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.

Reference range for ADAMTS13 antigen, activity and anti-ADAMTS13 antibody in the healthy adult Singapore population

INTRODUCTION@#ADAMTS13 (a disintegrin-like and metalloproteinase with a thrombospondin Type 1 motif, member 13) plays a fundamental role in the regulation of haemostasis and thrombosis. Its deficiency leads to an accumulation of ultra-large von Willebrand multimers, inducing spontaneous platelet aggregation, thrombosis in the microvasculature, and thrombotic thrombocytopenic purpura (TTP), a condition with 90% mortality when left untreated. Prompt quantification of ADAMTS13 antigen, activity and autoantibody plays a crucial role in the diagnosis and management of TTP and can help differentiate it from other thrombotic microangiopathies (TMAs). Reference ranges for ADAMTS13 are generally derived from Caucasian patients. Given that polymorphism in the ADAMTS13 gene can be associated with variable ADAMTS13 levels, we aimed to establish the first reference range in Singapore and provide a crucial laboratory test for institutions here and elsewhere.@*METHODS@#150 healthy voluntary donors (75 men, 75 women) aged 21-60 years, with an ethnic mix mirroring Singapore's population profile, were recruited. ADAMTS13 antigen, activity and autoantibody levels were measured using the fluorescence resonance energy transfer-vWF73 and enzyme-linked immunosorbent assay methodologies.@*RESULTS@#Levels (activity 0.65-1.79 IU/mL, antigen 0.36-1.17 IU/mL, autoantibody 1.4-12.5 U/mL) were not statistically different between the genders and various age groups.@*CONCLUSION@#TTP and TMAs are encountered in a wide range of specialties. The availability of new assays in Singapore will aid clinicians in the timely management of these conditions. Standardising reference ranges established for Singapore against World Health Organization standards allows harmonisation of measurements between laboratories and for future research collaborations.

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.

Púrpura trombocitopénica trombótica secundaria a lupus eritematoso sistémico / Thrombotic thrombocytopenic purpura secondary to systemic lupus erythematosus

La púrpura trombocitopénica trombótica asociada a lupus eritematoso sistémico es muy poco frecuente. Se presentó una paciente con síndrome febril prolongado, poliartralgias, cefalea, papiledema bilateral y cambios conductuales. Se describen la evolución clínica, los estudios imagenológicos, de laboratorio e inmunológicos que permitieron hacer el diagnóstico de púrpura trombocitopénica trombótica secundaria a lupus eritematoso sistémico. Se consideró importante presentar este caso por la poca frecuencia con que se diagnostica la asociación de ambas entidades, además, porque el diagnóstico constituyó un reto para especialistas y residentes de medicina interna(AU)

Thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus is very rare. One patient with prolonged febrile syndrome, polyarthralgia, headache, bilateral papilledema and behavioral changes is presented here. The clinical course, the imaging, laboratory and immunological studies that allowed the diagnosis of thrombotic thrombocytopenic purpura secondary to systemic lupus erythematosus are described. It was considered important to present this case by the infrequency with which the association of both entities also diagnosed because the diagnosis was a challenge for specialists and internal medicine residents(AU)

Púrpura trombótica trombocitopénica y tuberculosis: Una rara asociación / Thrombotic thrombocytopenic purpura and tuberculosis. A rare association

La púrpura trombótica trombocitopénica (PTT) es una microangiopatía trombótica asociada a cuadros de trasplante de células madre hematopoyéticas, embarazo y posparto, al uso de ciertas drogas, diarrea sanguinolenta, a un grupo heterogéneo de trastornos como enfermedades autoinmunes, hipertensión maligna, enfermedades neoplásicas, diversas infecciones y un grupo llamado idiopático, donde se incluyen aquellos en quienes no se cumplieron los criterios de las categorías clínicas anteriores. La tuberculosis (TBC) es una enfermedad de incidencia intermedia en Argentina, más frecuente en determinados grupos poblacionales. Presentamos el caso de un varón de 60 años que consulta por dolor abdominal, tos y sudoración nocturna; se detectó primero trombocitopenia y luego de algunos días anemia microangiopática, lo que llevó al diagnóstico de PTT. Posteriormente, al continuar con la evaluación, se diagnosticó TBC por: 1) baciloscopia positiva para bacilos ácido-alcohol resistentes (+++) por técnica de Ziehl Neelsen en lavado broncoalveolar, 2) lesiones en laringe y 3) lesiones en válvula ileocecal. La TBC ha sido pocas veces asociada con la PTT en la literatura, razón por la cual presentamos este caso.

Thrombocytopenic thrombotic purpura (TTP) is a thrombotic microangiopathy associated with hematopoietic stem cells transplantation, pregnancy, puerperium, drugs, bloody diarrhea, a heterogeneous group of illnesses, such as malignant hypertension, autoimmune and neoplastic diseases, infections, and an idiopathic group that includes the pathologies that don’t apply for the preceding clinical categories. Tuberculosis is an illness of intermediate incidence in Argentina, with increased frequency in high-risk groups. In this article, we present the case of a 60 years old male patient, with abdominal pain, cough and nocturnal sweating. He was diagnosed as having thrombocytopenia, and a few days later, microangiopathic anemia and TTP. Further examinations led TBC diagnosis based on: 1) acid fast bacillus (+++) for Ziehl Neelsen stain in bronco alveolar lavage, 2) laryngeal lesion and 3) ileocecal valve lesion. We report this case, because TBC has rarely been associated with TTP in medical literature.

Síndrome Hemolítico-Urêmica na infância / Hemolytic-Uremic Syndrome in childhood

O grupo de doenças que podem manifestar-se com MAT podem apresentar superposição clínica, dificultando o diagnóstico diferencial. Entre estas ressaltamos a PTT e SHU, sendo que esta última pode ocorrer pela ação de toxinas, doenças sistêmicas, hiperativação da via alterantiva descontrolada por alterações nas proteínas reguladoras desta via (SHUa) e por fim, idiopática. Deve-se proceder a uma série de exames para diferenciá-las. Ressaltando que SHUa é um diagnóstico de exclusão de outras causas de MAT. O tratamento da SHUa com infusão de plasma ou plasmaferese, resulta na maior parte dos casos com boa resposta, especialmente hematológica a curto-prazo, porém é uma doença grave e devastadora e, pode levar a óbito e doença renal crônica terminal. Tratamento com plasma apresenta grande recorrência da doença a longo-prazo e evolução renal desfavorável. Eculizumab, um anticorpo monoclonal anti-C5, tem surgido como uma esperança no prognóstico a curto e a longo-prazo nestes pacientes.

There is a group of diseases that may manifest with thrombotic microangiopathy and present clinical overlap. Among these we emphasize the thrombotic thrombocytopenic purpura and Hemolytic Uremic Syndrome, and the latter can occur by the action of toxins, systemic diseases, overactivation of the alternative complement system pathway, which can occur due to changes in regulatory proteins (atypical HUS) and finally, idiopathic. You must carry out a series of tests to differentiate them. aHUS is a diagnosis of exclusion of other causes of MAT. The treatment of aHUS with plasma therapy, results in most cases with good shortterm response, especially hematological; however, it is a progressive and devastating disease and can lead to death and terminal chronic renal disease. Treatment with plasma displays great recurrence of long-term disease and renal insufficiency. Eculizumab, a monoclonal antibody anti-C5, has been associated with hematological remission, benefits on renal function and no need of plasma therapy.

Microangiopatía trombótica atrombocitopénica: un diagnóstico no realizado con los criterios actuales / Athrombocitopenic thrombotic microangiopathy: diagnosis not performed with the present criteria

Las microangiopatías trombóticas (MAT), que incluyen la púrpura trombótica trombocitopénica (PTT) y al síndrome urémico-hemolítico (SUH), se diagnostican habitualmente por la presencia de anemia hemolítica no inmune y trombocitopenia, lo que lleva a tratarlas con plasmaféresis. Se reporta el caso de una paciente de 51 años que ingresó con insuficiencia renal aguda-subaguda de etiología desconocida cuya biopsia renal mostró microangiopatía trombótica pero sin trombocitopenia ni anemia hemolítica. Por lo tanto dicha patología no siempre seria diagnosticada con los criterios actuales, debiendo utilizarse otros marcadores como ADAMTS-13.

The disease category of thrornbotic microangiopathy (TM) encompass diffcrent entities such as thrombocvtopenic thrombotic purpura (TTP) and uremic hemolytic syndrorne (UHS) , both strongly related and whose diagnosis relies on the presence of non immune hemolytic anemia and trombocytopenia, findings that should urge the caring physician to start plasmapheresis promptly. We report the case of a 51 year old woman admitted with acute-subacute renal failure of unknown etiology whose renal biopsy finding was thrombotic microangiopathy, in absence of thrombocytopenia and haemolytic anemia. This inusual case and according to published literature can not be diagnosed on standard accepted criteria and others markers like ADAMTS-13 should be considered.

Microangiopathic Hemolytic Anemia as the First Manifestation of Metastatic Signet Ring Cell Carcinoma of Unknown Origin: A Case Report and Review of Literature / 대한진단검사의학회지

Microangiopathic hemolytic anemia (MAHA) occurs occasionally as a paraneoplastic syndrome in some solid tumors, but MAHA accompanied by signet ring cell carcinoma of an unknown origin is very rare. In this study, we present the case of an 80-yr-old man who was admitted to the hospital because of a 1-month history of lower back pain and dyspnea. He was diagnosed with MAHA on the basis of the laboratory findings that revealed anemia with schistocytes, decreased haptoglobin levels, and a negative direct Coombs' test. Bone marrow examination, which was performed because of the progression of anemia, revealed bone marrow metastases of signet ring cell carcinoma with extensive bone marrow necrosis. However, the primary origin of this signet ring cell carcinoma was not found. When the cause of progressive MAHA is unknown, the possibility of cancer-associated MAHA must be excluded by performing additional tumor workup, including the detection of tumor markers, gastric and colorectal endoscopic examinations, bone marrow examinations, and positron emission tomography-computed tomography or bone scans.

Microangiopathic Hemolytic Anemia as the First Manifestation of Metastatic Signet Ring Cell Carcinoma of Unknown Origin: A Case Report and Review of Literature / 대한진단검사의학회지

Microangiopathic hemolytic anemia (MAHA) occurs occasionally as a paraneoplastic syndrome in some solid tumors, but MAHA accompanied by signet ring cell carcinoma of an unknown origin is very rare. In this study, we present the case of an 80-yr-old man who was admitted to the hospital because of a 1-month history of lower back pain and dyspnea. He was diagnosed with MAHA on the basis of the laboratory findings that revealed anemia with schistocytes, decreased haptoglobin levels, and a negative direct Coombs' test. Bone marrow examination, which was performed because of the progression of anemia, revealed bone marrow metastases of signet ring cell carcinoma with extensive bone marrow necrosis. However, the primary origin of this signet ring cell carcinoma was not found. When the cause of progressive MAHA is unknown, the possibility of cancer-associated MAHA must be excluded by performing additional tumor workup, including the detection of tumor markers, gastric and colorectal endoscopic examinations, bone marrow examinations, and positron emission tomography-computed tomography or bone scans.

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.

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.

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 .

A Case of Behcet's Disease with Pericarditis, Thrombotic Thrombocytopenic Purpura, Deep Vein Thrombosis and Coronary Artery Pseudo Aneurysm

Behcet's disease with concomitant thrombotic thrombocytopenic purpura (TTP), coronary artery stenosis and coronary artery pseudo aneurysm is rare. Here we report a case of Behcet's disease with several cardiovascular complications, namely: pericarditis, deep vein thrombosis (DVT), TTP, coronary artery stenosis, and a coronary artery pseudo aneurysm. A 37-year-old female presented with sudden dyspnea and syncope at our emergency room and underwent pericardiectomy and pericardial window formation for the diagnosis of cardiac tamponade with acute hemorrhagic pericarditis. Thereafter, TTP and DVT complicated her illness. After confirmation of Behcet's disease on the basis of a history of recurrent oral and genital ulcers and erythema nodosum, remission was achieved after treatment with methylprednisolone pulse therapy, colchicine, catheter directed thrombolysis and thrombectomy. However, whilst maintaining anticoagulation therapy, a newly developed pericardial aneurysmal dilatation was noted on follow-up radiologic evaluation. Further evaluation revealed right coronary artery stenosis and a left coronary artery pseudo aneurysm; these additional problems were treated with the nonsurgical insertion of an endovascular graft stent . At the time of writing three months later after stent insertion, the aneurysm has continued to regress and no additional complications have intervened with combined immunosuppressive therapy.

Thrombotic Thrombocytopenic Purpura after Percutaneous Coronary Intervention

Thrombotic thrombocytopenic purpura (TTP) is a rapidly progressive hematological syndrome defined by the pentad of thrombocytopenia, microangiopathic hemolytic anemia, neurologic abnormalities, fever and renal dysfunction. TTP has been associated with major surgical procedures and specific medications. However, there is no known previously reported case in which acute TTP occurred after a percutaneous coronary intervention (PCI). We report a case of TTP after a PCI, that presented with the pentad of symptoms, as well as hepatitis and pancreatitis.

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.

Thrombotic thrombocytopenic purpura associated with Human Immunodeficiency Virus infection.

Thrombotic thrombocytopenic purpura (TTP) belongs to the group of diseases called Thrombotic microangiopathies (TMA). While several triggering conditions are known, often none is apparent in the individual case. We report a patient presenting with TTP that was associated with a Human Immunodeficiency Virus (HIV) infection, with its consequent diagnostic, therapeutic and prognostic implications. Further, our case had individual clinical features that were of interest within the TTP-HIV subgroup.