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.

Thrombotic thrombocytopenic purpura complicated with multiple cerebral infarction: report of two cases / 中华神经科杂志

Thrombotic thrombocytopenic purpura (TTP) is a rare hematological disease with typical clinical manifestations of thrombocytopenic purpura, microangiopathic hemolytic anemia, neurological symptoms, fever and kidney damage. Two patients with TTP-associated cerebral infarction complicated with microhemorrhage and their shared specific imaging findings manifestations were reported. The magnetic resonance imaging of the 2 patients showed multiple cerebral infarctions at different stages. Susceptibility-weighted imaging showed cerebral microbleeds in the infarcted area. This special imaging feature can provide important clues for early identification and diagnosis of TTP nervous system injury.

Clinical characteristics and outcome of 69 patients with thrombotic thrombocytopenic purpura / 中华内科杂志

To analyze the clinical characteristics, diagnosis, treatment and outcome of patients with thrombotic thrombocytopenic purpura (TTP). The clinical data of 69 adult patients with TTP were retrospectively analyzed. There were 19 males and 50 females with a median age of 42 (18-79) years. PLASMIC score 6-7 was recognized in 82.8% (53/64) patients. The activity of von Willebrand factor-cleaving protease (ADAMTS13), which was detected in 21 patients before treatment, was less than 5% in 17 patients and 5%-10% in 3 patients. All 69 patients were treated with plasma exchange (PEX) and/or fresh frozen plasma infusion (PI), 43 of whom were also given glucocorticoid. In addition to PEX/PI and glucocorticoid, rituximab and/or immunosuppressants were administrated in 20 patients. The median follow-up time was 12 (1-57) months. The remission rate was 69.6%, while the relapse rate was 11.6%. The 2-year overall survival (OS) rate was 69.6%±5.5%. The univariate and multivariate analysis showed that relapsed/refractory disease was an independent risk factor for OS. The 2-year OS rate of relapsed/refractory patients was significantly lower than that of the rest patients (41.5%±9.8% vs. 83.7%±5.6%, P<0.001). Regarding the unfavorable prognosis in relapsed/refractory patients, rituximab and/or immunosuppressants are strongly recommended for sake of improving the overall survival.

Thrombotic thrombocytopenic purpura: a case report / Púrpura trombocitopênica trombótica: relato de caso

ABSTRACT Thrombocytopenic thrombotic purpura (TTP) is a severe hemorrhagic syndrome characterized by thrombocytopenia, microangiopathic hemolytic anemia and microvascular occlusion, besides the associated symptoms that may or may not be present: fever, neurological and renal impairment. The pathophysiology involves the autoimmune or genetic deficiency of a metalloproteinases activity (ADAMTS-13), responsible for the von Willebrand Factor cleavage. The treatment is based on plasmapheresis; and in acute or recurrent cases, corticosteroids and immunosuppressants are associated. In this article, we will discuss a case report about this disease, initially treated in the Emergency Room and followed in the Intensive Care Unit of a public reference hospital in São Paulo city, Brazil. All clinical diagnostic criteria were completely filled, facilitating the therapeutic approach of the patient. The report evidences that rapid intervention when made early diagnosis evolves with a good prognosis, and this pathology must be present as a differential diagnosis in the medical routine.

RESUMO Púrpura trombocitopênica trombótica (PTT) é uma síndrome hemorrágica grave caracterizada por trombocitopenia, anemia hemolítica microangiopática e oclusão microvascular, bem como por sintomas associados que podem ou não estar presentes, como febre, comprometimento neurológico variável e comprometimento renal. A fisiopatologia implicada na doença envolve a deficiência, seja por inibição autoimune ou defeito genético, seja pela atividade de uma metaloproteinase (ADAMTS-13), responsável pela clivagem de multímeros do fator de von Willebrand (FvW). O tratamento consiste na plasmaférese e, em casos agudos graves ou recorrentes, associa-se a corticoterapia e imunossupressores. Neste artigo, abordaremos um relato de caso sobre essa doença, cuja paciente foi atendida inicialmente em pronto-socorro, sendo em seguida internada em uma unidade de terapia intensiva (UTI) de um hospital público de referência da cidade de São Paulo, Brasil. Todos os critérios clínicos diagnósticos foram completamente preenchidos, facilitando a abordagem terapêutica da paciente. O relato evidencia que a rápida intervenção, quando se faz o diagnóstico precoce, evolui com bom prognóstico, devendo esta patologia estar presente como diagnóstico diferencial no cotidiano médico.

Acute Thrombotic Thrombocytopenic Purpura with Right Heart Failure Following Total Knee Replacement Surgery / 대한내과학회지

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening condition characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal insufficiency, neurological abnormalities, and fever. Cardiac involvement is not uncommon and can be fatal; however, right ventricular heart involvement after surgery is rare. Here, we report a case of TTP presenting with right ventricular heart failure after total knee replacement surgery. TTP was successfully treated with four rounds of plasma exchange. The patient made a full recovery and was discharged after 11 weeks.

Relapse of congenital thrombotic thrombocytopenic purpura, after spontaneous remission, in a second-trimester primigravida: case report and review of the literature / Recidiva, após remissão espontânea, de púrpura trombocitopênica trombótica congênita em primigesta no segundo trimestre de gestação: relato de caso e revisão da literatura

ABSTRACT CONTEXT: Thrombotic microangiopathy syndrome or thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) describes distinct diseases sharing common pathological features: microangiopathic hemolytic anemia and thrombocytopenia, without any other apparent cause. CASE REPORT: An 18-year-old second-trimester primigravida presented with a history of fifteen days of intense weakness, followed by diarrhea over the past six days. She reported having had low platelets since childhood, but said that she had never had bleeding or menstrual abnormalities. Laboratory investigation showed anemia with schistocytes, thrombocytopenia and hypohaptoglobulinemia. Red blood cell concentrate and platelet transfusions were performed. The hypothesis of TTP or HUS was put forward and ADAMTS13 enzyme activity was investigated. The patient evolved with increasing platelet counts, even without specific treatment, and she was discharged. One month afterwards, she returned presenting weakness and swollen face and legs, which had developed one day earlier. The ADAMTS13 activity was less than 5%, without presence of autoantibodies. Regarding the two previous admissions (at 9 and 16 years of age), with similar clinical features, there was spontaneous remission on the first occasion and, on the second, the diagnosis of TTP was suspected and plasmapheresis was performed, but ADAMTS13 activity was not investigated. CONCLUSION: To date, this is the only report of congenital TTP with two spontaneous remissions in the literature This report reveals the importance of suspicion of this condition in the presence of microangiopathic hemolytic anemia and thrombocytopenia without any other apparent cause.

RESUMO CONTEXTO: A síndrome de microangiopatia trombótica, ou púrpura trombocitopênica trombótica-síndrome hemolítico urêmica (PTT-SHU), descreve doenças diversas com clínica e achados patológicos comuns: anemia hemolítica microangiopática e trombocitopenia, na ausência de outra causa aparente. RELATO DO CASO: Primigesta de 18 anos no segundo trimestre apresenta-se com quadro de 15 dias de fraqueza intensa seguida por diarreia há seis dias. Relata ter plaquetas baixas desde a infância e nega sangramentos e anormalidades menstruais. Investigação laboratorial identificou anemia com esquizócitos, plaquetopenia e hipo-haptoglobulinemia. Foi realizada transfusão de plaquetas e concentrado de hemácias. A hipótese de PTT ou SHU foi aventada e realizou-se pesquisa da atividade da enzima ADAMTS13. A paciente evoluiu com elevação das plaquetas, mesmo sem tratamento específico, tendo alta. Retornou após um mês da alta com queixa de fraqueza há um dia e inchaço de face e pernas. A atividade da ADAMTS13 foi menor que 5%, sem autoanticorpos. Nas duas internações anteriores (aos 9 e 16 anos), com quadros similares, houve remissão espontânea na primeira internação e, na segunda, o diagnóstico de PTT foi suspeitado e foi realizada plasmaférese, porém sem a pesquisa da atividade da ADAMTS13. CONCLUSÃO: Até esta data, este é único relato de TTP congênita com duas remissões espontâneas na literatura. Este relato revela a importância da suspeição desta patologia na presença de anemia hemolítica microangiopática e trombocitopenia sem outra causa aparente.

Adult-Onset Still's Disease with Thrombotic Thrombocytopenic Purpura / 대한내과학회지

Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder that affects multiple organs and is fatal in some cases. Thrombotic thrombocytopenic purpura (TTP), another rare disease, is characterized by multiple organ failure and microangiopathic hemolytic anemia. TTP is an extremely rare complication of AOSD. We report a 59-year-old woman who presented with TTP that manifested after she was diagnosed with AOSD. Initially, her clinical manifestations improved with glucocorticoid therapy. However, her disease worsened and was accompanied by acute kidney injury, thrombocytopenia, hemolytic anemia, petechiae, and impaired consciousness. These clinical findings led to a diagnosis of TTP. This is the first report of AOSD complicated by TTP in Korea. Awareness of the possible development of TTP as a complication of AOSD is important for early diagnosis and treatment.

Successful Treatment with Low-dose Rituximab in a Patient with Plasma Exchange-refractory Idiopathic Thrombotic Thrombocytopenic Purpura / 대한내과학회지

Thrombotic thrombocytopenic purpura (TTP) is a clinical syndrome characterized by micro-angiopathic hemolytic anemia, thrombocytopenia, fever, renal disorders, and neurological manifestations. Its clinical course is rapid and the mortality rate is high if untreated or relapse occurs. Previous studies reported that rituximab, a monoclonal antibody for CD20 surface antigen on B lymphocytes, may be effective in treating idiopathic TTP that is refractory to plasma exchange or relapses after remission. A 27-year-old Vietnamese man presented with fever and fatigue starting 3 days earlier, which was diagnosed as idiopathic TTP. To overcome his poor responsiveness to combined therapy using steroids and plasma exchange, rituximab was considered. In the current case, the patient was treated with a lower dose of rituximab, instead of the conventional 375 mg/m2/week, and achieved successful remission.

Thrombotic Thrombocytopenic Purpura after Stent Insertion in Patient with Colon Cancer

Thrombotic thrombocytopenic purpura (TTP), a fatal disease, is mostly idiopathic but can occur secondary to cancer, infection, transplantation, pregnancy, surgery, or drugs. The mechanism of TTP is still unknown, however, and detection is difficult because of unclear diagnosis criteria. Colonic stent insertion is commonly used in management of malignant colon obstruction. This is a very safe procedure with a low procedure-related mortality rate, but serious complications can develop. The authors first experienced a patient with TTP when the phenomenon occurred after stent insertion for palliation of obstructive colon cancer and therefore would like to report the case.

Clinical characteristics of systemic lupus erythematosus associated thrombotic thrombocytopenic purpura / 中华全科医师杂志

We retrospectively reviewed the clinical records of 12 systemic lupus erythematosus (SLE) patients with thrombotic thrombocytopenic purpura (TTP) admitted into Peking Union Medical College Hospital (PUMCH) during October 2008 to September 2013.TTP occurred in 0.45％ (12/2 693) of patients with SLE.The median age (2 males,10 females) was 23 years.Their SLEDAI scores ranged from 12 to 30.All patients had significant thrombocytopenia and renal abnormalities.Ten of them bad acute renal failure.Cardiac involvement and neurological deficits were observed in 9 and 8 of them respectively.Eight of them had injuries of more than 4 organs.Renal biopsy of 3 patients revealed lupus nephritis (type Ⅳ,n =2 ; type Ⅴ,n =1) and thrombotic microangiopathy.Eleven TTP patients received steroid pulse therapy (1 g/d,3 days) and six of them survived.Six patients were rescued by therapeutic plasma exchange and 4 of them recovered.Among another 6 patients not on plasma exchange therapy,only 3 recovered.Finally 2 died,3 gave up with exacerbated symptoms after therapy and 7 survived.

Rituximab Treatment in a Case of Dermatomyositis Accompanied by Thrombotic Thrombocytopenic Purpura / 대한내과학회지

Thrombotic thrombocytopenic purpura (TTP) is an uncommon, serious disease known to be related with infection, toxin, pregnancy and autoimmune disease. Autoimmune disease-related TTP is rare, difficult to diagnose and can rapidly become fatal if left untreated. We report the case of a 59 year-old Korean female with TTP associated with dermatomyositis flare. The patient was suspected to have amyopathic dermatomyositis and was treated with moderate doses of oral glucocorticoids. One month later, muscle weakness developed with dermatomyositis flare, and the patient showed confusion, acute renal failure, thrombocytopenia and microangiopathic hemolytic anemia. She was diagnosed with TTP associated with dermatomyositis flare. After prompt plasmapheresis treatment with high dose glucocorticoid therapy, her confusion, thrombocytopenia and anemia were improved. However, oliguric renal failure and myopathy remained, and thrombocytopenia and anemia recurred. After starting additional rituximab treatment, the clinical manifestation of dermatomyositis and TTP improved markedly.

The clinical analysis of 14 cases of systemic lupus erythematosus complicated by thrombotic thrombocytopenic purpura / 中华内科杂志

Objective To analyze the clinical features,diagnosis and treatment of thrombotic thrombocytopenic purpura (TTP) in patients with systemic lupus erythematosus (SLE).Methods Clinical manifestations,laboratory findings,diagnosis,treatment and prognosis of 14 SLE patients with TTP were retrospectively analyzed.Results Of the 14 patients diagnosed with SLE and TTP,4 were men and 10 were women.The median age at diagnosis was 23 (17-69) years old.In five patients,the onset of SLE preceded TTP,and in nine patients SLE and TTP occurred simultaneouslv.All the 14 patients had thrombocytopenia and hemolytic anemia,12 had fever,11 had neurologic abnormalities,and 11 had renal dysfunction.Eight patients presented with the classic pentad of symptoms.Six patients were given steroids (alone or in combination with intravenous immunoglobulin and cyclophosphamide),and eight patients were treated with steroids in combination with plasmapheresis,with response rates of 2/6 and 6/8,respectively.Six patients died,with overall mortality rate of 6/14.No patients relapsed during the follow-up period.Conclusions SLE and TTP share some similar clinical symptoms.As a result,repeated examinations of peripheral blood smears are very important for early diagnosis.The renal damage in patients of co-existing diseases is more serious than those with TTP alone or SLE alone.Early diagnosis and prompt treatment with plasma exchange and steroids may improve the prognosis in SLE patients with TTP.

Púrpura trombocitopênica trombótica: o papel do fator von Willebrand e da ADAMTS13 / Thrombotic thrombocytopenic purpura: the role of von Willebrand factor and ADAMTS13

A púrpura trombocitopênica trombótica (PTT) instala-se de modo abrupto e é caracterizada pela oclusão difusa de arteríolas e capilares da microcirculação, levando à isquemia de tecidos. A oclusão é causada por microtrombos compostos basicamente de plaquetas e fator von Willebrand (FvW). O FvW é uma glicoproteína de estrutura multimérica sintetizada exclusivamente por células endoteliais e megacariócitos. Este fator promove a adesão das plaquetas ao endotélio lesado, participa do processo de agregação plaquetária e é a proteína carreadora do fator VIII na circulação. Em condições fisiológicas, os grandes multímeros do FvW encontram-se dentro das células endoteliais e nas plaquetas e não estão presentes no plasma. Tão logo estes grandes multímeros são liberados da célula endotelial, são clivados e removidos da circulação pela enzima ADAMTS13 (A Desintegrin And Metalloprotease with eight Thrombo Spondin-1-like). A deficiência funcional ou quantitativa de ADAMTS13 resulta no acúmulo de grandes multímeros de FvW no plasma, propiciando a agregação das plaquetas e oclusão difusa das arteríolas e capilares. A maioria dos casos de PTT está associada à deficiência da ADAMTS13 e já estão disponíveis no mercado internacional conjuntos diagnósticos para a determinação dos níveis de antígenos desta enzima, da de sua atividade e dos anticorpos anti-ADAMTS13. A avaliação laboratorial da ADAMTS13 parece constituir um avanço para o diagnóstico precoce da PTT. No entanto, a interpretação dos resultados exige cautela e um conhecimento do princípio do método, bem como das etapas das reações envolvidas.

Thrombotic thrombocytopenic purpura (TTP) starts abruptly and is characterized by diffuse occlusion of microcirculation arterioles and capillaries, leading to ischemia of tissues. Occlusion is caused by microscopic clots primarily composed of platelets and von Willebrand factor (VWF). VWF is a multimeric glycoprotein synthesized exclusively by endothelial cells and megakaryocytes. This factor promotes adhesion of platelets to injured endothelium, participates in the process of platelet aggregation and is the carrier protein of factor VIII in the circulation. In physiological conditions, large VWF multimers are present in endothelial cells and platelets and are not present in plasma. As soon as these large multimers are released from the endothelial cell, they are cleaved and removed from circulation by the ADAMTS13 enzyme. A quantitative or functional deficiency of ADAMTS13 results in the accumulation of large VWF multimers in the plasma and may result in the aggregation of platelets and diffuse occlusion of arterioles and capillaries. Most cases of PTT are associated with ADAMTS13 deficiency. The levels of antigens, activity and antibodies of MTS13 can be evaluated using internationally manufactured kits. The laboratory evaluation of ADAMTS13 appears to be a useful tool for the early diagnosis of PTT. However, interpretation of the results requires caution, as well as knowledge of the principles of the method and the steps of the reactions involved.

Clinical-pathological features and prognosis of thrombotic tbrombocytopenic purpura in patients with lupus nephritis / 中华风湿病学杂志

Objective To investigate the clinical-pathological features, treatment and prognosis of thrombotic thrombocytopenic purpura in patients with lupus nephritis (LN). Methods A retrospective ana-lysis was carried out based on the clinical-pathological data for the treatment and prognosis of eight patients with LN related TIP. All patients had thrombocytopenia and hemolytic anemia, neurological symptoms and renal dysfunction. Six patients had fever. Results All 8 patients had sudden-onset of rapid progressive glomeurlonephritis (RPGN), one patient with continuous gross hematuria, the pathological features of these patients revealed TMA lesions. Immune suppressive therapy was initiated and blood purification therapy were applied in seven patients. Three cases had plasmapheresis and (or) immunoabsorption. One case was lost during follow-up, the other seven patients were followed with period at one year. One patient died, three patients went into peritoneal dialysis in which one of them was changed to hemodialysis finally. The other three patients had stable renal function. Conclusion The LN patients with TTP had severe clinical-patho-logical changes, rapid progressive and poor outcome, so we should diagnose and treat these patients as early as possible.

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 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.

A case of thrombotic thrombocytopenic purpura in systemic lupus erythematosus / 대한내과학회지

Thrombotic thrombocytopenic purpura (TTP) rarely may be seen in association with autoimmune processes such as scleroderma, rheumatoid arthritis, polyarteritis nodosa, Sj gren's syndrome, and systemic lupus erythematosusus (SLE). The diagnosis of TTP as a syndrome distinct from SLE may be challenging, because both processes may present with some or all elements of the classic pentad considered pathognomonic of the former: microangiopathic hemolytic anemia, fever, thrombocytopenia, neurological deficits, and renal abnormalities. We describe a patient with synchronous TTP and SLE, and review the literature.

A Case of Thrombotic Thrombocytopenic Purpura Associated with Ticlopidine

Ticlopidine, a widely used antiplatelet agent, has been rarely reported to cause thrombotic thrombocytopenic purpura (TTP). To the best of our knowledge, its occurrence has never before been reported in Korea. A 69 years old female patient suffered from an acute ischemic stroke. Ticlopidine 250mg bid was started and she followed an uneventful clin-ical course. The platelet count was normal on the 1st and the 12th day of ticlopidine administration. Around the 31st day, at home, she developed purpura, dyspnea and a stuporous mental status. Under the diagnosis of TTP, a plasma exchange was performed and her condition eventually returned to the baseline status. Ticlopidine induced TTP can developed abruptly despite close monitoring of platelet count, as illustrated by this case. Physicians prescribing ticlopi-dine should be aware of this potentially dangerous complication.