Department of Internal Medicine, Division of Vascular Medicine and Hemostaseology, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany.
J Allergy Clin Immunol. 2013 Jul;132(1):131-9. doi: 10.1016/j.jaci.2013.02.047. Epub 2013 May 30.
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.
We sought to determine the incidence and causes of heparin-induced skin reactions during pregnancy in a prospective cohort study.
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).
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.
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.
在皮下肝素治疗最常见的不良反应中，肝素诱导的皮肤损伤在非妊娠女性患者中的发生率为 10.3%。临床观察表明，在妊娠期间风险甚至更高。
我们旨在通过前瞻性队列研究确定妊娠期间肝素诱导皮肤反应的发生率和原因。
对接受皮下肝素治疗的孕妇进行前瞻性检查，以观察皮肤反应。如果观察到皮肤损伤，则进行进一步的诊断（皮肤活检、皮下激发试验、临床/实验室评估血栓形成、出血和肝素诱导的血小板减少症[HIT]）。还分析了安全参数（交叉过敏、血栓栓塞和出血并发症、HIT 和妊娠结局的发生率）。
在 111 名孕妇中，有 22 名（95%CI，13%至 29%）发生肝素诱导的皮肤反应。所有病变均由过敏迟发型超敏反应（DTH）引起，而非由 HIT 或其他罕见情况引起。发病中位时间为 50.5 天（范围，5-184 天）。交叉反应率为 33.3%。虽然那屈肝素治疗的 DTH 风险高于达肝素（危险比[HR]，26.7；95%CI，3.4-211.0；P =.00187），但依诺肝素治疗与达肝素治疗无显著差异（HR，5.6；95%CI，0.3-96.1；P =.238）。发生了 3 例血栓栓塞事件和 1 例大出血事件。
在接受长期肝素抗凝治疗的妊娠患者中，肝素诱导的皮肤损伤较为常见（发生率为 19.8%），且均由过敏 DTH 反应引起。那屈肝素的皮肤损伤发生率最高（100 天约为 65%），明显高于达肝素（HR，26.7）。因此，在可能的情况下，妊娠期间应避免使用那屈肝素。
