RESUMEN
Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy, in which a severe deficiency of von Willebrand factor lyase results in thrombocytopenic clots that block blood vessels and eventually lead to terminal organ failure. Therapeutic plasma exchange is the cornerstone of TTP treatment which can greatly improves the survival rate of the patients. With the further exploration to the pathophysiological mechanism of TTP, other alternative therapies, new immunosuppressive agents, targeted antagonists, gene therapy and other emerging means gradually emerge, which are expected to further reduce the mortality and recurrence rate of the patients. In this review, the new developments in TTP treatment were summarized briefly.
Asunto(s)
Púrpura Trombocitopénica Trombótica , Proteína ADAMTS13 , Humanos , Inmunosupresores , Intercambio Plasmático , Púrpura Trombocitopénica Trombótica/terapia , Factor de von WillebrandRESUMEN
Thrombotic thrombocytopenic purpura (TTP), a complex thrombotic microangiopathy, remains an evolving enigma. A 49-year-old African-American woman presented with acute left hemiplegia, an ischemic cerebrovascular accident involving the right middle cerebral artery. Sequential appearance of thrombocytopenia and evidence of microangiopathic haemolysis led to the diagnosis of acquired idiopathic autoimmune TTP. This was managed with plasma exchange (PEX) and steroids. Early haematologic relapse within a month was managed with the addition of rituximab attaining sustained remission. The patient presented 3 years later with acute confusion and expressive aphasia due to multiple infarcts involving the left parieto-occipital cortex. Transoesophageal echocardiography demonstrated a pedunculated 6âmm mitral valvular mass consistent with a papillary fibroelastoma. Anticoagulation was instituted and the patient was continued on therapeutic oral warfarin. A haematologic relapse of TTP eventually emerged and was managed with PEX, steroids and rituximab. This vignette demonstrates several dilemmas in the clinical presentation, diagnosis and management of TTP in current day practice. Rituximab has adjuvant benefits to PEX and is being investigated as potential first-line therapy. Monitoring ADAMTS13 activity and inhibitor titre, as in our case, prove to have prognostic significance. Cardiac fibroelastomas are rare benign cardiac tumours usually arising from valvular endocardium with thromboembolic potential. One of the proposed mechanisms of origin of these masses is organizing thrombi in the setting of endocardial injury and inflammation questioning a possible link to thrombotic microangiopathy. To the best of our knowledge, this is the first report of this unique coexistence.
Asunto(s)
Fibroma/patología , Neoplasias Cardíacas/patología , Hemiplejía/patología , Válvula Mitral/patología , Púrpura Trombocitopénica Trombótica/patología , Proteínas ADAM/sangre , Proteína ADAMTS13 , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Anticoagulantes/uso terapéutico , Femenino , Fibroma/complicaciones , Fibroma/terapia , Neoplasias Cardíacas/complicaciones , Neoplasias Cardíacas/terapia , Hemiplejía/complicaciones , Hemiplejía/terapia , Humanos , Persona de Mediana Edad , Válvula Mitral/efectos de los fármacos , Intercambio Plasmático , Púrpura Trombocitopénica Trombótica/complicaciones , Púrpura Trombocitopénica Trombótica/terapia , Rituximab , Esteroides/uso terapéutico , Warfarina/uso terapéuticoRESUMEN
These case reports demonstrated the diagnostic dilemma encountered in patients with systemic lupus erythematosus and thrombotic thrombocytopenic purpura particularly in settings with limited diagnostic facilities and laboratory support. The similarities in the diagnostic criteria for both conditions make clear distinction as well as management decisions difficult. We present the difficulties encountered with both the diagnosis and the management of these two patients that were managed in our facility.
Asunto(s)
Lupus Eritematoso Sistémico/complicaciones , Intercambio Plasmático/métodos , Trastornos Puerperales/terapia , Púrpura Trombocitopénica Trombótica/etiología , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia , Adulto , Automatización , Terapia Combinada , Países en Desarrollo , Resultado Fatal , Femenino , Filtración , Humanos , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Nefritis Lúpica/inducido químicamente , Nefritis Lúpica/tratamiento farmacológico , Nefritis Lúpica/etiología , Nefritis Lúpica/terapia , Membranas Artificiales , Nigeria , Fitoterapia/efectos adversos , Intercambio Plasmático/economía , Intercambio Plasmático/instrumentación , Transfusión de Plaquetas/efectos adversos , Embarazo , Complicaciones del Embarazo/tratamiento farmacológico , Complicaciones del Embarazo/inmunología , Trastornos Puerperales/inmunología , Púrpura Trombocitopénica Trombótica/tratamiento farmacológico , Púrpura Trombocitopénica Trombótica/terapia , Adulto JovenAsunto(s)
Echinacea , Extractos Vegetales/efectos adversos , Púrpura Trombocitopénica Trombótica/inducido químicamente , Adulto , Antiinflamatorios no Esteroideos/administración & dosificación , Antineoplásicos Fitogénicos/administración & dosificación , Aspirina/administración & dosificación , Transfusión de Componentes Sanguíneos , Glucocorticoides/administración & dosificación , Humanos , Inmunoglobulinas Intravenosas/administración & dosificación , Factores Inmunológicos , Masculino , Extractos Vegetales/administración & dosificación , Plasma , Plasmaféresis , Prednisona/administración & dosificación , Púrpura Trombocitopénica Trombótica/terapia , Vincristina/administración & dosificaciónRESUMEN
Chickenpox is a common infectious disease of the pediatric age group with rare complications such as hemorrhagic varicella and arterial thrombotic purpura. Medical support is the mainstay of treatment in such cases but for the rescue of necrotic tissues, hyperbaric oxygen (HBO) therapy should be applied in addition to anticoagulant intervention. We report an infant with acute arterial thrombotic purpura which developed after varicella eruption and who made full recovery with the help of HBO as an adjunctive treatment modality. Fresh frozen plasma and low molecular weight heparin were given for prolonged prothrombin time and thromboemboli on the 2nd-4th digits of his right foot. Protein C, protein S and factor V levels were found to be normal in our patient. Necrotic lesions on the toes regressed with repeated HBO treatment and amputation was not needed.
Asunto(s)
Varicela/complicaciones , Púrpura Trombocitopénica Trombótica/complicaciones , Púrpura Trombocitopénica Trombótica/terapia , Anticoagulantes/uso terapéutico , Heparina de Bajo-Peso-Molecular/uso terapéutico , Humanos , Oxigenoterapia Hiperbárica , Lactante , MasculinoRESUMEN
In order to evaluate the nature and frequency of adverse reactions associated with Therapeutic Apheresis (TA), database information from two large mobile apheresis services was analyzed. A total of 17,940 procedures performed on 3,583 patients were studied using an Access Database. Seventy percent (12,558) of the procedures were performed on a Fresenius AS104 blood cell separator and 30% (5,382) were performed on a COBE Spectra. The five most commonly treated diseases were Guillain-Barre Syndrome (25%), thrombotic thrombocytopenic purpura (20%), myasthenia gravis (18%), the hyperviscosity syndrome (12%), and chronic inflammatory demyelinating polyneuropathy (9%). All patients received calcium gluconate supplement during the procedures. Cardiac monitoring was used during 80% of the procedures and blood pressure monitoring was used during all procedures. All procedures were supervised by a physician. Both apheresis services fully comply with the ASFA Guidelines for Therapeutic Apheresis Providers. Adverse reactions occurred in 3.9% of all procedures. The following adverse reactions were documented: reactions related to ACD toxicity (3%), vasovagal reactions (0.5%), vascular access related complications (0.15%), reactions related to FFP (0.12%), hepatitis B from FFP (0.06%), arrhythmias (0.01%), hemolysis due to inappropriate dilution of 25% albumin (0.01%), and one death (from underlying disease) during a TA procedure (0.006%). These data demonstrate that therapeutic apheresis is associated with a low rate of side effects when performed by well-trained and certified nurses under the direction of experienced physicians, even in the diverse setting of large mobile therapeutic apheresis programs.
Asunto(s)
Eliminación de Componentes Sanguíneos/efectos adversos , Unidades Móviles de Salud/normas , Eliminación de Componentes Sanguíneos/normas , Eliminación de Componentes Sanguíneos/estadística & datos numéricos , Viscosidad Sanguínea , Cateterismo/efectos adversos , Bases de Datos Factuales , Síndrome de Guillain-Barré/complicaciones , Síndrome de Guillain-Barré/terapia , Enfermedades Hematológicas/complicaciones , Enfermedades Hematológicas/terapia , Humanos , Unidades Móviles de Salud/estadística & datos numéricos , Miastenia Gravis/complicaciones , Miastenia Gravis/terapia , Sistemas de Atención de Punto/normas , Sistemas de Atención de Punto/estadística & datos numéricos , Polineuropatías/complicaciones , Polineuropatías/terapia , Púrpura Trombocitopénica Trombótica/complicaciones , Púrpura Trombocitopénica Trombótica/terapiaRESUMEN
Results of treatment of 18 patients fulfilling the criteria for TTP are presented. Thrombocytopenia was present in all patients (100%). Sixteen of the 18 patients (88.8%) had mental status changes, and seven of the 18 patients (38.8%) had renal impairment. One patient had a secondary type of TTP, caused by non-Hodgkin's lymphoma of the large intestine (that was diagnosed later) and was excluded from the study. Immunosuppresive therapy with steroids, plasma exchange and replacement of removed volume with fresh frozen plasma in a dosage of 25 ml/kg body weight resulted in a statistically significant increase of platelet count (P = 0.00222), and a significant improvement in consciousness defined by increased GCS after 2 weeks (P = 0.00222). In two patients renal function recovered, and in one of them hemodialysis was no longer needed. This improvement in a small group of patients had no statistical significance. TTP recurred in seven patients. High doses of steroids caused serious side effects in two patients: in one patient, steroid diabetes, and in the other one, intestinal perforation.
Asunto(s)
Glucocorticoides/uso terapéutico , Metilprednisolona/uso terapéutico , Intercambio Plasmático , Púrpura Trombocitopénica Trombótica/terapia , Adolescente , Adulto , Anciano , Femenino , Humanos , Perforación Intestinal/inducido químicamente , Leptospirosis/complicaciones , Masculino , Persona de Mediana Edad , Púrpura Trombocitopénica Trombótica/microbiología , Estadísticas no Paramétricas , Resultado del TratamientoRESUMEN
Plasma exchange using fresh-frozen plasma (FFP) for replacement was given to two brothers during a relapse of thrombotic thrombocytopenic purpura (TTP). A constitutional deficiency of von Willebrand factor(vWF)-cleaving protease had been previously established in both patients. No inhibitor of vWF-cleaving protease was present in patients' plasmas. They received plasma exchange for four and three consecutive days, respectively. In both patients, the activity of vWF-cleaving protease after the first plasmapheresis session was evaluated and was found to be virtually identical to anticipated activity calculated from predicted patient plasma volume and volume of exchanged plasma. Pathologic platelet counts and lactate dehydrogenase levels were normalized in both patients within 4-6 days. The biologic half-life of vWF-cleaving protease was determined in these patients following the last plasma exchange. The respective half-lives of 3.3 and 2.1 days represent the lowest known clearance rates of proteases in circulating human plasma. Another patient with relapsing TTP was treated with plasma exchange and/or plasma infusion for 10 consecutive days during the first relapse, 221-231 days after the initial TTP event. Pharmacokinetic studies of vWF-cleaving protease were performed after plasma exchange on day 221 and after plasma infusion on day 231. High level of an IgG in patient plasma, capable of completely inhibiting protease activity in an equal volume of normal plasma, had been established prior to first plasmapheresis. There was no measurable protease activity at any time during plasma therapy. Following plasma exchange, the level of the inhibitor was transiently slightly depressed. After 10 days of plasma therapy, the concentration of the inhibitor in patient plasma was increased about 5-fold. We suggest that, in contrast to protease deficient patients without circulating inhibitor, complementary therapy including immunosuppressive treatment, vincristine and/or splenectomy is indicated in patients with acquired inhibitors of vWF-cleaving protease. Testing for vWF-cleaving protease inhibitor may be useful in predicting the response to plasma exchange in patients with TTP.
Asunto(s)
Metaloendopeptidasas/sangre , Intercambio Plasmático , Púrpura Trombocitopénica Trombótica/sangre , Factor de von Willebrand/metabolismo , Proteínas ADAM , Proteína ADAMTS13 , Adulto , Activación Enzimática , Semivida , Humanos , Masculino , Recuento de Plaquetas , Púrpura Trombocitopénica Trombótica/terapiaAsunto(s)
Lesión Renal Aguda/terapia , Plasmaféresis , Lesión Renal Aguda/clasificación , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/terapia , Sobredosis de Droga/terapia , Glomerulonefritis/terapia , Síndrome Hemolítico-Urémico/terapia , Humanos , Insuficiencia Multiorgánica/terapia , Intoxicación por Setas/terapia , Intercambio Plasmático , Intoxicación/terapia , Púrpura Trombocitopénica Trombótica/terapiaRESUMEN
Thrombotic thrombocytopenic purpura (TTP) and the hemolytic uremic syndrome (HUS) have in common a microangiopathic hemolytic anemia involving disseminated platelet aggregation and endothelial damage of the microvasculature mainly of the brain (TTP) and kidney (HUS). The underlying pathomechanism still remains unclear. The disease takes an acute, dramatic and frequently fatal course. Unfortunately a broadly approved therapeutic regimen is still lacking since the rarity of TTP and HUS makes study of a large group of patients impossible. We have observed and treated 14 patients with TTP and HUS during a period of 9 years. Most of the cases have been triggered by infectious diseases and pregnancy. Diagnostic cornerstones were hemolytic anemia, schistocytes on peripheral blood smears and consumption thrombocytopenia. Renal and cerebral symptoms were observed regularly, whereas lesions of the pancreas, liver and heart were much less frequent. The treatment included plasma transfusion (47%), plasma exchange (42%), high dose corticosteroids (74%), antiplatelet agents (53%), vitamin E (32%) and vincristin (11%). The outcome of 19 episodes of TTP or HUS was as follows: in 78% complete recovery, in 11% persistence of impaired renal function, and in 11% death. From analysis of our cases it is concluded that plasma transfusions and high dose corticosteroids improve the prognosis of TTP and HUS significantly.
Asunto(s)
Anemia Hemolítica/complicaciones , Síndrome Hemolítico-Urémico/complicaciones , Púrpura Trombocitopénica Trombótica/complicaciones , Adolescente , Corticoesteroides/uso terapéutico , Adulto , Anemia Hemolítica/fisiopatología , Anemia Hemolítica/terapia , Anticoagulantes/uso terapéutico , Transfusión Sanguínea , Femenino , Síndrome Hemolítico-Urémico/fisiopatología , Síndrome Hemolítico-Urémico/terapia , Humanos , Masculino , Persona de Mediana Edad , Intercambio Plasmático , Púrpura Trombocitopénica Trombótica/fisiopatología , Púrpura Trombocitopénica Trombótica/terapia , Síndrome , Vincristina/uso terapéuticoRESUMEN
Thrombocytopenia is a common haematological abnormality in pregnancy which has important implications for both mother and fetus. It may occur as part of the pathophysiology of pregnancy itself, but in many cases pregnancy is superimposed on a background of haematological disease. Failure of platelet production remains a difficult and dangerous problem to manage while the outlook for non-immune platelet destruction has improved as a result of a clearer understanding of the haemostatic changes taking place in the pregnant woman. Immune-mediated thrombocytopenia is now also better understood because of recent advances in antibody detection and quantitation but it has been difficult to translate this new knowledge into the planning of well considered treatment strategies. The administration of high-dose ivIgG to either mother or fetus shows promise as a new and safer method of managing delivery and neonatal life in autoimmune and alloimmune thrombocytopenia but further evaluation is necessary before the indications for giving ivIgG are clear. Close cooperation between obstetricians, haematologists and scientific staff is essential if the best treatment for the thrombocytopenia of pregnancy is to be given.