Letter to the Editor
Bullous hemorrhagic dermatosis induced by low molecular weight heparins
Dermatosis ampollosa hemorrágica por administración de heparinas de bajo peso molecular
Xabier Gutiérrez López de Ocáriz
, Nerea Castro Quismondo, Mario Rodríguez Rodríguez
Corresponding author
Servicio de Hematología y Hemoterapia, Hospital Universitario 12 de Octubre, Madrid, Spain
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Editor</span>" "titulo" => "Bullous hemorrhagic dermatosis induced by low molecular weight heparins" "tieneTextoCompleto" => true "saludo" => "Dear Editor:" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "137" "paginaFinal" => "138" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Xabier Gutiérrez López de Ocáriz, Nerea Castro Quismondo, Mario Rodríguez Rodríguez" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Xabier" "apellidos" => "Gutiérrez López de Ocáriz" "email" => array:1 [ 0 => "xabi_vg@hotmail.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Nerea" "apellidos" => "Castro Quismondo" ] 2 => array:2 [ "nombre" => "Mario" "apellidos" => "Rodríguez Rodríguez" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Hematología y Hemoterapia, Hospital Universitario 12 de Octubre, Madrid, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Dermatosis ampollosa hemorrágica por administración de heparinas de bajo peso molecular" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Low molecular weight heparins (LMWHs) are drugs widely used in the prophylaxis and treatment of different thrombotic events that have replaced, in almost all cases, non-fractionated heparins (NFH).</p><p id="par0010" class="elsevierStylePara elsevierViewall">There are several adverse reactions described, the most common being: haemorrhage, osteoporosis, elevated liver enzymes, headache, alopecia and skin disorders such as: bruising, skin necrosis, ecchymoses, eczema, type I hypersensitivity reactions (hives, angioedema), type IV (delayed hypersensitivity).<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The first case of bullous hemorrhagic dermatosis published in the literature dates from 2006, described by Perrinaud et al., in a man undergoing treatment with dalteparin without abnormalities in the coagulation study and with spontaneous resolution after discontinuation of the drug.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">This condition has been commonly described in association with the use of LMWH, characterized by the occurrence of well-defined hemorrhagic-looking bullous lesions, blackish in colour, in tension, asymptomatic and that can affect any part of the body.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Histologically, it is characterized by the formation of a subcorneal, intraepidermal or subepidermal blister, hematic and with a minimal inflammatory component (presence of polymorphonuclear cells) with total absence of vasculitis and thrombotic phenomena and negative immunofluorescence.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The pathogenesis is currently unknown, although it has been postulated that it could correspond to a type IV (delayed) hypersensitivity reaction favoured by an additional anticoagulation/antiplatelet status.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Forty-three cases of bullous hemorrhagic dermatosis associated with the use of different anticoagulant therapies were found after a literature search, which, including our case, would total 44 cases from 1998 to 2018.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The mean age of the patients was 70.1 years (range: 31–94), affecting men (30/44; 68.2%) more commonly than women (14/44; 31.8%).</p><p id="par0045" class="elsevierStylePara elsevierViewall">Regarding anticoagulant therapies, LMWHs have been the ones that have shown the highest relationship (39/44; 88.6%); in turn, enoxaparin was the most common (35/44; 79.5%).</p><p id="par0050" class="elsevierStylePara elsevierViewall">The distribution of the lesions is very wide, affecting practically the entire body surface.</p><p id="par0055" class="elsevierStylePara elsevierViewall">These lesions have a variable latency period from their onset to resolution ranging from one day to one month, with the most common being 1–2 weeks.</p><p id="par0060" class="elsevierStylePara elsevierViewall">In no case was the presence of these skin lesions associated with another bleeding symptoms or other major events.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Regarding the therapeutic management adopted, the most commonly used option was the discontinuation of anticoagulation (25/44; 58.8%), although changing to another anticoagulant therapy (13/44; 29.2%) and the continuation of treatment. (6/44; 12%) were also other alternatives used.</p><p id="par0070" class="elsevierStylePara elsevierViewall">We report the case of a 77-year-old male with a history of high blood pressure, diabetes, COPD, atrial <span class="elsevierStyleItalic">flutter</span> anticoagulated with acenocoumarol and acute myocardial infarction with revascularization and stent placement in the anterior descending and right circumflex arteries (antiplatelet therapy with acetylsalicylic acid).</p><p id="par0075" class="elsevierStylePara elsevierViewall">Currently diagnosed with advanced stage small cell lung carcinoma with dysphagia secondary to extrinsic compression from mediastinal tumour mass; reason why chemotherapy treatment is initiated. In order to decrease the risk of pharmacological interactions with acenocoumarol, it is decided to replace with LMWH (enoxaparin).</p><p id="par0080" class="elsevierStylePara elsevierViewall">One month after LMWH treatment was started, the patient came to the clinic due to the onset of blackish, well-defined, hemorrhagic bullous skin lesions, with minimal surrounding erythema without any another associated bleeding symptoms. A biopsy of the lesion was performed, detecting the presence of an intraepidermal blister with hematic content and without the presence of polymorphonuclear cells or thrombotic events.</p><p id="par0085" class="elsevierStylePara elsevierViewall">LMWH was discontinued and treatment with fondaparinux was started, without any incidents and with complete resolution of the skin lesions within 4 days.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Given the history of ischemic heart disease, the patient remained with ASA and anticoagulation therapy, which could support the hypothesis that the cause of this entity was an excessive anticoagulation status.</p><p id="par0095" class="elsevierStylePara elsevierViewall">In conclusion, it is a rare clinical entity that can affect patients of any age and sex, mostly associated with the use of LMWH.</p><p id="par0100" class="elsevierStylePara elsevierViewall">It is noteworthy that there are no differences in terms of resolution of the condition between the temporary discontinuation of treatment, the change to another anticoagulant therapy or the continuation of the same therapy.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,5</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Finally, it should be noted that there is no reported case of this dermatological abnormality with the new direct oral anticoagulants, nor are there any reported severe cases of associated bleeding symptoms in these patients.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Gutiérrez López de Ocáriz X, Castro Quismondo N, Rodríguez Rodríguez M. Dermatosis ampollosa hemorrágica por administración de heparinas de bajo peso molecular. Med Clin (Barc). 2020;155:137–138.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Heparin-induced skin lesions" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M. Schindewolf" 1 => "E. Lindhoff-Last" 2 => "R.J. Ludwig" 3 => "W.H. Boehncke" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(12)60409-7" "Revista" => array:5 [ "tituloSerie" => "Lancet." 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