Scientific Letter
Massive Pulmonary Thrombosis Following Haemoptysis in Type IV Ehlers–Danlos Syndrome
Trombosis pulmonar masiva tras hemoptisis en el Síndrome de Ehlers–Danlos tipo IV
Leonor Mendonça Almeidaa,
, Célia Sousab, Paulo Vilares Morgadob, Pedro Fernandesc, José Amadod, José Artur Paivad,e, Anabela Marinhoa, João Paulo Oliveiraf,g,h
Corresponding author
a Pulmonology Department, Centro Hospitalar e Universitário São João, Porto, Portugal
b Radiology Department, Centro Hospitalar e Universitário São João, Porto, Portugal
c Cardiothoracic Surgery Department, Centro Hospitalar e Universitário São João, Porto, Portugal
d Intensive Care Medicine Department, Centro Hospitalar e Universitário São João, Porto, Portugal
e Internal Medicine Department, Faculty of Medicine of University of Porto, Portugal
f Medical Genetics Department, Centro Hospitalar e Universitário São João, Porto, Portugal
g Unit of Genetics, Department of Pathology, Faculty of Medicine of University of Porto, Portugal
h i3S – Institute for Research and Innovation in Health/Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Portugal
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João, Porto, Portugal" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Internal Medicine Department, Faculty of Medicine of University of Porto, Portugal" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Medical Genetics Department, Centro Hospitalar e Universitário São João, Porto, Portugal" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Unit of Genetics, Department of Pathology, Faculty of Medicine of University of Porto, Portugal" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "i3S – Institute for Research and Innovation in Health/Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Portugal" "etiqueta" => "h" "identificador" => "aff0040" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Trombosis pulmonar masiva tras hemoptisis en el Síndrome de Ehlers–Danlos tipo IV" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 990 "Ancho" => 1255 "Tamanyo" => 153690 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Late arterial phase chest CT depicts bilateral peribronchovascular groundglass opacities (GGO), especially in the right lower lobe (black arrows). In the right lower lobe thick-walled cavitary lesions with air-blood levels are also seen (orange arrow). The high density of blood-containing cavities is illustrated in B (white arrow). The GGO translate diffuse alveolar haemorrhage and the cavitary lesions result from the spontaneous rupture of the lung. There was no evidence of haemothorax or pneumothorax.(C and D) CT pulmonary angiographic study shows bilateral pulmonary thromboembolism (white arrows) and enlarged haemorrhagic cavity in the right lower lobe (orange arrows). No signs of pulmonary hypertension or right ventricular strain were present.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Ehlers–Danlos syndromes (EDS) are a group of rare genetic disorders that affect connective tissue, characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. The majority of the currently recognized 13 EDS subtypes<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a> are due to gene variants leading to impaired synthesis or structural abnormalities of different collagen types. Type IV or vascular EDS (EDS-IV) is an autosomal dominant multisystem disease caused by defects in type III collagen, encoded by the <span class="elsevierStyleItalic">COL3A1</span> gene, in chromosome 2 (2q32.2).<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a> Type III collagen is a major constituent of the interstitial matrix in many tissues, including blood vessels. Accordingly, aneurysms and rupture of large arteries, spontaneous bowel perforation and uterine rupture during pregnancy are life-threatening complications of EDS-IV. EDS-IV is the most severe form of EDS, with most individuals dying before the 5th decade.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a> Pulmonary involvement may occur without extrathoracic manifestations,<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2–6</span></a> and the diagnosis of such cases may be made only at post-mortem examination.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a> Spontaneous pneumothorax or haemopneumothorax are the most frequent complications, but cavitary lesions, haemoptysis and pulmonary haemorrhage have also been reported.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2–6</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Herein, we report the occurrence of severe haemoptysis associated with massive pulmonary thrombosis, with a fatal outcome, in a young adult male with EDS-IV. The patient's diagnosis was established by genetic testing in mid-adolescence, as soon as the family's pathogenic <span class="elsevierStyleItalic">COL3A1</span> (c.3517_3519del/p.(Gly1173del)) variant was identified. The patient had been free of significant EDS-related complications until the age of 17 years. The patient's father and one maternal aunt died from spontaneous aortic dissection/rupture, early in the 4th decade of life.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Our patient had a first hospital admission for haemoptysis at the age of 17. At the time, small areas of ground-glass opacities suggestive of alveolar haemorrhage were observed on chest computed tomography (CT). Over the next two years, he had occasional episodes of small-volume haemoptysis, often preceded by a tingling sensation in the head and neck.</p><p id="par0020" class="elsevierStylePara elsevierViewall">At age 19, the patient needed hospitalization for large-volume haemoptysis. In the previous days, he had intermittent episodes of small-volume haemoptysis preceded by what he described as a “clicking” sensation in the head and, right-sided paraesthesia and mild motor weakness. The chest CT scan (late arterial phase) showed multiple bilateral ground-glass opacities suggestive of diffuse alveolar haemorrhage and large fluid-filled cavities with air-fluid levels suggestive of haemorrhagic cavitation (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A/B). Brain and cervical magnetic resonance (MR) imaging, MR angiography of the carotid and vertebrobasilar circulations, including the supra-aortic arches, and electroencephalogram were unremarkable. Despite the decrease in the haemoglobin level relative to baseline (respectively 15.3<span class="elsevierStyleHsp" style=""></span>g/dL and 13.8<span class="elsevierStyleHsp" style=""></span>g/dL), the patient remained hemodynamically stable without respiratory failure. Cough suppressive and antifibrinolytic therapies were initiated. Since the patient did not have any bronchial artery hypertrophy on CT scan and due to the high risk of vascular manipulation, bronchial arteriography was not performed. The surgical risk was also very high; therefore, the patient was not a candidate for thoracic surgery at that time.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">A pulmonary CT angiography obtained on day 7 of hospital stay showed extensive bilateral thrombosis and an enlargement of the haemorrhagic parenchymal cavitation, but no actively bleeding arteries (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>C/D). There were no signs of deep vein thrombosis on Doppler ultrasound examination of the lower limbs. Despite the striking radiological signs, the patient remained asymptomatic. Transthoracic echocardiogram did not show any signs of right ventricular dysfunction, and the Pulmonary Embolism Severity Index (PESI) score was 29 (class I), translating into a low mortality risk.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">7</span></a> Given the high bleeding risk and the low overall risk stratification, hypocoagulation was not prescribed.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Two days later, the patient was admitted to the intensive care unit, following a syncope episode with echocardiographic evidence of right ventricular dysfunction. Anticoagulation with unfractionated heparin and inotropic support were instituted. After about 24<span class="elsevierStyleHsp" style=""></span>h of clinical stability, his haemodynamic condition suddenly deteriorated due to supraventricular tachycardia, followed by cardiac arrest that did not respond to advanced life support measures and thrombolysis. Autopsy was not performed.</p><p id="par0035" class="elsevierStylePara elsevierViewall">To our knowledge, this is the first report of massive pulmonary thrombosis in a patient with EDS-IV seeking medical attention for recurrent haemoptysis. Arterial bleeding complications are typical of EDS-IV and several cases of severe haemoptysis, including with fatal outcomes, have been described.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2,4,6</span></a> Platelet dysfunction may additionally aggravate the constitutional haemorrhagic propensity.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">8</span></a> Contrastingly, thrombotic events seem to be exceedingly rare in patients with EDS,<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">9</span></a> but have been reported in EDS-IV<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">10–12</span></a> and other EDS subtypes.<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">9,13</span></a> In one of the EDS-IV cases, the patient had renal infarctions caused by emboli from a thrombotic renal artery aneurysm, and hypocoagulation was not prescribed either, with a favourable outcome<span class="elsevierStyleSup">.</span><a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Major treatment decisions taken in our patient were based on validated risk stratification algorithms for pulmonary embolism/thrombosis<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">7</span></a> and current clinical approaches to the management of haemoptysis.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a> The delay in starting anticoagulation and the antifibrinolytic therapy might have facilitated the thrombotic event. Furthermore, haemostatic abnormalities were not screened, such as coexisting prothrombotic conditions or vitamin-D deficiency, which have been suggested as prognostic modulators in EDS-IV.<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">8,11,15</span></a> However, taking into consideration the enlarging haemorrhagic cavitary lesion, the haemorrhagic propensity and the possibility of platelet dysfunction, the bleeding risk seemed to prevail when we decided not to initiate hypocoagulation therapy.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Despite the comprehensive neuroradiological and electroencephalographic evaluation, the aetiology of the neurological symptoms in close temporal association with the episodes of haemoptysis remained elusive, which is in line with previous observations in EDS-IV patients.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">3,4</span></a> In this case, a post-mortem examination could have been useful to characterize the lung pathology,<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">4,6</span></a> as well as to elucidate the aetiology of the pulmonary embolism/thrombosis, but could not be carried out.</p><p id="par0050" class="elsevierStylePara elsevierViewall">With this report, we aim to call the attention of respiratory physicians to this rare disorder, since haemoptysis, pneumothorax and pulmonary substance loss with cavitation can be the presenting manifestation of EDS-IV. Our patient illustrates the complexity of the pulmonary involvement in EDS-IV and the challenge of managing its haemorrhagic complications since the excessive vascular and tissue friability restricts diagnostic and therapeutic options. As in other rare, multisystem disorders, specific evidence-based treatment guidelines are not available, and patient care by multidisciplinary care teams is highly recommended.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a></p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 990 "Ancho" => 1255 "Tamanyo" => 153690 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Late arterial phase chest CT depicts bilateral peribronchovascular groundglass opacities (GGO), especially in the right lower lobe (black arrows). In the right lower lobe thick-walled cavitary lesions with air-blood levels are also seen (orange arrow). The high density of blood-containing cavities is illustrated in B (white arrow). The GGO translate diffuse alveolar haemorrhage and the cavitary lesions result from the spontaneous rupture of the lung. There was no evidence of haemothorax or pneumothorax.(C and D) CT pulmonary angiographic study shows bilateral pulmonary thromboembolism (white arrows) and enlarged haemorrhagic cavity in the right lower lobe (orange arrows). No signs of pulmonary hypertension or right ventricular strain were present.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib0080" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The Ehlers–Danlos syndromes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. Malfait" 1 => "M. Castori" 2 => "C.A. Francomano" 3 => "C. Giunta" 4 => "T. Kosho" 5 => "P.H. Byers" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/s41572-020-0194-9" "Revista" => array:5 [ "tituloSerie" => "Nat Rev Dis Primers" "fecha" => "2020" "volumen" => "6" "paginaInicial" => "64" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32732924" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0085" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Respiratory complications of Ehlers-Danlos syndrome type IV" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S.B. Dowton" 1 => "S. Pincott" 2 => "L. Demmer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1399-0004.1996.tb02724.x" "Revista" => array:4 [ "tituloSerie" => "Clin Genet" "fecha" => "1996" "paginaInicial" => "510" "paginaFinal" => "514" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0090" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ehlers-Danlos syndrome type IV with few extrathoracic findings: a newly recognized point mutation in the COL3A1 gene" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Watanabe" 1 => "Y. Kawabata" 2 => "O. Okada" 3 => "N. Tanabe" 4 => "H. Kimura" 5 => "A. Hatamochi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1183/09031936.02.00219202" "Revista" => array:6 [ "tituloSerie" => "Eur Respir J" "fecha" => "2002" "volumen" => "19" "paginaInicial" => "195" "paginaFinal" => "198" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11843319" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0095" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fatal hemoptysis in Ehlers-Danlos syndrome: old malady with a new curse" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "B.A. Yost" 1 => "J.P. Vogelsang" 2 => "J.T. Lic" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1378/chest.107.5.1465" "Revista" => array:6 [ "tituloSerie" => "Chest" "fecha" => "1995" "volumen" => "107" "paginaInicial" => "1465" "paginaFinal" => "1467" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7750352" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0100" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cavitary pulmonary lesions in type IV Ehlers-Danlos syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "T.E. Herman" 1 => "W.H. McAlister" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/BF02015451" "Revista" => array:6 [ "tituloSerie" => "Pediatr Radiol" "fecha" => "1994" "volumen" => "24" "paginaInicial" => "263" "paginaFinal" => "265" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7800447" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0105" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Respiratory complications of Ehlers-Danlos syndrome type IV" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "K. Hatake" 1 => "Y. Morimura" 2 => "R. Kudo" 3 => "W. Kawashima" 4 => "S. Kasuda" 5 => "H. Kuniyasu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.legalmed.2012.07.005" "Revista" => array:5 [ "tituloSerie" => "Leg Med" "fecha" => "2013" "volumen" => "15" "paginaInicial" => "23" "paginaFinal" => "27" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0110" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:1 [ "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European respiratory society (ERS)" "etal" => true "autores" => array:6 [ 0 => "S.V. Konstantinides" 1 => "G. Meyer" 2 => "H. Bueno" 3 => "N. Galié" 4 => "J.S.R. Gibbs" 5 => "W. Ageno" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/eurheartj/ehz405" "Revista" => array:6 [ "tituloSerie" => "Eur Heart J" "fecha" => "2020" "volumen" => "41" "paginaInicial" => "543" "paginaFinal" => "603" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31504429" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0115" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vascular type Ehlers-Danlos syndrome is associated with platelet dysfunction and low Vitamin D serum concentration" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Busch" 1 => "S. Hoffjan" 2 => "F. Bergmann" 3 => "B. Hartung" 4 => "H. Jung" 5 => "D. Hanel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s13023-016-0491-2" "Revista" => array:6 [ "tituloSerie" => "Orphanet J Rare Dis" "fecha" => "2016" "volumen" => "11" "paginaInicial" => "1" "paginaFinal" => "8" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26728142" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0120" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vascular phenotypes in nonvascular subtypes of the Ehlers-Danlos syndrome: a systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S. D’hondt" 1 => "T. Van Damme" 2 => "F. Malfait" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/gim.2017.138" "Revista" => array:6 [ "tituloSerie" => "Genet Med" "fecha" => "2018" "volumen" => "20" "paginaInicial" => "562" "paginaFinal" => "573" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28981071" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0125" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Large kindred with Ehlers-Danlos syndrome type IV due to a point mutation (G571S) in the COL3A1 gene of type III procollagen: low risk of pregnancy complications and unexpected longevity in some affected relatives" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "D. Gilchrist" 1 => "U. Schwarze" 2 => "K. Shields" 3 => "L. MacLaren" 4 => "P.J. Bridge" 5 => "P.H. Byers" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Med Genet" "fecha" => "1999" "volumen" => "82" "paginaInicial" => "305" "paginaFinal" => "311" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10051163" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0130" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Homozygous factor V Leiden mutation in type IV Ehlers-Danlos patient" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M. Refaat" 1 => "M. Hotait" 2 => "B. Winston" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.12998/wjcc.v2.i3.75" "Revista" => array:4 [ "tituloSerie" => "World J Clin Cases" "fecha" => "2014" "volumen" => "2" "paginaInicial" => "75" ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0135" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Thromboembolic renal infarction due to a renal artery aneurysm in a patient with Ehlers-Danlos syndrome type IV" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A. Yigal" 1 => "H. Tal" 2 => "H. Nurit" 3 => "C.S. Tova" 4 => "T. Hershcovici" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ejim.2006.02.008" "Revista" => array:6 [ "tituloSerie" => "Eur J Intern Med" "fecha" => "2006 Aug" "volumen" => "17" "paginaInicial" => "377" "paginaFinal" => "379" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16864020" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0140" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recurrent venous thrombosis in Ehlers-Danlos syndrome type III: an atypical manifestation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "E. Jiménez-Encarnación" 1 => "L.M. Vilá" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/bcr-2013-008922" "Revista" => array:4 [ "tituloSerie" => "BMJ Case Rep" "fecha" => "2013" "paginaInicial" => "1" "paginaFinal" => "3" ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0145" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnóstico y tratamiento de la hemoptisis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Cordovilla" 1 => "A. Bollo de Miguel" 2 => "A. Nuñez Ares" 3 => "F.J. Cosano Povedano" 4 => "I. Herráez Ortega" 5 => "R. Jiménez Merchán" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.arbr.2016.05.010" "Revista" => array:6 [ "tituloSerie" => "Arch Bronconeumol" "fecha" => "2016" "volumen" => "52" "paginaInicial" => "368" "paginaFinal" => "377" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26873518" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0150" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hemostatic abnormalities in patients with Ehlers–Danlos syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Artoni" 1 => "A. Bassotti" 2 => "M. Abbattista" 3 => "B. Marinelli" 4 => "A. Lecchi" 5 => "F. Gianniello" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/jth.14310" "Revista" => array:6 [ "tituloSerie" => "J Thromb Haemost" "fecha" => "2018" "volumen" => "16" "paginaInicial" => "2425" "paginaFinal" => "2431" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30312027" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/15792129/0000005700000004/v1_202104020819/S1579212921000975/v1_202104020819/en/main.assets" "Apartado" => array:4 [ "identificador" => "49861" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Scientific letters" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/15792129/0000005700000004/v1_202104020819/S1579212921000975/v1_202104020819/en/main.pdf?idApp=UINPBA00003Z&text.app=https://archbronconeumol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212921000975?idApp=UINPBA00003Z" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 8 | 3 | 11 |
| 2024 October | 57 | 18 | 75 |
| 2024 September | 44 | 16 | 60 |
| 2024 August | 54 | 24 | 78 |
| 2024 July | 49 | 20 | 69 |
| 2024 June | 39 | 17 | 56 |
| 2024 May | 64 | 22 | 86 |
| 2024 April | 24 | 18 | 42 |
| 2024 March | 29 | 15 | 44 |
| 2024 February | 31 | 25 | 56 |
| 2024 January | 40 | 24 | 64 |
| 2023 December | 70 | 20 | 90 |
| 2023 November | 38 | 15 | 53 |
| 2023 October | 96 | 28 | 124 |
| 2023 September | 30 | 32 | 62 |
| 2023 August | 25 | 22 | 47 |
| 2023 July | 46 | 21 | 67 |
| 2023 June | 49 | 15 | 64 |
| 2023 May | 33 | 13 | 46 |
| 2023 April | 27 | 27 | 54 |
| 2023 March | 46 | 45 | 91 |
| 2023 February | 33 | 11 | 44 |
| 2023 January | 28 | 32 | 60 |
| 2022 December | 54 | 18 | 72 |
| 2022 November | 42 | 19 | 61 |
| 2022 October | 55 | 24 | 79 |
| 2022 September | 25 | 20 | 45 |
| 2022 August | 31 | 39 | 70 |
| 2022 July | 25 | 32 | 57 |
| 2022 June | 28 | 26 | 54 |
| 2022 May | 36 | 32 | 68 |
| 2022 April | 32 | 24 | 56 |
| 2022 March | 32 | 26 | 58 |
| 2022 February | 18 | 15 | 33 |
| 2021 June | 1 | 0 | 1 |
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