Faustino García‐Candel

Hospital Universitario Virgen de la Arrixaca

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María Eva Mingot‐Castellano

Instituto de Biomedicina de Sevilla

Pascual Marco

Hospital General Universitario de Alicante Doctor Balmis

José M. Moraleda

Hospital Universitario Virgen de la Arrixaca

Rocío Pérez‐Montes

Marqués de Valdecilla University Hospital

Nieves Alonso

Centro de Implantología Cirugía Oral y Maxilofacial

Víctor Jiménez‐Yuste

Hospital Universitario La Paz

Ramón Rodríguez‐González

Hospital Universitario Severo Ochoa

María José Paloma

Hospital Virgen del Camino

María Fernanda López Fernández

Complexo Hospitalario Universitario A Coruña

Inmaculada Soto

Viña del Mar University

Cooperative Institutions

Hospital Universitario Virgen de la Arrixaca

Universidad de Murcia

Instituto Murciano de Investigación Biosanitaria

Instituto de Salud Carlos III

Banc de Sang i Teixits

Universitat Autònoma de Barcelona

Complexo Hospitalario Universitario A Coruña

Hospital Universitari i Politècnic La Fe

Vall d'Hebron Institut de Recerca

Vall d'Hebron Hospital Universitari

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ADAMTS13 recovery in acute thrombotic thrombocytopenic purpura after caplacizumab therapy

Blood (2024)

María Eva Mingot‐Castellano Faustino García‐Candel Jorge Martínez Nieto José García-Arroba Javier de la Rubia-Comos

ADAMTS13

Rescue therapy

10.1182/blood.2023022725

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Citations (5)

Real-life behaviour of direct oral anticoagulants in a Spanish cohort with non-valvular atrial fibrillation: Refase Registry

Current Medical Research and Opinion (2019)

Begoña Navarro-Almenzar Juan José Cerezo-Manchado César Caro Martínez Faustino García‐Candel P J Flores Blanco

Aim: To analyse the effectiveness and safety of DOAC (direct oral anticoagulants) in non-valvular atrial fibrillation (NVAF) patients attending clinical practice.Methods: Retrospective study of AF patients who started treatment with DOAC from January 1, 2013 to December 31, 2016 in three Spanish hospitals. Mean follow-up was 1.6 years. The primary outcomes were rates of all-cause death, ischaemic stroke, and bleeding. These outcomes were also studied depending on correct dosage adjustment and standard/adjusted dose.Results: The study included 2494 patients (age = 76.0 ± 9.5 years, CHA2DS2-VASc = 4.0 ± 1.6). The most prescribed DOAC was rivaroxaban (41.1%). Patients taking dabigatran were the youngest (mean age = 73.1 ± 10.3 years), with better kidney function (mean CrCl = 80.6 ± 35.8 ml/min) and lower CHA2DS2-VASc (3.7 ± 1.4) and HAS-BLED (2.1 ± 0.9) scores. Patients taking apixaban were the oldest, and had the highest CHA2DS2-VASc and HAS-BLED scores (4.3 ± 1.6 and 2.6 ± 0.9, respectively). Rates of stroke/major bleeding/intracranial bleeding were 1.8/3.0/0.3 events per 100 patient-years, respectively, with no differences among DOAC. Based on dose adjustment according to technical data, it was observed that 517 patients (23.5%) received DOAC doses inconsistent with labelling (p < .001) and, within this group, under-dosed patients had a higher death rate although it did not reach a significant result after multivariate adjustment.Conclusions: The results of safety and efficacy are very similar to those of other previously published national registries. There were no differences among the different types of DOAC regarding outcomes. However, it was found that people taking the adjusted dose of the drug seemed to have a higher risk of death. A non-negligible proportion of patients received DOAC doses inconsistent with labelling (mostly underdose).

Apixaban

Stroke

CHA2DS2–VASc score

10.1080/03007995.2019.1647735

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Citations (12)

Effect of Caplacizumab in the Recovery of ADAMTS13 Level in Patients with Autoimmune Thrombotic Thrombocytopenic Purpura. Analysis from the Spanish Registry (REPTT)

Blood (2023)

María Eva Mingot‐Castellano Cristina Izquierdo Pascual Faustino García‐Candel Jorge Martínez Nieto José García-Arroba Peinado

Interquartile range

ADAMTS13

Refractory (planetary science)

10.1182/blood-2023-182876

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Citations (2)

Real life behaviour of direct oral anticoagulants in patients with nonvalvular atrial fibrillation and morbid obesity

IJC Heart & Vasculature (2021)

Begoña Navarro-Almenzar Juan José Cerezo-Manchado Faustino García‐Candel

Atrial fibrillation (AF) is the most prevalent arrhythmia worldwide and the main cause of anticoagulation, being direct oral anticoagulants (DOAC) increasingly used in this context. On the other hand, obesity is a known risk thromboembolic factor. In the clinical trials that led to the approval of DOAC for ischemic stroke prevention, patients with morbid obesity were underrepresented. The International Society of Thrombosis and Haemostasis suggests not using these drugs in morbid obese patients. Thus, the primary objectives of this study were to analyse the rates of mortality, thrombotic and haemorrhagic events in patients with morbid obesity. As secondary objectives, factors statistically associated with these events were analysed. Methods: multicentre retrospective study that included patients diagnosed with AF on treatment with DOAC from January 2013 to December 2016. The subgroup of patients with morbid obesity (BMI > 40 and / or weight > 120 kg) was analysed. Mean follow-up was 1.7 years. Results: Amongst 2,492 patients included in the study, 135 patients had morbid obesity (mean age was 71 ± 11 years). The mean scores of the CHA2DS2-VASc and HAS-BLED risk scales were 3.7 ± 1.6 and 2.2 ± 0.9, respectively. Neither differences were found regarding mortality (5.2 vs 6/100 patient-years, p = 0.662), ischemic stroke (0.8 vs 1.9/100 patient-years, p = 0.261) and major bleeding rates (3 vs 3.1/100 patient-years, p = 0.983) between morbidly obese population and general population. Nor was there an association found between the degree of obesity and any of the events studied. Conclusion: DOAC are safe and effective in morbidly obese patients.

Stroke

10.1016/j.ijcha.2021.100913

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Citations (9)

Severe thrombocytopenia after an infusion of abciximab.

PubMed (2001)

AM Martín Rubio Carmen González-Lois Majado Mj Eduardo Salido Faustino García‐Candel

Abciximab

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Decrease of Aggregation By Platelet Impedance Aggregometry ( MULTIPLATE ) in Patients Treated with Dabigatran

Blood (2016)

Valentín Cabañas Juan José Cerezo-Manchado Faustino García‐Candel Eduardo Salido Raúl López-Pérez

Apixaban

10.1182/blood.v128.22.5022.5022

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Citations (0)

Unraveling the effect of silent, intronic and missense mutations on VWF splicing: contribution of next generation sequencing in the study of mRNA

Haematologica (2018)

Nina Borràs Gerard Orriols Javier Batlle Almudena Pérez‐Rodríguez Teresa Fidalgo

Large studies in von Willebrand disease patients, including Spanish and Portuguese registries, led to the identification of >250 different mutations. It is a challenge to determine the pathogenic effect of potential splice site mutations on VWF mRNA. This study aimed to elucidate the true effects of 18 mutations on VWF mRNA processing, investigate the contribution of next-generation sequencing to in vivo mRNA study in von Willebrand disease, and compare the findings with in silico prediction. RNA extracted from patient platelets and leukocytes was amplified by RT-PCR and sequenced using Sanger and next generation sequencing techniques. Eight mutations affected VWF splicing: c.1533+1G>A, c.5664+2T>C and c.546G>A (p.=) prompted exon skipping; c.3223-7_3236dup and c.7082-2A>G resulted in activation of cryptic sites; c.3379+1G>A and c.7437G>A) demonstrated both molecular pathogenic mechanisms simultaneously; and the p.Cys370Tyr missense mutation generated two aberrant transcripts. Of note, the complete effect of three mutations was provided by next generation sequencing alone because of low expression of the aberrant transcripts. In the remaining 10 mutations, no effect was elucidated in the experiments. However, the differential findings obtained in platelets and leukocytes provided substantial evidence that four of these would have an effect on VWF levels. In this first report using next generation sequencing technology to unravel the effects of VWF mutations on splicing, the technique yielded valuable information. Our data bring to light the importance of studying the effect of synonymous and missense mutations on VWF splicing to improve the current knowledge of the molecular mechanisms behind von Willebrand disease. clinicaltrials.gov identifier:02869074.

Sanger sequencing

von Willebrand Disease

Exon skipping

Silent mutation

10.3324/haematol.2018.203166

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Citations (18)

Joint status in Spanish haemophilia B patients assessed using the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD‐US) score

Haemophilia (2018)

Víctor Jiménez‐Yuste María Román Mónica Martín‐Salces Hortensia De la Corte‐Rodríguez Carmen Altisent

The use of musculoskeletal ultrasound (MSK-US) following protocols for haemophilic arthropathy and the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) score can help standardize monitoring in haemophilia. This study evaluated the joint status (elbows, knees and ankles) of patients with haemophilia B (HB) in Spain using MSK-US and the HEAD-US score.Haemophilia B patients ≥14 years old were included in this observational, multicentre, cross-sectional study, regardless of their clinical condition, HB severity and treatment received. Two blinded observers were involved in image acquisition and scoring in each centre.Eighty-two patients from 12 centres were enrolled: 27% mild HB, 23% moderate, 50% severe HB. Mean age was 38.9 ± 16.4 years, 60% were treated on demand (OD) and 40% were on prophylaxis. HEAD-US was zero in all joints in 28.6% OD patients and 36.4% on prophylaxis. Mean scores significantly worsened with HB severity, except for the left knee. Patients on primary and secondary prophylaxis had significantly better joint health vs OD patients in all joints, except the right ankle. Among OD patients, those with severe disease presented significantly worse scores in all HEAD-US items related to permanent damage.Joint status of HB patients in Spain is influenced by severity and treatment modality, related to the development of arthropathy, which appears prevalent in OD patients with severe HB. Routine assessment with an imaging tool such as ultrasound and HEAD-US system may help to improve joint health by personalizing and adjusting treatment in this population.

Arthropathy

Haemophilia B

10.1111/hae.13628

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Citations (19)

Incidence, diagnosis, and outcome of immune‐mediated thrombotic thrombocytopenic purpura: A nationwide survey by the Spanish registry of thrombotic thrombocytopenic purpura

Journal of Clinical Apheresis (2021)

Cristina Pascual Julio del Río-Garma Javier de la Rubia Aurora Viejo María Eva Mingot‐Castellano

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare disease characterized by the presence of anti-ADAMTS13 autoantibodies. Achieving accurate information on incidence and customary disease management is important to provide appropriate diagnostic and therapeutic resources. The aim of this study was to determine the incidence and outcomes of iTTP in Spain.A cross-sectional survey was carried out among Spanish hospitals, focused on iTTP patients ≥16 years old attended between 2015 and 2017, and those at follow-up before that interval. Incidence, prevalence, mortality, refractoriness, exacerbations, treatment complications, relapses, and sequelae were estimated.Forty-two hospitals covering roughly 20 million inhabitants answered the survey and reported 203 episodes (138 newly-diagnosed and 65 relapses), of which 193 (95.1%) were treated. Incidence was 2.67 (95% CI 1.90-3.45) patients per million inhabitants per year and prevalence 21.44 (95% CI% 19.10-23.73) patients per million inhabitants. At diagnosis, ADAMTS13 activity and anti-ADAMTS13 autoantibody were measured in 97% and 84.3% of reported episodes, respectively. Fifteen patients (7.4%) died as a direct consequence of iTTP, 6 of them before receiving any iTTP-specific treatment. Thirty-one (16.1%) of the 193 treated episodes were refractory to plasma exchange and corticosteroids, and 51 (26.4%) suffered at least one exacerbation.iTTP incidence and prevalence were somewhat higher than those documented in neighboring countries. Together with data on treatments and outcomes, this information will allow us to better estimate what is needed to improve diagnosis and prognosis of iTTP patients in Spain.

ADAMTS13

Thrombocytopenic purpura

10.1002/jca.21894

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Citations (16)

Involvement of antifactor VIII autoantibodies specificity in the outcome of inhibitor eradication therapies in acquired hemophilia a patients

Blood Coagulation & Fibrinolysis (2019)

María Eva Mingot‐Castellano Andrés Moret Carmen de Cos Faustino García‐Candel Raquel Garrido

We hypothesized that inhibitor specificity may predict the outcome of antifactor VIII autoantibodies eradication treatment in acquired hemophilia A. Our objective was to analyze the association between factor VIII domains recognized by inhibitors and outcome of the immunosuppressive therapies (ISTs) in a prospective, observational study. 16 patients were recruited. Inhibitor specificities were assessed at diagnosis and throughout the study. Their association with IST outcome was addressed. First-line IST succeeded in 56% of patients. Inhibitors reacted mainly with light chain domains (69%) and/or the A2 domain (44%). 31% inhibitors recognized more than one domain. Significantly, the number of patients whose inhibitors recognized the light chain was significantly higher in the group of those who did not reach complete remission after first line IST when compared with those who did [6/7 (85.7%) vs. 4/9 (44.4%), P < 0.05]. Therefore, inhibitor specificity could predict the success of IST in acquired hemophilia A.

10.1097/mbc.0000000000000804

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Citations (2)