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AIM: To assess risk factors of retroperitoneal and lower extremity musculoskeletal bleed in acquired haemophilia (AHA) and perform an objective assessment of disability and influence on survival. METHODS: We included 49 patients with AHA from November 2017 to May 2023. The occurrence of any retroperitoneal or/and lower extremities bleeding manifestation was investigated. On clinical follow-up, we search for compressive femoral neuropathy and quadriceps amyotrophy. The lower extremity functional scale (LEFS) was carried out one year after the last bleeding event in all AHA patients. RESULTS: A 61.2% of patients in our AHA cohort presented with any retroperitoneal and/or lower extremities musculoskeletal manifestation. Those patients had higher percentage of major bleeding EACH2/ISTH criteria (90% vs. 57%, p = .01), needs of blood transfusions (86% vs. 57% of patients, p = .03), and haemostatic by-pass products (90% vs. 63%, p = .02). Hypertension (HR 2.6, 95% CI 1.1-5.9, p = .02), presence of autoimmune disease (HR 13, 95% CI 1.7-99, p = .01), and inhibitor level > 20 BU (HR 2.6 95% CI 1.0-6.8, p = .04) significantly predicted retroperitoneal/lower extremities clinical manifestations. Most frequent sequelae were quad atrophy (30.6%) and femoral nerve palsy (20.4%). Quad atrophy and LEFS scores under 50 were associated with increased mortality (HR 3, 95% CI 1.1-8.6 and HR 12, 95% CI 3.3-45, respectively). CONCLUSION: AHA with retroperitoneal/lower extremities bleeding involvement is of greater severity and shows high disability and worst survival outcomes. Quadriceps atrophy and LEFS scale scoring under 50 predicted mortality in our AHA patients.
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BACKGROUND: Long-term anticoagulant therapy is generally recommended for thrombotic antiphospholipid syndrome (TAPS) patients, however it may be withdrawn or not introduced in routine practice. OBJECTIVES: To prospectively evaluate the risk of thrombosis recurrence and major bleeding in non-anticoagulated TAPS patients, compared to anticoagulated TAPS, and secondly, to identify different features between those two groups. PATIENTS/METHODS: Using an international registry, we identified non-anticoagulated TAPS patients at baseline, and matched them with anticoagulated TAPS patients based on gender, age, type of previous thrombosis, and associated autoimmune disease. Thrombosis recurrence and major bleeding were prospectively analyzed using Kaplan-Meier method and compared using a marginal Cox's regression model. RESULTS: As of June 2022, 94 (14 %) of the 662 TAPS patients were not anticoagulated; and 93 of them were matched with 181 anticoagulated TAPS patients (median follow-up 5 years [interquartile range 3 to 8]). The 5-year thrombosis recurrence and major bleeding rates were 12 % versus 10 %, and 6 % versus 7 %, respectively (hazard ratio [HR] 1.38, 95 % confidence interval [CI] 0.53 to 3.56, p = 0.50 and HR 0.53; 95 % CI 0.15 to 1.86; p = 0.32, respectively). Non-anticoagulated patients were more likely to receive antiplatelet therapy (p < 0.001), and less likely to have more than one previous thrombosis (p < 0.001) and lupus anticoagulant positivity (p = 0.01). CONCLUSION: Fourteen percent of the TAPS patients were not anticoagulated at recruitment. Their recurrent thrombosis risk did not differ compared to matched anticoagulated TAPS patients, supporting the pressing need for risk-stratified secondary thrombosis prevention trials in APS investigating strategies other than anticoagulation.
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Síndrome Antifosfolipídica , Trombose , Humanos , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/tratamento farmacológico , Hemorragia/etiologia , Estudos Prospectivos , Recidiva , Sistema de Registros , Trombose/complicações , Ensaios Clínicos como Assunto , Masculino , FemininoRESUMO
Acquired hemophilia A (AHA) is a rare bleeding disorder caused by the presence of autoantibodies against factor VIII (FVIII). As with other autoimmune diseases, its etiology is complex and its genetic basis is unknown. The aim of this study was to identify the immunogenetic background that predisposes individuals to AHA. HLA and KIR gene clusters, as well as KLRK1, were sequenced using next-generation sequencing in 49 AHA patients. Associations between candidate genes involved in innate and adaptive immune responses and AHA were addressed by comparing the alleles, genotypes, haplotypes, and gene frequencies in the AHA cohort with those in the donors' samples or Spanish population cohort. Two genes of the HLA cluster, as well as rs1049174 in KLRK1, which tags the natural killer (NK) cytotoxic activity haplotype, were found to be linked to AHA. Specifically, A*03:01 (p = 0.024; odds ratio (OR) = 0.26[0.06-0.85]) and DRB1*13:03 (p = 6.8 × 103, OR = 7.56[1.64-51.40]), as well as rs1049174 (p = 0.012), were significantly associated with AHA. In addition, two AHA patients were found to carry one copy each of the low-frequency allele DQB1*03:09 (nallele = 2, 2.04%), which was completely absent in the donors. To the best of our knowledge, this is the first time that the involvement of these specific alleles in the predisposition to AHA has been proposed. Further molecular and functional studies will be needed to unravel their specific contributions. We believe our findings expand the current knowledge on the genetic factors involved in susceptibility to AHA, which will contribute to improving the diagnosis and prognosis of AHA patients.
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Hemofilia A , Humanos , Hemofilia A/genética , Genótipo , Haplótipos/genética , Alelos , Frequência do Gene , Sequenciamento de Nucleotídeos em Larga Escala , Sistema Imunitário , Predisposição Genética para DoençaRESUMO
Our report shows a case of primary light-chain amyloidosis in a young patient that reflects the potential severity of bleeding diathesis associated with this plasma cell dyscrasia and the difficulty of diagnosis when only hemorrhagic manifestations are present at the onset of disease. The patient presented with recurrent and severe muscular bleeding secondary to associated acquired von Willebrand disease and fibrinolysis dysfunction. Treatment with bortezomib-cyclophosphamide and sequential hematopoietic stem cell transplantation solved coagulation alterations. On the basis of our case, we review previous reports and discuss the potential mechanism of dysfunction of coagulation in light-chain amyloidosis.
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Amiloidose , Transtornos Hemorrágicos , Doenças de von Willebrand , Humanos , Fibrinólise , Suscetibilidade a Doenças , Amiloidose/complicações , Hemorragia/etiologiaRESUMO
OBJECTIVES: To investigate the impact of thrombocytopenia on survival in patients with APS. METHODS: Thrombocytopenia and other predictors of outcome were retrospectively evaluated in an aPL-positive and APS cohort with 38-year follow-up (1980-2018). Thrombocytopenia was defined as <150 × 109 platelets/l. Hazard ratios (HR) of mortality were calculated using Cox-regression models. RESULTS: Among 114 patients, 64% had primary APS, 25% secondary APS and 10% asymptomatic aPL. Mean follow-up was 19 (range 5-38) years. ANA [hazard ratio (HR) 1.8, 95% CI 0.8, 3.6, P = 0.10], arterial thrombotic events (HR 7.0, 95% CI 1.4, 3.5, P = 0.016), myocardial infarction (HR 8.3, 95% CI 1.1, 59, P = 0.03), intracardiac thrombosis (HR 17, 95% CI 1, 279, P = 0.04) and thrombocytopenia (HR 2.9, 95% CI 1.4, 6.1, P = 0.004) were risk factors for all-cause mortality, but in multivariate analysis only thrombocytopenia (HR 2.7, 95% CI 1.3, 6.0, P = 0.01) remained significant. Persistent (HR 4.4, 95% CI 2.1, 9.2, P = 0.001) and low-moderate thrombocytopenia (HR 2.8, 95% CI 1.2, 6.4, P = 0.01) were associated with a significant increase in mortality compared with acute (HR 1.6, 95% CI 0.5, 5.3, P = 0.40) and severe (HR 2.1, 95% CI 0.5, 9.2, P = 0.30) forms. APS patients with vs without thrombocytopenia were more frequently male (58 vs 24%, P = 0.001) with arterial thrombosis (55 vs 32%, P = 0.04), LA positivity (100 vs 87%, P = 0.04), type I aPL profile (89% vs 71%, P = 0.05) and anticoagulant treatment (89 vs 63%, P = 0.01). Thrombosis caused 13% of deaths in thrombocytopenic patients and 1% in those without (P = 0.01). CONCLUSION: Thrombocytopenia is an aPL-related manifestation that identifies patients with severe disease phenotype and high thrombotic risk. Persistent low-moderate thrombocytopenia is associated with a reduced long-term survival.
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Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/mortalidade , Trombocitopenia/complicações , Trombocitopenia/mortalidade , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
: Acquired von Willebrand syndrome (AVWS) is a rare hemorrhagic condition that poses both a diagnostic and a therapeutic challenge. Here we report a singular case of AVWS with two associated conditions, small lymphocytic lymphoma (SLL) and Sjögren's syndrome. The patient presented with recurrent and severe digestive bleeding that forced us to raise a curative attempt of AVWS. A first immunosuppressive therapy with immunoglobulins was unsuccessful and it was later decided to treat lymphoproliferative entity with bendamustine and rituximab effectively achieving SLL and AVWS remission. On the basis of our case and through literature review, we discuss potential strategies to achieve AVWS remission when it appears in the setting of several causative associated conditions.
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Leucemia Linfocítica Crônica de Células B/complicações , Síndrome de Sjogren/complicações , Doenças de von Willebrand/complicações , Idoso , Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Cloridrato de Bendamustina/uso terapêutico , Feminino , Hemorragia/etiologia , Hemorragia/terapia , Humanos , Imunoglobulinas/uso terapêutico , Leucemia Linfocítica Crônica de Células B/terapia , Rituximab/uso terapêutico , Síndrome de Sjogren/terapia , Doenças de von Willebrand/terapiaAssuntos
Contratura/etiologia , Eosinofilia/complicações , Fasciite/complicações , Dedos , Adulto , Contratura/diagnóstico por imagem , Eosinofilia/diagnóstico por imagem , Fasciite/diagnóstico por imagem , Feminino , Dedos/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Tendões/diagnóstico por imagemRESUMO
Introduction/objectives autoantibodies to types I and IV collagen have been described in rheumatic fever and infective endocarditis. We tried to elucidate if an autoimmune response against collagens I and IV exists, associated with heart valve disease in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). A cohort of 172 patients with SLE (n = 79), primary APS (PAPS, n = 83), and secondary APS (n = 10) were assessed for valvulopathy by transthoracic echocardiograms. Autoantibodies to types I and IV collagen were assessed in patients and 50 controls, setting autoantibody positivity at two standard deviations above the mean antibody level of controls. Positive anticollagen IV antibody rate was significantly higher in SLE patients (17.7%) in respect to the rest of groups (PAPS 2.4%, controls 2%; P = 0.001). Percentage of positive autoantibodies to collagen I was similar in SLE and APS cohort of patients with and without valvular disease (48.4 vs 51.6%, respectively; P = 0.45). Percentage of positive autoantibodies to collagen IV was increased but not significantly in SLE and APS cohort of patients with respect to those without valvular disease (62.5 vs 37.5%, respectively; P = 0.08). Mean (standard deviation) levels of positive anticollagen I and IV antibodies did not differ between patients with and without valvular disease (85.6 ± 55 vs 81 ± 85 U/ml, respectively; P = 0.86 for anticollagen I) (0.05 ± 0.02 vs 0.12 ± 0.16 U/ml, respectively; P = 0.34 for anticollagen IV). Our data indicate a lack of association of autoantibodies to types I and IV collagen with heart valve disease in SLE and APS.
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Síndrome Antifosfolipídica/complicações , Colágeno Tipo IV/imunologia , Colágeno Tipo I/imunologia , Doenças das Valvas Cardíacas/imunologia , Lúpus Eritematoso Sistêmico/complicações , Adulto , Idoso , Síndrome Antifosfolipídica/imunologia , Autoanticorpos/sangue , Estudos de Casos e Controles , Feminino , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-IdadeRESUMO
IgG4-related disease (IgG4-RD) is a rare entity consisting of inflammation and fibrosis that has been described in multiple organs. Concrete diagnostic criteria have been established recently and there is a lack of large series of patients.To describe the clinical presentation, histopathological characteristics, treatment and evolution of a series of IgG4-RD Spanish patients.A retrospective multicenter study was performed. Twelve hospitals across Spain included patients meeting the current 2012 consensus criteria on IgG4-RD diagnosis.Fifty-five patients were included in the study, 38 of whom (69.1%) were male. Median age at diagnosis was 53 years. Thirty (54.5%) patients were included in the Histologically Highly Suggestive IgG4-RD group and 25 (45.5%) in the probable IgG4-RD group. Twenty-six (47.3%) patients had more than 1 organ affected at presentation. The most frequently affected organs were: retroperitoneum, orbital pseudotumor, pancreas, salivary and lachrymal glands, and maxillary sinuses.Corticosteroids were the mainstay of treatment (46 patients, 83.6%). Eighteen patients (32.7%) required additional immunosuppressive agents. Twenty-four (43.6%) patients achieved a complete response and 26 (43.7%) presented a partial response (<50% of regression) after 22 months of follow-up. No deaths were attributed directly to IgG4-RD and malignancy was infrequent.This is the largest IgG4-RD series reported in Europe. Patients were middle-aged males, with histologically probable IgG4-RD. The systemic form of the disease was frequent, involving mainly sites of the head and abdomen. Corticosteroids were an effective first line treatment, sometimes combined with immunosuppressive agents. Neither fatalities nor malignancies were attributed to IgG4-RD.
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Doenças Autoimunes/diagnóstico , Imunoglobulina G , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/epidemiologia , Humanos , Imunossupressores/uso terapêutico , Paraproteinemias/tratamento farmacológico , Paraproteinemias/epidemiologia , Paraproteinemias/patologia , Sistema de Registros , Espanha/epidemiologiaAssuntos
Doenças Autoimunes/imunologia , Deficiência de IgG/complicações , Imunoglobulina G/sangue , Neutropenia/imunologia , Doenças Autoimunes/diagnóstico , Biomarcadores/sangue , Doença Crônica , Humanos , Deficiência de IgG/sangue , Deficiência de IgG/diagnóstico , Deficiência de IgG/imunologia , Masculino , Pessoa de Meia-Idade , Neutropenia/diagnósticoRESUMO
AIM: Non-valvular cardiac disease in the antiphospholipid syndrome (APS) has been scanty studied. We wanted to assess the prevalence and evolution of left myocardial disease, pulmonary hypertension and intracardiac thrombi in a cohort of APS patients. METHOD: A total of 53 patients with APS, either primary (n = 34, 64%) or associated to lupus (n = 19, 36%) and 20 controls were included. Initial transthoracic echocardiography assessment was performed in patients at diagnosis, with echocardiography controls performed along mean follow-up of 12 years. Prevalence of myocardial disease in APS cohort was assessed taking into account primary risk factors (hemodynamically significant valvular disease, systemic hypertension, diabetes, alcoholism, myocardial infarction or myocarditis), the same as for pulmonary hypertension (severe left ventricular dysfunction or chronic lung disease). RESULTS: Left myocardial disease had a prevalence of 3.8% (2/53 patients), not different from controls (P = 0.12). Both patients had diastolic dysfunction grade I that maintained stability throughout echocardiographic follow-up period. Pulmonary hypertension had a prevalence of 11.3% (6/53 patients), not different from controls (P = 0.12); all cases were related to pulmonary embolism. Patients diagnosed with pulmonary hypertension in baseline maintained stable pressures throughout follow-up in the absence of new thrombosis. Intracardiac thrombi had a prevalence of 1.8% (1/53 patients), not different from controls (P = 0.4), without changes along echocardiographic follow-up. CONCLUSION: Pulmonary hypertension is the most prevalent non-valvular cardiac manifestation in APS, with an evolution associated with thromboembolic disease, while left myocardial disease and intracardiac thrombi would be rare manifestations in APS.
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Síndrome Antifosfolipídica/epidemiologia , Ecocardiografia Doppler , Cardiopatias/diagnóstico por imagem , Cardiopatias/epidemiologia , Adulto , Idoso , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/diagnóstico , Estudos de Casos e Controles , Ecocardiografia Doppler de Pulso , Feminino , Seguimentos , Cardiopatias/fisiopatologia , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/epidemiologia , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Fatores de Risco , Espanha/epidemiologia , Trombose/diagnóstico por imagem , Trombose/epidemiologia , Fatores de Tempo , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Although home intravenous antimicrobial infusion therapy (HIVAIT) has proved its safety and efficacy in a great number of common infections, there are few published studies about its role in the treatment of infections caused by multi-drug resistant microorganisms. Our objectives are to study clinical and epidemiological characteristics of patients with multi-drug resistant microorganism infections treated with HIVAIT, and its usefulness in this type of infections. METHODS: We analyzed all patients diagnosed of infections requiring HIVAIT and admitted to our Hospital at Home Unit (HHU) from March 2007 to February 2010. Subjects were divided into two groups: patients with multi-drug resistant microorganism infections as a study group, and the remaining patients as a control group. RESULTS: A total of 487 patients were included, 82 in the study group. Comorbidity and physical dependence were higher in this group than in the control group (p=0.000 and p=0.002 respectively). The majority of patients were discharged because of a satisfactory clinical evolution. However, 17 (20.7%) patients in the study group required readmission to hospital during treatment and another 22 (26.8%) were re-admitted to hospital 3 months after discharge from HHU. There were significant differences between the results from the control group in clinical readmissions. CONCLUSIONS: Patients with multi-drug resistant microorganism infections and HIVAIT have higher comorbidity, physical dependence, and frequency of hospital readmissions. However, HIVAIT is useful in this kind of infections if the patients are appropriately selected.
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Anti-Infecciosos/administração & dosagem , Infecções Bacterianas/tratamento farmacológico , Serviços de Assistência Domiciliar , Farmacorresistência Bacteriana Múltipla , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-IdadeAssuntos
Antibacterianos/uso terapêutico , Empiema Pleural/tratamento farmacológico , Terapia por Infusões no Domicílio , Infusões Intravenosas , Abscesso Pulmonar/tratamento farmacológico , Adulto , Idoso , Antibacterianos/administração & dosagem , Terapia Combinada , Comorbidade , Drenagem , Empiema Pleural/cirurgia , Feminino , Humanos , Abscesso Pulmonar/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVE: Few data exists in the literature about intravenous antibiotic treatment of hepatic abscess in hospital based care units. Our objectives were to analyze the efficacy and safety of intravenous antibiotic therapy and the predictors of hospital readmission. PATIENTS AND METHODS: The study included all the patients admitted in our home care unit for intravenous antibiotic treatment of hepatic abscess from March 2006 to June 2009. RESULTS: We included 30 patients in the study. Five patients (16,6%) had phlebitis during treatment and none presented a major secondary effect. Mean size reduction of abscess during admission in our home care unit was 49,3% (36,6%). Nine (30%) patients were readmitted, 6 (20%) during admission at home and 3 (10%) along the year after. Four (13.3%) patients died along follow-up. Patients readmitted had a higher mean size of abscess at discharge from our home care unit as compared to the non readmitted ones (4,5 vs 1,5 cms P=0,001), besides a minor percentage of reduction of size (19% vs 64% P=0,001). Female patients were readmitted more frequently than male ones (77,8% vs 28,6% P=0,02), but they had minor scores of Barthel scale (75 vs. 92 P=0,01). CONCLUSIONS: Home intravenous antibiotic treatment of hepatic abscess seems to be a safe and effective alternative in most patients. The size and reduction of abscess at patient discharge, the female gender and dependence degree constituted the principal predictors of readmission.
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Antibacterianos/administração & dosagem , Serviços de Assistência Domiciliar , Abscesso Hepático/tratamento farmacológico , Readmissão do Paciente/estatística & dados numéricos , Idoso , Feminino , Humanos , Injeções Intravenosas , Masculino , Estudos ProspectivosRESUMO
BACKGROUND AND OBJECTIVE: Intravenous antibiotic therapy at home has showed its efficacy as an alternative to hospitalization care in many infectious pathologies. The objectives of this study are: a) to expose our experience, as hospital at home unit (HHU) integrated within a service of internal medicine, in the antibiotic treatment, and b) to define those parameters that can predict hospital readmissions. PATIENTS AND METHOD: This study included all patients with infectious pathology and intravenous antibiotic therapy who were admitted in our HHU from March 2006 to March 2007. RESULTS: 145 patients were included in this study. Successful treatment was observed in 92% of patients. Eleven patients were re-admitted at hospital during the episode by infectious disease, and only 2 of them showed adverse effects to treatment. Twenty-two patients were re-admitted at hospital 3 months after due to chronic pathology. CONCLUSIONS: Intravenous antibiotic therapy at home is a good alternative in many infectious pathologies. Infectious pathology and baseline state can be predictors of hospital readmissions.
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Antibacterianos/administração & dosagem , Serviços Hospitalares de Assistência Domiciliar , Readmissão do Paciente , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/tratamento farmacológico , Cateterismo Venoso Central , Interpretação Estatística de Dados , Feminino , Humanos , Infecções/tratamento farmacológico , Infusões Intravenosas , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Tempo , Resultado do TratamentoRESUMO
INTRODUCTION: The thrombotic risk associated with protein Z (PZ) deficiency is unclear. Anti-protein Z (anti-PZ) has been described as a risk factor in unexplained embryo demise. The aim of our study was to evaluate a possible PZ deficiency and presence of anti-PZ antibodies on thrombotic diseases. MATERIAL AND METHODS: We performed a case-control study on 114 patients with preexisting arterial or venous thrombosis (50 and 64, respectively). Thrombosis was studied based on etiology (creating factor risk subgroups) and on specific thrombotic disease. RESULTS: PZ levels of patients were significantly lower compared to controls (1709+-761.3 ng/mL vs. 2437+-964.7 ng/mL P=0.001). The high arterial risk factor subgroup showed the lowest PZ level (1267.5+-609 ng/mL) whereas the rest of arterial and venous etiological subgroups presented similar PZ levels. Patients with peripheral artery disease had the lowest PZ level (1022+-966 ng/mL). The rest of arterial and venous thrombotic diseases presented similar PZ levels. A significant increased risk for arterial and venous thrombosis for the lowest (<1685 ng/mL) quartile of PZ has been founded (OR:52, P=0.001 and OR:18, P=0.007, respectively). Anti-PZ antibodies were negative in the majority of patients, although mean anti-PZ IgG antibody levels in the arterial thrombosis group were significantly higher compared to venous thrombosis and control groups (P=0.05 and P=0.005, respectively). CONCLUSIONS: The results suggest that both arterial and venous thrombotic events are related to low PZ levels and that low PZ concentrations are associated with thrombosis in our study. In arterial thrombosis our findings strengthen previous studies that related low PZ levels to atherosclerotic disease. Anti-PZ antibodies do not seem to play a potent role in thrombosis.