , Masculino , Células Madre Mesenquimatosas/citología , Persona de Mediana Edad , Recuento de Plaquetas , Púrpura Trombocitopénica/sangre , Púrpura Trombocitopénica/inmunología , Púrpura Trombocitopénica/patología , Grasa Subcutánea Abdominal/citología , Grasa Subcutánea Abdominal/metabolismo , Grasa Subcutánea Abdominal/trasplante , Factor de Crecimiento Transformador beta1/sangre , Adulto JovenAsunto(s)
Crioglobulinemia/complicaciones , Mieloma Múltiple/complicaciones , Púrpura Trombocitopénica/etiología , Anciano , Crioglobulinemia/diagnóstico , Humanos , Masculino , Mieloma Múltiple/diagnóstico , Síndromes Paraneoplásicos/diagnóstico , Síndromes Paraneoplásicos/etiología , Púrpura Trombocitopénica/patologíaRESUMEN
PURPOSE OF REVIEW: Thrombotic microangiopathies (TMAs) manifest as a spectrum of related disorders in the form of thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). New data on both diseases support more and more the relatedness of the disorders and reveal related pathomechanisms, which, however, manifest in different organs. TTP develops primarily at neurological sites, and also in the kidney, and HUS is a kidney disease. In TTP thrombi formation occurs subsequently to the release of multimers of von Willebrand factor (vWF), and in HUS endothelial cell damage is considered the reason for complement and platelet activation leading to thrombus formation. RECENT FINDINGS: Genetic mutations are associated with both disorders: in TTP the ADAMTS13 gene, the vWF cleaving protease, is affected, and in HUS several complement genes are mutated. In addition autoimmune forms, with acquired, de-novo generated inhibitors in the form of autoantibodies exist for both disorders, affecting ADAMTS13 in TTP or the central complement inhibitor factor H in HUS. In HUS autoantibodies can develop in the context of a specific mostly homozygous chromosomal deletion that represents a new subform of the disease, which is termed DEAP-HUS (deficient for CFHR proteins and autoantibody positive HUS). SUMMARY: As the underlying disease mechanisms of TMA are now being better understood new options for a more precise diagnosis, improved therapy and prognosis for kidney transplantation become available for the benefit of patients. Here we summarize the recent developments in this rapidly progressing field.