Mortalidad en pacientes con hemorragia intracerebral asociada a anticoagulación oral. Eficacia de un protocolo de reversión y seguimiento clínico (proyecto HIC-ACO) / Mortality in patients with intracerebral haemorrhage associated with oral anticoagulation. Efficacy of a reversal protocol and clinical follow-up (ICH-OAC project)

Introducción: La hemorragia intracerebral espontánea asociada a anticoagulantes orales (HIC-ACO) presenta una elevada mortalidad. La aparición de nuevos fármacos anticoagulantes y protocolos de reversión aumenta el interés por esta entidad. Objetivos: El objetivo principal es determinar la tasa de mortalidad en pacientes con HIC-ACO (precoz, hospitalaria, global) en nuestra área sanitaria y analizar las principales variables relacionadas. El objetivo secundario es determinar la eficacia de las terapias de reversión de la anticoagulación (TRA), reflejada por la expansión radiológica del hematoma y el pronóstico funcional. Pacientes y métodos: Estudio prospectivo observacional que introdujo un protocolo dirigido al manejo de pacientes con HIC-ACO. Incluyó medidas generales y neuromonitorización, administración individualizada de TRA, tomografía craneal y seguimiento durante seis meses. Se recogieron los fármacos prescritos en el área durante este período, mortalidad y pronóstico funcional. Se diseñó un estudio bivariante y regresión logística para investigar variables relacionadas con la mortalidad. Resultados: Se incluyó a 49 pacientes durante tres años; de ellos, un 71,4% recibió TRA. La mortalidad fue del 16,3% (primeras 24 horas), el 53,1% (ingreso) y el 61,2% (180 días). Se observó una menor supervivencia entre pacientes con puntuaciones basales mayores en la National Institutes of Healt Stroke Scale (NIHSS) (p < 0,0001), valor de creatinina (p = 0,02), índice internacional normalizado (p = 0,048), volumen hemorrágico (p = 0,008), hidrocefalia (p = 0,015) y toma de acenocumarol (p = 0,030). Los pacientes que no recibieron TRA tuvieron una mayor mortalidad precoz (p = 0,003). La única variable relacionada con la mortalidad global de forma independiente fue la puntuación en la NIHSS basal (odds ratio = 1,282; intervalo de confianza al 95%: 1,023-1,608; p = 0,031)...(AU)

Introduction: Spontaneous intracerebral haemorrhage associated with oral anticoagulants (ICH-OAC) has a high mortality rate. The emergence of new anticoagulant drugs and reversal protocols increases interest in this entity. Objectives: The main objective is to determine the mortality rate in patients with ICH-OAC (early, in-hospital, global) in our health area and to analyse the main variables related to it. The secondary objective is to determine the efficacy of anticoagulation reversal therapies (ART) as reflected by radiological expansion of the haematoma and the functional prognosis. Patients and methods: A prospective observational study that introduced a protocol aimed at the management of patients with ICH-OAC. It included general measures and neuromonitoring, individualised administration of ART, cranial tomography and a six-month follow-up. Data on the drugs prescribed in the area during this period, mortality and functional prognosis were collected. A bivariate and logistic regression study was designed to investigate mortality-related variables. Results: Forty-nine patients were included over three years; of these, 71.4% received ART. Mortality was 16.3% (first 24 hours), 53.1% (admission) and 61.2% (180 days). Lower survival was observed among patients with higher baseline scores on the National Institutes of Health Stroke Scale (NIHSS) (p < 0.0001), creatinine value (p = 0.02), International Normalised Index (p = 0.048), bleeding volume (p = 0.008), hydrocephalus (p = 0.015) and acenocoumarol intake (p = 0.030). Patients who did not receive ART had a greater rate of early mortality (p = 0.003). The only variable independently related to overall mortality was the baseline NIHSS score (odds ratio = 1.282; 95% confidence interval: 1.023-1.608; p = 0.031)...(AU)

[Mortality in patients with intracerebral haemorrhage associated with oral anticoagulation. Efficacy of a reversal protocol and clinical follow-up (ICH-OAC project)]. / Mortalidad en pacientes con hemorragia intracerebral asociada a anticoagulación oral. Eficacia de un protocolo de reversión y seguimiento clínico (proyecto HIC-ACO).

INTRODUCTION: Spontaneous intracerebral haemorrhage associated with oral anticoagulants (ICH-OAC) has a high mortality rate. The emergence of new anticoagulant drugs and reversal protocols increases interest in this entity. OBJECTIVES: The main objective is to determine the mortality rate in patients with ICH-OAC (early, in-hospital, global) in our health area and to analyse the main variables related to it. The secondary objective is to determine the efficacy of anticoagulation reversal therapies (ART) as reflected by radiological expansion of the haematoma and the functional prognosis. PATIENTS AND METHODS: A prospective observational study that introduced a protocol aimed at the management of patients with ICH-OAC. It included general measures and neuromonitoring, individualised administration of ART, cranial tomography and a six-month follow-up. Data on the drugs prescribed in the area during this period, mortality and functional prognosis were collected. A bivariate and logistic regression study was designed to investigate mortality-related variables. RESULTS: Forty-nine patients were included over three years; of these, 71.4% received ART. Mortality was 16.3% (first 24 hours), 53.1% (admission) and 61.2% (180 days). Lower survival was observed among patients with higher baseline scores on the National Institutes of Health Stroke Scale (NIHSS) (p < 0.0001), creatinine value (p = 0.02), International Normalised Index (p = 0.048), bleeding volume (p = 0.008), hydrocephalus (p = 0.015) and acenocoumarol intake (p = 0.030). Patients who did not receive ART had a greater rate of early mortality (p = 0.003). The only variable independently related to overall mortality was the baseline NIHSS score (odds ratio = 1.282; 95% confidence interval: 1.023-1.608; p = 0.031). CONCLUSIONS: ICH-OAC has a high mortality rate, related to the use of acenocoumarol and regardless of the initial clinical situation. A lower rate of early mortality was found among patients who received ART.

TITLE: Mortalidad en pacientes con hemorragia intracerebral asociada a anticoagulación oral. Eficacia de un protocolo de reversión y seguimiento clínico (proyecto HIC-ACO).Introducción. La hemorragia intracerebral espontánea asociada a anticoagulantes orales (HIC-ACO) presenta una elevada mortalidad. La aparición de nuevos fármacos anticoagulantes y protocolos de reversión aumenta el interés por esta entidad. Objetivos. El objetivo principal es determinar la tasa de mortalidad en pacientes con HIC-ACO (precoz, hospitalaria, global) en nuestra área sanitaria y analizar las principales variables relacionadas. El objetivo secundario es determinar la eficacia de las terapias de reversión de la anticoagulación (TRA), reflejada por la expansión radiológica del hematoma y el pronóstico funcional. Pacientes y métodos. Estudio prospectivo observacional que introdujo un protocolo dirigido al manejo de pacientes con HIC-ACO. Incluyó medidas generales y neuromonitorización, administración individualizada de TRA, tomografía craneal y seguimiento durante seis meses. Se recogieron los fármacos prescritos en el área durante este período, mortalidad y pronóstico funcional. Se diseñó un estudio bivariante y regresión logística para investigar variables relacionadas con la mortalidad. Resultados. Se incluyó a 49 pacientes durante tres años; de ellos, un 71,4% recibió TRA. La mortalidad fue del 16,3% (primeras 24 horas), el 53,1% (ingreso) y el 61,2% (180 días). Se observó una menor supervivencia entre pacientes con puntuaciones basales mayores en la National Institutes of Healt Stroke Scale (NIHSS) (p lower than 0,0001), valor de creatinina (p = 0,02), índice internacional normalizado (p = 0,048), volumen hemorrágico (p = 0,008), hidrocefalia (p = 0,015) y toma de acenocumarol (p = 0,030). Los pacientes que no recibieron TRA tuvieron una mayor mortalidad precoz (p = 0,003). La única variable relacionada con la mortalidad global de forma independiente fue la puntuación en la NIHSS basal (odds ratio = 1,282; intervalo de confianza al 95%: 1,023-1,608; p = 0,031). Conclusiones. La HIC-ACO presenta una elevada mortalidad, relacionada con la toma de acenocumarol y de forma independiente con la situación clínica inicial. Se comprobó una menor tasa de mortalidad precoz entre pacientes que recibieron TRA.

Statin-associated autoimmune myopathy: A distinct new IFL pattern can increase the rate of HMGCR antibody detection by clinical laboratories.

BACKGROUND AND OBJECTIVE: Statin-associated autoimmune myopathy (SAAM) with anti-HMGCR antibodies has recently been described. Several specific immunoassays are in use to detect HMGCR antibodies. In the course of systematic autoantibody screening we recognized a new distinct IFL staining pattern on rat liver sections that regularly coincided with anti-HMGCR antibodies. In this study we investigated whether this new IFL pattern is specifically associated to statin-associated autoimmune myopathy and corresponds to anti-HMGCR antibodies. PATIENTS AND METHODS: Twenty-three patients positive for anti-HMGCR antibodies (14 diagnosed with SAAM) were investigated for anti-HMGCR antibodies by two ELISA assays and confirmed by immmunoblot. HMGCR associated liver IFL pattern (HALIP) was detected by indirect IFL and the reactivity against HMGCR was confirmed by immunoabsorption using purified human HMGCR antigen. 90 patients with other autoimmune diseases and 45 non-autoimmune statin treated patients were studied as controls. RESULTS: 21 out of 23 (91%) anti-HMGCR positive patients were HALIP positive. The staining was completely and specifically removed by immunoabsorption with human purified HMGCR. None of the control sera from autoimmune patients or non-autoimmune statin treated subjects was positive for HALIP. Statistical concordance between HALIP and anti-HMGCR antibody specific tests was 98.7%, kappa 0.95. CONCLUSIONS: A new and distinct IFL staining pattern (HALIP) is associated to HMGCR associated myopathy. Absorption and concordance studies indicate that the antigen recognized in the liver by HALIP is HMGCR or a closely related protein. Awareness of this new pattern can help to detect HMGCR autoantibodies in statin treated patients tested for autoimmune serology.

Genetics of Graves' Disease: Special Focus on the Role of TSHR Gene.

As most autoimmune diseases, inherited predisposition to Graves' disease (GD) is polygenic with the main contributory genes being located in the HLA region. Also, as in other autoimmune diseases, family linkage, candidate gene association, and GWAS studies have identified an expanding number of predisposing genes (CTLA4, CD40, PTPN22...) and 2 of them, TG and TSHR, are thyroid specific. In spite of this expanding number of associated genes, it has been estimated that all together they account for only a 20% of the heritability of GD. TSHR is of special interest as it codes for the target of TSHR stimulating antibodies (TSAbs), which are unequivocally pathogenic and an exception in autoimmunity by being stimulating rather than neutral, blocking, or cytotoxic. This is surprising because the generation of stimulating TSHR antibodies by immunisation of laboratory animals has been remarkably difficult, suggesting an underlying mechanism that favours stimulating over neutral or blocking anti-TSHR antibodies must be operating in GD patients. Besides, after HLA, TSHR is the gene most tightly associated to GD. The TSHR polymorphisms conferring susceptibility are located in the unusually large intron 1. Two mechanisms have been already put forward to explain its association with GD. According to one, the risk alleles determine an increase in the expression of TSHR mRNA splice variants that code for a soluble form of the receptor. The wider distribution of soluble TSHR would favour its immunogenicity and the development of an autoimmune response to it. It does not explain why it becomes immunogenic, as immunogenicity and distribution are not necessarily connected, nor why the immune response focus to the production of stimulating antibodies. According to the second mechanism proposed, the risk alleles determine a lower TSHR expression in the thymus and this would favour the escape of more TSHR reactive T cells, that is, central tolerance failure. The unexpected finding that thymocytes express TSHR and that TSAbs stimulate them lead to postulate that this would accelerate their egress from the thymus and a less efficient deletion of the TSHR self-reactive T cells. It can be envisaged that these autoreactive T cells may enhance the production of TSHR-Abs in the germinal centres of the thyroid draining lymph nodes, especially of those capable of further stimulating the egress of autoreactive T cells from the thymus. This mechanism, which does not exclude the former, provides and insight of the way in which TSAbs are favoured over neutral or blocking antibodies. Finally this would explain the frequent finding of thymic hyperplasia in GD patients.

Réplica al artículo «Gestante con hemólisis, enzimas hepáticas elevadas y trombocitopenia: diagnóstico diferencial» / Reply to the article "Hemolysis, elevated liver enzymes and low platelet count in pregnancy: Differential diagnosis"

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