Excellent Long-term Clinical Response to Rivaroxaban in Livedoid Vasculopathy: A Retrospective Study

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Respuesta completa tras 3 meses de tratamiento con rivaroxabán." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "D. Morgado-Carrasco, J. Ibaceta, P. Iranzo, X. Bosch-Amate, J.M. Mascaró-Galy" "autores" => array:5 [ 0 => array:2 [ "nombre" => "D." "apellidos" => "Morgado-Carrasco" ] 1 => array:2 [ "nombre" => "J." "apellidos" => "Ibaceta" ] 2 => array:2 [ "nombre" => "P." "apellidos" => "Iranzo" ] 3 => array:2 [ "nombre" => "X." "apellidos" => "Bosch-Amate" ] 4 => array:2 [ "nombre" => "J.M." 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"apellidos" => "Mascaró-Galy" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731022007876?idApp=UINPBA000044" "url" => "/00017310/0000011400000002/v3_202302211823/S0001731022007876/v3_202302211823/es/main.assets" ] ] "en" => array:15 [ "idiomaDefecto" => true "cabecera" => "Case and Research Letter" "titulo" => " Excellent Long-term Clinical Response to Rivaroxaban in Livedoid Vasculopathy: A Retrospective Study" "tieneTextoCompleto" => true "saludo" => "To the Editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "T183" "paginaFinal" => "T185" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "D. Morgado-Carrasco, J. Ibaceta, P. Iranzo, X. Bosch-Amate, J.M. Mascaró-Galy" "autores" => array:5 [ 0 => array:2 [ "nombre" => "D." "apellidos" => "Morgado-Carrasco" ] 1 => array:2 [ "nombre" => "J." "apellidos" => "Ibaceta" ] 2 => array:2 [ "nombre" => "P." "apellidos" => "Iranzo" ] 3 => array:2 [ "nombre" => "X." "apellidos" => "Bosch-Amate" ] 4 => array:4 [ "nombre" => "J.M." "apellidos" => "Mascaró-Galy" "email" => array:1 [ 0 => "jmmascaro_galy@ub.edu" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Dermatología, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Excelente respuesta clínica a largo plazo con rivaroxabán en vasculopatía livedoide. Un estudio retrospectivo" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 927 "Ancho" => 757 "Tamanyo" => 109675 ] ] "descripcion" => array:1 [ "en" => "Livedoid vasculopathy (patient #1). A, Ulcers and erosions, erythema, and atrophic scars on the ankles and feet. B, Complete response after 3 months of treatment with rivaroxaban." ] ] ] "textoCompleto" => "Livedoid vasculopathy (LV) is a cutaneous thrombotic vascular disease of unknown etiology that is associated with a clotting disorder in approximately 40% of patients.<a class="elsevierStyleCrossRef" href="#bib0050">1</a> It is characterized by painful ulcers on the lower limbs, whitish scars (atrophie blanche), and livedo racemosa. It has a major impact on quality of life, is difficult to treat, and lacks clear treatment guidelines.<a class="elsevierStyleCrossRef" href="#bib0055">2</a> Intravenous immunoglobulins, danazole, corticosteroids, immunosuppressive agents, anticoagulants and antithrombotic agents, and hyperbaric oxygen are some of the treatments used, but response rates are highly variable and many patients relapse.<a class="elsevierStyleCrossRef" href="#bib0055">2</a> A phase II clinical trial (n=25),<a class="elsevierStyleCrossRef" href="#bib0050">1</a> 2 small retrospective studies,<a class="elsevierStyleCrossRefs" href="#bib0060">3,4</a> and a case series<a class="elsevierStyleCrossRef" href="#bib0070">5</a> all recently showed that rivaroxaban, a modern direct-acting oral anticoagulant, is very effective in LV.<a class="elsevierStyleCrossRef" href="#bib0055">2</a> The vast majority of patients evaluated in these studies, however, were followed for under 6 months (12 weeks in the phase II clinical trial).<a class="elsevierStyleCrossRef" href="#bib0055">2</a> The aim of this study was to evaluate clinical response to rivaroxaban in LV patients with follow-up data spanning at least 12 months.We performed a retrospective study of patients with LV who were treated with rivaroxaban at the dermatology department of a tertiary care hospital in Spain between January 1, 2017 and October 30, 2021. We performed a chart review and collected information on clinical and epidemiological characteristics and treatment responses. Four women aged between 42 and 61 years were included (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). They all had severe leg pain and ulcers and atrophic scars. Coagulation tests and skin biopsies had been performed in all cases. Diagnosis was established by integrating clinical and pathologic findings. The 4 women had shown inadequate responses to multiple previous treatments. Rivaroxaban was started at 10mg/12h. All the patients achieved complete clinical response within 3 months of treatment initiation (<a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>). Maintenance doses ranged from 5 to 10mg/d. Two of the patients (#3 and #4) experienced an LV flare-up following dose reduction, but this was resolved by increasing the dose to 10mg/12h. Following progressive dose reductions, treatment was discontinued in patient #2 after 7 months of treatment. No recurrences were observed over the following 8 months. The other 3 patients continued to receive treatment and maintain complete response. Follow-up times ranged from 12 to 28 months, and no adverse effects were reported.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia>Rivaroxaban is a selective, reversible inhibitor of factor Xa used in the treatment of thromboembolic diseases and the secondary prevention of thromboembolism following hip or knee replacement surgery.<a class="elsevierStyleCrossRef" href="#bib0055">2</a> It is administered orally and does not require coagulation monitoring, giving it an advantage over warfarin, acenocoumarol, and low-molecular–weight heparins. It also has fewer drug–drug interactions compared with conventional oral anticoagulants.<a class="elsevierStyleCrossRef" href="#bib0055">2</a> A recent systematic review evaluating the effectiveness of rivaroxaban in LV in 13 studies involving 73 patients (65 of whom were on rivaroxaban monotherapy) described an effectiveness rate of 82%. The patients had similar clinical responses, regardless of the presence or absence of an associated clotting disorder.<a class="elsevierStyleCrossRef" href="#bib0055">2</a> Most patients responded rapidly, with significant pain relief observed within 11 days of treatment initiation,<a class="elsevierStyleCrossRefs" href="#bib0050">1,2</a> although in some patients it took more than a month.<a class="elsevierStyleCrossRef" href="#bib0060">3</a> The most common starting dose was 10–20mg/d, followed by a maintenance dose of 10mg/d.<a class="elsevierStyleCrossRef" href="#bib0055">2</a> In our series, the dose was reduced to 5mg/d after 6 months in one patient and 14 months in another. One of the patients achieved excellent control, but the other experienced disease worsening.In our review of the literature, we identified just 9 LV patients treated with rivaroxaban who had follow-up data spanning 12 months or more: 4 responded within 12 months,<a class="elsevierStyleCrossRefs" href="#bib0070">5,6</a> 2 within 14 months,<a class="elsevierStyleCrossRefs" href="#bib0080">7,8</a> 1 within 18 months,<a class="elsevierStyleCrossRef" href="#bib0090">9</a> and 2 within 23 months.<a class="elsevierStyleCrossRef" href="#bib0090">9</a> All 9 patients were treated with LV 10mg/d. Just 1 experienced a flare-up after exertion at work, but it was managed successfully with wound care and silver dressings. No adverse effects were reported for any of the patients. The 4 patients in our series were followed for more than 1 year, and 2 of them for 2 years or longer. They all responded fully. Two patients relapsed following a dose reduction, but this was resolved by increasing the dose to 10mg/12h. LV flare-ups inadequately controlled by rivaroxaban can be managed by a dose increase and/or the addition of subcutaneous enoxaparin, which has been found to achieve disease control in 95% of cases.<a class="elsevierStyleCrossRef" href="#bib0050">1</a> Enoxaparin was not needed in any of our patients. Patients can often relapse after discontinuation of treatment, with reports showing a mean time to recurrence of 25 weeks and a higher frequency in the summer.<a class="elsevierStyleCrossRef" href="#bib0060">3</a>Rivaroxaban has shown an excellent safety profile in the treatment of LV. Adverse effects are mild and mostly consist of menorrhagia and hypermenorrhea.<a class="elsevierStyleCrossRef" href="#bib0055">2</a> No adverse effects were reported in our series.Rivaroxaban appears to be a generally well-tolerated treatment for LV, with rapid onset of action, flexible dosage, and excellent long-term response. We recommend its use as a first-line treatment for this disease.Conflicts of InterestThe authors declare that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of Interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 927 "Ancho" => 757 "Tamanyo" => 109675 ] ] "descripcion" => array:1 [ "en" => "Livedoid vasculopathy (patient #1). A, Ulcers and erosions, erythema, and atrophic scars on the ankles and feet. B, Complete response after 3 months of treatment with rivaroxaban." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1092 "Ancho" => 756 "Tamanyo" => 121831 ] ] "descripcion" => array:1 [ "en" => "Livedoid vasculopathy (patient #3). A, Ulcers and erosions, erythema, and atrophic scars on the ankles and feet. B, Complete response after 3 months of treatment with rivaroxaban." ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "Abbreviations: ANA, antinuclear antibodies; ASA, acetylsalicylic acid; CS, oral corticosteroids; F, female: IVIG, intravenous immunoglobulin; LMWH, low-molecular-weight heparin; LPP, lichen planopilaris." "tablatextoimagen" => array:1 [ 0 => array:1 [ "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">Case \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">Sex/age, y \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">Family history \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">Personal history \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">Associated clotting disorder \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">Clinical presentation \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">Time to diagnosis<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \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">Previous treatments \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">Rivaroxaban doses \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">Clinical response \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">Follow-up time \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">1 \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">F/42 \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">No \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">Seronegative arthritisANA+ 1/80Smoking \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">Yes<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \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">Pain and ulcers on the feet \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">28 y \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">CS, LMWH, ASA, pentoxifylline, sulfasalazine, hyperbaric oxygen, colchicine, anakinra, alprostadil, etanercept \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">Start: 10mg/12hAfter 5 mo: 10mg/d \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">Complete \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">12 moNo recurrences \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">2 \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">F/61 \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">No \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">High blood pressure, glaucoma \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">No \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">Foot pain and ulcers; livedo and atrophic scars \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">1 y \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">Pentoxifylline, ASA, dipyridamole \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">Start: 10mg/12hAfter 2 mo: 10mg/d, then 5mg/d. Discontinued after 7 mo \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">Complete \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">7 moNo recurrences \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">3 \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">F/42 \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">Brother with retinal thrombosis \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">LPPANA+ 1/320 \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">Yes<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \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">Foot pain and ulcers; livedo and atrophic scars \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">9 y \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">CS, azathioprine, ASA, dipyridamole \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">Start: 10mg/12hAfter 10 mo: 10mg/d<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \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">Complete \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">28 moRecurrence after 6 mo of treatment<a class="elsevierStyleCrossRef" href="#tblfn0015">c</a> \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">4 \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">F/49 \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">No \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">No \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">No \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">Foot pain and ulcers; purpura, atrophic scars \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">24 y \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">ASA, dipyridamole, LMWH, IVIG \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">Start: 10mg/12hAfter 6 mo: 10mg/d \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">Complete \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">23 moRecurrence on dose reduction<a class="elsevierStyleCrossRef" href="#tblfn0015">c</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] "notaPie" => array:3 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Patient #1 had a heterozygous Factor V Leiden mutation and patient #3 a mutation in the antithrombin iii gene." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "Dose reduced to a 5mg/d at 14 mo and 5mg/48h at 16 mo; increased to 10mg/12h at 24 mo due to reappearance of pain and ulcers on the ankles." ] 2 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "c" "nota" => "In both cases, flare-ups were controlled by increasing the rivaroxaban dose to 10mg/12h." ] ] ] "descripcion" => array:1 [ "en" => "Clinical and Epidemiological Characteristics and Response to Rivaroxaban in Patients With Livedoid Vasculopathy." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:9 [ 0 => array:3 [ "identificador" => "bib0050" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anticoagulation with rivaroxaban for livedoid vasculopathy (RILIVA): a multicentre, single-arm, open-label, phase 2a, proof-of-concept trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Weishaupt" 1 => "A. Strölin" 2 => "B. Kahle" 3 => "A. Kreuter" 4 => "S.W. Schneider" 5 => "J. Gerss" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S2352-3026(15)00251-3" "Revista" => array:6 [ "tituloSerie" => "Lancet Haematol" "fecha" => "2016" "volumen" => "3" "paginaInicial" => "e72" "paginaFinal" => "e79" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26853646" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0055" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rivaroxaban for treatment of livedoid vasculopathy: a systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Y. Gao" 1 => "H. 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Cho" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/jdv.16129" "Revista" => array:6 [ "tituloSerie" => "J Eur Acad Dermatol Venereol" "fecha" => "2020" "volumen" => "34" "paginaInicial" => "e176" "paginaFinal" => "e178" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31793049" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0065" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Livedoid vasculopathy in 75 Brazilian patients in a single-center institution: clinical, histopathological and therapy evaluation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.R. Criado" 1 => "C. Pagliari" 2 => "T.C.A.B. Morita" 3 => "G.F. Marques" 4 => "T.P.H. Pincelli" 5 => "N.Y.S. Valente" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/dth.14810" "Revista" => array:5 [ "tituloSerie" => "Dermatol Ther" "fecha" => "2021" "volumen" => "34" "paginaInicial" => "e14810" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33496999" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0070" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatment of livedoid vasculopathy with rivaroxaban: a potential use of new oral anticoagulants for dermatologists" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "D. Jiménez-Gallo" 1 => "I. Villegas-Romero" 2 => "M.E. Rodríguez-Mateos" 3 => "M. 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Goerge" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/bjd.12100" "Revista" => array:6 [ "tituloSerie" => "Br J Dermatol" "fecha" => "2013" "volumen" => "168" "paginaInicial" => "898" "paginaFinal" => "899" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23106384" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0080" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Case series of recalcitrant livedoid vasculopathy treated with rivaroxaban" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.M. Lee" 1 => "I.-H. Kim" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Clin Exp Dermatol" "fecha" => "2016" "volumen" => "41" "paginaInicial" => "559" "paginaFinal" => "561" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0085" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevention of livedoid vasculopathy recurrence by prolonged administration of rivaroxaban" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C. Drerup" 1 => "T. 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Case and Research Letter

Excellent Long-term Clinical Response to Rivaroxaban in Livedoid Vasculopathy: A Retrospective Study

Excelente respuesta clínica a largo plazo con rivaroxabán en vasculopatía livedoide. Un estudio retrospectivo

D. Morgado-Carrasco, J. Ibaceta, P. Iranzo, X. Bosch-Amate, J.M. Mascaró-Galy

Corresponding author

jmmascaro_galy@ub.edu

Corresponding author.

Servicio de Dermatología, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Livedoid vasculopathy &#40;LV&#41; is a cutaneous thrombotic vascular disease of unknown etiology that is associated with a clotting disorder in approximately 40&#37; of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> It is characterized by painful ulcers on the lower limbs&#44; whitish scars &#40;atrophie blanche&#41;&#44; and livedo racemosa&#46; It has a major impact on quality of life&#44; is difficult to treat&#44; and lacks clear treatment guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a> Intravenous immunoglobulins&#44; danazole&#44; corticosteroids&#44; immunosuppressive agents&#44; anticoagulants and antithrombotic agents&#44; and hyperbaric oxygen are some of the treatments used&#44; but response rates are highly variable and many patients relapse&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a> A phase II clinical trial &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>25&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> 2 small retrospective studies&#44;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">3&#44;4</span></a> and a case series<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">5</span></a> all recently showed that rivaroxaban&#44; a modern direct-acting oral anticoagulant&#44; is very effective in LV&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a> The vast majority of patients evaluated in these studies&#44; however&#44; were followed for under 6 months &#40;12 weeks in the phase II clinical trial&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a> The aim of this study was to evaluate clinical response to rivaroxaban in LV patients with follow-up data spanning at least 12 months&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">We performed a retrospective study of patients with LV who were treated with rivaroxaban at the dermatology department of a tertiary care hospital in Spain between January 1&#44; 2017 and October 30&#44; 2021&#46; We performed a chart review and collected information on clinical and epidemiological characteristics and treatment responses&#46; Four women aged between 42 and 61 years were included &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; They all had severe leg pain and ulcers and atrophic scars&#46; Coagulation tests and skin biopsies had been performed in all cases&#46; Diagnosis was established by integrating clinical and pathologic findings&#46; The 4 women had shown inadequate responses to multiple previous treatments&#46; Rivaroxaban was started at 10<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&#46; All the patients achieved complete clinical response within 3 months of treatment initiation &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1 and 2</a>&#41;&#46; Maintenance doses ranged from 5 to 10<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#46; Two of the patients &#40;&#35;3 and &#35;4&#41; experienced an LV flare-up following dose reduction&#44; but this was resolved by increasing the dose to 10<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&#46; Following progressive dose reductions&#44; treatment was discontinued in patient &#35;2 after 7 months of treatment&#46; No recurrences were observed over the following 8 months&#46; The other 3 patients continued to receive treatment and maintain complete response&#46; Follow-up times ranged from 12 to 28 months&#44; and no adverse effects were reported&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Rivaroxaban is a selective&#44; reversible inhibitor of factor Xa used in the treatment of thromboembolic diseases and the secondary prevention of thromboembolism following hip or knee replacement surgery&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a> It is administered orally and does not require coagulation monitoring&#44; giving it an advantage over warfarin&#44; acenocoumarol&#44; and low-molecular&#8211;weight heparins&#46; It also has fewer drug&#8211;drug interactions compared with conventional oral anticoagulants&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a> A recent systematic review evaluating the effectiveness of rivaroxaban in LV in 13 studies involving 73 patients &#40;65 of whom were on rivaroxaban monotherapy&#41; described an effectiveness rate of 82&#37;&#46; The patients had similar clinical responses&#44; regardless of the presence or absence of an associated clotting disorder&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a> Most patients responded rapidly&#44; with significant pain relief observed within 11 days of treatment initiation&#44;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">1&#44;2</span></a> although in some patients it took more than a month&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">3</span></a> The most common starting dose was 10&#8211;20<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#44; followed by a maintenance dose of 10<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a> In our series&#44; the dose was reduced to 5<span class="elsevierStyleHsp" style=""></span>mg&#47;d after 6 months in one patient and 14 months in another&#46; One of the patients achieved excellent control&#44; but the other experienced disease worsening&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In our review of the literature&#44; we identified just 9 LV patients treated with rivaroxaban who had follow-up data spanning 12 months or more&#58; 4 responded within 12 months&#44;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">5&#44;6</span></a> 2 within 14 months&#44;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">7&#44;8</span></a> 1 within 18 months&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">9</span></a> and 2 within 23 months&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">9</span></a> All 9 patients were treated with LV 10<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#46; Just 1 experienced a flare-up after exertion at work&#44; but it was managed successfully with wound care and silver dressings&#46; No adverse effects were reported for any of the patients&#46; The 4 patients in our series were followed for more than 1 year&#44; and 2 of them for 2 years or longer&#46; They all responded fully&#46; Two patients relapsed following a dose reduction&#44; but this was resolved by increasing the dose to 10<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&#46; LV flare-ups inadequately controlled by rivaroxaban can be managed by a dose increase and&#47;or the addition of subcutaneous enoxaparin&#44; which has been found to achieve disease control in 95&#37; of cases&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> Enoxaparin was not needed in any of our patients&#46; Patients can often relapse after discontinuation of treatment&#44; with reports showing a mean time to recurrence of 25 weeks and a higher frequency in the summer&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">3</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Rivaroxaban has shown an excellent safety profile in the treatment of LV&#46; Adverse effects are mild and mostly consist of menorrhagia and hypermenorrhea&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a> No adverse effects were reported in our series&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Rivaroxaban appears to be a generally well-tolerated treatment for LV&#44; with rapid onset of action&#44; flexible dosage&#44; and excellent long-term response&#46; We recommend its use as a first-line treatment for this disease&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0035" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 927
            "Ancho" => 757
            "Tamanyo" => 109675
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Livedoid vasculopathy &#40;patient &#35;1&#41;&#46; A&#44; Ulcers and erosions&#44; erythema&#44; and atrophic scars on the ankles and feet&#46; B&#44; Complete response after 3 months of treatment with rivaroxaban&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 1092
            "Ancho" => 756
            "Tamanyo" => 121831
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Livedoid vasculopathy &#40;patient &#35;3&#41;&#46; A&#44; Ulcers and erosions&#44; erythema&#44; and atrophic scars on the ankles and feet&#46; B&#44; Complete response after 3 months of treatment with rivaroxaban&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; ANA&#44; antinuclear antibodies&#59; ASA&#44; acetylsalicylic acid&#59; CS&#44; oral corticosteroids&#59; F&#44; female&#58; IVIG&#44; intravenous immunoglobulin&#59; LMWH&#44; low-molecular-weight heparin&#59; LPP&#44; lichen planopilaris&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "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">Case&nbsp;\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">Sex&#47;age&#44; y&nbsp;\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">Family history&nbsp;\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">Personal history&nbsp;\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">Associated clotting disorder&nbsp;\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">Clinical presentation&nbsp;\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">Time to diagnosis<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\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">Previous treatments&nbsp;\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">Rivaroxaban doses&nbsp;\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">Clinical response&nbsp;\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">Follow-up time&nbsp;\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">1&nbsp;\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">F&#47;42&nbsp;\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">No&nbsp;\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">Seronegative arthritisANA<span class="elsevierStyleSup">&#43;</span> 1&#47;80Smoking&nbsp;\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">Yes<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\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">Pain and ulcers on the feet&nbsp;\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">28 y&nbsp;\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">CS&#44; LMWH&#44; ASA&#44; pentoxifylline&#44; sulfasalazine&#44; hyperbaric oxygen&#44; colchicine&#44; anakinra&#44; alprostadil&#44; etanercept&nbsp;\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">Start&#58; 10<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>hAfter 5 mo&#58; 10<span class="elsevierStyleHsp" style=""></span>mg&#47;d&nbsp;\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">Complete&nbsp;\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">12 moNo recurrences&nbsp;\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">2&nbsp;\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">F&#47;61&nbsp;\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">No&nbsp;\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">High blood pressure&#44; glaucoma&nbsp;\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">No&nbsp;\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">Foot pain and ulcers&#59; livedo and atrophic scars&nbsp;\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">1 y&nbsp;\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">Pentoxifylline&#44; ASA&#44; dipyridamole&nbsp;\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">Start&#58; 10<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>hAfter 2 mo&#58; 10<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#44; then 5<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#46; Discontinued after 7 mo&nbsp;\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">Complete&nbsp;\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">7 moNo recurrences&nbsp;\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">3&nbsp;\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">F&#47;42&nbsp;\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">Brother with retinal thrombosis&nbsp;\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">LPPANA<span class="elsevierStyleSup">&#43;</span> 1&#47;320&nbsp;\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">Yes<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\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">Foot pain and ulcers&#59; livedo and atrophic scars&nbsp;\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">9 y&nbsp;\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">CS&#44; azathioprine&#44; ASA&#44; dipyridamole&nbsp;\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">Start&#58; 10<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>hAfter 10 mo&#58; 10<span class="elsevierStyleHsp" style=""></span>mg&#47;d<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\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">Complete&nbsp;\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">28 moRecurrence after 6 mo of treatment<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&nbsp;\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">4&nbsp;\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">F&#47;49&nbsp;\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">No&nbsp;\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">No&nbsp;\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">No&nbsp;\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">Foot pain and ulcers&#59; purpura&#44; atrophic scars&nbsp;\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">24 y&nbsp;\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">ASA&#44; dipyridamole&#44; LMWH&#44; IVIG&nbsp;\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">Start&#58; 10<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>hAfter 6 mo&#58; 10<span class="elsevierStyleHsp" style=""></span>mg&#47;d&nbsp;\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">Complete&nbsp;\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">23 moRecurrence on dose reduction<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
          "notaPie" => array:3 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Patient &#35;1 had a heterozygous Factor V Leiden mutation and patient &#35;3 a mutation in the antithrombin <span class="elsevierStyleSmallCaps">iii</span> gene&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Dose reduced to a 5<span class="elsevierStyleHsp" style=""></span>mg&#47;d at 14 mo and 5<span class="elsevierStyleHsp" style=""></span>mg&#47;48<span class="elsevierStyleHsp" style=""></span>h at 16 mo&#59; increased to 10<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h at 24 mo due to reappearance of pain and ulcers on the ankles&#46;</p>"
            ]
            2 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "c"
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Article information

ISSN: 00017310
Original language: English

DOI:10.1016/j.ad.2022.03.029

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