A combined regimen based on bortezomib and glucocorticoids for 6 patients with recurrent/refractory immune thrombotic thrombocytopenic purpura / 中华血液学杂志

Objective: To observe the efficacy and adverse reactions of a combination therapy regimen based on bortezomib and glucocorticoids in recurrent/refractory immune thrombocytopenic purpura (iTTP) . Methods: Six patients with recurrent/refractory TTP were included and treated with a glucocorticoid and two courses of bortezomib-based regimen. The clinical remission status of patients, changes in ADAMTS13 activity/ADAMTS13 inhibitor, and the occurrence of treatment-related adverse reactions were observed. Results: Of the 6 patients, 2 were males and 4 were females, with a median age of 21.5 (18-68) years. Refractory TTP was found in 1 case and recurrent TTP in 5 cases. Glucocorticoids were administered with reference to prednisone at 1 mg·kg(-1)·d(-1), and gradually reduced in dosage after achieving clinical remission. Bortezomib is subcutaneously administered at 1.3 mg/m(2) on days 1, 4, 8, and 11 with a 28-day treatment course consisting of 2 courses. Six patients achieved clinical remission after receiving bortezomib as the main treatment. ADMATS13 activity returned to normal in all patients with TTP after treatment, and the ADAMTS13 inhibitor turned negative. Thrombocytopenia is the most common adverse reaction after treatment, with other adverse reactions, including peripheral neuritis and abdominal pain, but ultimately all patients returned to normal. In a median follow-up of 26 (9-41) months, 5 patients maintained sustained remission, and 1 patient relapsed after 16 months of bortezomib treatment. Conclusion: Combination therapy of bortezomib and glucocorticoids has a satisfactory therapeutic effect and controllable adverse reactions for recurrent/refractory iTTP.

Experiencia de un hospital universitario en el manejo de púrpura trombótico trombocitopénico-microangiopatía trombótica no inmune refractaria o en recaída tratado con rituximab: Report of eight cases / Treatment of thrombotic thrombocytopenic purpura with rituximab

Thrombotic thrombocytopenic purpura, an immune/non-immune thrombotic microangiopathy (TTP/TMA) is associated with high morbidity and mortality, even with appropriate treatment. In patients refractory to standard treatment with plasmapheresis there is no certainty about the best therapeutic strategy. This report shows our experience in eight refractory patients who survived after treatment with rituximab.

High-dose Immunoglobulin Infusion for Thrombotic Thrombocytopenic Purpura Refractory to Plasma Exchange and Steroid Therapy

The outcomes of the treatment of thrombotic thrombocytopenic purpura (TTP) have been shown to be improved by the administration of plasma exchange. However, treatment options are currently limited for cases refractory to plasma exchange. The autoantibodies that block the activity of ADAMTS13 have been demonstrated to play a role in the pathogenesis of TTP; therefore, high-dose immunoglobulin, which can neutralize these autoantibodies, may be useful for refractory TTP. However, successful treatment with high-dose immunoglobulin for TTP refractory to plasma exchange and corticosteroids has yet to be reported in Korea. Herein, we describe a refractory case which was treated successfully with high-dose immunoglobulin. A 29-year-old male diagnosed with TTP failed to improve after plasma exchange coupled with additional high-dose corticosteroid therapy. As a salvage treatment, we initiated a 7-day regimen of high-dose immunoglobulin (400 mg/kg) infusions, which resulted in a complete remission, lasting up to the last follow-up at 18 months. High-dose immunoglobulin may prove to be a useful treatment for patients refractory to plasma exchange; it may also facilitate recovery and reduce the need for plasma exchange.

Púrpura trombótica trombocitopenica en adultos / Trombocitopenica trombótica purple in adults

Se revisa la presentación de 6 pacientes adultos con púrpura trombótica trombocitopénica (PTT), que fueron atendidos en el Servicio de Clínica Médica del Hospital Escuela de Corrientes durante un período de 11 años. La púrpura trombótica trombocitopénica es una anemia hemolítica microangiopática caracterizada por una pentada clínica típica: trombocitopenia, anemia hemolítica microangiopática, fallo renal, fiebre y manifestaciones neurológicas. Todos los pacientes presentaron trombocitopenia y anemia hemolítica microangiopática. El compromiso neurológico fue la segunda característica más frecuente. Todos los pacientes fueron tratados con plasmaféresis. Tres pacientes se recuperaron completamente y 3 fallecieron. El pilar del tratamiento es la transfusión de plasma y la plasmaféresis. Se hace hincapié en su implementación inmediata dada la alta mortalidad de esta patología.

Cerebellar degeneration and immune thrombocytopenic purpura associated with human immunodefi ciency virus infection (HIV)

Cerebellar disorders associated with HIV infection are usually caused by opportunistic infections, central nervous system lymphoma, and toxic effects of medicines, nutritional and metabolic disorders, and cerebrovascular disease. We present an unusual association of cerebellar degeneration and immune thrombocytopenic purpura in a 28-years-old woman HIV infected. An autoimmune aetiology is likely.

Transtornos cerebelares associados a infecção pelo HIV são comumente causados por infecções oportunistas, linfoma do sistema nervoso central, efeitos tóxicos de medicamentos anti-retrovirais, alterações metabólicas e nutricionais, e doença cerebrovascular. Apresentamos um caso incomum de associação de degeneração cerebelar e púrpura trombocitopênica imunológica em um mulher de 28 anos infectada pelo HIV. Discutimos uma possível etiologia autoimune para justificar o quadro.

Púrpura trombocitopénico trombótico con respuesta exitosa a vincristina / Successful treatment of thrombotic thrombocytopenic purpura with vincristine report of one case

Thrombotic thrombocytopenic purpura presents as a multisystemic disease with thrombocytopenia, microangiopathic hemolytic anemia, fever, neurological and renal involvement. We report a 24 years-old male presenting with purpura and a generalized seizure. His blood tests showed an hemolytic anemia, unconjungated hyperbilirubinemia, increased lactated dehydrogenase, thrombocytopenia and impairment of renal function. He was initially treated with daily plasmapheresis and steroids without improvement. Due to persistence of the disease, he was treated with two doses of intravenous vincristine in four days, with clinical and laboratory improvement. He was discharged 40 days after the last dose of vincristine, in good conditions.

Eficacia de la asociación rituximab-vindesina en el tratamiento de un caso de púrpura trombótico-trombopénico (PTT) adquirido idiopático refractario / Successful treatment of idiopathic acquired refractory thrombotic thrombocytopenic purpura with an association of rituximab - vindesine. Report of one case

We report a 23 years old female who presented a second episode of thrombotic thrombocytopenic purpura (TTP). She was treated with fresh frozen plasma infusions and 14 plasma exchange (PE) sessions without response. Therefore a second-line therapy was started, associating a weekly cycle administration of vindesine (Vds) 2 mg/m2 and rituximab (R) 375 mg/m2. Five cycles of this association plus one cycle of R exclusively, were administered. After the third course, biological signs of improvement were observed and complete normalization of blood cell counts and other specific parameters was seen after 8 weeks. From the beginning of her second relapse we detected a severe deficit (<5%) in von Willebrand-cleaving factor (ADAMTS13) associated to the presence of ADAMTS13 inhibitors. The combined treatment induced an improvement in ADAMTS13 values without detectable inhibitors. After 21 months of follow-up the patient was well, without signs of relapse but ADAMTS13 values were still under normal, which may be an unfavorable prognostic factor. PE is the treatment of choice for acquired idiopathic TTP, but for refractory cases or TTP cases with severe ADAMTS13 values/high inhibitor titers, PE associated to an immunosuppressive treatment should be considered.

Púrpura trombocitopénica trombótica y síndrome hemolítico urémico en el adulto

La púrpura trombocitopénica trombótica y el síndrome hemolítico urémico en el adulto son expresiones distintas de una misma enfermedad. Su incidencia es muy baja, aproximadamente uno en un millón de habitantes, pero su mortalidad sin tratamiento adecuado es alta. Las manifestaciones clínicas son heterogéneas y se pueden confundir con las producidas por otras entidades. En este informe se presentan y discuten las características clínicas de nueve pacientes vistos en seis años en un hospital universitario de referencia y se enfatizan los hallazgos que deben hacer sospechar la existencia de la enfermedad.