RESUMO
SARS-CoV-2 vaccine ChAdOx1 nCoV-19 (AstraZeneca) causes a thromboembolic complication termed vaccine-induced immune thrombotic thrombocytopenia (VITT). Using biophysical techniques, mouse models, and analysis of VITT patient samples, we identified determinants of this vaccine-induced adverse reaction. Super-resolution microscopy visualized vaccine components forming antigenic complexes with platelet factor 4 (PF4) on platelet surfaces to which anti-PF4 antibodies obtained from VITT patients bound. PF4/vaccine complex formation was charge-driven and increased by addition of DNA. Proteomics identified substantial amounts of virus production-derived T-REx HEK293 proteins in the ethylenediaminetetraacetic acid (EDTA)-containing vaccine. Injected vaccine increased vascular leakage in mice, leading to systemic dissemination of vaccine components known to stimulate immune responses. Together, PF4/vaccine complex formation and the vaccine-stimulated proinflammatory milieu trigger a pronounced B-cell response that results in the formation of high-avidity anti-PF4 antibodies in VITT patients. The resulting high-titer anti-PF4 antibodies potently activated platelets in the presence of PF4 or DNA and polyphosphate polyanions. Anti-PF4 VITT patient antibodies also stimulated neutrophils to release neutrophil extracellular traps (NETs) in a platelet PF4-dependent manner. Biomarkers of procoagulant NETs were elevated in VITT patient serum, and NETs were visualized in abundance by immunohistochemistry in cerebral vein thrombi obtained from VITT patients. Together, vaccine-induced PF4/adenovirus aggregates and proinflammatory reactions stimulate pathologic anti-PF4 antibody production that drives thrombosis in VITT. The data support a 2-step mechanism underlying VITT that resembles the pathogenesis of (autoimmune) heparin-induced thrombocytopenia.
Assuntos
Complexo Antígeno-Anticorpo/imunologia , Autoanticorpos/imunologia , COVID-19/prevenção & controle , Proteínas do Capsídeo/efeitos adversos , ChAdOx1 nCoV-19/efeitos adversos , Contaminação de Medicamentos , Vetores Genéticos/efeitos adversos , Células HEK293/imunologia , Imunoglobulina G/imunologia , Fator Plaquetário 4/imunologia , Púrpura Trombocitopênica Idiopática/etiologia , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/efeitos adversos , Adenoviridae/imunologia , Animais , Complexo Antígeno-Anticorpo/ultraestrutura , Autoanticorpos/biossíntese , Síndrome de Vazamento Capilar/etiologia , Proteínas do Capsídeo/imunologia , Linhagem Celular Transformada , ChAdOx1 nCoV-19/química , ChAdOx1 nCoV-19/imunologia , ChAdOx1 nCoV-19/toxicidade , Difusão Dinâmica da Luz , Epitopos/química , Epitopos/imunologia , Armadilhas Extracelulares/imunologia , Extravasamento de Materiais Terapêuticos e Diagnósticos/etiologia , Vetores Genéticos/imunologia , Células HEK293/química , Humanos , Imageamento Tridimensional , Imunoglobulina G/biossíntese , Inflamação , Camundongos , Microscopia/métodos , Ativação Plaquetária , Proteômica , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/imunologia , Trombose dos Seios Intracranianos/diagnóstico por imagem , Trombose dos Seios Intracranianos/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Cultura de VírusRESUMO
Importance: Cases of cerebral venous sinus thrombosis in combination with thrombocytopenia have recently been reported within 4 to 28 days of vaccination with the ChAdOx1 nCov-19 (AstraZeneca/Oxford) and Ad.26.COV2.S (Janssen/Johnson & Johnson) COVID-19 vaccines. An immune-mediated response associated with platelet factor 4/heparin antibodies has been proposed as the underlying pathomechanism. Objective: To determine the frequencies of admission thrombocytopenia, heparin-induced thrombocytopenia, and presence of platelet factor 4/heparin antibodies in patients diagnosed with cerebral venous sinus thrombosis prior to the COVID-19 pandemic. Design, Setting, and Participants: This was a descriptive analysis of a retrospective sample of consecutive patients diagnosed with cerebral venous sinus thrombosis between January 1987 and March 2018 from 7 hospitals participating in the International Cerebral Venous Sinus Thrombosis Consortium from Finland, the Netherlands, Switzerland, Sweden, Mexico, Iran, and Costa Rica. Of 952 patients, 865 with available baseline platelet count were included. In a subset of 93 patients, frozen plasma samples collected during a previous study between September 2009 and February 2016 were analyzed for the presence of platelet factor 4/heparin antibodies. Exposures: Diagnosis of cerebral venous sinus thrombosis. Main Outcomes and Measures: Frequencies of admission thrombocytopenia (platelet count <150 ×103/µL), heparin-induced thrombocytopenia (as diagnosed by the treating physician), and platelet factor 4/heparin IgG antibodies (optical density >0.4, in a subset of patients with previously collected plasma samples). Results: Of 865 patients (median age, 40 years [interquartile range, 29-53 years], 70% women), 73 (8.4%; 95% CI, 6.8%-10.5%) had thrombocytopenia, which was mild (100-149 ×103/µL) in 52 (6.0%), moderate (50-99 ×103/µL) in 17 (2.0%), and severe (<50 ×103/µL) in 4 (0.5%). Heparin-induced thrombocytopenia with platelet factor 4/heparin antibodies was diagnosed in a single patient (0.1%; 95% CI, <0.1%-0.7%). Of the convenience sample of 93 patients with cerebral venous sinus thrombosis included in the laboratory analysis, 8 (9%) had thrombocytopenia, and none (95% CI, 0%-4%) had platelet factor 4/heparin antibodies. Conclusions and Relevance: In patients with cerebral venous sinus thrombosis prior to the COVID-19 pandemic, baseline thrombocytopenia was uncommon, and heparin-induced thrombocytopenia and platelet factor 4/heparin antibodies were rare. These findings may inform investigations of the possible association between the ChAdOx1 nCoV-19 and Ad26.COV2.S COVID-19 vaccines and cerebral venous sinus thrombosis with thrombocytopenia.
Assuntos
Vacinas contra COVID-19/efeitos adversos , Heparina/imunologia , Fator Plaquetário 4/imunologia , Trombose dos Seios Intracranianos/complicações , Trombocitopenia/etiologia , Adulto , Anticorpos/sangue , Feminino , Heparina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Trombose dos Seios Intracranianos/imunologia , Trombocitopenia/epidemiologiaRESUMO
BACKGROUND: Although Sjögren's syndrome has been known to complicate with white matter lesions, encephalopathy, or stroke, reports of cerebral venous sinus thrombosis due to Sjögren's syndrome with atypical antibodies are rare. CASE REPORT: A 50-year-old woman was admitted to our neurological ward with nausea and vomiting following acute onset of severe headache in the left occipital region. Brain computed tomography revealed no abnormalities. The patient was fully conscious, with normal cognitive functioning, but exhibited unsteady tandem gait. Both magnetic resonance venography and computed tomography venography suggested left transverse sinus blockage. Intravenous enoxaparin, followed by oral warfarin, was initiated as treatment for cerebral venous sinus thrombosis. After investigation, Sjögren's syndrome was diagnosed and lupus anticoagulant antibody test was positive. The patient was treated with hydroxychloroquine, and appeared fully recovered at the 6-month follow-up, with no clinical or radiological signs of relapse. CONCLUSION: This case reports the relationship between cerebral venous sinus thrombosis and Sjögren's syndrome. It is necessary to screen autoimmune disorders in patients with cerebral venous sinus thrombosis that present with no common risk factors of venous thrombosis in order to prevent inappropriate management, and potentially adverse outcomes.
Assuntos
Inibidor de Coagulação do Lúpus/imunologia , Trombose dos Seios Intracranianos , Síndrome de Sjogren , Feminino , Humanos , Pessoa de Meia-Idade , Trombose dos Seios Intracranianos/diagnóstico , Trombose dos Seios Intracranianos/etiologia , Trombose dos Seios Intracranianos/imunologia , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/imunologiaRESUMO
OBJECTIVE: YB current affiliation: Department of Pediatrics, Hadassah-Hebrew University Medical Center, Mount Scopus, Israel YB and MJS contributed equally to the study and should be regarded as joint first authors on this manuscript. Antiphospholipid syndrome (APS) may present with thrombosis and persistently elevated titers of antiphospholipid antibodies (aPL) in the neonatal period. Our aim was to investigate the course and impact of elevated titers of aPL in a cohort of infants presenting with either perinatal arterial ischemic stroke (PAS) or cerebral sinus vein thrombosis (CSVT) during the perinatal period. STUDY DESIGN: Sixty-two infants with clinically and radiologically confirmed PAS or CSVT presenting in the neonatal period underwent thrombophilia workup that included Factor V Leiden (FVL), PII20210A mutation, MTHFR 677T polymorphism, protein C, protein S, aPL namely either circulating lupus anticoagulant (CLA), anticardiolipin antibodies (aCL) or anti-ß2-glycoprotein-1 (ß2GP1). Mothers also underwent thrombophilia workup. RESULTS: Twelve infants with persistently elevated aPL were prospectively followed. Infants with positive aPL showed no concordance with presence of maternal aPL. All children were followed for a median of 3.5 years (range: nine months to 19 years) with repeated aPL testing every three to six months. Anticoagulant therapy initiation and therapy duration varied at the physician's discretion. In 10/12 cases aPL decreased to normal range within 2.5 years; one female with complex thrombophilia risk factors required indefinite prolonged anticoagulation. None of the infants showed recurrent thrombosis or any other APS manifestations, despite lack of prolonged anticoagulation. CONCLUSIONS: The presence of aPL may be important in the pathogenesis of cerebral thrombosis in neonates. Nevertheless, the nature of thrombophilia interactions in this period and their therapeutic impact warrants further investigation.
Assuntos
Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/imunologia , Isquemia Encefálica/imunologia , Doenças do Recém-Nascido/imunologia , Trombose dos Seios Intracranianos/imunologia , Acidente Vascular Cerebral/imunologia , Adolescente , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/classificação , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/tratamento farmacológico , Biomarcadores/sangue , Isquemia Encefálica/sangue , Isquemia Encefálica/classificação , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/prevenção & controle , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido/sangue , Doenças do Recém-Nascido/classificação , Doenças do Recém-Nascido/diagnóstico , Doenças do Recém-Nascido/tratamento farmacológico , Israel , Masculino , Estudos Prospectivos , Recidiva , Sistema de Registros , Fatores de Risco , Trombose dos Seios Intracranianos/sangue , Trombose dos Seios Intracranianos/classificação , Trombose dos Seios Intracranianos/diagnóstico , Trombose dos Seios Intracranianos/prevenção & controle , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/classificação , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/prevenção & controle , Trombofilia/sangue , Trombofilia/diagnóstico , Trombofilia/imunologia , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima , Adulto JovemRESUMO
OBJECTIVES: Behçet's disease is a multisystemic, relapsing, inflammatory disorder of unknown origin. Among Turkish cohorts, 5-15% of patients show involvement of the central nervous system (CNS) at some time during their disease. There are mainly two types of clinical presentation: parenchymal CNS inflammation manifesting mainly as meningoencephalitis of the brainstem, or dural sinus thrombosis. Several drugs like high-dose steroids or immunosuppressive agents, mainly azathioprine, are used in the treatment. For patients who do not respond sufficiently to these agents or are not able tolerate them, other options are needed. PATIENTS: We are presenting 4 cases with parenchymal neuro-Behçet's disease, where commonly used immunosuppressive drugs could not be continued due to intolerance or inefficacy. However, the patients benefited well from mycophenolate mofetil. The benefit was sustained during 3-7 years of follow-up (median 6.5 years). CONCLUSIONS: Mycophenolate mofetil seems to be an alternative drug in parenchymal neuro-Behçet's disease; however, large controlled studies should be performed for verification of our results.
Assuntos
Síndrome de Behçet/tratamento farmacológico , Imunossupressores/uso terapêutico , Meningoencefalite/tratamento farmacológico , Ácido Micofenólico/análogos & derivados , Adulto , Síndrome de Behçet/complicações , Síndrome de Behçet/imunologia , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Meningoencefalite/etiologia , Meningoencefalite/imunologia , Mesencéfalo/patologia , Ácido Micofenólico/uso terapêutico , Ponte/patologia , Trombose dos Seios Intracranianos/tratamento farmacológico , Trombose dos Seios Intracranianos/etiologia , Trombose dos Seios Intracranianos/imunologia , Resultado do Tratamento , Uveíte/tratamento farmacológico , Uveíte/etiologia , Uveíte/imunologiaRESUMO
OBJECTIVE: To evaluate the prognosis values of systemic immune-inflammation index (SII) in non-chronic cerebral venous sinus thrombosis (CVST). METHODS: patients with CVST, admitted to the First Affiliated Hospital of Zhengzhou University, were retrospectively identified from January 2013 to December 2018. We selected patients in acute/subacute phase from database. Functional outcomes of patients were evaluated with the modified Rankin Scale (mRS)-mRS 3-6 as poor outcomes and mRS 6 as death. The overall survival time was defined as the date of onset to the date of death or last follow-up date. Survival analysis was described by the Kaplan-Meier curve and Cox regression analysis. Multivariate logistic regression analysis assessed the relationship between SII and poor functional outcome. The area under the Receiver Operating Curve curve (AUC) was estimated to evaluate the ability of SII in prediction. RESULTS: A total of 270 patients were included and their duration of follow-up was 22 months (6-66 months), of whom 31 patients had poor outcomes and 24 patients dead. Cox regression analysis showed that SII (HR=1.304, 95% CI: 1.101 to 1.703, p=0.001) was a predictor of death in non-chronic CVST. Patients with higher SII presented lower survival rates (p=0.003). The AUC of SII was 0.792 (95% CI: 0.695 to 0.888, p=0.040) with a sensitivity of 69.6% and specificity of 80.1%. Subgroups analysis demonstrated that SII was an important predictor of poor outcomes in male (OR=1.303, 95% CI: 1.102 to 1.501, p=0.011) and pregnancy/puerperium female (OR=1.407, 95% CI: 1.204 to 1.703, p=0.034). CONCLUSIONS: SII was a potential predictor in the poor prognosis of patients with acute/subacute CVST, especially in male and pregnancy/puerperium female.
Assuntos
Plaquetas/imunologia , Inflamação/diagnóstico , Contagem de Linfócitos , Linfócitos/imunologia , Neutrófilos/imunologia , Contagem de Plaquetas , Trombose dos Seios Intracranianos/diagnóstico , Adulto , Feminino , Humanos , Inflamação/sangue , Inflamação/imunologia , Inflamação/mortalidade , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Trombose dos Seios Intracranianos/sangue , Trombose dos Seios Intracranianos/imunologia , Trombose dos Seios Intracranianos/mortalidade , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND Antiphospholipid syndrome (APS) is an autoimmune disease characterized by antibodies directed against phospholipids on plasma membranes. Through unclear mechanisms, APS confers hypercoagulability. APS may cause recurrent thromboses in the arterial and venous vasculature. We report a case of primary APS resulting in cerebral venous thrombosis and ST-elevation myocardial infarction (STEMI) for which only antiphosphatidylserine (aPS) IgM antibody was positive after extensive investigation. CASE REPORT A 48-year-old male was admitted after a witnessed generalized seizure with subsequent confusion. Imaging demonstrated thrombosis of multiple central nervous system (CNS) sinuses, including the superior sagittal sinus and bilateral transverse sinuses. The patient was heparinized with aggressive hydration, which proved inadequate, prompting endovascular thrombectomy. Three months later, despite anticoagulation therapy, the patient developed a STEMI when International Normalized Ratio (INR) was 1.8. Echocardiogram (ECHO) and PAN CT scan were normal. Initial coagulation studies demonstrated normal anticardiolipin antibody, prothrombin time, partial thromboplastin time, and platelet count. Outpatient coagulation studies revealed normal antithrombin III, protein C/S, hemoglobin electrophoresis, homocysteine, anti-ß2 glycoprotein 1 antibodies, and D-Dimer. Factor V Leiden, JAK 2 mutation, prothrombin gene mutation, and tests for paroxysmal nocturnal hemoglobinuria (PNH) were negative. A positive phosphatidylserine IgM was detected. The patient was continued on warfarin (10 mg daily) with a target INR of 3.0-3.5 and clopidogrel (75 mg daily). CONCLUSIONS Despite extensive investigation, this patient only showed evidence of elevated aPS IgM antibodies, likely contributing to his CNS venous sinus thromboses and STEMI. It is important to screen for antiphosphatidylserine antibodies in cases of unprovoked thrombosis when standard thrombophilia analysis is unrevealing. This will assist in identifying pathogenicity and help prevent recurrence of subsequent thromboses.
Assuntos
Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/diagnóstico , Infarto do Miocárdio/imunologia , Fosfatidilserinas/imunologia , Trombose dos Seios Intracranianos/diagnóstico , Anticorpos Antifosfolipídeos/efeitos adversos , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/etiologia , Fosfatidilserinas/antagonistas & inibidores , Trombose dos Seios Intracranianos/etiologia , Trombose dos Seios Intracranianos/imunologiaAssuntos
Citocinas/líquido cefalorraquidiano , Inflamação/imunologia , Inflamação/fisiopatologia , Pseudotumor Cerebral/imunologia , Pseudotumor Cerebral/fisiopatologia , Biomarcadores/análise , Biomarcadores/líquido cefalorraquidiano , Causalidade , Líquido Cefalorraquidiano/imunologia , Citocinas/análise , Doenças Desmielinizantes/complicações , Doenças Desmielinizantes/imunologia , Doenças Desmielinizantes/fisiopatologia , Humanos , Inflamação/complicações , Trombose dos Seios Intracranianos/imunologia , Trombose dos Seios Intracranianos/fisiopatologiaRESUMO
Anticardiolipin antibodies are circulating autoantibodies directed against phospholipids. They have been previously associated with systemic venous and arterial but not with cerebral venous thrombosis. We describe the case of a middle aged woman with circulating anticardiolipin antibodies who suffered from dural sinus transversus and jugular venous thrombosis documented by Nuclear Magnetic Resonance (NMR).
Assuntos
Anticorpos Anticardiolipina/isolamento & purificação , Trombose dos Seios Intracranianos/imunologia , Infarto Cerebral/etiologia , Feminino , Humanos , Espectroscopia de Ressonância Magnética , Pessoa de Meia-Idade , Trombose dos Seios Intracranianos/complicações , Trombose dos Seios Intracranianos/diagnóstico , Lobo Temporal/irrigação sanguíneaRESUMO
Antiphospholipid antibodies have been recognized as a marker for an increased risk of thrombosis, including cerebral venous thrombosis. This is a clinical study of three patients who presented with features of raised intracranial tension. Investigations revealed normal CT of brain and CSF examination in two patients. MRI of brain revealed dural venous sinus thrombosis in all the patients and positive antiphospholipid antibodies in the blood. All patients recovered with anticoagulant therapy. Antiphospholipid antibodies should be considered in the differential diagnosis of pseudotumor syndrome related to cerebral venous thrombosis.
Assuntos
Anticorpos Antifosfolipídeos/análise , Pseudotumor Cerebral/etiologia , Trombose dos Seios Intracranianos/diagnóstico , Adolescente , Adulto , Síndrome Antifosfolipídica/complicações , Feminino , Humanos , Masculino , Trombose dos Seios Intracranianos/complicações , Trombose dos Seios Intracranianos/imunologiaRESUMO
We describe a case of cerebral deep venous and venous sinus thromboses with anti-cardiolipin antibody. A 62-year-old male with no previous illness of thrombosis but with alcohol abuse was admitted with acute onset unconsciousness. He recovered two days after with no severe sequela. Laboratory findings suggested the preceding conditions of dehydration and inflammation. X-ray CT of the head revealed symmetrical low density areas in the thalami and basal ganglia, high density signs in the cerebral deep veins, and dilation of the lateral ventricles. MRI on the second hospital day showed abnormal intensities in the thalami and basal ganglia (high signal on T 2-weighed and FLAIR image, low signals on T 1-weighed image, but almost isointensity on diffusion weighed image) and acute to subacute phase thrombus in the superior sagittal sinus. Abnormal intensities observed on MRI disappeared gradually in the following studies. Venous phase images of cerebral angiography performed in chronic phase disclosed occlusion of the superior sagittal sinus and stenosis of the vein of Galen. These radiological findings support the diagnosis of cerebral deep vein and venous sinus thromboses. Hematological examination revealed positive anti-cardiolipin IgG antibody. Several cases of cerebral deep venous thrombosis with anti-cardiolipin antibody have been reported. In our case, dehydration induced by alcohol abuse would have been the trigger of thrombosis, while the existence of anti-cardiolipin antibody might contribute to the risk of thrombosis as an underlying condition.
Assuntos
Anticorpos Anticardiolipina/análise , Trombose dos Seios Intracranianos/imunologia , Trombose Venosa/imunologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Trombose dos Seios Intracranianos/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
The patient is a 30-year-old man who has suffered from recurrent attacks of tonsilitis, oral aphthae and scrotal ulcerations, erythema nodosum and thrombophlebitis. In April, 1980, he gradually developed headache and visual disturbance. On April 14, 1980, he was pointed out remarked bilateral choked disc by an ophthalmologist and then admitted to the Miyazaki Medical College Hospital. On admission to our service, he showed atypical symptoms of Behçet's disease, namely, oral aphthae and scrotal ulcerations, erythema nodosum and bilateral choked disc. Laboratory data demonstrated hyperimmunoglobulinemia, increased clotting factors and decreased fibrinolytic activity. Immunogenetically, HLA BW51 type was demonstrated. The angiograms showed complete obstructions of the superior sagittal sinus and the common trunk of the femoral artery. Histological examination of the skin lesion demonstrated atypical chronic inflammation and thrombophlebitis. A diagnosis of atypical Vasculo-Behçet's disease was made. The response to the steroid therapy was dramatic, though the fibrinolytic drugs, anticoagulants and vasodilators were not effective. Thrombophlebitis is a well recognized complication of Behçet's disease occurring in major vessels, however thrombosis of the dural sinus has rarely reported. This case may be the first one which had superior sagittal sinus thrombosis with Vasculo-Behçet's disease in literature. We discussed the mechanism of the thrombogenesis, the relationship to HLA, the coexistence of Neuro-Behçet's disease and the therapy of Vasculo-Behçet's disease.
Assuntos
Síndrome de Behçet/complicações , Trombose dos Seios Intracranianos/etiologia , Adulto , Síndrome de Behçet/imunologia , Angiografia Cerebral , Antígenos HLA/genética , Humanos , Masculino , Trombose dos Seios Intracranianos/diagnóstico , Trombose dos Seios Intracranianos/imunologiaRESUMO
TITLE: Etanercept: constituye un factor de riesgo para el desarrollo de trombosis venosa cerebral?
Assuntos
Síndrome Antifosfolipídica/complicações , Antirreumáticos/efeitos adversos , Imunoglobulina G/efeitos adversos , Trombose dos Seios Intracranianos/induzido quimicamente , Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Idoso , Anticorpos Anticardiolipina/sangue , Antirreumáticos/uso terapêutico , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Autoanticorpos/sangue , Transtornos da Consciência/etiologia , Quimioterapia Combinada , Emergências , Etanercepte , Feminino , Humanos , Hidrocefalia/etiologia , Imunoglobulina G/uso terapêutico , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Paresia/etiologia , Receptores do Fator de Necrose Tumoral/uso terapêutico , Trombose dos Seios Intracranianos/etiologia , Trombose dos Seios Intracranianos/imunologia , Síndrome de Sjogren/tratamento farmacológico , Síndrome de Sjogren/etiologia , Tomografia Computadorizada por Raios X , beta 2-Glicoproteína I/imunologiaRESUMO
Cerebral venous and sinus thrombosis (CVST) is a multifaceted disorder. The frequency of inherited and acquired thrombophilia among 16 CVST patients was evaluated. The mean age of the patients was 22.9 years. Five out of the 16 CVST patients (31.2%) showed the G1691A mutation of factor V. The frequency of the C677T methylenetetrahydrofolate reductase (MTHFR) genotype was 50% (8/16) in patients (2 of them were homozygous). Four of the patients (25%) had both factor V Leiden and MTHFR mutation. Three of the patients had positive antiphospholipid antibodies. At the time of CVST, 2 female patients were taking oral contraceptive pills. Four patients were known to have malignancies. Despite the limitation of the sample size, we identified an inherited coagulopathy at high rate in our patients. Combined inherited thrombophilia was also present in 25% of patients. This finding supports the impression of a multifactorial process leading to CVST in Lebanese patients.
Assuntos
Fator V/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Trombose dos Seios Intracranianos/etiologia , Trombofilia/complicações , Adolescente , Adulto , Idoso de 80 Anos ou mais , Anticorpos Antifosfolipídeos/sangue , Criança , Estudos de Coortes , Anticoncepcionais Orais/efeitos adversos , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Líbano , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Fatores de Risco , Trombose dos Seios Intracranianos/genética , Trombose dos Seios Intracranianos/imunologia , Trombofilia/genéticaRESUMO
Heparin-associated thrombocytopenia may be a potentially devastating event when linked with thrombosis. Two cases of heparin-associated thrombocytopenia are presented, one with thrombosis that culminated in maternal death. Heparin-associated platelet antibody was seen in both patients. The incidence and management of heparin-associated thrombocytopenia are discussed.
Assuntos
Anticorpos/análise , Heparina/imunologia , Complicações Hematológicas na Gravidez/imunologia , Adolescente , Adulto , Plaquetas/imunologia , Seio Cavernoso , Feminino , Heparina/efeitos adversos , Humanos , Imunoglobulina G/análise , Gravidez , Complicações Hematológicas na Gravidez/etiologia , Trombose dos Seios Intracranianos/etiologia , Trombose dos Seios Intracranianos/imunologia , Trombocitopenia/etiologia , Trombocitopenia/imunologiaRESUMO
Thromboembolic disease is a well-recognized but very uncommon complication of inflammatory bowel disease. The mechanisms of the increased risk of thrombosis are not well understood: although several coagulation abnormalities have been described in inflammatory bowel disease patients, it is not clear whether they actually contribute to hypercoagulation or whether they are nonspecific markers of inflammation. Antiphospholipid antibodies (anticardiolipin antibodies and/or lupus anticoagulant) have recently been associated with an increased risk of thrombosis, particularly cerebrovascular disease in young patients. We report the case of a 33-yr-old female with severe ulcerative colitis at first attack who developed thrombosis of the superior and inferior longitudinal dural sinuses. No risk factors for thrombosis or coagulation abnormalities were observed; however, lupus anticoagulant was detected in the serum. The patient was successfully treated with osmotic agents, prophylactic anticonvulsant, and antiplatelet therapy, combined with i.v. steroids. After 6 months, the colitis is in remission, and the neurological recovery is good even if not yet complete.
Assuntos
Colite Ulcerativa/complicações , Inibidor de Coagulação do Lúpus/análise , Trombose dos Seios Intracranianos/etiologia , Adulto , Síndrome Antifosfolipídica/complicações , Testes de Coagulação Sanguínea , Colite Ulcerativa/sangue , Colite Ulcerativa/imunologia , Colite Ulcerativa/terapia , Feminino , Humanos , Trombose dos Seios Intracranianos/sangue , Trombose dos Seios Intracranianos/imunologia , Trombose dos Seios Intracranianos/terapiaRESUMO
We describe the first case in which de novo production of multiple IgG antinuclear antibodies (ANA) occurred in a female neonate of an ANA negative mother. The infant presented at 4 weeks of age with hemorrhagic panencephalitis, diffuse intraparenchymal hemorrhages, and straight sinus thrombosis. She had been vaccinated against hepatitis B at birth. No other cause was found and maternal prenatal care was unremarkable. The infant's screening ANA test by ELISA was positive at 6 weeks with specificity for ssDNA, Sm, and nRNP/Sm. At 8 weeks antibodies to dsDNA and centromere were detected as well. By 8 months, she still had slightly elevated anti-dsDNA, Sm, and nRNP/Sm antibodies. The ANA test by immunofluorescence was abnormal at 8 weeks through 13 weeks with centromere and then homogeneous pattern. Based on similarities with other reported cases, we speculate that hepatitis B vaccination may have been involved in the development of antinuclear antibodies.
Assuntos
Anticorpos Antinucleares/imunologia , Imunoglobulina G/análise , Ribonucleoproteínas Nucleares Pequenas , Adulto , Autoantígenos/imunologia , Centrômero/imunologia , DNA/imunologia , DNA de Cadeia Simples/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Recém-Nascido , Valores de Referência , Trombose dos Seios Intracranianos/complicações , Trombose dos Seios Intracranianos/imunologia , Trombose dos Seios Intracranianos/patologia , Panencefalite Esclerosante Subaguda/complicações , Panencefalite Esclerosante Subaguda/imunologia , Panencefalite Esclerosante Subaguda/patologia , Proteínas Centrais de snRNPRESUMO
OBJECTIVE: Our goal was to describe the neuroradiologic findings in hemorrhagic venous infarction related to a hypercoagulable state caused by antiphospholipid antibodies (aPA). MATERIALS AND METHODS: Magnetic resonance imaging was performed on two patients with superior sagittal thrombosis related to the presence of aPA. RESULTS: A parenchymal region of hyperintense signal due to hemorrhagic venous infarction was demonstrated in both patients, along with abnormal signal within the thrombosed superior sagittal sinus. CONCLUSION: Hemorrhagic venous infarction may result from the hypercoagulable state related to aPA. The presence of these antibodies should be considered in the setting of otherwise unexplained dural sinus thrombosis and/or venous infarction.
Assuntos
Anticorpos Antifosfolipídeos/análise , Hemorragia Cerebral/diagnóstico , Infarto Cerebral/diagnóstico , Veias Cerebrais/patologia , Dura-Máter/patologia , Imageamento por Ressonância Magnética , Trombose dos Seios Intracranianos/diagnóstico , Adulto , Hemorragia Cerebral/imunologia , Infarto Cerebral/imunologia , Veias Cerebrais/imunologia , Dura-Máter/imunologia , Humanos , Inibidor de Coagulação do Lúpus/análise , Masculino , Pessoa de Meia-Idade , Trombose dos Seios Intracranianos/imunologiaRESUMO
OBJECTIVE: The purpose of this study was to determine the spectrum of neuroradiologic findings in patients with antiphospholipid antibodies (APA) and to compare findings in systemic lupus erythematosus (SLE) and non-SLE patients. MATERIALS AND METHODS: We identified 110 patients with APA who underwent CT or MR imaging, of whom 59 (54%) had abnormal studies. Of these 59 patients, abnormalities were categorized as large infarcts, cortical infarcts, lacunar infarcts, hyperintense white matter foci on T2-weighted images, or dural sinus thrombosis. White matter foci were designated as small (< 5mm) or large (> 5 mm). RESULTS: Large infarcts were the most common abnormality, seen in 24 of 110 (22%) patients, followed in frequency by hyperintense white matter foci, seen in 19 of 110 (17%) patients. Ninety-five percent of patients with hyperintense white matter foci had at least one large lesion, and 76% had five or more small foci, three or more large foci, or both. Small cortical infarcts and lacunar infarcts were seen in 11 of 110 (10%) and 10 of 110 (9%) patients, respectively. Dural sinus thrombosis was seen in five patients. The frequency of abnormalities was high in both the SLE (57%) and the non-SLE (41%) groups. Large infarcts were more common in the non-SLE group (26%) than in the SLE group (5%). Although hyperintense white matter foci and cortical infarcts were more common in SLE patients, the differences were not statistically significant. CONCLUSION: Infarcts of various sizes and hyperintense white matter foci are the most common abnormalities seen on CT and MR imaging in patients with APA. We found no significant differences in frequencies of abnormalities seen between non-SLE and SLE patients.