11 results on '"Nuria Revilla"'
Search Results
2. A pilot study on the impact of congenital thrombophilia in COVID-19
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Sonia Herrero, Nuria Revilla, José Padilla, María Teresa Herranz, Kristin Jochmans, Vicente Vicente, Maria Luisa Lozano, Carlos Bravo-Pérez, Javier Corral, Enrique Bernal, Jose Miguel Gómez-Verdú, Shally Marcellini, Christelle Orlando, Belén de la Morena-Barrio, María Eugenia de la Morena-Barrio, Antonia Miñano, Rosa Cifuentes, Hematology, Basic (bio-) Medical Sciences, Clinical Biology, Faculty of Medicine and Pharmacy, Clinical sciences, and Reproductive immunology and implantation
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Adult ,Male ,2019-20 coronavirus outbreak ,Protein S Deficiency ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Clinical Biochemistry ,Antithrombin III ,Pilot Projects ,Thrombophilia ,Biochemistry ,Severity of Illness Index ,Protein S ,Cohort Studies ,Fibrin Fibrinogen Degradation Products ,congenital thrombophilia ,Severity of illness ,Research Letter ,Medicine ,Humans ,Mortality ,Hypoprothrombinemias ,Aged ,Respiratory Distress Syndrome ,Antithrombin III Deficiency ,business.industry ,SARS-CoV-2 ,hematology ,Protein C Deficiency ,COVID-19 ,Thrombosis ,General Medicine ,Middle Aged ,medicine.disease ,Intensive Care Units ,Logistic Models ,Immunology ,Female ,Factor V Deficiency ,business ,Cohort study ,Protein C - Published
- 2021
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3. Author Correction: Deciphering predictive factors for choice of thrombopoietin receptor agonist, treatment free responses, and thrombotic events in immune thrombocytopenia
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Tomás José González-López, Vicente Vicente, María Fernanda López-Fernández, Gonzalo Carreño-Tarragona, Rosa M. Campos-Alvarez, Maria Luisa Lozano, Nuria Revilla, Nuria Bermejo, María Teresa Álvarez-Román, David Valcárcel, Aurora de Andrés, Isidro Jarque, Estefanía Bolaños, Luis F. Casado-Montero, Maria Eva Mingot-Castellano, José Ramón González-Porras, Manuel A. Rodríguez-López, Silvana Novelli, María Isabel Orts, Elisa Orna-Montero, and María Perera
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Agonist ,Thrombopoietin receptor ,Multidisciplinary ,business.industry ,medicine.drug_class ,Science ,Immunology ,Medicine ,business ,Immune thrombocytopenia - Published
- 2021
4. Multirefractory primary immune thrombocytopenia; targeting the decreased sialic acid content
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Francisco Velasco, Eva Galvez, Tomás José González-López, Rubén Berrueco, Nicolas Gonzalez, Inmaculada Fuentes, Maria Eva Mingot-Castellano, Vicente Vicente, Maria Eugenia de la Morena-Barrio, Rosa Campos, José Ramón González-Porras, Nuria Revilla, Antonia Miñano, Maria Luisa Lozano, and Javier Corral
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Adult ,Male ,0301 basic medicine ,Oseltamivir ,Adolescent ,030204 cardiovascular system & hematology ,Young Adult ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,hemic and lymphatic diseases ,Humans ,Medicine ,Platelet ,Prospective Studies ,Platelet activation ,Young adult ,Child ,Aged ,Purpura, Thrombocytopenic, Idiopathic ,Primary (chemistry) ,biology ,business.industry ,Hematology ,General Medicine ,Middle Aged ,N-Acetylneuraminic Acid ,Sialic acid ,030104 developmental biology ,chemistry ,Child, Preschool ,Immunology ,biology.protein ,Female ,Antibody ,business ,N-Acetylneuraminic acid - Abstract
Patients with multirefractory immune thrombocytopenia (ITP) have limited treatment options. Recent data suggest that specific anti-platelet antibodies may cause destruction of platelets by favoring platelet loss of sialic acid. In this multicenter study 35 patients with ITP, including 16 with multirefractory disease, were analyzed for antiplatelet-antibodies, thrombopoietin (TPO) levels, and platelet desialylation. In selected cases, responses to a novel treatment strategy using oseltamivir were tested. We found that antibodies against GPIbα were overrepresented in multirefractory patients compared to responders (n = 19). In contrast to conventional ITP patients, multirefractory patients exhibited a significant increased platelet activation state (granule secretion) and desialylation (RCA-1 binding) (p These findings suggest that desialylation may play a key pathogenic role in some multirefractory ITP patients, and provide diagnostic tools for the identification of such patients. Furthermore, we show that sialidase inhibitor treatment in combination with therapies that help to increase platelet production can induce sustained platelet responses in some patients with anti-GPIbα -mediated thrombocytopenia that have failed previous therapies.
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- 2018
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5. An early increase of CD56brightnatural killer subset as dominant effect and predictor of response to extracorporeal photopheresis for graft-versus-host disease
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Vicente Vicente, Ana María Hurtado, Nuria Revilla, Tzu Hua Chen-Liang, Maria Luisa Lozano, Inmaculada Heras, Pastora Iniesta, and Andres Jerez
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biology ,medicine.diagnostic_test ,business.industry ,CD3 ,medicine.medical_treatment ,education ,Immunology ,Hematology ,medicine.disease ,CD19 ,Flow cytometry ,03 medical and health sciences ,0302 clinical medicine ,Graft-versus-host disease ,Immune system ,Photopheresis ,030220 oncology & carcinogenesis ,Extracorporeal Photopheresis ,medicine ,biology.protein ,Immunology and Allergy ,business ,CD8 ,030215 immunology - Abstract
Background CD56bright natural killer (NK) regulatory cells were recently shown to display a differential impact on the risk of developing extensive chronic graft-versus-host disease (GVHD). To date no study has definitively established which immune populations are most responsible for the immunomodulatory effects or response to extracorporeal photopheresis (ECP) for GVHD. Study design and methods To test the role of CD56bright NK cells in ECP, a prospective enhanced flow cytometry follow-up of immune subsets (CD19+, CD3+, CD3+/CD4+, CD3+/CD8+, CD3-/CD56+, CD3-/CD56bright , and CD3-/CD56dim ) was performed in 32 patients with GVHD who underwent 552 procedures. Results An early increase of CD56bright NK cells was found as a hallmark effect to ECP, particularly during the first 3 months of treatment. This was also supported by the ability to predict for complete responses when this increase was expressed as a higher CD56bright versus CD56dim NK cells ratio. Among the immune subsets tested, the only variable that had direct influence on response to ECP was a CD56bright/dim ratio more than 0.16 (hazard ratio [HR] 4.32, p = 0.014; HR 5.8, p = 0.007, at 2 and 3 months of ECP treatment, respectively). Conclusion These findings argue for exploring strategies for priming a CD56bright NK cell expansion during ECP and providing additional and potentially relevant data for revisiting the underpinning cellular mechanisms of ECP that could generate that expansion.
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- 2018
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6. Idarucizumab for Reversal of Dabigatran: Multicenter Real-World Experience
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Isabel Gutiérrez, Gloria Pérez-Rus, Begoña Fernández, Belén Rosado Sierra, Susana Asenjo Correa, María Elena Sola Aparicio, Mar Meijón, Paola Alejandra Barzallo Burbano, Ramón Rodríguez-González, José Luis Díez-Martín, Maria Pilar Llamas Sillero, María Jesús Blanco Bañares, Nuria Revilla Calvo, and Cristina Pascual Izquierdo
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medicine.medical_specialty ,business.industry ,Immunology ,Medicine ,Idarucizumab ,Cell Biology ,Hematology ,business ,Intensive care medicine ,Biochemistry ,Dabigatran ,medicine.drug - Abstract
Introduction: Idarucizumab is a humanized monoclonal antibody fragment that binds to dabigatran and reverses its anticoagulant activity. It has been available in Spain since June 2016 and is indicated for imminent surgery or invasive procedures and life-threatening bleeding. The aim of the study was to describe the actual experience with idarucizumab in different centers in Madrid. Methods: Patients with electronic prescription of idarucizumab between June 2016 and July 2021 were included. Demographic information, comorbidities, laboratory parameters, dabigatran indication, anticoagulation resumption, adverse events related to idarucizumab and death within 30 days were collected from medical records. Qualitative data are presented as frequencies and percentages. Quantitative data are presented as mean ± standard deviation (SD) or median (interquartile range -IQR-). Cumulative survival was calculated by dividing the number of patients alive by the number of patients in each indication category for idarucizumab in a 30-day post-infusion period. Results: A total of 69 patients from 8 hospitals in Madrid were included. Ninety-six percent received dabigatran for prevention of stroke and embolism in nonvalvular atrial fibrillation and 4% received it for the treatment of thromboembolic disease. The mean age was 73.5 ± 13.9 years, and 55.6% were men. Median aPTT was 45.6 seconds and was prolonged in 72.1% (49). Patient characteristics, concomitant conditions and laboratory parameters are reviewed in Table 1. The main indication for idarucizumab was reversal of anticoagulation for persistent bleeding (46.4%), followed by surgery (44.9%). Fibrinolysis due to ischemic stroke was performed in 3 patients (4.3%), dabigatran intoxication occurred in 3 patients due to acute renal failure (4.3%). Gastrointestinal bleeding was the most common type of bleeding. Two of the patients intoxicated with dabigatran also had gastrointestinal bleeding. Cardiac surgery was the most common type of intervention, with heart transplant being a common indication (9/13). Minor surgical procedures included 2 lumbar punctures and 1 central venous catheterization. In one case, the type of surgery was not available. Figure 1 A and B summarize the bleeding location and type of surgery. The median time between infusion of idarucizumab and cessation of bleeding or onset of surgery was 3 hours, however this information was only available in 43 patients. No reports of excessive bleeding during surgery or after fibrinolysis were noted. One patient with dabigatran intoxication was reported to have an episode of persistent melena in which the trough plasma level was 1178.1 ng/mL. This patient died of an aggressive lymphoproliferative disorder that couldn´t be biopsied due to altered coagulation. A case of auricular thrombosis occurred in a patient with a heart transplant due to hyperthophic cardiomiopathy and end-stage heart failure requiring thrombectomy. The patient required a biventricular assistance and died of myocardial infarction. Full 30-day follow-up was available for 68 patients, during this period 11 died. Five patients in the bleeding group died, 3 from hypovolemic shock, 1 from intraparenchymal hemorrhage and data were missing for 1. Two patients who received a heart transplant died, one as described previously 10 days after the transplant and the other 2 days after the transplant from hemorrhagic shock. Three patients who underwent abdominal surgery died of septic shock. One patient with dabigatran intoxication died. Cumulative survival after a follow-up period of 30 days was 86% (Figure 2). Seventy-seven percent (53) resumed anticoagulation after a median of 3 days (0-180), and 62.3% (33) were bridged with low molecular weight heparin (LMWH) at prophylactic doses. Finally, 75% (40) maintained LMWH (7) or restarted dabigatran or another direct oral anticoagulant (33). A total of 13 patients didn´t resume any anticoagulation. Conclusions: Idarucizumab is an effective drug for reversal of dabigatran anticoagulation in bleeding or imminent surgery/invasive procedures. In this cohort it was used safely in patients awaiting a heart transplant. No cases of bleeding after infusion or during surgery were reported, except for a single case of auricular thrombosis. Most patients resumed anticoagulation at discharge. The experience described confirms the safety of idarucizumab in daily clinical practice. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
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- 2021
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7. Transient desialylation in combination with a novel antithrombin deficiency causing a severe and recurrent thrombosis despite anticoagulation therapy
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Maria Luisa Lozano, Javier Corral, Raquel López-Gálvez, José Padilla, Nuria Revilla, Dirk Lefeber, Mara Toderici, María Eugenia de la Morena-Barrio, Vicente Vicente, Antonia Miñano, and Ángel García-Avello
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0301 basic medicine ,Adult ,medicine.medical_specialty ,Renal function ,030204 cardiovascular system & hematology ,medicine.disease_cause ,Article ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,law ,medicine ,Humans ,Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase ,Thrombophilia ,Thrombolytic Therapy ,GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) ,chemistry.chemical_classification ,Mutation ,Fibrin ,Multidisciplinary ,biology ,business.industry ,Antithrombin ,Anticoagulants ,Thrombosis ,Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] ,medicine.disease ,Blood proteins ,Surgery ,Pedigree ,030104 developmental biology ,chemistry ,Transferrin ,Immunology ,biology.protein ,Recombinant DNA ,Female ,Blood Coagulation Tests ,business ,Neuraminidase ,medicine.drug - Abstract
An in-depth focused study of specific cases of patients with recurrent thrombosis may help to identify novel circumstances, genetic and acquired factors contributing to the development of this disorder. The aim of this study was to carry out a detailed and sequential analysis of samples from a patient suffering from early and recurrent venous and arterial thrombosis. We performed thrombophilic tests, biochemical, functional, genetic and glycomic analysis of antithrombin and other plasma proteins. The patient carried a new type I antithrombin mutation (p.Ile218del), whose structural relevance was verified in a recombinant model. Experiments with N-glycosidase F and neuraminidase suggested a nearly full desialylation of plasma proteins, which was confirmed by mass spectrometry analysis of transferrin glycoforms. However, partial desialylation and normal patterns were detected in samples collected at other time-points. Desialylation was noticeable after arterial events and was associated with low antithrombin activity, reduced platelet count and glomerular filtration rate. This is the first description of a global and transient desialylation of plasma proteins associated with thrombosis. The decrease in the strong electronegative charge of terminal glycans may modulate hemostatic protein-protein interactions, which in combination with a strong prothrombotic situation, such as antithrombin deficiency, could increase the risk of thrombosis.
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- 2017
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8. A New Molecular Variant in the PTGS1 Gene That Abrogates Generation of Thromboxane A2 Synthesis and Associates with Platelet Dysfunction and Bleeding
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Jose Maria Bastida, José Rivera, Jesús María Hernández-Rivas, Maria Luisa Lozano, Matthew L. Edin, Natalia Bohdan, José Padilla, Verónica Palma-Barqueros, Sara Suarez Varela, Ignacio Casas-Aviles, Cristina Mesa-Núñez, Nuria Revilla Calvo, Vicente Vicente, José Ramón González-Porras, DC Zelding, Jf Ruiz-Pividal, Marilena Crescente, Ana Marín-Quílez, Melissa V. Chan, Juan A. Bueren, Elena Almarza, Marta Martín Izquierdo, Timothy D. Warner, and Rocío Benito
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biology ,P-selectin ,Chemistry ,Platelet disorder ,Immunology ,Cell Biology ,Hematology ,Biochemistry ,Molecular biology ,chemistry.chemical_compound ,Thromboxane A2 ,Coagulation ,biology.protein ,Platelet ,Thromboxane-A synthase ,Ristocetin ,Blood Platelet Disorders - Abstract
Introduction: Thromboxane A2 [TxA2] is generated from arachidonic acid by cyclooxigenase-1 (COX-1) (prostaglandin H synthase-1) and thromboxane synthase. Aspirin, which irreversibly inhibits COX-1, is a widely used antiplatelet therapy with proven clinical efficacy. Inherited platelet disorders (IPD) are rare diseases caused by alterations of relevant genes in platelet formation and/or function. Despite the relevance of the TxA2 pathway in platelet physiology, few patients with mutations in PTGS1, the gene encoding COX-1, have been identified ( Objective: Characterization of a patient with aspirin-like platelet defect and moderate bleeding, enrolled in the Spanish multicentric project "Functional and molecular characterization of patients with IPD". Methods: The index case is a 13-year-old adopted girl of Asian origin, referred because of moderate chronic bleeding (BAT-ISTH=6) and an aspirin-like platelet dysfunction. No coagulation defect or other relevant clinical symptoms were present. Platelet phenotyping included: blood count, PFA-100; platelet aggregation [LTA], glycoproteins (GP), activation and secretion of granules by flow cytometry (FC), TxA2 synthesis by enzyme-immunoassay, synthesis of eicosanoids by tandem gas chromatography with mass spectrometry (LC-MS), western-blot (WB) of platelet lysates, and immunofluorescence (IF) assays. The patient's DNA was analyzed with a HTS-gene panel (Bastida et al, Haematologica 2018). A HEK 293T cell transfection model was established to further assess the pathogenicity of the candidate variant found in the patient. Results: The index case has normal platelet size and count (206x109/L; 11.4 fL). PFA-100 times were normal for COL-ADP and prolonged for COL-EPI (>300s). The FC analysis showed normal expression of GPs (Ib/IX, IIb/IIIa, Ia, GPVI) and reduced fibrinogen*488 binding (20-30%) in response to ADP, TRAP and low dose CRP (2ug/mL). P-selectin and CD63 secretion with agonists was comparable to those of controls. LTA was normal with ristocetin (1.25mg/mL) and TRAP (25uM), reduced by 40-50% with ADP (10uM) and collagen (3ug/mL) and absent with epinephrine (10uM), low dose collagen (1ug/mL) and arachidonic acid (1.6mM). LTA with U46619 (5uM), a direct agonist of the TxA2 receptor, was normal, suggesting a defect in TxA2 synthesis. Indeed, TxA2 levels in LTA supernatants in the patient were very low (5ng/mL; G, [p.Asn143Ser] in PTGS1. This variant, not previously described, affects a conserved residue in the catalytic domain of COX-1, which is one of the three N-glycosylation sites in the enzyme. The variant was not associated with reduced COX-1 expression as evaluated by WB in platelet lysates, and by IF in spread washed platelets and leukocytes. HEK 293T cells transfected with wild-type COX-1 construct (validated by RT-PCR and WB), displayed substantial TxA2 synthesis (500ng/mL; 2.5x105 transfected cells) in response to arachidonic acid. In contrast, similar transfection of p.143Ser COX-1 mutant almost abrogated this TxA2 production (≈50-75ng/mL in 2.5x105 transfected cells). Conclusion: We have identified a novel autosomal dominant COX-1 variant, p.Asn143Ser, associated with functional haploinsufficiency of the enzyme and platelet aggregation defects. To our knowledge, this case represents the third description of variants in PTGS1 (Nance, JTH 2016; Sivapalaratnam, Blood 2018), which cause platelet dysfunction and bleeding. Disclosures Almarza: Rocket Pharmaceuticals: Equity Ownership, Patents & Royalties, Research Funding. Bueren:Rocket Pharmaceuticals, Inc.: Consultancy, Equity Ownership, Patents & Royalties: Inventor on patents on lentiviral vectors filled by CIEMAT, CIBERER and F.J.D and may be entitled to receive financial benefits from the licensing of such patents, Research Funding.
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- 2019
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9. Predictive Factors for Thrombopoietin Receptor Agonist Free Responses in Chronic ITP Patients: A Multicenter Retrospective Study with Long-Term Follow-up
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Nuria Revilla, Aurora de Andrés, Maria Eva Mingot-Castellano, José Ramón González-Porras, Tomás José González-López, Maria Luisa Lozano, Maria Fernanda Lopez Fernandez, Teresa Álvarez Roman, David Valcárcel, Vicente Vicente Garcia, Nuria Bermejo, Gonzalo Carreño Gomez-Tarragona, Felipe Casado, Estefanía Bolaños, Silvana Novelli, Elisa Orna, María Perera, Isidro Jarque, María Isabel Orts, Manuel Rodríguez López, and Rosa Campos
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Univariate analysis ,Thrombopoietin Receptor Agonists ,Pediatrics ,medicine.medical_specialty ,Intention-to-treat analysis ,Romiplostim ,business.industry ,Medical record ,Immunology ,Retrospective cohort study ,Cell Biology ,Hematology ,Biochemistry ,Discontinuation ,Cohort ,Medicine ,business ,medicine.drug - Abstract
Background . In clinical practice, tapering off thrombopoietin receptor agonists (TPO-RA) in immune thrombocytopenia (ITP) is considered if therapy is no longer needed due to a decrease in the disease activity favoring sustained treatment-free responses (TFR). To date, there are no predictors to identify when this approach is likely to be successful, other than earlier start of TPO-RA, and robust platelet responses. Aim. To evaluate clinical predictors of TFR in a real-world cohort of ITP patients treated with TPO-RA by dealing with confounding variables that could be minimized at the stage of the analysis. Methods. In this retrospective, multicenter study from 19 secondary and tertiary Spanish hospitals, patients aged >18 years with chronic ITP who had initiated TPO-RA (eltrombopag [EPG] or romiplostim [ROM]) between January 2012 and December 2014 were included. Data were collected from medical records (November 2016 to January 2018) on patient characteristics, history of disease and previous therapies, TPO-RA administration, response and discontinuation. Results. A total of 82 patients with a median age of 63 years (range 19-90 years), 59.9% females initiated TPO-RA (ROM, n=37; EPG, n=45). The median time from diagnosis of ITP to therapy with TPO-RA was 5.5 years (1.1-50.3 years). In all cases the TPO-RA was started with intention to treat indefinitely; the median initial doses of EPG were 350 mg/week (175-525 mg/week), and those of ROM 2.0 μg/kg/week (1.0-7.0 μg/kg/week). The median time on TPO-RA treatment was 2.9 years (0.1 to 5.6 years), and the median follow-up from start of TPO-RA until collection of data was of 3.9 years (1.3 to 5.6 years). A total of 29 patients (35.4%) switched TPO-RA during follow-up. The most frequent cause for switching was lack of efficacy (44.8% of cases -in all cases the initial TPO-RA was EPG-). Due to switching, 58 patients received ROM, and 53 were treated with EPG, yielding 122.3, and 100.8 patient-years of total exposure, respectively. During follow-up almost one half of the patients (47.6%, n=39) stopped TPO-RA. After a median of 1.4 years (0.1-3.3 yrs) under TPO-RA treatment, 19 patients (23.2% of the whole cohort) maintained TFR defined as platelet counts >50x109/l for a median follow-up of 2.8 years (1.5-4.4 years) in the absence of any platelet increasing drug. Remarkably, while the specific TPO-RA that was discontinued did not influence the probability to achieve TFR (P=0.582), there was a trend towards receiving ROM as first TPO-RA and attaining sustained responses (P=0.073), while switching TPO-RA negatively predicted TFR (P=0.010). In univariate analysis with logistic regression, switching TPO-RA was associated with a 6.4 risk of not achieving TFR (P= 0.019). The overall comparison of the Kaplan-Meier curves indicated an association (log-rank P=0.041) among the initial TPO-RA that was prescribed and the probability of TFR (Fig 1A), but the estimated median time to achieve TFR was not reached for either TPO-RA. When switching and initial TPO-RA were considered, patients receiving ROM and not experiencing switching were the best performing group in terms of achieving TFR; the median time to taper off the drug and sustain platelet responses was 3.3 years (95% CI 2.7-4.0 years) (Fig. 1B). Conclusion. In this observational research analysis, we have tried to minimize the possible bias of some studies that could mistakenly attribute TPO-RA induced TFR, when in fact it may be the natural course of the underlying disease. By analyzing a group of chronic ITP patients with a particularly poor baseline prognosis (median time from diagnosis 5.5 years) we address potential confounding variables by disease severity. Our data show that assuring that long duration under TPO-RA therapy is provided (median of 3.3 years), one half of chronic ITP patients treated with ROM and not undergoing switching can achieve TFR. Disclosures Mingot-Castellano: Roche: Consultancy; Bayer: Consultancy; Novartis: Consultancy; Takeda: Consultancy; Sobi: Consultancy; Amgen: Consultancy; Novonordisk: Consultancy; CSL Behring: Consultancy. Jarque:Abbie: Consultancy, Speakers Bureau; Alexion: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Grifols: Consultancy; Gilead: Consultancy, Speakers Bureau; CellTrion: Consultancy; Celgene: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Servier: Speakers Bureau; Roche: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Shire: Consultancy, Speakers Bureau; Shionogi: Consultancy, Speakers Bureau. Campos:Novartis: Speakers Bureau; Amgen: Speakers Bureau. Lopez Fernandez:Amgen: Consultancy, Speakers Bureau. Casado:Amgen: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau. Álvarez Roman:Amgen: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Speakers Bureau; Sobi: Consultancy, Speakers Bureau; Takeda: Research Funding; NovoNordisk: Consultancy, Speakers Bureau.
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- 2019
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10. Wiskott–Aldrich syndrome in a child presenting with macrothrombocytopenia
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Berta González, Rocío Benito, Nuria Revilla, Mónica del Rey, David Bueno, Susana Riesco, Ramon González-Porras, Elena Blanco, Maria Hernández-Rivas, José Rivera, José María Bastida, Martin Perez-Andres, Ana Hortal Benito-Sendin, Maria Luisa Lozano, Kamila Janusz, Vicente Vicente, and José Padilla
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Male ,0301 basic medicine ,Wiskott–Aldrich syndrome ,Platelet disorder ,Disease ,030204 cardiovascular system & hematology ,Biology ,Frameshift mutation ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Inherited thrombocytopenia ,hemic and lymphatic diseases ,medicine ,Humans ,Gene ,Immunodeficiency ,Genetics ,Hematology ,General Medicine ,medicine.disease ,Thrombocytopenia ,Stop codon ,Wiskott-Aldrich Syndrome ,Immune thrombocytopenia ,030104 developmental biology ,Child, Preschool ,Genetic diagnosis ,Immunology ,Next-generation sequencing - Abstract
Wiskott–Aldrich syndrome (WAS) is a rare X-linked recessive disease resulting from variants in the WAS gene, characterized by a triad of immunodeficiency, eczema, and thrombocytopenia. Despite the fact that WAS is traditionally differentiated from immune thrombocytopenia (ITP) by small size of WAS platelets, in practice, microthrombocytopenia may occasionally not be present, and in certain cases, WAS patients exhibit some parallelism to ITP patients. We characterized one patient presenting with the classic form of the disease but increased mean platelet volume. Molecular studies revealed a novel hemizygous 1-bp deletion in WAS gene, c.802delC, leading to a frameshift and stop codon at amino acid 308 (p.Arg268Glyfs*40). Next-generation sequencing of a total of 70 additional genes known to harbor variants implicated in inherited platelet disorders did not identify additional defects. The pathogenesis of macrothrombocytopenia in this case is not known, but probably the coexistence of a still unidentified additional genetic variant might be involved.
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- 2017
11. Multicentric, Retrospective Study of Extracorporeal Photopheresis, Off-Line System, in Corticosteroid Refractory Acute and Chronic Graft-Versus-Host Disease
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Cristina Amunarriz, Jose Luis Arroyo, Aurora Viejo, Maria Luisa Lozano, Iniesta Pastora, José Luis Díez-Martín, Gillen Oarbeascoa, Mi Kwon, Grupo Español de Aferesis, Cristina Pascual, Cynthia Acosta Fleitas, Concepcion Andon Saavedra, Eva Martinez Revuelta, Nuria Revilla, Dolores Hernández-Maraver, Jose Maria Garcia-Gala, Luisa Maria Guerra, and Andrea Galego
- Subjects
medicine.medical_specialty ,business.industry ,medicine.drug_class ,medicine.medical_treatment ,Immunology ,Retrospective cohort study ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Biochemistry ,Gastroenterology ,Transplantation ,Graft-versus-host disease ,Photopheresis ,immune system diseases ,Interquartile range ,hemic and lymphatic diseases ,Internal medicine ,Extracorporeal Photopheresis ,Medicine ,Corticosteroid ,business - Abstract
BACKGROUND Graft-versus-host disease (GvHD) remains an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation, despite the improvements in GvHD prophylaxis. First line treatment of GvHD (acute or chronic) consists of high dose corticosteroids, with a response rate of around 50%. Extracorporeal photopheresis (ECP) is an effective and safe treatment strategy in corticosteroid refractory GvHD, although most of the studies are limited to retrospective series. The main objectives of this study were to analyze the clinical response and impact of ECP therapy in corticosteroid dose reduction. METHODS 114 patients from 7 Spanish transplantation centers were analyzed retrospectively. The characteristics of the patients are shown on Table 1. A total of 1940 ECP procedures were performed from January-2011 to June-2017 in 65 patients (57%) with acute GvHD (aGvHD) and 49 (43%) with chronic GvHD (cGvHD). Glucksberg and the NIH criteria were used for the diagnosis and grading of acute and chronic GvHD, respectively. All ECP procedures were performed with the off-line system: after the lymphoapheresis, 8-MOP was added to the apheresis product and finally photoinactivated in the Macogenic G1 (Macopharma®) irradiator. During the first 4 weeks, patients underwent 1-2 weekly procedures, followed by 1-2 procedures every 2 weeks and tailored by clinical response. The response was classified as complete response (CR), partial response (PR) or no response (NR). % of the initial corticosteroid dose reduction was registered at the end of treatment. RESULTS Patients with aGvHD underwent a median of 13 processes (interquartile range 9-19), and those with cGvHD a median of 19 processes (IQR 13-24). The median number of processes until response was 3 in patients with aGvHD and 4 for patients with cGvHD. ECP was the second line therapy in the 47% of aGvHD cases and 49% in cGvHD. 71% of the cases of aGvHD were grade 3-4, and 69% of the cases of cGvHD corresponded to severe forms. The overall response rate in aGvHD was 66% (CR 55%), whereas in cGvHD the rate was 67% (CR 22%). The most involved organ was the skin, with a response rate of 80% (CR 68%) in aGvHD and 69% (CR 22%) in cGvHD. In acute digestive GvHD, the response rate was 61% (CR 50%), and 75% (CR 50%) in the chronic form. For liver involvement, response rates were 67% (CR 57%) in acute and 70% (CR 30%) in cGvHD. 80% of the patients with chronic lung involvement showed an overall response (20%CR). At the end of ECP treatment, 71% of the patients treated for aGvHD and 61% of patients with cGvHD were able to reduce the corticosteroid dose, with a median dose reduction of 90% and 100% in all patients, respectively. With a median follow-up of 31 months in aGvHD and 68 months in cGvHD, the 2-year overall survival (OS) was 47% and 83%, respectively. Significant OS differences were noted between responding (CR+PR, 2-year OS 62%) and no responding (NR, 2 year OS 18%, HR=2.5, p CONCLUSIONS ECP is a valid therapeutic alternative in patients with corticosteroid refractory acute and cGvHD, with higher CR rates in patients with aGvHD. ECP allowed for significant corticosteroid dose reductions in more than 2/3 of the patients in both GvHD settings, and granted longer OS in responding patients. The results obtained are similar to those published by other groups. Disclosures No relevant conflicts of interest to declare.
- Published
- 2018
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