Case report
Transient familial factor V Leiden-linked hip osteoporosis
Osteoporosis transitoria de cadera familiar ligada al factor v de Leiden
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Serrano-Toledano, M. del Río-Arteaga, J. Ribera-Zabalbeascoa" "autores" => array:3 [ 0 => array:4 [ "nombre" => "D." "apellidos" => "Serrano-Toledano" "email" => array:1 [ 0 => "serranotoledano@gmail.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "M." "apellidos" => "del Río-Arteaga" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 2 => array:3 [ "nombre" => "J." "apellidos" => "Ribera-Zabalbeascoa" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Unidad de Cadera y Rodilla, Hospital Viamed Santa Ángela de la Cruz, Sevilla, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Hospital Comarcal Básico de Riotinto, Huelva, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Unidad de Cadera y Rodilla, Hospital San Juan de Dios Aljarafe, Sevilla, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Osteoporosis transitoria de cadera familiar ligada al factor v de Leiden" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1258 "Ancho" => 2500 "Tamanyo" => 325409 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Previous MRI images showing bone marrow oedema at the level of the femoral head and intertrochanteric area. Control MRI images showing complete disappearance of the area of oedema in all cases.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">In 1959, Curtiss and Kincaid first described 3 cases of hip or thigh pain in the third trimester of pregnancy that presented radiologically as a subtle demineralisation of the femoral head and, to a lesser extent, of the femoral neck and acetabulum, and which recovered spontaneously a few months later.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> In 1988, Wilson et al. used the term “transient bone marrow oedema” to refer to patients with hip and knee pain who presented with osteopenia or normal bone mineral density on densitometry.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The term “bone marrow oedema syndrome” (BMOS) encompasses 2 clinical entities, transient osteoporosis of the hip (TOH) and regional migratory osteoporosis (RMO). TOH is more common in middle-aged men. In women, it is most often found in the third trimester of pregnancy. It usually affects the proximal area of the femur and rarely the acetabulum, and the gold standard for diagnosis is magnetic resonance imaging (MRI). Although a matter of debate, TOH can be considered an early stage of avascular necrosis (AN). However, while TOH generally resolves without sequelae, AN is normally an irreversible and progressive disease, which results in interrupted vascular supply to the femoral head, occasionally causing permanent loss of joint function.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The anticoagulant effect of protein C was first described by Mammen et al.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Inherited resistance to activated protein C was described by Dahlbäck et al. and associated with familial thrombophilia.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> More frequently, resistance to activated protein C is caused by a genetic mutation that results in loss of the binding site to factor V, giving rise to what has been termed factor V Leiden, a severe hypercoagulability disorder. Factor V Leiden has been identified as a risk factor for the development of AN.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5–8</span></a> This article provides a first description of factor V Leiden mutation in three siblings with TOH.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Clinical cases</span><p id="par0020" class="elsevierStylePara elsevierViewall">A case-series study. Three siblings, 2 males and one female aged between 40 and 42 years, were attended consecutively in consultation for disabling hip pain of approximately one month’s duration. None of them had risk factors for developing AN (habitual alcohol consumption, steroid treatment or hyperlipidaemia) or a history of trauma that could have caused it. None of the siblings had a previous history of deep vein thrombosis, although the female patient had a previous history of repeated miscarriages.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Measurement of lipids, cholesterol, platelets and G1691A mutation</span><p id="par0025" class="elsevierStylePara elsevierViewall">Lipids, cholesterol levels, platelets and antinuclear antibodies (ANA) were quantified in peripheral blood using standard enzymatic methods (the detailed test parameters are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Nuclear magnetic resonance</span><p id="par0030" class="elsevierStylePara elsevierViewall">MRI studies were performed on a 3.0 Tesla system (Magnetom Expert, Siemens, Erlangen, Germany). In all 3 cases, MRI revealed the presence of bone marrow oedema (BMO) in the right femoral head and intertrochanteric area, without signs of associated bone necrosis (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Genetic study</span><p id="par0035" class="elsevierStylePara elsevierViewall">The female patient’s history of repeated miscarriage motivated the genetic study. Given the identical symptoms in the male patients, and ruling out the presence of known risk factors, a genetic study was recommended for all the cases.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The G1691A mutation was detected by extracting DNA from peripheral blood using the NucleoSpin (Manchery-Nagel) kit for extracting genomic DNA from tissue samples. The G1691A mutation was positive in all three cases.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Treatment and progression</span><p id="par0045" class="elsevierStylePara elsevierViewall">After overall assessment of the patients, they were defined as cases of TOH and were treated conservatively by keeping the joint fully non-weight bearing for 4 weeks combined with magnetotherapy, conventional analgesic treatment and gentle physiotherapy to prevent contractures, followed by partial weight bearing with a stick for 4 further weeks. No antiresorptive drugs were used. Control MRI at 6 months showed full resolution of the oedema in all cases with no progression to AN (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Clinically, the patients made a full functional recovery with no sequelae.</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discussion</span><p id="par0050" class="elsevierStylePara elsevierViewall">Resistance to activated protein C is the most common genetic defect in patients with thrombosis, particularly thrombosis where there is an association with family members.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> The substitution of arginine at nucleotide position 506 by glutamine results in an alteration in the activated protein C binding site to factor V, which is known as Leiden factor V.</p><p id="par0055" class="elsevierStylePara elsevierViewall">The limitations of this study are the small number of cases described and its descriptive nature. It is, however, the first description of familial TOH linked to factor V Leiden. Factor V Leiden could also behave as a confounder of another aetiological factor that is unknown at this time.</p><p id="par0060" class="elsevierStylePara elsevierViewall">States of hypercoagulability and hypofibrinolysis were established as risk factors for the development of BMOS by Berger et al., who related elevated levels of lipoprotein (a) and activated plasminogen inhibitor with the development of the disease.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> The first description of familial BMOS was by Berger et al.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Of the 3 patients described, 2 were sisters and the third was the daughter of one of them. Plasma lipoprotein (a) levels were elevated in all 3 patients. A relationship between elevated lipoprotein (a) levels and the development of BMOS and AN due to inadequate lysis of intraosseous thrombi and subsequent increase in venous pressure was proposed. Most cases of familial AN of the femoral head are associated with Gaucher disease, sickle cell anaemia or thrombophilia, and familial hypofibrinolysis, although sporadic cases with no known predisposing factors have been published. Glueck et al. conducted a study to analyse whether inherited thrombophilia and hypofibrinolysis were risk factors for the development of femoral head AN in patients with idiopathic or high-dose steroid-associated AN.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> The presence of thrombophilia and hereditary hypofibrinolysis was more common in patients with idiopathic or secondary AN than in healthy subjects, and therefore they were considered risk factors for the development of the disease.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Factor V Leiden has been identified as a risk factor for the development of AN in numerous studies.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5–8</span></a> Björkman et al. concluded that factor V and prothrombin gene 20210A mutations, as well as thromboembolic events were significantly more common in patients with idiopathic NA, NA secondary to steroid use or alcohol-induced AN than in the healthy population.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Glueck et al. highlighted factor V Leiden as a risk factor for the development of AN, being present in 9.3% of patients with idiopathic NA and 9.6% of patients with secondary AN.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> In another similar study, Glueck et al. found that factor V Leiden mutation was more frequent in patients with secondary multifocal AN than in healthy controls.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> In these familial hypercoagulability states it has also been shown that testosterone therapy can worsen the progression of AN.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conclusions</span><p id="par0070" class="elsevierStylePara elsevierViewall">We present the first description of transient familial factor V Leiden-linked TOH. The results of this study support an ischaemic aetiology and establish TOH as an early and reversible stage of AN of the hip. Factor V Leiden promotes a state of hypercoagulablity and hypofibrinolysis that favours the development of TOH of ischaemic cause.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Level of evidence</span><p id="par0075" class="elsevierStylePara elsevierViewall">Level of evidence IV.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflict of interests</span><p id="par0080" class="elsevierStylePara elsevierViewall">The authors have no conflict of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1357875" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Clinical cases" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Discussion" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1248828" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1357876" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Casosclínicos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Discusión" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1248829" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Clinical cases" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Measurement of lipids, cholesterol, platelets and G1691A mutation" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Nuclear magnetic resonance" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Genetic study" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Treatment and progression" ] ] ] 6 => array:2 [ "identificador" => "sec0035" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0040" "titulo" => "Conclusions" ] 8 => array:2 [ "identificador" => "sec0045" "titulo" => "Level of evidence" ] 9 => array:2 [ "identificador" => "sec0050" "titulo" => "Conflict of interests" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-09-29" "fechaAceptado" => "2019-12-21" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1248828" "palabras" => array:5 [ 0 => "Bone marrow oedema" 1 => "Transient osteoporosis" 2 => "Hip" 3 => "Osteoporosis" 4 => "Factor V Leiden" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1248829" "palabras" => array:5 [ 0 => "Edema médula ósea" 1 => "Osteoporosis transitoria" 2 => "Cadera" 3 => "Osteonecrosis" 4 => "Factor V Leiden" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Transient osteoporosis of the hip (THO) is a rare disease of unknown pathogenesis that has traditionally been considered an early and reversible stage of avascular necrosis (AN). Thrombophilia or familial hypofibrinolysis is considered a risk factor for the development of AN and THO. Factor V Leiden is one of the most common hereditary hypercoagulability disorders.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Clinical cases</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Case series study. The development and course of 3 THO cases in 3 siblings (two males and one female) aged between 40 and 43 years are described consecutively. Clinical and nuclear magnetic resonance imaging (MRI) studies confirmed the diagnosis of THO and ruled out the presence of AN. The G1691A mutation of factor v Leiden was positive in all cases. The clinical and radiological outcome was favourable, with healing without sequelae and disappearance of bone oedema on control MRI at 6 months in all cases.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Discussion</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">The results of this study support the ischaemic aetiology and establish HTO as an early and reversable stage of hip AN. Factor V Leiden causes a state of hypercoagulability and hypofibrinolysis that encourages the development of THO due to ischaemic causes.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">This study outlines the first familiar description of factor v Leiden-linked THO.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Clinical cases" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Discussion" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducción</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">La osteoporosis transitoria de cadera (OTC) es una enfermedad poco frecuente y de patogenia desconocida que ha sido considerada tradicionalmente una fase precoz y reversible de la necrosis avascular (NA). La trombofilia o la hipofibrinólisis familiar se considera un factor de riesgo para el desarrollo de NA y OTC. Dentro de los trastornos heredados de hipercoagulabilidad, el factor v de Leiden es uno de los más prevalentes.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Casosclínicos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Estudio tipo serie de casos. Se describen el desarrollo y la evolución de 3 casos de OTC en 3 hermanos (2 varones y una mujer) con edades comprendidas entre los 40 y 43 años de forma consecutiva. El estudio clínico y de imagen con resonancia magnética nuclear (RM) confirmó el diagnóstico de OTC y descartó la presencia de NA. La mutación G1691A para el factor v de Leiden fue positiva en todos los casos. La evolución clínica y radiológica fue favorable, con curación sin secuelas y desaparición del edema óseo en la RM de control a los 6 meses en todos los casos.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Discusión</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Los resultados del presente estudio apoyan la etiología isquémica y establecen a la OTC como una fase precoz y reversible de la NA de cadera. El factor v de Leiden promueve un estado de hipercoagulabilidad e hipofibrinólisis que favorece el desarrollo de la OTC por causa isquémica.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">El presente estudio desarrolla la primera descripción familiar de la OTC ligada al factor v de Leiden.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Casosclínicos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Discusión" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Serrano-Toledano D, del Río-Arteaga M, Ribera-Zabalbeascoa J. Osteoporosis transitoria de cadera familiar ligada al factor v de Leiden. Rev Esp Cir Ortop Traumatol. 2020;64:286–289.</p>" ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1258 "Ancho" => 2500 "Tamanyo" => 325409 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Previous MRI images showing bone marrow oedema at the level of the femoral head and intertrochanteric area. Control MRI images showing complete disappearance of the area of oedema in all cases.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Test \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patient 1 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patient 2 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patient 3 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Normal \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cholesterol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">210 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">215 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">205 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30−200 mg/dl \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Triglycerides \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">78 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">110 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50−150 mg/dl \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HDL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">45−130 mg/dl \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LDL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">110 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">93 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">83 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><130 mg/dl \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Platelets \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">207,000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">225,000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">190,000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">150−360,000 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ANA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">G1691A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2332762.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Test parameters.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:12 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Transitory demineralization of the hip in pregnancy. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 6 | 0 | 6 |
| 2024 October | 23 | 5 | 28 |
| 2024 September | 45 | 7 | 52 |
| 2024 August | 39 | 19 | 58 |
| 2024 July | 25 | 4 | 29 |
| 2024 June | 34 | 8 | 42 |
| 2024 May | 29 | 3 | 32 |
| 2024 April | 26 | 7 | 33 |
| 2024 March | 35 | 2 | 37 |
| 2024 February | 48 | 4 | 52 |
| 2024 January | 73 | 16 | 89 |
| 2023 December | 56 | 9 | 65 |
| 2023 November | 50 | 8 | 58 |
| 2023 October | 49 | 8 | 57 |
| 2023 September | 30 | 5 | 35 |
| 2023 August | 48 | 4 | 52 |
| 2023 July | 54 | 2 | 56 |
| 2023 June | 50 | 4 | 54 |
| 2023 May | 55 | 6 | 61 |
| 2023 April | 30 | 3 | 33 |
| 2023 March | 24 | 1 | 25 |
| 2023 February | 27 | 1 | 28 |
| 2023 January | 36 | 3 | 39 |
| 2022 December | 53 | 2 | 55 |
| 2022 November | 49 | 5 | 54 |
| 2022 October | 34 | 8 | 42 |
| 2022 September | 37 | 5 | 42 |
| 2022 August | 48 | 7 | 55 |
| 2022 July | 49 | 8 | 57 |
| 2022 June | 40 | 7 | 47 |
| 2022 May | 36 | 7 | 43 |
| 2022 April | 43 | 7 | 50 |
| 2022 March | 76 | 7 | 83 |
| 2022 February | 78 | 9 | 87 |
| 2022 January | 41 | 6 | 47 |
| 2021 December | 30 | 7 | 37 |
| 2021 November | 43 | 9 | 52 |
| 2021 October | 16 | 10 | 26 |
| 2021 September | 19 | 7 | 26 |
| 2021 August | 14 | 6 | 20 |
| 2021 July | 18 | 10 | 28 |
| 2021 June | 12 | 4 | 16 |
| 2021 May | 15 | 2 | 17 |
| 2021 April | 54 | 7 | 61 |
| 2021 March | 15 | 4 | 19 |
| 2021 February | 12 | 8 | 20 |
| 2021 January | 15 | 9 | 24 |
| 2020 December | 1 | 0 | 1 |
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