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1.
Medicine (Baltimore) ; 100(5): e24297, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33592875

RESUMO

RATIONALE: Cardiac thrombus and stroke are rare complications in Mycoplasma pneumoniae infection, which is a common cause of community-acquired pneumonia in children. Early detection and prevention of thrombus in children with M pneumoniae pneumonia is relatively difficult. PATIENT CONCERNS: A 5-year-old boy with severe M pneumoniae pneumonia was referred to our center. During the treatment with sufficient antibiotics, an echocardiography surprisingly revealed a thrombus in the left atrium, with significant changes in D-dimer level and anti-phospholipid antibodies. At day 12 after admission, the patient showed impaired consciousness, aphasia, and reduced limb muscle power. Magnetic resonance angiography (MRA) showed right middle cerebral artery infarction. DIAGNOSES: Cardiac thrombus and stroke associated with M pneumoniae pneumonia. INTERVENTIONS: He was started on aggressive antibiotic therapy and urokinase thrombolytic therapy for 24 hours, continued with low molecular heparin calcium and aspirin along with rehabilitation training. OUTCOMES: On follow up, the D-dimer decreased slowly and echocardiograms showed a steadily decreasing size of thrombus with eventual disappearance at day 22 after admission. His left limb muscle power was improved after rehabilitation for 2 months. LESSONS: Early diagnosis and treatment with multiple modalities maybe useful for improving prognosis of cardiac thrombus and stroke in M pneumoniae pneumonia. Changes in D-dimer level and anti-phospholipid antibodies should be routinely monitored in severe M pneumoniae pneumonia.


Assuntos
Cardiopatias/microbiologia , Mycoplasma pneumoniae , Pneumonia por Mycoplasma/microbiologia , Acidente Vascular Cerebral/microbiologia , Trombose/microbiologia , Antibacterianos/uso terapêutico , Anticorpos Antifosfolipídeos/sangue , Pré-Escolar , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Cardiopatias/sangue , Cardiopatias/tratamento farmacológico , Humanos , Masculino , Pneumonia por Mycoplasma/sangue , Pneumonia por Mycoplasma/tratamento farmacológico , Prognóstico , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/tratamento farmacológico , Trombose/sangue , Trombose/tratamento farmacológico
6.
J Am Heart Assoc ; 9(21): e017773, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-32972320

RESUMO

Background Recent literature reports a strong thrombotic tendency in patients hospitalized for a coronavirus disease 2019 (COVID-19) infection. This characteristic is unusual and seems specific to COVID-19 infections, especially in their severe form. Viral infections can trigger acquired thrombophilia, which can then lead to thrombotic complications. We investigate for the presence of acquired thrombophilia, which could participate in this phenomenon, and report its prevalence. We also wonder if these thrombophilias participate in the bad prognosis of severe COVID-19 infections. Methods and Results In 89 consecutive patients hospitalized for COVID-19 infection, we found a 20% prevalence of PS (protein S) deficiency and a high (ie, 72%) prevalence of antiphospholipid antibodies: mainly lupus anticoagulant. The presence of PS deficiency or antiphospholipid antibodies was not linked with a prolonged activated partial thromboplastin time nor with D-dimer, fibrinogen, or CRP (C-reactive protein) concentrations. These coagulation abnormalities are also not linked with thrombotic clinical events occurring during hospitalization nor with mortality. Conclusions We assess a high prevalence of positive tests detecting thrombophilia in COVID-19 infections. However, in our series, these acquired thrombophilias are not correlated with the severity of the disease nor with the occurrence of thrombotic events. Albeit the strong thrombotic tendency in COVID-19 infections, the presence of frequent acquired thrombophilia may be part of the inflammation storm of COVID-19 and should not systematically modify our strategy on prophylactic anticoagulant treatment, which is already revised upwards in this pathological condition. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT04335162.


Assuntos
Síndrome Antifosfolipídica/epidemiologia , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Deficiência de Proteína S/epidemiologia , Trombose/epidemiologia , Idoso , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/diagnóstico , Biomarcadores/sangue , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Prevalência , Prognóstico , Proteína S/análise , Deficiência de Proteína S/sangue , Deficiência de Proteína S/diagnóstico , Fatores de Risco , Índice de Gravidade de Doença , Trombose/sangue , Trombose/diagnóstico
8.
PLoS One ; 15(7): e0236664, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32722684

RESUMO

BACKGROUND: Systemic lupus erythematosus (SLE) is a severe autoimmune disease in which immune tolerance defects drive production of pathogenic anti-nuclear autoantibodies. Anergic B cells are considered a potential source of these autoantibodies due to their autoreactivity and overrepresentation in SLE patients. Studies of lupus-prone mice have shown that genetic defects mediating autoimmunity can breach B cell anergy, but how this breach occurs with regards to endogenous nuclear antigen remains unclear. We investigated whether B and T cell defects in congenic mice (c1) derived from the lupus-prone New Zealand Black strain can breach tolerance to nuclear self-antigen in the presence of knock-in genes (Vκ8/3H9; dKI) that generate a ssDNA-reactive, anergic B cell population. METHODS: Flow cytometry was used to assess splenic B and T cells from 8-month-old c1 dKI mice and serum autoantibodies were measured by ELISA. dKI B cells stimulated in vitro with anti-IgM were assessed for proliferation and activation by examining CFSE decay and CD86. Cytokine-producing T cells were identified by flow cytometry following culture of dKI splenocytes with PMA and ionomycin. dKI B cells from 6-8-week-old mice were adoptively transferred into 4-month-old wild type recipients and assessed after 7 days via flow cytometry and immunofluorescence microscopy. RESULTS: c1 dKI mice exhibited B cell proliferation indicative of impaired anergy, but had attenuated autoantibodies and germinal centres compared to wild type littermates. This attenuation appeared to stem from a decrease in PD-1hi T helper cells in the dKI strains, as c1 dKI B cells were recruited to germinal centres when adoptively transferred into c1 wild type mice. CONCLUSION: Anergic, DNA-specific autoreactive B cells only seem to drive profound autoimmunity in the presence of concomitant defects in the T cell subsets that support high-affinity plasma cell production.


Assuntos
Anticorpos Antinucleares/genética , Anticorpos Antifosfolipídeos/genética , Antígenos/imunologia , Linfócitos B/imunologia , Anergia Clonal , Lúpus Eritematoso Sistêmico/imunologia , Animais , Linfócitos B/citologia , Proliferação de Células , DNA de Cadeia Simples/imunologia , Suscetibilidade a Doenças , Técnicas de Introdução de Genes , Lúpus Eritematoso Sistêmico/genética , Camundongos
9.
Clin Exp Rheumatol ; 38(4): 754-759, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32723434

RESUMO

OBJECTIVES: COVID-19 features include disseminated intravascular coagulation and thrombotic microangiopathy indicating a hypercoagulable state. We aimed to investigate antiphospholipid antibodies (aPL) prevalence and clinical relationships in a large cohort of COVID-19 patients. METHODS: We analysed the prevalence and titres of serum aPL in 122 patients with COVID-19 and 157 with primary antiphospholipid syndrome (PAPS) and 91 with other autoimmune rheumatic diseases (oARD) for comparison. IgG/IgM anticardiolipin (aCL) and IgG/IgM anti-beta2glycoprotein I (ß2GPI) were assayed using homemade ELISA, IgA aCL and anti-ß2GPI by commercial ELISA kits and lupus anticoagulant (LAC) by multiple coagulation tests following updated international guidelines. RESULTS: Prevalence of IgG and IgM aCL and of IgG and IgM anti-ß2GPI across COVID-19 patients were 13.4%, 2.7%, 6.3% and 7.1%, being significantly lower than in PAPS (p<0.0001 for all). Frequency of IgG aCL and IgM anti-ß2GPI was comparable to oARD (13.4% vs. 13.2% and 7.1% vs. 11%, respectively), while IgG anti-ß2GPI and IgM aCL were lower (p<0.01). IgA aCL and IgA anti-ß2GPI were retrieved in 1.7% and 3.3% of COVID-19 patients, respectively. Positive LAC was observed in 22.2% COVID-19 vs. 54.1% of PAPS (p<0.0001) and 14.6% of oARD (p=0.21). Venous or arterial thromboses occurred in 18/46 (39.1%) COVID-19 patients and were not associated with positive aPL (p=0.09). CONCLUSIONS: Thrombosis is a frequent manifestation during COVID-19 infection. However, prevalence and titres of aPL antibodies or LAC were neither consistently increased nor associated with thrombosis when measured at a single timepoint, therefore not representing a suitable screening tool in the acute stage of disease.


Assuntos
Anticorpos Antifosfolipídeos/sangue , Infecções por Coronavirus/imunologia , Pneumonia Viral/imunologia , Anticorpos Anticardiolipina/sangue , Síndrome Antifosfolipídica/sangue , Betacoronavirus , Infecções por Coronavirus/sangue , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Pandemias , Pneumonia Viral/sangue , Trombose/complicações , Trombose/virologia , beta 2-Glicoproteína I/imunologia
10.
J Thromb Thrombolysis ; 50(3): 580-586, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32648093

RESUMO

The outbreak of novel coronavirus disease 2019 (COVID-19) has now become a global pandemic. Coagulopathy has been reported widely in critically ill COVID-19 patients and was related to high mortality. However, the comprehensive coagulation profiles have not been examined and the underlying mechanism of the coagulopathy in COVID-19 patients is unclear. To study the coagulation profiles of routine hemostasis tests, natural anticoagulants, coagulant factors and antiphospholipid antibodies in critically ill COVID-19 patients. This single-center and cross-section study included 19 patients with COVID-19, who were admitted to intensive care unit (ICU) at Tongji hospital in Wuhan, China, from Feb 23 to Mar 3, 2020. Demographic data, laboratory parameters, treatments and clinical outcomes of the patients were collected and analyzed. The final date of follow-up was Mar 31, 2020. In this study, 12 thrombotic events occurred in 9 patients, including 4 cerebral infarctions, 7 acro-ischemia and 1 internal jugular vein thrombosis. The common abnormalities of routine coagulation tests included evelated D-Dimer level (100%), prolonged prothrombin time (73.7%) and hyperfibrinogenemia (73.7%). The median activities of natural anticoagulants including protein C, protein S and antithrombin were all below the normal range. Factor VIII activities were significantly above normal range (median value 307%, IQR 198-441) in all patients. Factor V and factor VII activities were significantly lower in near-terminal stage patients. Anti-phospholipid antibodies were present in 10 patients. Strikingly, 4 cerebral infarction events were in patients had anti-phospholipid antibodies of multiple isotypes. Sustained hypercoagulable status and thrombotic events were common in critically ill patients with COVID-19. The low activities of natural anticoagulants, elevated factor VIII level and the presence of antiphospholipid antibodies, together, may contribute to the etiopathology of coagulopathy in COVID-19 patients.


Assuntos
Anticorpos Antifosfolipídeos/sangue , Betacoronavirus/patogenicidade , Inibidores dos Fatores de Coagulação Sanguínea/sangue , Fatores de Coagulação Sanguínea/análise , Coagulação Sanguínea , Infecções por Coronavirus/sangue , Pneumonia Viral/sangue , Trombose/sangue , Idoso , Proteínas Antitrombina/análise , Biomarcadores/sangue , China , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Estado Terminal , Estudos Transversais , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Interações Hospedeiro-Patógeno , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Proteína C/análise , Proteína S/análise , Fatores de Risco , Trombose/diagnóstico , Trombose/virologia
11.
Rheumatol Int ; 40(10): 1539-1554, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32666137

RESUMO

The coronavirus disease-2019 (COVID-19) pandemic is likely to pose new challenges to the rheumatology community in the near and distant future. Some of the challenges, like the severity of COVID-19 among patients on immunosuppressive agents, are predictable and are being evaluated with great care and effort across the globe. A few others, such as atypical manifestations of COVID-19 mimicking rheumatic musculoskeletal diseases (RMDs) are being reported. Like in many other viral infections, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can potentially lead to an array of rheumatological and autoimmune manifestations by molecular mimicry (cross-reacting epitope between the virus and the host), bystander killing (virus-specific CD8 + T cells migrating to the target tissues and exerting cytotoxicity), epitope spreading, viral persistence (polyclonal activation due to the constant presence of viral antigens driving immune-mediated injury) and formation of neutrophil extracellular traps. In addition, the myriad of antiviral drugs presently being tried in the treatment of COVID-19 can result in several rheumatic musculoskeletal adverse effects. In this review, we have addressed the possible spectrum and mechanisms of various autoimmune and rheumatic musculoskeletal manifestations that can be precipitated by COVID-19 infection, its therapy, and the preventive strategies to contain the infection.


Assuntos
Doenças Autoimunes/fisiopatologia , Infecções por Coronavirus/fisiopatologia , Doenças Musculoesqueléticas/fisiopatologia , Pneumonia Viral/fisiopatologia , Doenças Reumáticas/fisiopatologia , Anticorpos Antinucleares/imunologia , Anticorpos Antifosfolipídeos/imunologia , Antivirais/efeitos adversos , Artralgia/etiologia , Artralgia/imunologia , Artralgia/fisiopatologia , Doenças Autoimunes/etiologia , Doenças Autoimunes/imunologia , Betacoronavirus , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/imunologia , Transtornos da Coagulação Sanguínea/fisiopatologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Reações Cruzadas/imunologia , Armadilhas Extracelulares/imunologia , Produtos de Degradação da Fibrina e do Fibrinogênio , Síndrome de Guillain-Barré/etiologia , Síndrome de Guillain-Barré/imunologia , Síndrome de Guillain-Barré/fisiopatologia , Humanos , Inibidor de Coagulação do Lúpus/imunologia , Mimetismo Molecular , Síndrome de Linfonodos Mucocutâneos/etiologia , Síndrome de Linfonodos Mucocutâneos/imunologia , Síndrome de Linfonodos Mucocutâneos/fisiopatologia , Debilidade Muscular/etiologia , Debilidade Muscular/imunologia , Debilidade Muscular/fisiopatologia , Doenças Musculoesqueléticas/etiologia , Doenças Musculoesqueléticas/imunologia , Mialgia/etiologia , Mialgia/imunologia , Mialgia/fisiopatologia , Miocardite/etiologia , Miocardite/imunologia , Miocardite/fisiopatologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Doenças Reumáticas/etiologia , Doenças Reumáticas/imunologia
12.
Sci Rep ; 10(1): 12221, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32699227

RESUMO

Functional tests for lupus anticoagulants (LA) as part of a thrombophilia workup are commonly performed in patients under anticoagulant therapy that may interfere with assay results. There is no consensus on how these tests should be assessed in patients on direct oral anticoagulants (DOACs). In this retrospective cohort study, we analysed data from patients with a history of thrombosis in whom dilute Russell viper venom time (dRVVT), LA-sensitive aPTT, and solid phase assays for antiphospholipid antibodies (aPL) were performed (n = 3,147, thereof 588 on rivaroxaban, 144 on apixaban, 1,179 on other anticoagulant drugs). The dRVVT ratio was correlated with rivaroxaban (r = 0.30, P < 10-4) but not with apixaban plasma levels. The LA-sensitive aPTT/aPTT ratio showed no correlation with DOAC levels. Correspondingly, the rate of patients with abnormal dRVVT test was significantly higher (P < 10-4) under rivaroxaban (88%) than in thrombosis patients without anticoagulant medication (6%), independent from their aPL plasma levels. No isolated positive results of functional LA testing in patients on anticoagulants could be confirmed in repeated testing after discontinuation of the medication (n = 40). These data indicate that rivaroxaban should be discontinued before functional LA testing is performed. However, viable interpretation of these tests appears to be less affected in patients on apixaban.


Assuntos
Anticoagulantes/uso terapêutico , Inibidor de Coagulação do Lúpus/uso terapêutico , Trombose/tratamento farmacológico , Administração Oral , Adulto , Anticorpos Antifosfolipídeos/uso terapêutico , Síndrome Antifosfolipídica/tratamento farmacológico , Coagulação Sanguínea/efeitos dos fármacos , Testes de Coagulação Sanguínea/métodos , Dabigatrana/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial/métodos , Tempo de Protrombina/métodos , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Estudos Retrospectivos , Rivaroxabana/uso terapêutico , Trombofilia/tratamento farmacológico
13.
Autoimmun Rev ; 19(9): 102620, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32682986

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of intravenous immunoglobulin (IVIg) in secondary prevention of pregnancy complications for patients with obstetric antiphospholipid syndrome (APS) and history of stillbirth. METHODS: We described three cases of obstetric APS patients with history of stillbirth treated with IVIg in four pregnancies. In addition, we conducted a systematic literature review on the use of IVIg in obstetric APS with history of stillbirth. RESULTS: Three patients with obstetric APS and history of stillbirth were treated with prophylactic IVIg, in addition to standard treatment (hydroxychloroquine, low-dose aspirin, low molecular weight heparin, and prednisone), in four pregnancies (three singleton and one twin). All pregnancies resulted in live healthy newborns. Long-term follow-up re-evaluations (24-53 months) did not shown any sign or symptom of active systemic disease, and the children were healthy. The systematic literature review retrieved only three cases of use of IVIg in obstetric APS patients with history of stillbirth. All three cases resulted in live healthy newborns. Only in one case, mild thrombocytopenia occurred during treatment, although this event was unlikely to be related to IVIg. CONCLUSION: Our experience suggests that IVIg as secondary prevention of APS-related stillbirth is associated with good pregnancy and long-term outcomes, with no relevant safety concerns. However, the literature evidence on this topic is limited to few isolated cases, and further studies are needed to clarify which obstetric APS patients may benefit the most from IVIg.


Assuntos
Síndrome Antifosfolipídica , Imunoglobulinas Intravenosas/uso terapêutico , Complicações na Gravidez , Prevenção Secundária , Natimorto , Anticorpos Antifosfolipídeos , Anticoagulantes , Feminino , Humanos , Recém-Nascido , Gravidez
16.
Diab Vasc Dis Res ; 17(3): 1479164120922123, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32506943

RESUMO

BACKGROUND: Cardiovascular disease is a serious complication in patients with dysglycaemia, defined as either type 2 diabetes or impaired glucose tolerance. Research focusing on the identification of potential markers for atherothrombotic disease in these subjects is warranted. The antiphospholipid syndrome is a common acquired prothrombotic condition, defined by a combination of thrombotic events and/or obstetric morbidity and positivity of specific antiphospholipid antibodies. Available information on antiphospholipid antibodies in dysglycaemia is scarce. OBJECTIVE: This study investigates the association between antiphospholipid antibodies and dysglycaemia. PATIENTS/METHODS: The PAROKRANK (periodontitis and its relation to coronary artery disease) study included 805 patients, investigated 6-10 weeks after a first myocardial infarction, and 805 matched controls. Participants without known diabetes (91%) underwent an oral glucose tolerance test. Associations between antiphospholipid antibodies (anti-cardiolipin and anti-ß2 glycoprotein-I IgG, IgM and IgA) and dysglycaemia were analysed. RESULTS: In total, 137 (9%) subjects had previously known type 2 diabetes and 371 (23%) newly diagnosed dysglycaemia. Compared with the normoglycaemic participants, those with dysglycaemia had a higher proportion with first myocardial infarction (61% vs 45%, p < 0.0001) and were more often antiphospholipid antibody IgG positive (8% vs 5%; p = 0.013). HbA1c, fasting glucose and 2-h glucose were significantly associated to antiphospholipid antibody IgG. Odds ratios (ORs) were 1.04 (95% confidence interval [CI] 1.02-1.06), 1.14 (95% CI 1.00 - 1.27) and 1.12 (95% CI 1.04 - 1.21), respectively, after adjustments for age, gender and smoking. CONCLUSIONS: This study reports an association between antiphospholipid antibody IgG positivity and dysglycaemia. Further studies are needed to verify these findings and to investigate if antithrombotic therapy reduces vascular complications in antiphospholipid antibody positive subjects with dysglycaemia.


Assuntos
Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/sangue , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Infarto do Miocárdio/sangue , Idoso , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Biomarcadores/sangue , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/etiologia , Prognóstico , Medição de Risco , Fatores de Risco , Suécia
17.
Pediatr Pulmonol ; 55(8): 1879-1881, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32558285

RESUMO

The spectrum of clinical manifestations of coronavirus disease 2019 in children is yet to be fully elucidated. We report the case of an infant who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and developed mild cardiovascular inflammation, a novelty for patients of very young age, that contributes to defining the puzzling nature of this disease in pediatric patients. The potential cardiovascular involvement of SARS-CoV-2 in children should always be taken into account.


Assuntos
Infecções por Coronavirus , Pandemias , Pneumonia Viral , Anticorpos Antifosfolipídeos , Betacoronavirus , Criança , Humanos , Lactente
18.
Ter Arkh ; 92(5): 92-103, 2020 Jun 05.
Artigo em Russo | MEDLINE | ID: mdl-32598781

RESUMO

Mental disorders (mainly anxiety and depressive disorders) and cognitive impairment are often found in patients with antiphospholipid syndrome (APS), but their prevalence, structure, and mechanisms of occurrence are not well researched. The review provides literature data on the frequency, spectrum and possible causes of mental disorders and cognitive impairment in patients with APS, the pathogenetic mechanisms of these disorders (in particular, the important role of antiphospholipid antibodies, stress factors, chronic inflammation), the relationship between APS, mental disorders and as well as cognitive impairment is examined. Special attention is paid to the influence of mental disorders and cognitive impairment on patients adherence to treatment, their quality of life, as well as the particularities of psychopharmacotherapy of mental disorders in patients with APS. The aim of the review is to actualize the interdisciplinary problem of mental disorders and cognitive impairment in patients with APS and the need to introduce a partnership model of care.


Assuntos
Síndrome Antifosfolipídica , Disfunção Cognitiva , Anticorpos Antifosfolipídeos , Transtornos de Ansiedade , Humanos , Qualidade de Vida
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