Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 132, Issue 1, Pages 131-139Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2013.02.047
Keywords
Heparin; low-molecular-weight heparin; delayed-type hypersensitivity reaction; pregnancy; heparin-induced thrombocytopenia; skin; allergy
Categories
Funding
- Department of Internal Medicine (Division of Vascular Medicine and Hemostaseology)
- Department of Dermatology
- Goethe University Hospital Frankfurt, Frankfurt am Main, Germany
- Excellence Cluster Inflammation at Interfaces [EXC 306/1]
- GlaxoSmithKline
- Bayer
- Boehringer Ingelheim
- Sanofi-Aventis
- Biotest AG
- Biogen-Idec
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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 heparin-induced 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 cross-reactivity 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.
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