Case report
Bullous Hemorrhagic Dermatosis at Distant Sites: A Report of 2 New Cases Due to Enoxaparin Injection and a Review of the Literature
Dermatosis ampollosa hemorrágica a distancia; dos nuevos casos por enoxaparina y revisión de la literatura
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Estudio prospectivo" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 813 "Ancho" => 2337 "Tamanyo" => 151732 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Case 6. A, Scalp hemangioma before treatment with propranolol. B, Excellent results after 6 months.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "I. Betlloch-Mas, M.T. Martínez-Miravete, A. Lucas-Costa, A.I. Martin de Lara, J. Selva-Otalaurruchi" "autores" => array:5 [ 0 => array:2 [ "nombre" => "I." "apellidos" => "Betlloch-Mas" ] 1 => array:2 [ "nombre" => "M.T." 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Villanueva, L. Nájera, P. Espinosa, J. Borbujo" "autores" => array:4 [ 0 => array:4 [ "nombre" => "C.A." "apellidos" => "Villanueva" "email" => array:2 [ 0 => "cvillanueva.hflr@salud.madrid.org" 1 => "candidavilleneuve@hotmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "L." "apellidos" => "Nájera" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "P." "apellidos" => "Espinosa" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "J." "apellidos" => "Borbujo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, Spain" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, Spain" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Dermatosis ampollosa hemorrágica a distancia; dos nuevos casos por enoxaparina y revisión de la literatura" ] ] "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" => 1425 "Ancho" => 1587 "Tamanyo" => 173600 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Multiple noninflammatory hemorrhagic vesicles in the right malar region.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Enoxaparin is a low-molecular-weight heparin (LMWH) that is used for the prevention and treatment of pulmonary venous thromboembolism and other thrombotic disorders, such as myocardial infarction. The drug is administered once or twice daily, depending on the indication. The most common complication associated with these anticoagulants is bleeding. Adverse skin reactions may be localized or generalized and can be immediate or delayed; the most common are ecchymoses, skin necrosis, urticaria, angioedema, and eczema.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Seven cases of hemorrhagic bullous dermatosis occurring in areas distant from the site of injection have been reported in patients receiving treatment with various LMWHs (dalteparin,<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> enoxaparin,<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a> tinzaparin<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,6</span></a>) or unfractionated heparins (calcium heparin<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>). We present 2 new cases related to the administration of enoxaparin.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Patient 1</span><p id="par0015" class="elsevierStylePara elsevierViewall">Our first patient was a 68-year-old man with a past history of systemic hypertension, diabetes mellitus, hypercholesterolemia and a progressive, stage IV undifferentiated carcinoma, probably of pulmonary origin, diagnosed in 2009 and for which he had received 3 cycles of palliative chemotherapy with cisplatin and etoposide. He was also on treatment with prednisone, metformin, enalapril, and simvastatin. During his most recent admission he had been started on treatment with enoxaparin, 60<span class="elsevierStyleHsp" style=""></span>mg subcutaneously every 12<span class="elsevierStyleHsp" style=""></span>hours, for superior vena cava syndrome. Fifteen days later he came to the emergency department for asymptomatic, hemorrhagic vesicular-bullous lesions on the dorsum of the hand, around the lower jaw and in the malar region on the right side. The lesions had appeared 1 week earlier and had been treated with silver nitrate. The patient did not report bleeding in any other area of the body.</p><p id="par0020" class="elsevierStylePara elsevierViewall">On physical examination there was a tense, noninflammatory blood-filled vesicle of 7<span class="elsevierStyleHsp" style=""></span>mm in diameter on the dorsum of the hand right and about 15 vesicular lesions of the same characteristics, measuring between 2 and 8<span class="elsevierStyleHsp" style=""></span>mm in diameter, in groups on the right side of the neck and right malar region (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Laboratory tests were within the normal ranges for platelet count and coagulation studies (prothrombin time [PT], prothrombin activity, international normalized ratio [INR], thromboplastin time, and fibrinogen level). A biopsy taken from the lesion on the dorsum of the hand revealed a purulent, fibrin-covered necrotic ulcer, with fibrosis and granulation tissue in its base and residual reparative epithelial changes.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Patient 2</span><p id="par0030" class="elsevierStylePara elsevierViewall">The second patient was a 78-year-old man with a past history of recently diagnosed stage IV non-small-cell lung cancer with lung and liver metastases, ischemic heart disease, and a biological mitral valve replacement in 2006. He was on treatment with prednisone, codeine, ticlopidine, omeprazole, atorvastatin, nitroglycerine, and enoxaparin, 80<span class="elsevierStyleHsp" style=""></span>mg by subcutaneous injection every 12<span class="elsevierStyleHsp" style=""></span>hours. We were asked to evaluate asymptomatic hemorrhagic skin lesions that had developed 10 days earlier on both knees, the right forearm, and the facial region. The patient reported that 10 days before the lesions appeared, he had started treatment with enoxaparin. There were no other symptoms.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Examination revealed dry, tense hemorrhagic vesicles of up to 5<span class="elsevierStyleHsp" style=""></span>mm in diameter occurring in groups on the right knee and forearm and an isolated vesicle in the facial region.</p><p id="par0040" class="elsevierStylePara elsevierViewall">A complete blood count, biochemistry, and coagulation studies were performed, as well as biopsy of a lesion on the right forearm. Histology revealed an intraepidermal vesicle containing blood, fibrin and occasional neutrophils. There was red blood cell extravasation in the underlying dermis and a mixed inflammatory infiltrate with neutrophils; there were no signs of vasculitis (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The results of the complete blood count, including platelet count, and coagulation studies (PT, INR, prothrombin activity, thromboplastin time, fibrinogen, antithrombin III, protein C, and protein S) were within normal limits.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Treatment was continued with enoxaparin at the recommended dose in both cases, and no topical or systemic treatments were added. The lesions resolved without sequelae in 2 to 3 weeks.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0050" class="elsevierStylePara elsevierViewall">Enoxaparin, a LMWH obtained by depolymerization of standard heparin, is used both for prophylaxis and for the treatment of thrombotic phenomena. It acts by binding to antithrombin III, causing inhibition of factor Xa. Bleeding is the most common complication of enoxaparin therapy.</p><p id="par0055" class="elsevierStylePara elsevierViewall">In 2006, Perrinaud et al.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> were the first to describe patients with hemorrhagic bullous lesions occurring at a distance from the site of injection and that were related to the administration of 2 types of heparin molecule: LMWHs (dalteparin, tinzaparin) and an unfractionated heparin (calcium heparin). Those authors described 3 patients with eruptions of tense, noninflammatory hemorrhagic blisters distributed in groups at a distance from the site of subcutaneous injection of the heparin.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Later, in 2009, Beltraminelli et al.,<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Thuillier et al.,<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> and Gonzales et al.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> reported a total of 4 cases similar to those described by Perrinaud et al. and that were associated with the administration of enoxaparin sodium and tinzaparin (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">The etiology and pathogenesis of these lesions is unknown. In our cases there were no alterations of routine coagulation studies. Two of the patients reported by Perrinaud et al.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> were also taking acetylsalicylic acid and the third was on dipyridamole (an antiplatelet drug) concomitantly with the heparin. Our second patient was also taking ticlopidine.</p><p id="par0065" class="elsevierStylePara elsevierViewall">As in the 2 cases we present, the histopathology of lesions in the previously published cases was nonspecific: blood-filled intraepidermal or subcorneal vesicles and blisters with no signs of vasculitis or capillary thrombosis. Subepidermal spongiosis and the presence of eosinophils were only observed in the patient described by Thuillier et al.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Management of the lesions and the decision on whether to interrupt heparin treatment varied in the previously published cases. Perrinaud et al.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> stated that they replaced the heparin with oral anticoagulants in their first patient, but the patient died 7 days later due to hemorrhagic stroke, and thus the clinical course could not be studied. In their second patient, they discontinued tinzaparin and the lesions resolved at 10 days; in their third patient the lesions resolved even with no change in therapy. Beltraminelli et al.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> only described the clinical course of 1 of their patients, in whom they substituted the heparin with an oral anticoagulant; the lesions resolved within 2 weeks. In the patients reported by Gonzales et al.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> and Thuiller et al.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> the authors decided to withdraw the heparin and the lesions disappeared within a few weeks. We decided to maintain heparin therapy in our patients and the lesions resolved without treatment within 2 to 3 weeks. As occurred in our patients, the lesions in at least 3 of the patients described in the literature resolved despite continuing heparin treatment.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Enoxaparin belongs to the group of LMWHs, which also includes bemiparin, dalteparin, nadroparin, and tinzaparin. In the literature reviewed, enoxaparin was the heparin most frequently associated with the appearance of hemorrhagic blisters—it was being administered in 6 of the 9 cases reported, including ours. The more frequent use of enoxaparin may be due to the influence on prescribers of its ease of administration, the absence of a need for blood tests to monitor therapy, and its safety profile.</p><p id="par0080" class="elsevierStylePara elsevierViewall">In conclusion, heparin-induced hemorrhagic bullous dermatosis occurring at a distance from the site of injection is a rare adverse skin reaction, although the fact that it is typically self-limiting, even without discontinuation of the medication, could mean that it is an underdiagnosed phenomenon or one that is under-reported in the literature. Only 7 cases have been reported prior to the cases we describe. We would like to draw attention to the favourable clinical course of these eruptions in our patients and in those described in the literature, even without treatment modification, and to the absence of associated complications.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflicts of Interest</span><p id="par0085" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:2 [ "identificador" => "xres96607" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec83762" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres96606" "titulo" => "Resumen" ] 3 => array:2 [ "identificador" => "xpalclavsec83763" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Patient 1" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Patient 2" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflicts of Interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec83762" "palabras" => array:3 [ 0 => "Bullous hemorrhagic dermatosis" 1 => "Enoxaparin" 2 => "Heparin" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec83763" "palabras" => array:3 [ 0 => "Dermatosis ampollosa hemorrágica" 1 => "Enoxaparina" 2 => "Heparinas" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Enoxaparin is a low-molecular-weight heparin used in the prevention and treatment of pulmonary thromboembolism and other thrombotic disorders. The most common adverse reactions to enoxaparin are ecchymosis, skin necrosis, urticaria, angioedema, and eczema. The first 2 cases of bullous hemorrhagic dermatosis in areas distant from heparin injection sites were described in 2006.</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We present the cases of 2 men, aged 68 and 78 years, with progressive, advanced-stage lung cancer, who consulted with bullous hemorrhagic lesions without associated symptoms. Both patients reported that the lesions had appeared after initiation of heparin therapy at therapeutic doses.</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">In our review of the literature, we found just 7 cases of heparin-induced bullous hemorrhagic dermatosis. We report a further 2 cases, caused by enoxaparin, in which treatment was continued and in which the lesions resolved in 2 to 3 weeks.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">La enoxaparina pertenece al grupo de heparinas de bajo peso molecular. Se utiliza en el manejo terapéutico y profiláctico del tromboembolismo venoso pulmonar y otros cuadros trombóticos. Las reacciones adversas cutáneas más frecuentes son equimosis, necrosis cutánea, urticaria, angioedema y eccema. En el año 2006 se describieron los primeros casos de dermatosis ampollosa hemorrágica a distancia por heparina.</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Presentamos dos varones de 68 y 78 años, con carcinomas de pulmón en estadios avanzados y en progresión, que consultaban por lesiones ampollosas hemorrágicas, sin otra sintomatología acompañante. Ambos referían la aparición de las lesiones tras comenzar con la administración de heparina a dosis terapéuticas.</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">En la literatura revisada solo hemos encontrado descritos 7 casos de dermatosis ampollosa hemorrágica por heparina. Aportamos dos nuevos casos por enoxaparina, en los que se mantuvo el tratamiento y se resolvió el cuadro en dos a tres semanas.</p>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara">Please cite this article as: Villanueva CA, et al. Dermatosis ampollosa hemorrágica a distancia; dos nuevos casos por enoxaparina y revisión de la literatura. Actas Dermosifiliogr. 2012;103:816-9.</p>" ] ] "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" => 1425 "Ancho" => 1587 "Tamanyo" => 173600 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Multiple noninflammatory hemorrhagic vesicles in the right malar region.</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" => 1132 "Ancho" => 1587 "Tamanyo" => 91712 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Intraepidermal vesicle containing blood, fibrin and occasional neutrophils. There are no signs of vasculitis (hematoxylin-eosin, original magnification ×10).</p>" ] ] 2 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "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"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Age \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Sex \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Heparin \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Time to Onset<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>, d \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Histology \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Treatment Withdrawal \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Perrinaud et al.</span><a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></td></tr><tr title="table-row"><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"><span class="elsevierStyleHsp" style=""></span>Patient 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75 \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">Male \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">Dalteparin \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \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">Intraepidermal \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 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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"><span class="elsevierStyleHsp" style=""></span>Patient 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">82 \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">Female \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">Tinzaparin \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \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">Intraepidermal \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 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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"><span class="elsevierStyleHsp" style=""></span>Patient 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">64 \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">Male \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">Sodium heparin \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 \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">Intraepidermal \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></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Beltraminelli et al.</span><a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></td></tr><tr title="table-row"><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"><span class="elsevierStyleHsp" style=""></span>Patient 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">72 \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">Female \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">Enoxaparin \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="char" 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">Intraepidermal and subcorneal \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 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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"><span class="elsevierStyleHsp" style=""></span>Patient 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">67 \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">Male \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">Enoxaparin \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="char" 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="" 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" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Gonzales et al.</span><a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></td></tr><tr title="table-row"><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"><span class="elsevierStyleHsp" style=""></span>Patient 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">88 \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">Male \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">Enoxaparin \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 \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">Subcorneal \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 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Thuillier et al.</span><a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></td></tr><tr title="table-row"><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"><span class="elsevierStyleHsp" style=""></span>Patient 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">51 \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">Male \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">Enoxaparin/tinzaparin \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="char" 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">Subcorneal \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 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Present cases</span></td></tr><tr title="table-row"><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"><span class="elsevierStyleHsp" style=""></span>Patient 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">68 \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">Male \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">Enoxaparin \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \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">Fibronecrotic scar \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></tr><tr title="table-row"><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"><span class="elsevierStyleHsp" style=""></span>Patient 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="char" 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">Male \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">Enoxaparin \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 \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">Intraepidermal \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></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab182580.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara">Time to onset defined as the time between starting the administration of the drug and the appearance of the lesions<span class="elsevierStyleSup">.</span></p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Heparin-induced Hemorrhagic Bullous Dermatosis at a Site Distant From the Injection.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Necrosis cutánea por heparina: una forma posiblemente fatal de hipersensibilidad a la heparina" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Campo" 1 => "C. González" 2 => "J. Soler" 3 => "L. Gómez" 4 => "J. Piulachs" 5 => "J. Palou" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Actas Dermosifiliogr" "fecha" => "1998" "volumen" => "89" "paginaInicial" => "613" "paginaFinal" => "619" "itemHostRev" => array:3 [ "pii" => "S0016510707024066" "estado" => "S300" "issn" => "00165107" ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Placas eritematosas por heparina de bajo peso molecular" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "D. Ruiz-Genao" 1 => "T. Sanz-Sánchez" 2 => "J. Sánchez-Pérez" 3 => "J. Fernández-Herrera" 4 => "A. 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Sánchez-Pérez" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Actas Dermosifiliogr" "fecha" => "2011" "volumen" => "101" "paginaInicial" => "556" "paginaFinal" => "558" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20738979" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hemorrhagic dermatosis occurring at sites distant from subcutaneous injections of heparin: Three cases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. Perrinaud" 1 => "D. Jacobi" 2 => "M.C. Machet" 3 => "C. Grodet" 4 => "Y. Gruel" 5 => "L. Machet Bullous" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Am Acad Dermatol" "fecha" => "2006" "numero" => "Suppl 2" "paginaInicial" => "S5" "paginaFinal" => "S7" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Intraepidermal bullous haemorrhage during anticoagulation with low-molecular-weight heparin; two cases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "H. Beltraminelli" 1 => "P. Itin" 2 => "L. Cerroni" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2133.2009.09162.x" "Revista" => array:6 [ "tituloSerie" => "Br J Dermatol" "fecha" => "2009" "volumen" => "161" "paginaInicial" => "191" "paginaFinal" => "193" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19416231" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dermatose bulleuse hémorragique associée a une réaction d’hypersensibilité retardée sous héparine de bas poids" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Thuillier" 1 => "G. Chaby" 2 => "A. Dadban" 3 => "E. Dascotte" 4 => "D. Miquel-Christophe" 5 => "M. 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Pentland" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/archdermatol.2009.70" "Revista" => array:7 [ "tituloSerie" => "Arch Dermatol" "fecha" => "2009" "volumen" => "145" "paginaInicial" => "604" "paginaFinal" => "605" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19451517" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0002939411008191" "estado" => "S300" "issn" => "00029394" ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/15782190/0000010300000009/v1_201304241357/S157821901200279X/v1_201304241357/en/main.assets" "Apartado" => array:4 [ "identificador" => "6183" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Case Reports" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/15782190/0000010300000009/v1_201304241357/S157821901200279X/v1_201304241357/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S157821901200279X?idApp=UINPBA000044" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 10 | 9 | 19 |
| 2024 October | 83 | 45 | 128 |
| 2024 September | 85 | 24 | 109 |
| 2024 August | 93 | 76 | 169 |
| 2024 July | 81 | 28 | 109 |
| 2024 June | 92 | 40 | 132 |
| 2024 May | 88 | 40 | 128 |
| 2024 April | 84 | 20 | 104 |
| 2024 March | 98 | 35 | 133 |
| 2024 February | 78 | 32 | 110 |
| 2024 January | 64 | 33 | 97 |
| 2023 December | 87 | 40 | 127 |
| 2023 November | 102 | 66 | 168 |
| 2023 October | 89 | 35 | 124 |
| 2023 September | 102 | 26 | 128 |
| 2023 August | 68 | 29 | 97 |
| 2023 July | 101 | 33 | 134 |
| 2023 June | 63 | 22 | 85 |
| 2023 May | 74 | 34 | 108 |
| 2023 April | 58 | 22 | 80 |
| 2023 March | 76 | 31 | 107 |
| 2023 February | 55 | 22 | 77 |
| 2023 January | 44 | 36 | 80 |
| 2022 December | 54 | 52 | 106 |
| 2022 November | 38 | 32 | 70 |
| 2022 October | 34 | 36 | 70 |
| 2022 September | 28 | 37 | 65 |
| 2022 August | 26 | 34 | 60 |
| 2022 July | 35 | 42 | 77 |
| 2022 June | 27 | 21 | 48 |
| 2022 May | 80 | 41 | 121 |
| 2022 April | 81 | 46 | 127 |
| 2022 March | 129 | 69 | 198 |
| 2022 February | 68 | 34 | 102 |
| 2022 January | 80 | 53 | 133 |
| 2021 December | 73 | 55 | 128 |
| 2021 November | 67 | 49 | 116 |
| 2021 October | 55 | 59 | 114 |
| 2021 September | 51 | 52 | 103 |
| 2021 August | 42 | 48 | 90 |
| 2021 July | 40 | 42 | 82 |
| 2021 June | 50 | 39 | 89 |
| 2021 May | 35 | 49 | 84 |
| 2021 April | 93 | 68 | 161 |
| 2021 March | 52 | 36 | 88 |
| 2021 February | 52 | 35 | 87 |
| 2021 January | 29 | 25 | 54 |
| 2020 December | 19 | 19 | 38 |
| 2020 November | 19 | 18 | 37 |
| 2020 October | 26 | 17 | 43 |
| 2020 September | 25 | 20 | 45 |
| 2020 August | 17 | 21 | 38 |
| 2020 July | 20 | 14 | 34 |
| 2020 June | 28 | 27 | 55 |
| 2020 May | 19 | 38 | 57 |
| 2020 April | 19 | 31 | 50 |
| 2020 March | 28 | 23 | 51 |
| 2020 February | 7 | 10 | 17 |
| 2020 January | 2 | 13 | 15 |
| 2019 December | 4 | 8 | 12 |
| 2019 November | 4 | 3 | 7 |
| 2019 October | 0 | 4 | 4 |
| 2019 September | 4 | 5 | 9 |
| 2019 August | 4 | 12 | 16 |
| 2019 July | 4 | 10 | 14 |
| 2019 June | 4 | 30 | 34 |
| 2019 May | 4 | 64 | 68 |
| 2019 April | 5 | 40 | 45 |
| 2019 March | 0 | 12 | 12 |
| 2019 February | 2 | 2 | 4 |
| 2018 December | 4 | 7 | 11 |
| 2018 November | 3 | 0 | 3 |
| 2018 September | 6 | 0 | 6 |
| 2018 June | 0 | 2 | 2 |
| 2018 March | 3 | 1 | 4 |
| 2018 February | 73 | 9 | 82 |
| 2018 January | 78 | 9 | 87 |
| 2017 December | 66 | 10 | 76 |
| 2017 November | 57 | 17 | 74 |
| 2017 October | 67 | 12 | 79 |
| 2017 September | 45 | 10 | 55 |
| 2017 August | 79 | 8 | 87 |
| 2017 July | 86 | 15 | 101 |
| 2017 June | 101 | 17 | 118 |
| 2017 May | 83 | 15 | 98 |
| 2017 April | 70 | 15 | 85 |
| 2017 March | 64 | 18 | 82 |
| 2017 February | 61 | 24 | 85 |
| 2017 January | 50 | 7 | 57 |
| 2016 December | 95 | 19 | 114 |
| 2016 November | 128 | 18 | 146 |
| 2016 October | 143 | 20 | 163 |
| 2016 September | 244 | 19 | 263 |
| 2016 August | 196 | 28 | 224 |
| 2016 July | 76 | 16 | 92 |
| 2016 June | 7 | 29 | 36 |
| 2016 May | 5 | 27 | 32 |
| 2016 April | 4 | 6 | 10 |
| 2016 March | 10 | 14 | 24 |
| 2016 February | 6 | 4 | 10 |
| 2016 January | 6 | 2 | 8 |
| 2015 December | 11 | 10 | 21 |
| 2015 November | 12 | 9 | 21 |
| 2015 October | 9 | 5 | 14 |
| 2015 September | 11 | 2 | 13 |
| 2015 August | 19 | 3 | 22 |
| 2015 July | 181 | 1 | 182 |
| 2015 June | 106 | 21 | 127 |
| 2015 May | 114 | 33 | 147 |
| 2015 April | 129 | 33 | 162 |
| 2015 March | 101 | 19 | 120 |
| 2015 February | 101 | 18 | 119 |
| 2015 January | 114 | 23 | 137 |
| 2014 December | 73 | 26 | 99 |
| 2014 November | 105 | 20 | 125 |
| 2014 October | 79 | 15 | 94 |
| 2014 September | 68 | 10 | 78 |
| 2014 August | 122 | 11 | 133 |
| 2014 July | 78 | 11 | 89 |
| 2014 June | 91 | 6 | 97 |
| 2014 May | 89 | 9 | 98 |
| 2014 April | 57 | 12 | 69 |
| 2014 March | 74 | 14 | 88 |
| 2014 February | 72 | 19 | 91 |
| 2014 January | 52 | 11 | 63 |
| 2013 December | 48 | 6 | 54 |
| 2013 November | 44 | 16 | 60 |
| 2013 October | 40 | 7 | 47 |
| 2013 September | 40 | 11 | 51 |
| 2013 August | 39 | 25 | 64 |
| 2013 July | 18 | 24 | 42 |
| 2013 June | 15 | 10 | 25 |
| 2013 May | 13 | 6 | 19 |
| 2013 April | 9 | 12 | 21 |
| 2013 March | 19 | 6 | 25 |
| 2013 February | 41 | 10 | 51 |
| 2013 January | 58 | 14 | 72 |
| 2012 December | 22 | 9 | 31 |
| 2012 November | 3 | 2 | 5 |
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