title: Nadroparin carries a potentially high risk of inducing cutaneous delayed-type hypersensitivity responses.
abstract: BACKGROUND
  Heparins are widely used for the prophylaxis/treatment of thromboembolic events. As adverse effects, heparin-induced skin lesions occur frequently (in 7.5-39% of patients). Skin lesions may be the only clinical manifestation of life-threatening immune-mediated heparin-induced thrombocytopenia, but are commonly caused by a delayed-type hypersensitivity response [heparin-induced delayed-type hypersensitivity (HIHS)]. Risk factors have not been prospectively identified.
  
  
  OBJECTIVE
  To identify possible risk factors for heparin-induced skin lesions from three independent clinical trials in a combined analysis.
  
  
  METHODS
  A pooled analysis from prospective studies was performed, and possible risk factors were included in a multiple logistic regression analysis.
  
  
  RESULTS
  Obesity (body mass index of > 25), prolonged anticoagulant therapy, prior heparin exposure and younger age (< 55 years) were confirmed as independent risk factors for HIHS. The choice of anticoagulant preparation had the greatest influence. On comparison of dalteparin, enoxaparin, fondaparinux, unfractionated heparin, and nadroparin, the latter was associated with the highest risk of eliciting HIHS (odds ratio of 30.2, 95%CI: 11.7-77.9).
  
  
  CONCLUSIONS
  The high risk associated with nadroparin has been validated in controlled trials, and this emphasizes the singularity of each heparin preparation in terms of allergenicity and that individualized anticoagulation is required.
authors.affiliation: Division of Haemostaseology, Department of Internal Medicine, Goethe University Hospital, 60590, Frankfurt am Main, Germany.|Division of Vascular Medicine, Swiss Cardiovascular Centre, University Hospital Bern, 3010, Bern, Switzerland.
authors.forename: Marc
authors.identifier: http://orcid.org/0000-0003-4597-0759
authors.initials: M
authors.lastname: Schindewolf
authors.affiliation: Department of Dermatology and Lübeck Institute of Experimental Dermatology, University of Lübeck, 23538, Lübeck, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Recke
authors.affiliation: Department of Dermatology and Lübeck Institute of Experimental Dermatology, University of Lübeck, 23538, Lübeck, Germany.
authors.forename: Detlef
authors.initials: D
authors.lastname: Zillikens
authors.affiliation: Division of Haemostaseology, Department of Internal Medicine, Goethe University Hospital, 60590, Frankfurt am Main, Germany.|Agaplesion Bethanien Hospital, Cardiovascular Centre Bethanien (CCB), 60389, Frankfurt am Main, Germany.
authors.forename: Edelgard
authors.initials: E
authors.lastname: Lindhoff-Last
authors.affiliation: Department of Dermatology and Lübeck Institute of Experimental Dermatology, University of Lübeck, 23538, Lübeck, Germany.
authors.forename: Ralf J
authors.initials: RJ
authors.lastname: Ludwig
mesh_terms: D000328:Adult; D000367:Age Factors; D000925:Anticoagulants / Q000009:adverse effects*; D015992:Body Mass Index; D017449:Dermatitis, Allergic Contact / Q000209:etiology*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017762:Nadroparin / Q000009:adverse effects*; D011247:Pregnancy; D012044:Regression Analysis; D012307:Risk Factors; D013923:Thromboembolism / Q000517:prevention & control
chemical_list: D000925:Anticoagulants; D017762:Nadroparin
keywords: HIHS; HIT; allergy; heparin; heparin-induced delayed-type hypersensitivity response; heparin-induced thrombocytopenia; low molecular weight heparin; skin