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1</a>C&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">Based on the patient&#8217;s clinical picture a suspected diagnosis of heparin-induced skin necrosis was established&#46; Laboratory tests&#44; including a complete blood count and coagulation parameters&#44; revealed no findings of interest&#44; apart from thrombocytopenia &#40;107<span class="elsevierStyleHsp" style=""></span>000 platelets&#47;mL&#41;&#46; Tests for anti-platelet factor 4 antibodies were negative&#46; Heparin treatment was immediately discontinued and oral anticoagulation treatment with warfarin was initiated&#46; Fifteen days after heparin discontinuation a clear improvement in the patient&#8217;s lesions was observed &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41; and the platelet count returned to 130<span class="elsevierStyleHsp" style=""></span>000 platelets&#47;mL&#46; Skin necrosis in response to anticoagulant treatment is a rare adverse reaction&#44; and is rarer in patients treated with heparin than in those treated with oral anticoagulants &#40;0&#46;01&#37; of patients&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Although the pathogenesis of this adverse effect is unclear&#44; most authors suspect an immune mechanism whereby heparin-induced production of anti-platelet antibodies triggers platelet aggregation and consequent vascular occlusion&#46; Heparin-induced skin necrosis is considered part of heparin-induced thrombocytopenia syndrome&#44; although a decrease in platelet count is observed in only 50&#37; of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Clinical signs appear between 5 and 15 days after beginning treatment&#44; usually close to the injection site&#44; although rarer cases involving lesions at a distance from the injection site have also been described&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Lesions initially appear as painful&#44; well-delimited erythematous or hemorrhagic macules that become indurated over the following days&#46; Subsequently&#44; the lesions become necrotic and give way to tense&#44; painful serosanguineous sores and blisters that evolve into marked necrosis of the skin and subcutaneous cellular tissue&#46; In addition to marked necrotic lesions&#44; affected patients may present with other abortive erythematous or cyanotic lesions&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Blood tests typically reveal thrombocytopenia and the presence of anti-platelet factor IV antibodies&#44; although their absence is insufficient to rule out heparin-induced skin necrosis&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Diagnosis is mainly clinical&#44; with histological confirmation in doubtful cases&#46; The main differential diagnoses are warfarin-induced skin necrosis and heparin-induced type-IV hypersensitivity reaction&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Treatment consists of immediate discontinuation of heparin administration and replacement with other anticoagulants such as direct thrombin inhibitors &#40;hirudins&#41; or warfarin&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a> Substitution with other LMWHs is not recommended&#46; Discontinuation of heparin treatment is followed by rapid recovery of the platelet count and progressive healing of necrotic lesions&#44; as occurred in the present case&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The most common adverse effects of heparin include bleeding&#44; alopecia &#40;in up to 50&#37; of patients undergoing prolonged treatment&#41;&#44; osteoporosis&#44; hypersensitivity phenomena&#44; and thrombocytopenia&#46; Skin necrosis is a rare adverse reaction to heparin&#44; but should be taken into consideration&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Diagnosis is primarily clinical&#44; and early withdrawal of heparin treatment is essential to avoid the development of potentially fatal visceral thrombotic complications&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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Case and Research Letters
Heparin-Induced Skin Necrosis Occurring at a Distance From Injection Sites
Necrosis cutánea por heparina con afectación a distancia del punto de administración
A. Estébanez
Corresponding author
andreaestebanez_7@hotmail.com

Corresponding author.
, E. Silva, P. Cordero, J.M. Martín
Servicio de Dermatología, Hospital Clínico Universitario, Valencia, Spain
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    "titulo" => "Heparin-Induced Skin Necrosis Occurring at a Distance From Injection Sites"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">A 67-year-old man who had been diagnosed 1 year earlier with inoperable glioblastoma multiforme that was refractory to multiple treatments was treated with low-molecular-weight heparin &#40;LMWH&#41; after an episode of pulmonary thromboembolism and deep venous thrombosis&#46; Disseminated asymptomatic skin lesions appeared 5 days after beginning LMWH therapy&#46; Despite the spectacular appearance of the skin lesions the patient&#8217;s general condition was excellent&#46; Fever and other clinical signs of infection were absent&#46; Physical examination revealed large&#44; noninfiltrated ecchymotic plaques located mainly on the abdomen without underlying fluid collection &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41;&#44; necrotic lesions on the right thigh &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B&#41;&#44; and tense blisters with hemorrhagic content in the distal area of the right leg &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>C&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">Based on the patient&#8217;s clinical picture a suspected diagnosis of heparin-induced skin necrosis was established&#46; Laboratory tests&#44; including a complete blood count and coagulation parameters&#44; revealed no findings of interest&#44; apart from thrombocytopenia &#40;107<span class="elsevierStyleHsp" style=""></span>000 platelets&#47;mL&#41;&#46; Tests for anti-platelet factor 4 antibodies were negative&#46; Heparin treatment was immediately discontinued and oral anticoagulation treatment with warfarin was initiated&#46; Fifteen days after heparin discontinuation a clear improvement in the patient&#8217;s lesions was observed &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41; and the platelet count returned to 130<span class="elsevierStyleHsp" style=""></span>000 platelets&#47;mL&#46; Skin necrosis in response to anticoagulant treatment is a rare adverse reaction&#44; and is rarer in patients treated with heparin than in those treated with oral anticoagulants &#40;0&#46;01&#37; of patients&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Although the pathogenesis of this adverse effect is unclear&#44; most authors suspect an immune mechanism whereby heparin-induced production of anti-platelet antibodies triggers platelet aggregation and consequent vascular occlusion&#46; Heparin-induced skin necrosis is considered part of heparin-induced thrombocytopenia syndrome&#44; although a decrease in platelet count is observed in only 50&#37; of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Clinical signs appear between 5 and 15 days after beginning treatment&#44; usually close to the injection site&#44; although rarer cases involving lesions at a distance from the injection site have also been described&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Lesions initially appear as painful&#44; well-delimited erythematous or hemorrhagic macules that become indurated over the following days&#46; Subsequently&#44; the lesions become necrotic and give way to tense&#44; painful serosanguineous sores and blisters that evolve into marked necrosis of the skin and subcutaneous cellular tissue&#46; In addition to marked necrotic lesions&#44; affected patients may present with other abortive erythematous or cyanotic lesions&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Blood tests typically reveal thrombocytopenia and the presence of anti-platelet factor IV antibodies&#44; although their absence is insufficient to rule out heparin-induced skin necrosis&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Diagnosis is mainly clinical&#44; with histological confirmation in doubtful cases&#46; The main differential diagnoses are warfarin-induced skin necrosis and heparin-induced type-IV hypersensitivity reaction&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Treatment consists of immediate discontinuation of heparin administration and replacement with other anticoagulants such as direct thrombin inhibitors &#40;hirudins&#41; or warfarin&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a> Substitution with other LMWHs is not recommended&#46; Discontinuation of heparin treatment is followed by rapid recovery of the platelet count and progressive healing of necrotic lesions&#44; as occurred in the present case&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The most common adverse effects of heparin include bleeding&#44; alopecia &#40;in up to 50&#37; of patients undergoing prolonged treatment&#41;&#44; osteoporosis&#44; hypersensitivity phenomena&#44; and thrombocytopenia&#46; Skin necrosis is a rare adverse reaction to heparin&#44; but should be taken into consideration&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Diagnosis is primarily clinical&#44; and early withdrawal of heparin treatment is essential to avoid the development of potentially fatal visceral thrombotic complications&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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Idiomas
Actas Dermo-Sifiliográficas
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