Púrpura trombótica trombocitopénica en pediatría. Reporte de un caso / Thrombotic thrombocytopenic purpura in pediatrics. A case report

La púrpura trombótica trombocitopénica es una entidad poco frecuente en pediatría, pero de alta mortalidad sin tratamiento adecuado y oportuno. Se caracteriza por presentar anemia hemolítica microangiopática asociada a signos y síntomas neurológicos, cardíacos, abdominales y menos frecuentemente renales; puede estar acompañada de fiebre. En niños, el diagnóstico se basa en los hallazgos clínicos y de laboratorio. La actividad de ADAMTS13 <10 % apoya, pero no confirma el diagnóstico y, dada la gravedad de la patología, el resultado no debe retrasar el inicio del tratamiento. Se presenta una paciente de 15 años, previamente sana, con signos neurológicos asociados a anemia hemolítica y trombocitopenia. Durante su internación, se arribó al diagnóstico de púrpura trombótica trombocitopénica adquirida.

Thrombotic thrombocytopenic purpura is a rare disease in pediatrics, but it has a high mortality if not managed in an adequate and timely manner. It is characterized by microangiopathic hemolytic anemia associated with neurological, cardiac, abdominal, and less frequently, renal signs and symptoms; it may be accompanied by fever. In children, diagnosis is based on clinical and laboratory findings. ADAMTS13 activity < 10% supports the diagnosis but does not confirm it and, given its severity, the result should not delay treatment initiation. Here we describe the case of a previously healthy 15-year-old female patient with neurological signs associated with hemolytic anemia and thrombocytopenia. During hospitalization, she was diagnosed with acquired thrombotic thrombocytopenic purpura.

Clinical diagnosis and treatment of hereditary thrombocytopenia and purpura: a report of five cases and literature review / 中华血液学杂志

Objective: To report the clinical manifestations and laboratory features of five patients with congenital thrombotic thrombocytopenic purpura (cTTP) and explore its standardized clinical diagnosis and treatment along with a review of literature. Methods: Clinical data of patients, such as age of onset, disease manifestation, personal history, family history, and misdiagnosed disease, were collected. Treatment outcomes, therapeutic effects of plasma infusion, and organ function evaluation were observed. The relationship among the clinical manifestations, treatment outcomes, and ADAMTS13 gene mutation of patients with cTTP was analyzed. Additionally, detection of ADAMTS13 activity and analysis of ADAMTS13 gene mutation were explored. Results: The age of onset of cTTP was either in childhood or adulthood except in one case, which was at the age of 1. The primary manifestations were obvious thrombocytopenia, anemia, and different degrees of nervous system involvement. Most of the patients were initially suspected of having immune thrombocytopenia. Acute cTTP was induced by pregnancy and infection in two and one case, respectively. ADAMTS13 gene mutation was detected in all cases, and there was an inherent relationship between the mutation site, clinical manifestations, and degree of organ injury. Therapeutic or prophylactic plasma transfusion was effective for treating cTTP. Conclusions: The clinical manifestations of cTTP vary among individuals, resulting in frequent misdiagnosis that delays treatment. ADAMTS13 activity detection in plasma and ADAMTS13 gene mutation analysis are important bases to diagnose cTTP. Prophylactic plasma transfusion is vital to prevent the onset of the disease.

Research Advance in Treatment of Thrombotic Thrombocytopenic Purpura --Review / 中国实验血液学杂志

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.

Advance in the diagnosis and treatment of hereditary thrombotic thrombocytopenic purpura / 中华医学遗传学杂志

Congenital thrombotic thrombocytopenic purpura, also known as Upshaw-Schulman syndrome, is a rare autosomal recessive genetic disorder. The main pathogenesis is homozygous or compound heterozygous variants of von Willebrand factor lyase (ADAMTS13) gene mapped to chromosome 9q34, which may result in severe lack of ADAMTS13 which cleaves von Willebrand factor (vWF) multimers in the plasma and increase the risk of microvascular thrombosis, leading to various complications. The advance of research on the pathogenesis of cTTP, recombinant human ADAMTS13 and gene therapy have made breakthroughs which may lead to cure of cTTP. This article has provided a review for the latest progress made in the diagnosis and treatment of cTTP.

Púrpura trombocitopénica trombótica en un paciente con infección por VIH / Thrombotic thrombocytopenic purpura, in a HIV-infected patient: case report

Resumen Las manifestaciones hematológicas de la infección por el VIH son frecuentes y variadas debido a su capacidad de afectar prácticamente todas las líneas celulares. Dentro de éstas, la púrpura trombocitopénica trombótica (PTT) es una de las entidades que constituyen las microangiopatías trombóticas. Se caracteriza por la presencia de trombocitopenia y anemia hemolítica microangiopática con alteración de la función renal. Actualmente, la co-existencia de estas dos entidades es poco frecuente debido a la terapia anti-retroviral de alta efectividad (TARV) Presentamos el caso de un paciente de 28 años, quien consultó por fiebre asociada a episodios de gingivorragia, palidez mucocutánea generalizada y debilidad progresiva. Los estudios evidenciaron una anemia y trombocitopenia grave. Se encontraron esquistocitos y microesferocitos en el frotis de sangre periférica con actividad de la enzima ADAMTS 13 disminuida (6,8%). Se confirmó el diagnóstico de una PTT como manifestación inicial de una infección por VIH. Se indicó manejo con plasmaféresis e inicio de TARV con buena respuesta.

Abstract Hematological manifestations for human immunodeficiency virus (HIV) infection are frequent and diverse due to its ability to affect almost all cell lines. Among these, thrombotic thrombocytopenic purpura (TTP) is one of the thrombotic microangiopathies syndromes, characterized by the presence of thrombocytopenia and microangiopathic hemolytic anemia with impaired renal function. Nowadays, the relationship between these two entities is rare given the current highly active antiretroviral therapy (HAART). We report the case of a 28-year-old patient, who presented with fever associated with gingival bleeding, generalized mucocutaneous pallor and progressive weakness. Routine investigations showed anemia and severe thrombocytopenia, schistocytes and micro spherocytes in peripheral blood smear. Required blood transfusion, with decreased ADAMTS 13 enzyme activity (6.8%). With these findings,TTP was diagnosed as the initial manifestation of the HIV infection. The patient received management with five sessions of plasmapheresis and HAART with subsequent improvement.

Clinical analysis of 61 patients with thrombotic thrombocytopenic purpura / 北京大学学报(医学版)

OBJECTIVE@#To analyze and summarize the clinical features, diagnosis, treatment and prognosis of 61 patients with thrombotic thrombocytopenic purpura (TTP), so as to improve the ability of diagnosis and treatment.@*METHODS@#The clinical data of 61 TTP patients admitted to Peking University People's Hospital from January 2004 to March 2019 were retrospectively analyzed, and the clinical manifestations, blood routine, hemolysis indicators, and von Willebrand factor lyase (von Willebrand factor-cleaving protease, vWF-CP, also known as ADAMTS13) of these patients were observed. According to the outcome at the time of discharge, they were divided into survival group and death group, and the differences in clinical characteristics, neutrophil to lymphocyte ratio (NLR) and plasma exchange between the two groups were compared. The PLASMIC scores were calculated and compared with ADAMTS13 to determine the accuracy of the PLASMIC score in predicting ADAMTS13.@*RESULTS@#Among the 61 TTP patients, 22 were males and 39 were females, with an average age of (48±17) years. In the study, 48 cases had pentalogy, only 9 had triad, and the remaining 4 had no neuropsychiatric symptoms. Twenty-seven cases (44.3%) died and 34 cases (55.7%) survived. Among the 61 TTP patients, the platelet count was (12.9±9.5)×109/L, the hemoglobin (66.5±20.7) g/L, the percentage of erythrocyte fragments 3% (2%, 7%), and the plasma free hemoglobin increased to 360 (200, 457) mg /L, and the lactate dehydrogenase 1 508 (811, 2 133.8) U/L. The blood clotting was basically normal. The ADAMTS13 value of 30 patients was 49.0 (40.8, 61.3) μg/L, the ADAMTS activity of 10 patients was < 5%, and the remaining 21 patients were not checked. The PLASMIC score was 6-7 in 58 cases, 5 in 2 cases, and 4 in 1 case. The PLASMIC score predicted the decreased activity or the reduction of ADAMTS with a sensitivity as high as 97.5%. The NLR in the death group was higher than that in the survival group, but the difference was not statistically significant (P>0.05). The total amount and frequency of plasma exchange (PEX) in the death group were significantly less than those in the survival group, and the difference was statistically significant (P < 0.05). There was no significant difference in the treatment of glucocorticoids and human immunoglobulin between the two groups (P>0.05).@*CONCLUSION@#PEX can significantly improve the survival rate of TTP patients. PLASMIC score can easily and quickly predict the possibility of ADAMTS13 activity reduction, which is beneficial to the early diagnosis of TTP and PEX treatment. NLR can reflect the systemic inflammatory process, but its significance in TTP needs further study.

Plasmaféresis, experiencia del Hospital Regional de Talca en pacientes con indicaciones nefrológicas / Plasmapheresis, experience of the Regional Hospital of Talca, in patients with nephrological indications

INTRODUCTION: Plasmapheresis is an extracorporeal procedure that allows the plasma to be separated from the figurative elements of the blood, removing specific elements involved in pathological processes. OBJECTIVE: To show the experience of the Regional Hospital of Talca (HRT) in the use of Plasmapheresis from 2017 to March 2019. METHODS: Corresponds to a retrospective study of all patients undergoing plasmapheresis from January 2017 to March 2019 (27 months). The clinical profile of this group of patients is analyzed, emphasizing in the nephrological etiologies and showing the clinical evolution of the diseases submitted to this procedure and aspects such as number of sessions, complications and associated therapies. RESULTS: In this period 14 patients have required plasmapheresis in our center, 9 cases for renal causes (64.2%) and 5 for non-renal causes (35.7%). A deceased was recorded during the acute stage of the disease (7.14%), in the context of a negative antineutrophil cytoplasmic antibody (ANCA) in patient with pulmonary-renal syndrome. 78% of those who needed plasmapheresis for renal etiologies are on hemodialysis at the end of the work. The clinical improvement experienced in the majority of the cases studied allows us to attribute a beneficial effect of plasmapheresis.

Uso del rituximab en púrpura trombocitopénica trombótica / Rituximab use in thrombotic thrombocytopenic purpura

La púrpura trombocitopénica trombótica (PTT) es un síndrome clínico caracterizado por anemia hemolítica microangiopática, fiebre, trombocitopenia, compromiso neurológico y daño renal. Su incidencia es rara y la etiología desconocida en un 90%. Se presenta el caso de una paciente de 49 años que ingresó por dolor intenso en epigastrio acompañado de debilidad, náuseas, vómitos y metrorragia. Los exámenes de ayuda diagnóstica presentaron valores alterados: hemoglobina, 7,4 g/dL; hematocrito 24,4%; plaquetas, 30 000/mm3 y bilirrubinas, aumentadas. Un día después, se añadió hemiparesia facio-braquio-crural derecha y equimosis difusa. La tomografía espiral multicorte (TEM) cerebral no mostró evidencia de patología. Presentó dos convulsiones tónico-clónicas y hubo deterioro clínico. En el frotis de sangre se evidenció esquistocitos y plaquetopenia (18 400/mm3); la hemoglobina llegó a 6,8 g/dL. Se planteó el diagnóstico de PTT y se inició tratamiento con plasmaféresis y metilprednisolona. Siete días después no hubo mejoría. Entonces, se indicó rituximab y a los dos días las plaquetas subieron a 60 000/mm3. La mejoría clínica y de los resultados de laboratorio fueron evidentes...

Thrombotic thrombocytopenic purpura (TTP) is a clinical syndrome characterized by microangiopathic hemolytic anemia, fever, thrombocytopenia, neurological involvement and renal damage. Its incidence is rare and its cause unknown in 90%. We report the case of a patient of 49 years who was admitted with epigastric pain accompanied by weakness, nausea, vomiting and metrorrhagia. She showed hemoglobin about 7,4 g/dL, hematocrit 24,4%, platelets 30000/ mm3 and increased bilirubins. A day after, right faciobrachio-crural hemiparesis and diffuse ecchymosis were added. The brain TEM shows no pathological evidence. She has two tonic-clonic seizures and there is important deterioration. In the blood smear is evidenced schistocytes, platelets 18400/mm3, and hemoglobin 6,8 gr/dL. We propose the diagnosis of TTP and started treatment with plasmapheresis and methylprednisolone. At 7 days there is no improvement. Rituximab is indicated and the platelets in two days rose to 60000/mm3. Improvements in clinical and laboratory parameters are observed...

[ case report of successful treatment of hellp syndrome and thrombotic thrombocytopenic purpura by plasmapheresis]

HELLP syndrome was described in 1982 by Weinstein as a triad of hemolysis, elevated liver enzymes and thrombocytopenia. This syndrome develops antepartum in 70% and postpartum in 30% of cases. HELLP syndrome occurs in 0.5 to 0.9% of all pregnancies and is accompanied by disseminated intravascular coagulation [DIC] in 38% of patients. Maternal mortality rate is reported to be 1.1%. Although thrombotic thrombocytopenic purpura [TTP] is rare, it is one of the most important differential diagnoses for HELLP syndrome, which may be lethal without appropriate treatment. Plasmapheresis is one of the recommended treatments in complicated and/or resistant to treatment cases. In this article we introduce a 22 years old primiparous woman with a term pregnancy that developed HELLP syndrome and DIC after delivery. Due to the lack of improvement, an accompany of TTP was diagnosed. So, she underwent plasmapheresis treatment and was discharged with full recovery after 22 sessions of treatments

Medicina transfusional basada en la evidencia / Evidence-based transfusional medicine

La idea de publicar este trabajo, es estimular la utilización de preguntas surgidas de la práctica médica, para obtener respuestas con base en la mejor evidencia publicada. La medicina basada en la evidencia, es una herramienta fundamental para la toma de decisiones, no sólo en lo que respecta a un paciente o caso puntual, sino también para la salud y la sociedad en general. El caso que motiva esta publicación es una de las entidades que, como equipo dedicado a la medicina transfusional más nos convoca, ya que no sólo es una patología que requiere de nuestra participación activa como integrantes de un equipo médico, sino que además depende en gran medida del desarrollo de los bancos de sangre como servicios activos y pensados para dar respuesta a este tipo de problemática.

Publishing this paper aims to encourage doctors to take questions that arise from their medical practice to be answered basing their research on the best evidence published. Evidence-based medicine is an essential tool when making decisions not only when it comes to a patient or a particular case but also when these decisions have an impact on health and societies in general. The case that inspires this publication is one that concerns us the most because it consists in a pathology that requires our whole active participation as members of a transfusion medicine team. Furthermore, it heavily depends on the development of blood banks as an active service that is conceived to salve this type of problem.

role of aspirin in thrombotic thrombocytopenic purpura: a randomized control trial

To assess the safety and efficacy of aspirin in acute Thrombotic Thrombocytopenic Purpura [TTP] and to evaluate it as a maintenance therapy. Randomized controlled trial. Hematology/Oncology Department, Salmaniya Medical Complex [SMC], Kingdom of Bahrain. Nine patients with TTP admitted between August 2003 to December 2005 were included in the study. Seven were females [77.8%] and one was pregnant. Five Patients were randomized to receive the standard therapy with aspirin [group I] and four [group II/control] received the standard therapy only [plasma exchange, one single plasma volume daily using fresh frozen plasma from healthy donors and Methylprednisolone 1 gram intravenously once daily for three days]. Safety and efficacy of aspirin were assessed during the acute phase [4 weeks] and as maintenance for one year. Statistically significant reduction in the number of plasma exchange sessions were noted in the aspirin group [p = 0.0315]. Other parameters such as days of hospitalization, red blood cells transfusion were lower in the aspirin group compared to non aspirin group. No cases of mortality or morbidity were observed in patients receiving aspirin. Two patients [50%] developed deep vein thrombosis [DVT] in the control group and one of them eventually died [25%]. Though these were statistically insignificant, possibly due to the small number of patients, it would suggest the efficacy of aspirin in TTP. The study showed a significant reduction in the number of plasma exchange sessions in the aspirin group and probable advantages. Accordingly, we recommend a multicenter RCTs to address the role of aspirin in the management of TTP patients

Púrpura trombótico trombocitopénico: revisión de la literatura a partir de 18 casos / Thrombotic thrombocytopenic purpura: experience in 18 cases and literature review

Background: Thrombotic thrombocytopenic purpura (TTP) is characterized by anemia, thrombocytopenia, neurological and renal involvement of variable severity and it has a dismal prognosis. Platelet-derived von Willebrand Factor-cleaving metalloprotease ADAMTS-13 activity may orient the diagnosis, but normal levels do not discard it. The most effective therapy thus known is plasmapheresis. Aim: To report the experience in 18 patients with TTP. Material and methods: Retrospective assessment of 11 patients and prospective assessment of seven subjects with TTP, aged 15 to 81 years. Results: All presented with anemia, thrombocytopenia and LDH elevation. Sixteen had neurological symptoms, five had fever, four had macroscopic urinary excretion of pigments, four had petechiae, and two had nosebleeds. Haptoglobin was low in 10 of 11 patients in whom it was measured. ADAMTS-13 had low activity in 15 of 17 patients (in 11, the inhibitor was found). Seventeen patients were treated with plasmapheresis and nine received steroids also. Seven patients died due to shock with respiratory involvement or múltiple organic failure. Conclusions: TTP has heterogeneous modes of presentation. If the diagnosis is strongly suspected, plasmapheresis can be started without laboratory confirmation. An ADAMTS-13 activity below 6 percent is almost exclusive of TTP .

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.

Thrombotic thrombocytopenic purpura, at a tertiary care centre in lahore, Pakistan

Thrombotic thrombocytopenic purpura is a syndrome, characterized by microangiopathic hae-molytic anaemia, thrombocytopaenia, neurological symptoms, renal disease and fever. Commonly considered rare, but actually it is one of the most under diagnosed disorders. This study was aimed at evaluating the clinical features, course, prognostic factors and treatment outcome in 17 patients diagnosed as having thrombotic thrombocytopaenic purpura [TTP]. It was a cross-sectional descriptive study at Shaikh Zayed Hospital Lahore. This study includes patients diagnosed as having TTP by the department of haematology from January 2005 to December 2007. Eight of 17 patients were treated with plasma exchange. Six of these 8 patients survived. Plasma infusions were performed in 9 patiejits, 5 of them recovered. Overall 65% patients recovered and mortality was 35%

Aspectos neurológicos del púrpura trombótico trombocitopénico: Presentación de un caso / Thrombotic thrombocytopenic purpura with neurological involvement: Report of one case

Neurological manifestations, secondary to perfusion problems, vasogenic edema or small infarcts, are common in thrombotic purpura. Moreover, they are the first symptoms of the disease in 50% of patients. We report a 50 year-old woman who presented with focal intermittent neurological signs with aphasia and right hemiparesis, who then developed progressive impairment of consciousness with stupor and generalized tonic-clonic seizures. Despite the severe neurological impairment, first neuroimaging studies were normal. A second magnetic resonance imaging showed small cortical infarcts, that were visible only with the technique of diffusion weighted imaging. The standard electroencephalograms showed focal left temporal slowing and low voltage first and then diffuse slowing accordind to the clinical condition of the patients. She was treated with plasmapheresis and had a partial neurological recovery at the fifth day, but died at the twelfth day of therapy .

Microangiopatía trombótica en adultos / Thrombotic microangiopathy in adults

Thrombotic microangiopathic hemolytic anemias include thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS) and pregnancy associated thrombotic microangiopathy (TMA). Eight adult patients (four males and four females) with TMA who were treated between 2003 and 2004 at the Hospital Italiano de Buenos Aires were reviewed. The average age was 40. Clinical diagnosis of TMA was made on admission in four patients. During their stay in hospital, 4 patients developed HUS characteristics, three as TTP and one presented pregnancy associated TMA. All of them revealed thrombocytopenia and microangiophatic hemolytic anemia. Renal impairment was the third most frequent characteristic at presentation. The patients with TTP revealed the most severe condition. All patients received daily plasma exchange. Immunosuppressants were also used. Four patients recovered completely, 2 passed away, one remains with renal impairment and requires hemodialysis, and a colectomy was performed on one of them. The TMA syndromes are occlusive disorders associated to platelet microvascular thrombi. Systemic and renal circulations are primarily affected. TTP/HUS might represent an overlapping spectrum of idiopathic or secondary disease. Prompt recognition and treatment are vital, because high mortality occurs due to these disorders. Among the differential diagnosis of TMA we can refer to sepsis, neoplasms, systemic vasculitis, eclampsia and others. The mainstay treatments are daily plasma exchange and infusion with fresh frozen plasma. Improving the management of these diseases is required considering their high morbidity and mortality.