Association of heparin-induced skin lesions, intracutaneous tests, and heparin-induced IgG

Allergy. 1999 May;54(5):473-7. doi: 10.1034/j.1398-9995.1999.00048.x.


Background: Cutaneous heparin-induced allergic reactions to subcutaneous heparin may begin 2-5 days after administration. The relation of the delayed-type hypersensitivity and a systemic immunologic response is controversial. The present investigation aimed to analyze the occurrence of thromboembolic complication, pathologic heparin-induced platelet activation (HIPA), and the presence of circulating heparin-induced IgG in patients with heparin-induced skin reactions.

Methods: Intracutaneous tests, HIPA assay, and heparin-heparin IgG antibodies were performed in nine patients with heparin-induced skin lesions.

Results: Six of eight patients showed positive intracutaneous tests to heparin and to four low-molecular-weight heparins. Three of six heparin-positive patients presented hypersensitivity to a heparinoid, too. Two of three patients had a positive HIPA test and elevated heparin-induced IgG antibodies. Both patients developed complications presenting as heparin-induced skin necrosis or arterial thrombosis. Two of nine patients were treated with danaparoid, 4/9 patients received r-hirudin, and 1/9 received oral coumarin. In 2/9 patients, anticoagulant therapy was stopped, but these patients will receive r-hirudin if indicated.

Conclusions: On the basis of the coincidence of local and systemic hyperreactivity to heparin and danaparoid, patients with heparin-induced skin lesions should receive r-hirudin, a nonheparin compound, for anticoagulant treatment.

MeSH terms

  • Adult
  • Aged
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use
  • Antithrombins / adverse effects
  • Antithrombins / therapeutic use
  • Chondroitin Sulfates / adverse effects
  • Chondroitin Sulfates / therapeutic use
  • Dermatan Sulfate / adverse effects
  • Dermatan Sulfate / therapeutic use
  • Drug Combinations
  • Drug Eruptions / complications
  • Drug Eruptions / etiology*
  • Drug Eruptions / immunology
  • Drug Eruptions / therapy
  • Female
  • Heparin / administration & dosage
  • Heparin / adverse effects*
  • Heparin / immunology
  • Heparin, Low-Molecular-Weight / adverse effects
  • Heparin, Low-Molecular-Weight / immunology
  • Heparitin Sulfate / adverse effects
  • Heparitin Sulfate / therapeutic use
  • Hirudin Therapy
  • Hirudins / adverse effects
  • Humans
  • Hypersensitivity, Delayed / etiology*
  • Hypersensitivity, Delayed / immunology
  • Immunoglobulin G / blood
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Platelet Activation
  • Skin Tests
  • Thrombocytopenia / etiology


  • Anticoagulants
  • Antithrombins
  • Drug Combinations
  • Heparin, Low-Molecular-Weight
  • Hirudins
  • Immunoglobulin G
  • Dermatan Sulfate
  • Heparin
  • Chondroitin Sulfates
  • Heparitin Sulfate
  • danaparoid