Delayed-type hypersensitivity to low molecular weight heparins and heparinoids: cross-reactivity does not depend on molecular weight

Br J Dermatol. 2007 Sep;157(3):514-7. doi: 10.1111/j.1365-2133.2007.08007.x. Epub 2007 Jun 15.


Background: Cross-reactivity is a widespread phenomenon in patients who develop cutaneous delayed-type hypersensitivity (DTH) reactions to low molecular weight heparins (LMWHs). As molecular weight is believed to be a key determinant of sensitization to heparins, the recently developed LMWH bemiparin, with the lowest molecular weight of all LMWHs, appeared to be a significant improvement.

Objectives: To evaluate cross-reactivity between bemiparin and several other LMWHs and heparinoids by means of subcutaneous testing. Methods Test doses of bemiparin and several other LMWHs/heparinoids were given to eight patients with a history of local eczematous reactions after subcutaneous injection of enoxaparin.

Results: Seven of eight patients showed cross-reactivity following subcutaneous injection of bemiparin. In addition, nearly all tested substances caused local eczematous reactions in at least some patients, with the exception of fondaparinux, which was well tolerated by all patients. Of all substances tested, bemiparin had the highest cross-reactivity with enoxaparin. Substances with a lower molecular weight did not cross-react less frequently than the others.

Conclusions: No significant correlation was found between the molecular weight of the tested substances and the frequency of DTH reactions. In patients with DTH to enoxaparin, the LMWH bemiparin is not a suitable alternative.

MeSH terms

  • Aged
  • Anticoagulants / adverse effects*
  • Anticoagulants / chemistry
  • Anticoagulants / immunology
  • Cross Reactions / immunology
  • Drug Eruptions / etiology*
  • Drug Eruptions / immunology
  • Female
  • Heparin, Low-Molecular-Weight / administration & dosage
  • Heparin, Low-Molecular-Weight / adverse effects*
  • Heparin, Low-Molecular-Weight / immunology
  • Heparinoids / adverse effects*
  • Heparinoids / chemistry
  • Heparinoids / immunology
  • Humans
  • Hypersensitivity, Delayed / chemically induced*
  • Hypersensitivity, Delayed / immunology
  • Male
  • Middle Aged
  • Molecular Weight
  • Skin Tests


  • Anticoagulants
  • Heparin, Low-Molecular-Weight
  • Heparinoids