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1.
Clin Appl Thromb Hemost ; 26: 1076029620938149, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32677459

RESUMO

The novel coronavirus infection (COVID-19) is caused by the new coronavirus SARS-CoV-2 and is characterized by an exaggerated inflammatory response that can lead to severe manifestations such as adult respiratory syndrome, sepsis, coagulopathy, and death in a proportion of patients. Among other factors and direct viral effects, the increase in the vasoconstrictor angiotensin II, the decrease in the vasodilator angiotensin, and the sepsis-induced release of cytokines can trigger a coagulopathy in COVID-19. A coagulopathy has been reported in up to 50% of patients with severe COVID-19 manifestations. An increase in d-dimer is the most significant change in coagulation parameters in severe COVID-19 patients, and progressively increasing values can be used as a prognostic parameter indicating a worse outcome. Limited data suggest a high incidence of deep vein thrombosis and pulmonary embolism in up to 40% of patients, despite the use of a standard dose of low-molecular-weight heparin (LMWH) in most cases. In addition, pulmonary microvascular thrombosis has been reported and may play a role in progressive lung failure. Prophylactic LMWH has been recommended by the International Society on Thrombosis and Haemostasis (ISTH) and the American Society of Hematology (ASH), but the best effective dosage is uncertain. Adapted to the individual risk of thrombosis and the d-dimer value, higher doses can be considered, especially since bleeding events in COVID-19 are rare. Besides the anticoagulant effect of LMWH, nonanticoagulant properties such as the reduction in interleukin 6 release have been shown to improve the complex picture of coagulopathy in patients with COVID-19.


Assuntos
Anticoagulantes/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/complicações , Pandemias , Pneumonia Viral/complicações , Trombofilia/etiologia , Trombose/prevenção & controle , Angiotensina II/metabolismo , Arteriopatias Oclusivas/sangue , Arteriopatias Oclusivas/epidemiologia , Arteriopatias Oclusivas/etiologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/epidemiologia , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/etiologia , Surtos de Doenças , Coagulação Intravascular Disseminada/etiologia , Coagulação Intravascular Disseminada/prevenção & controle , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinolíticos/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Incidência , Inflamação , Pneumonia Viral/sangue , Pneumonia Viral/epidemiologia , Prognóstico , Embolia Pulmonar/etiologia , Embolia Pulmonar/prevenção & controle , Risco , Sepse/sangue , Sepse/complicações , Síndrome Respiratória Aguda Grave/sangue , Síndrome Respiratória Aguda Grave/complicações , Síndrome Respiratória Aguda Grave/epidemiologia , Trombofilia/sangue , Trombofilia/tratamento farmacológico , Trombose/sangue , Trombose/epidemiologia , Trombose/etiologia , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/prevenção & controle , Ativador de Plasminogênio Tecidual/uso terapêutico
3.
Anticancer Res ; 40(7): 3995-4000, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620643

RESUMO

We present here the case of a 39-year-old man with metastatic pancreatic carcinoma receiving chemotherapy with the combination of gemcitabine and nab-paclitaxel as part of a clinical trial. Despite an impressive response to therapy, he ultimately developed profound anasarca, renal insufficiency, progressive cytopenias, and malignant hypertension 6 months into his treatment course. The diagnosis of gemcitabine-associated thrombotic microangiopathy (G-TMA) was made based on renal biopsy, and receipt of the anti-C5 monoclonal antibody eculizumab proved successful at reversing his deteriorating clinical course and improving his laboratory parameters. This case illustrates the importance of recognizing this rare but serious complication, and highlights one potential therapeutic option that can be used in the appropriate clinical context.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antimetabólitos Antineoplásicos/efeitos adversos , Inativadores do Complemento/uso terapêutico , Desoxicitidina/análogos & derivados , Microangiopatias Trombóticas/tratamento farmacológico , Adulto , Albuminas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/efeitos adversos , Evolução Fatal , Humanos , Masculino , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Microangiopatias Trombóticas/induzido quimicamente
5.
Ceska Gynekol ; 85(1): 18-28, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32414281

RESUMO

OBJECTIVE: The aim of this study is to draw attention to a nosological unit called thrombotic microangiopathy (TMA). This syndrome represents a serious pathological condition characterized by microangiopathic haemolytic anemia (MAHA), thrombocytopenia and various organ dysfunction. Patients are most often presented with symptoms of the HELLP syndrome but if the clinical picture is not restituted within 48-72 hours after delivery, other TMAs should be considered. SETTING: Department of Obstetrics and Gynecology, 1st Medical Faculty and General Teaching Hospital Prague; Clinic of Nephrology, 1st Medical Faculty and General Teaching Hospital Prague; Department of Obstetrics and Gynecology, Regional Hospital Kolín. DESIGN: Review article and case reports. METHODS: Review of the literature and description of two cases of TMA. CONCLUSION: The authors present a basic overview of the issue of TMA, which requires interdisciplinary cooperation of obstetricians, anesthesiologists, nephrologists and hematologists. In the second part of the article, we present two TMA case reports and finally show the differential diagnostic and therapeutic scheme as agreed by the authorities in the field.


Assuntos
Complicações Cardiovasculares na Gravidez/diagnóstico , Microangiopatias Trombóticas/diagnóstico , Feminino , Humanos , Equipe de Assistência ao Paciente , Gravidez , Complicações Cardiovasculares na Gravidez/terapia , Púrpura Trombocitopênica Trombótica , Microangiopatias Trombóticas/terapia
6.
Ceska Gynekol ; 85(1): 30-34, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32414282

RESUMO

OBJECTIVE: Case of a primigravid woman who suffered from severe PTMS (postpartum thrombotic microangiopathy syndrome) in the 26th week of pregnancy. DESIGN: Case report. SETTING: Department of Gynecology and Obstetrics, Hospital Nový Jičín; Department of Gynecology and Obstetrics, University Hospital Ostrava; Department of Hematooncology, University Hospital Ostrava; Department of Anaesthesiology and Resuscitation, University Hospital Ostrava. RESULTS: A thirty-one-year old primigravid woman was admitted to a secondary level institution due to epigastric pain and spontaneous rupture of membranes at 26th week of pregnancy. On admission her blood pressure was 140/90 mm Hg and an intrauterine fetal death was confirmed. The patients condition deteriorated quickly, resulting in a hypertensive crisis (220/120 mm Hg), which did not respond to medication over a two hour period. Emergency caesarean section was performed, but the patients condition progressed to HELLP syndrome class I, DIC and MOF. She was transferred to the intensive care unit (ICU) of the district referral hospital 38 hours postpartum. On admission to ICU, liver rupture was diagnosed which was managed conservatively. Therapeutic plasma exchange (TPEX) was initiated on day 2 postpartum in response to falling platelets and continued for 6 days. Due to acute kidney injury (AKI), the patient required dialysis for 21 days. The patients condition improved gradually and at 28 days after admission to ICU she was transferred back to the referring hospital. The consensus reached by the treating teams was that PTMS was the most likely diagnosis. CONCLUSION: This case demonstrates that PTMS improves (usually rapidly) after TPEX is initiated. It also emphasises the importance of maintaining a high index of suspicion for PTMS so that life-saving TPEX can be initiated, because it does not respond to classical treat-ment used in the management of HELLP syndrome. Other research suggests patients may also require a terminal complement blockade with the anti-C5 monoclonal antibody (eculizumab). Further research could focus on diagnostic tests to distinguish PTMS from HELLP to identify which patients would most benefit from these treatments.


Assuntos
Troca Plasmática/métodos , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/terapia , Adulto , Cesárea , Feminino , Síndrome HELLP , Humanos , Gravidez , Complicações Hematológicas na Gravidez , Resultado da Gravidez , Resultado do Tratamento
9.
Int Heart J ; 61(3): 624-628, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32350209

RESUMO

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare malignancy-related respiratory complication, showing rapid progression of respiratory dysfunction and pulmonary hypertension (PH). Accumulating evidence suggests that imatinib, a platelet-derived growth factor (PDGF) receptor-tyrosine kinase inhibitor, might be effective and improve severe PH in patients with PTTM associated with gastric cancer. However, its efficacy in PTTM with breast cancer is generally believed as very limited. We experienced a rare case of PTTM associated with metastatic breast cancer, a rare case who were treated with imatinib, exhibiting significant improvement of respiratory dysfunction and PH.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/complicações , Hipertensão Pulmonar/tratamento farmacológico , Mesilato de Imatinib/uso terapêutico , Microangiopatias Trombóticas/complicações , Adulto , Feminino , Humanos , Hipertensão Pulmonar/etiologia
10.
Am J Med Sci ; 359(5): 296-302, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32265009

RESUMO

Thrombotic microangiopathy (TMA) is characterized by microangiopathic hemolytic anemia with thrombocytopenia. In addition to the primary TMA syndromes, microangiopathic hemolytic anemia with thrombocytopenia can be seen in many systemic diseases. Transplant associated TMA (TA-TMA) affects patients following stem cell or solid organ transplant. A 48-year-old male who underwent autologous stem cell transplant for nonsecretory multiple myeloma was admitted to our hospital with worsening anemia, thrombocytopenia, renal dysfunction and hepatosplenomegaly. Initial blood work revealed rare schistocytes and normal lactate dehydrogenase and haptoglobin levels. He underwent an extensive workup looking for an infectious, inflammatory or malignant etiology but a definitive diagnosis could not be reached. Over his prolonged stay at the hospital, he suffered from multiorgan failure and eventually passed away. An autopsy revealed TMA involving all clinically affected organ systems and was deemed to be the cause of his demise. The absence of typical blood work suggestive of hemolysis does not rule out a diagnosis of TA-TMA. Knowledge of this rare disease entity will help physicians identify and treat this life-threatening condition early and effectively.


Assuntos
Eritrócitos Anormais , Hemólise , Microangiopatias Trombóticas/complicações , Biópsia , Evolução Fatal , Hepatomegalia/complicações , Humanos , Inflamação , Integrina beta3/metabolismo , L-Lactato Desidrogenase/metabolismo , Fígado/patologia , Pulmão/patologia , Masculino , Microcirculação , Pessoa de Meia-Idade , Esplenomegalia/complicações , Transplante de Células-Tronco , Trombocitopenia/complicações , Trombose/metabolismo , Microangiopatias Trombóticas/terapia , Transplante Autólogo
11.
Zhonghua Nei Ke Za Zhi ; 59(3): 250-252, 2020 Mar 01.
Artigo em Chinês | MEDLINE | ID: mdl-32146758

RESUMO

The 21-year-old male patient was admitted to the Department of Rheumatology and Immunology at Peking Union Medical College Hospital with chief complaints of "skin rash for 1 year and edema for 2 months". He was diagnosed with systemic lupus erythematosus (SLE) with renal, cardiac and hematological involvement. Remission was not achieved after glucocorticoid pulse treatment. The patient experienced oliguria, malignant hypertension, accompanied by thrombocytopenia and low serum complements, and elevated lactate dehydrogenase and serum creatinine. Schistocytes were seen in the peripheral blood smear. Thrombotic microangiopathy (TMA) secondary to SLE was diagnosed. Though plasma exchange was partially effective, TMA could not be controlled yet. The activity of serum von Willebrand factor -cleaving protease (ADAMTS 13) was 100%, and ADAMTS 13 inhibitor was negative. Finally, remission of the disease was achieved after second glucocorticoid pulse therapy and rituximab treatment. At the 3-month follow-up, the patient's condition was stable with mild anemia and normal platelet count. Patients with TMA secondary to SLE are heterogenous, while normal ADAMT 13 activity indicates poor prognosis. Early and aggressive treatment is important for disease control, and plasma exchange is helpful as a supportive care.


Assuntos
Lúpus Eritematoso Sistêmico/diagnóstico , Microangiopatias Trombóticas/diagnóstico , Proteína ADAMTS13/genética , Anemia , Edema , Exantema , Glucocorticoides/uso terapêutico , Humanos , Lúpus Eritematoso Sistêmico/complicações , Masculino , Troca Plasmática , Rituximab/uso terapêutico , Microangiopatias Trombóticas/complicações , Adulto Jovem
14.
Int Heart J ; 61(2): 409-412, 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32173712

RESUMO

We report here a 70-year-old female patient with a history of breast cancer who presented with dyspnea that had lasted for 2 weeks following a long-distance trip by bus. She was at first suspected of having a pulmonary embolism given the typical presentation, elevated D-dimer level, and enlargement of the right-side heart. However, her systemic condition deteriorated despite the initiation of anti-coagulation therapy. Given the absence of a major thrombus in the pulmonary major arteries but multiple low perfusion lesions in the periphery of the lungs, refractoriness to conventional therapy, an increase in tumor markers, and anaplastic cells demonstrated by aspiration cytology from the pulmonary artery, we diagnosed her as pulmonary tumor thrombotic microangiopathy (PTTM). She died on day 23 due to respiratory failure despite administration of inotropes and prostaglandin I2. The patient had an obvious history of malignancy, but we should emphasize that PTTM can develop even in patients with early-stage or completely cured malignancies. Although an early and definite diagnosis of PTTM is currently challenging, an optimal diagnostic and therapeutic strategy is warranted.


Assuntos
Neoplasias da Mama/complicações , Embolia Pulmonar/diagnóstico , Microangiopatias Trombóticas/diagnóstico , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/terapia
16.
Intern Med ; 59(1): 93-99, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31902910

RESUMO

Atypical hemolytic uremic syndrome (aHUS) is an extremely rare condition caused by an excessive activation of the complement pathway based on genetic or acquired dysfunctions in complement regulation, leading to thrombotic microangiopathy (TMA). A complement-amplifying condition (CAC) can trigger aHUS occurrence along with complement abnormality. We herein report a case of severe TMA after laparoscopic myomectomy in a healthy woman. This case was eventually diagnosed as complement-mediated TMA secondary to surgical invasive stress as a CAC, with no definitive diagnosis of aHUS despite a genetic test. The patient fully recovered after several eculizumab administrations.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Laparoscopia/efeitos adversos , Hemorragia Pós-Operatória/complicações , Microangiopatias Trombóticas/tratamento farmacológico , Miomectomia Uterina/efeitos adversos , Adulto , Inativadores do Complemento/uso terapêutico , Feminino , Humanos , Doenças Raras , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/etiologia
17.
PLoS One ; 15(1): e0227445, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31923282

RESUMO

INTRODUCTION: Thrombotic microangiopathy (TMA) in post-transplant setting has heterogeneous clinical manifestations. METHODS: We retrospectively studied data of 89 patients with post-transplant TMA, which was characterized by thrombi in at least one glomerulus and/or arteriole. Systemic TMA was defined by thrombocytopenia and microangiopathic anemia and early onset TMA, when occurred less than 90 days post transplant. RESULTS: The cumulative incidence was 0.93%. The majority of the recipients were young (mean age 39 years), female (52%) and Caucasian (48%) with primary kidney disease of unknown etiology (37%). Early TMA occurred in 51% of the patients and systemic TMA, in 25%. Underlying precipitating factors were: infection (54%), acute rejection (34%), calcineurin inhibitor toxicity (13%) and pregnancy (3%). 18% of the patients had several triggers. Glomerular TMA was observed in 50% of the biopsies and endothelial cell activation, in 61%. The 1-year patient survival was 97% and corresponding graft survival, 66%. Allograft survival was inferior when acute antibody mediated rejection (ABMR) occurred (with 41%; without 70%, p = 0.01), however no differences were determined by hemolysis, time of onset, thrombi location or endothelial cell activation. CONCLUSIONS: Our results suggest that post-transplant TMA is a rare but severe condition, regardless of its clinical and histological presentation, mainly when associated to ABMR.


Assuntos
Transplante de Rim/efeitos adversos , Microangiopatias Trombóticas/etiologia , Adulto , Feminino , Rejeição de Enxerto/complicações , Rejeição de Enxerto/imunologia , Humanos , Incidência , Infecções/complicações , Nefropatias/complicações , Nefropatias/terapia , Masculino , Pessoa de Meia-Idade , Gravidez , Estudos Retrospectivos , Microangiopatias Trombóticas/patologia , Transplante Homólogo/efeitos adversos
18.
Bull Cancer ; 107(1S): S28-S35, 2020 Jan.
Artigo em Francês | MEDLINE | ID: mdl-31303250

RESUMO

Acute and chronic renal failures are very common after allogeneic HSCT. These complications have a real impact on mortality and morbidity of transplant recipients. Within the framework of the ninth workshops of practice harmonization of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) held in Lille in September 2018, various causes and mechanisms of renal failure, diagnostic work-up, treatment and recommendations to limit renal failure after transplantation are reviewed. Recommendations to adjust medications to avoid renal failure are also proposed in this article.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Insuficiência Renal/etiologia , Insuficiência Renal/prevenção & controle , Anti-Infecciosos/efeitos adversos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/terapia , Humanos , Imunossupressores/efeitos adversos , Incidência , Síndrome Nefrótica/etiologia , Insuficiência Renal/diagnóstico , Insuficiência Renal/terapia , Índice de Gravidade de Doença , Microangiopatias Trombóticas , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo
20.
Pediatr Blood Cancer ; 67(3): e28070, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31774252

RESUMO

BACKGROUND: Transplant-associated thrombotic microangiopathy (TA-TMA) occurs after hematopoietic stem cell transplantation (HSCT) and is characterized by microvascular thrombosis and end-organ injury particularly of the kidneys. TA-TMA is challenging to diagnose and treat, which can lead to long-term complications and death in patients with severe disease. Studies have shown that genetic abnormalities of the alternative complement pathway (AP) are associated with TA-TMA. We hypothesized that patients with TA-TMA may generate elevated levels of the AP activation product, Ba, compared with HSCT patients without TA-TMA. PROCEDURE: We longitudinally measured plasma levels of complement activation products C3a, Ba, and C5a in 14 HSCT patients: 7 with TA-TMA and 7 without TA-TMA. We assessed renal function by calculating estimated glomerular filtration rate (eGFR) and correlated the extent of AP activation with renal dysfunction in both patient populations. RESULTS: The median days from HSCT to study enrollment were 154 (39-237) in the TA-TMA group and 84 (39-253) in the HSCT group without TA-TMA. Median Ba levels (ng/mL) at enrollment were 1096.9 (826.5-1562.0) in the TA-TMA group and 725.7 (494.7-818.9) in the HSCT group without TA-TMA (P = 0.007). Over the study duration, Ba levels inversely correlated with eGFR. There were no differences in C3a, C5a, or sC5b9 levels between the two populations at any measured interval. CONCLUSIONS: We conclude in this preliminary study that Ba protein may serve as a marker for TA-TMA, and furthermore, that components generated in the early phase of AP activation may be involved in the pathogenesis of renal endothelial injury in TA-TMA.


Assuntos
Biomarcadores/metabolismo , Complemento C3b/metabolismo , Fator B do Complemento/metabolismo , Via Alternativa do Complemento , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Microangiopatias Trombóticas/diagnóstico , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Ativação do Complemento , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Prognóstico , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/metabolismo , Adulto Jovem
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