Division of Haemostaseology, Department of Internal Medicine, Goethe University Hospital, 60590, Frankfurt am Main, Germany.
Division of Vascular Medicine, Swiss Cardiovascular Centre, University Hospital Bern, 3010, Bern, Switzerland.
Contact Dermatitis. 2017 Jul;77(1):35-41. doi: 10.1111/cod.12764. Epub 2017 Mar 14.
Heparins are widely used for the prophylaxis/treatment of thromboembolic events. As adverse effects, heparin-induced skin lesions occur frequently (in 7.5-39% of patients). Skin lesions may be the only clinical manifestation of life-threatening immune-mediated heparin-induced thrombocytopenia, but are commonly caused by a delayed-type hypersensitivity response [heparin-induced delayed-type hypersensitivity (HIHS)]. Risk factors have not been prospectively identified.
To identify possible risk factors for heparin-induced skin lesions from three independent clinical trials in a combined analysis.
A pooled analysis from prospective studies was performed, and possible risk factors were included in a multiple logistic regression analysis.
Obesity (body mass index of > 25), prolonged anticoagulant therapy, prior heparin exposure and younger age (< 55 years) were confirmed as independent risk factors for HIHS. The choice of anticoagulant preparation had the greatest influence. On comparison of dalteparin, enoxaparin, fondaparinux, unfractionated heparin, and nadroparin, the latter was associated with the highest risk of eliciting HIHS (odds ratio of 30.2, 95%CI: 11.7-77.9).
The high risk associated with nadroparin has been validated in controlled trials, and this emphasizes the singularity of each heparin preparation in terms of allergenicity and that individualized anticoagulation is required.
肝素被广泛用于预防/治疗血栓栓塞事件。作为不良反应，肝素诱导的皮肤损伤经常发生（在 7.5-39%的患者中）。皮肤损伤可能是危及生命的免疫介导的肝素诱导的血小板减少症的唯一临床表现，但通常是由迟发型超敏反应[肝素诱导的迟发型超敏反应（HIHS）]引起的。尚未前瞻性确定危险因素。
通过对三项独立临床试验的综合分析，确定肝素诱导的皮肤损伤的可能危险因素。
对前瞻性研究进行了汇总分析，并将可能的危险因素纳入多元逻辑回归分析。
肥胖（体重指数>25）、抗凝治疗时间延长、既往肝素暴露和年龄较小（<55 岁）被确认为 HIHS 的独立危险因素。抗凝药物制剂的选择影响最大。在达肝素、依诺肝素、磺达肝素、未分馏肝素和那屈肝素的比较中，后者与 HIHS 的发生风险最高相关（比值比为 30.2，95%CI：11.7-77.9）。
在对照试验中验证了那屈肝素的高风险，这强调了每种肝素制剂在变应原性方面的独特性，需要个体化抗凝治疗。
