title: High incidence of heparin-induced allergic delayed-type hypersensitivity reactions in pregnancy.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Internal Medicine, Division of Vascular Medicine and Hemostaseology, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany. marc.schindewolf@yahoo.com
authors.forename: Marc
authors.initials: M
authors.lastname: Schindewolf
authors.forename: Corinna
authors.initials: C
authors.lastname: Gobst
authors.forename: Hartmut
authors.initials: H
authors.lastname: Kroll
authors.forename: Andreas
authors.initials: A
authors.lastname: Recke
authors.forename: Frank
authors.initials: F
authors.lastname: Louwen
authors.forename: Manfred
authors.initials: M
authors.lastname: Wolter
authors.forename: Roland
authors.initials: R
authors.lastname: Kaufmann
authors.forename: Wolf-Henning
authors.initials: WH
authors.lastname: Boehncke
authors.forename: Edelgard
authors.initials: E
authors.lastname: Lindhoff-Last
authors.forename: Ralf J
authors.initials: RJ
authors.lastname: Ludwig
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000009:adverse effects*; D004342:Drug Hypersensitivity / Q000453:epidemiology*; D005260:Female; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000453:epidemiology*; D015994:Incidence; D011247:Pregnancy; D011248:Pregnancy Complications / Q000453:epidemiology*; D012307:Risk Factors
chemical_list: D000925:Anticoagulants; D006493:Heparin