High incidence of heparin-induced allergic delayed-type hypersensitivity reactions in pregnancy

Marc Schindewolf*, Corinna Gobst, Hartmut Kroll, Andreas Recke, Frank Louwen, Manfred Wolter, Roland Kaufmann, Wolf Henning Boehncke, Edelgard Lindhoff-Last, Ralf J. Ludwig

*Corresponding author for this work
16 Citations (Scopus)


Background: Among the most frequent adverse effects of subcutaneous heparin treatment, heparin-induced skin lesions occur with an incidence of 10.3% in nonpregnant female patients. Clinical observations suggest an even higher risk during pregnancy. Objectives: We sought to determine the incidence and causes of heparin-induced skin reactions during pregnancy in a prospective cohort study. Methods: Pregnant women with subcutaneous heparin treatment were prospectively examined for skin reactions. If a skin lesion was observed, further diagnostics were performed (skin biopsy, subcutaneous provocation, clinical/laboratory assessment for thrombosis, bleeding, and heparin-induced thrombocytopenia [HIT]). Safety parameters were also analyzed (cross-allergies, frequency of thromboembolic and bleeding complications, HIT, and pregnancy outcome). Results: Among 111 pregnant patients, 22 (19.8%) had heparininduced skin reactions (95% CI, 13% to 29%). All lesions were caused by allergic delayed-type hypersensitivity (DTH) reactions and not by HIT or other rare conditions. The median time of onset was 50.5 days (range, 5-184 days). The crossreactivity rate was 33.3%. While nadroparin treatment exhibited a higher DTH risk than dalteparin (hazard ratio [HR], 26.7; 95% CI, 3.4-211.0; P =.00187), enoxaparin treatment was not significantly different from dalteparin treatment (HR, 5.6; 95% CI, 0.3-96.1; P =.238). Three thromboembolic events and 1 major bleeding event occurred. Conclusions: Among patients receiving long-term heparin anticoagulation during pregnancy, heparin-induced skin lesions are frequent (incidence, 19.8%) and are all caused by allergic DTH reactions. Nadroparin has the highest frequency of skin lesions (approximately 65% at 100 days), which is significantly higher than that of dalteparin (HR, 26.7). Therefore nadroparin use should be avoided in pregnancy when possible.

Original languageEnglish
JournalJournal of Allergy and Clinical Immunology
Issue number1
Pages (from-to)131-139
Number of pages9
Publication statusPublished - 01.01.2013


Dive into the research topics of 'High incidence of heparin-induced allergic delayed-type hypersensitivity reactions in pregnancy'. Together they form a unique fingerprint.

Cite this