High incidence of heparin-induced allergic delayed-type hypersensitivity reactions in pregnancy - 27/06/13
, Corinna Gobst, MD a, Hartmut Kroll, MD b, Andreas Recke, MD c, Frank Louwen, MD d, Manfred Wolter, MD e, Roland Kaufmann, MD e, Wolf-Henning Boehncke, MD e, f, Edelgard Lindhoff-Last, MD a, Ralf J. Ludwig, MD c, eAbstract |
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.
Le texte complet de cet article est disponible en PDF.Key words : Heparin, low-molecular-weight heparin, delayed-type hypersensitivity reaction, pregnancy, heparin-induced thrombocytopenia, skin, allergy
Abbreviations used : BMI, DTH, HIT, HR, LMWH, PE
Plan
| Supported by the Departments of Internal Medicine (Division of Vascular Medicine and Hemostaseology) and Dermatology; Goethe University Hospital Frankfurt, Frankfurt am Main, Germany; and the Excellence Cluster Inflammation at Interfaces (EXC 306/1). |
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| Disclosure of potential conflict of interest: M. Schindewolf has received payment for lectures from GlaxoSmithKline and has received travel support from Bristol-Myers Squibb. E. Lindhoff-Last has received consulting fees from Bayer, Boehringer-Ingelheim, GlaxoSmithKline, and Sanofi-Aventis. R. J. Ludwig has received payment for lectures from Biotest AG and Biogen-Idec. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 132 - N° 1
P. 131-139 - juillet 2013 Retour au numéro
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