A clinical examination was performed of the anticoagulant injection sites, as well as a full-body examination of the skin. 25 (odds ratio [OR] 4.6, 95% CI 1.7C15.3), duration of heparin therapy longer than 9 days (OR 5.9, 95% CI 1.9C26.3) and female sex (OR 3.0, 95% CI 1.1C8.8). Interpretation Heparin-induced skin lesions are relatively common, have identifiable risk factors and are commonly caused by a delayed-type hypersensitivity reaction (type IV allergic response). (ClinicalTrials.gov trial register no. “type”:”clinical-trial”,”attrs”:”text”:”NCT00510432″,”term_id”:”NCT00510432″NCT00510432.) Hpeparin has been used as an anticoagulant for over 60 years.1 Well-known adverse effects of heparin therapy are bleeding, osteoporosis, hair loss, and immune and nonimmune heparin-induced thrombocytopenia. The incidence of heparin-induced skin lesions is unknown, despite being increasingly reported.2C4 Heparin-induced skin lesions Saikosaponin D may be caused by at least 5 mechanisms: delayed-type (type IV) hypersensitivity responses,2,4C6 immune-mediated thrombocytopenia,3 type I allergic reactions,7,8 skin necrosis9 and pustulosis.10 Heparin-induced skin lesions may indicate the presence of life-threatening heparin-induced thrombocytopenia11 even in Saikosaponin D the absence of thrombocytopenia.3 There are no data available on the incidence of heparin-induced skin lesions or their causes. Given the rising number of reports of heparin-induced skin lesions and the importance of correctly diagnosing this condition, we sought to determine the incidence of heparin-induced skin lesions. Methods Study design and patient recruitment In this study, heparin-induced thrombocytopenia refers to immune heparin-induced thrombocytopenia unless stated otherwise. We enrolled over a 12-month period (April 2007 to February 2008) patients receiving subcutaneous anticoagulant therapy on an in- or out-patient basis at the Hospital of the Johann Wolfgang Goethe University, Frankfurt, Ger-many. At monthly intervals, we assessed for eligibility all medical inpatients in the Department of Internal Medicine and all outpatients of the Division of Angiology. We included patients aged 18 years or older who had been taking subcutaneous heparin (unfractionated and low-molecular-weight heparins) for a minimum of 7 days.2 We obtained informed consent from each patient. We excluded patients with a history of heparin-induced thrombocytopenia or type I or type IV allergic reactions to heparin. We aimed to include a minimum of 300 patients. We planned to end recruitment after at least 20 patients with heparin-induced skin lesions were enrolled or after 500 patients were enrolled. The investigation and procedures were approved by the ethics committee of Saikosaponin D the Johann Wolfgang Goethe University and were registered at ClinicalTrials.gov Saikosaponin D (“type”:”clinical-trial”,”attrs”:”text”:”NCT00510432″,”term_id”:”NCT00510432″NCT00510432). Study procedures Eligible patients were seen by 1 or more of the study investigators. The investigator recorded each patients age, sex, indication for admission and previous exposure to subcutaneous anticoagulants. For female patients, the inspector asked whether they were pregnant or taking hormonal contraceptives. From each patients clinical records the investigator obtained information about the patients current anticoagulant therapy (preparation, duration and dose of anticoagulant therapy), height and weight (to calculate body mass index). A clinical examination was performed of the anticoagulant injection sites, as well as a full-body examination of the skin. If a heparin-induced skin lesion was suspected, a second investigator examined the Saikosaponin D patient. If required, further diagnostic procedures were performed, including a skin biopsy for hematoxylinCeosin staining, platelet count monitoring, heparin-induced platelet activation test and a enzyme-linked immunosorbent assay (ELISA) to detect antiplatelet-factor 4/heparin antibodies.12 If heparin-induced thrombocytopenia was excluded, patients with skin lesions underwent allergy testing (prick, epicutaneous, intracutaneous and subcutaneous provocation). Any investigations that needed to be repeated to confirm the diagnosis were performed 1C3 weeks later. Skin biopsies Biopsy samples were obtained from suspected heparin-induced lesions under local anesthesia. The samples were stained with hematoxylinCeosin and evaluated by 2 experienced dermatopathologists (M.W. and R.K.). We considered the presence of spongiosis and infiltration with leukocytes (eosinophils and Rabbit polyclonal to PDK4 lymphocytes) to indicate a delayed-type hypersensitivity reaction. We diagnosed heparin-induced thrombocytopenia if the dermal vessels were occluded. Allergy testing Testing (prick, epicutaneous, intracutaneous and subcutaneous provocation) was initiated no earlier than 6 weeks after resolution of the suspected delayed-type hypersensitivity lesions. We used undiluted original drug formulations as described elsewhere.13 The.