CMAJ • October 13, 2009; 181 (8). First published September 28, 2009; doi:10.1503/cmaj.081729
© 2009 Canadian Medical Association or its licensors
All editorial matter in CMAJ represents the opinions of the authors and not necessarily those of the Canadian Medical Association.
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Research

Incidence and causes of heparin-induced skin lesions

Marc Schindewolf, MD, Svantje Schwaner, MD, Manfred Wolter, MD, Hartmut Kroll, MD, Andreas Recke, MD, Roland Kaufmann, MD, Wolf-Henning Boehncke, MD, Edelgard Lindhoff-Last, MD and Ralf J. Ludwig, MD

From the Departments of Internal Medicine, Division of Angiology (Schindewolf, Lindhoff-Last), and Dermatology (Schwaner, Wolter, Kaufmann, Boehncke, Ludwig), Hospital of the Johann Wolfgang Goethe University, Frankfurt am Main, Germany, the DRK-Blooddonorservice (Kroll), Dessau, Germany, and the Department of Dermatology (Recke), University of Lübeck, Lübeck, Germany

Correspondence to: Prof. Ralf J. Ludwig, Department of Dermatology; University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck Germany; fax 49 451 500-2981; ralf.ludwig{at}uk-sh.de

Background: Little is known about the incidence and causes of heparin-induced skin lesions. The 2 most commonly reported causes of heparin-induced skin lesions are immune-mediated heparin-induced thrombocytopenia and delayed-type hypersensitivity reactions.

Methods: We prospectively examined consecutive patients who received subcutaneous heparin (most often enoxaparin or nadroparin) for the presence of heparin-induced skin lesions. If such lesions were identified, we performed a skin biopsy, platelet count measurements, and antiplatelet-factor 4 antibody and allergy testing.

Results: We enrolled 320 patients. In total, 24 patients (7.5%, 95% confidence interval [CI] 4.7%–10.6%) had heparin-induced skin lesions. Delayed-type hypersensitivity reactions were identified as the cause in all 24 patients. One patient with histopathologic evidence of delayed-type hypersensitivity tested positive for antiplatelet-factor 4 antibodies. We identified the following risk factors for heparin-induced skin lesions: a body mass index greater than 25 (odds ratio [OR] 4.6, 95% CI 1.7–15.3), duration of heparin therapy longer than 9 days (OR 5.9, 95% CI 1.9–26.3) and female sex (OR 3.0, 95% CI 1.1–8.8).

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. NCT00510432.)


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Can. Med. Assoc. J. 2009 181: 449. [Full Text] [PDF]

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Can. Med. Assoc. J. 2009 181: E122. [Full Text] [PDF]



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Immunity towards heparin
Heikki Savolainen
CMAJ, 20 Oct 2009 [Full text]