Department of Internal Medicine, Division of Hemostaseology, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany; Swiss Cardiovascular Center, Division of Vascular Medicine, University Hospital Bern, Bern, Switzerland.
Department of Internal Medicine, Division of Hemostaseology, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany.
J Am Coll Cardiol. 2017 Nov 28;70(21):2636-2648. doi: 10.1016/j.jacc.2017.09.1099.
Life-threatening heparin-induced thrombocytopenia (HIT) is treated with the alternative nonheparin anticoagulants argatroban, lepirudin, or danaparoid. Frequently, the pentasaccharide fondaparinux is used off-label.
The authors sought to investigate the safety and efficacy of the different anticoagulants for treating HIT.
In a national, multicenter registry study, hospitalized patients who were diagnosed with HIT, an at least intermediate clinical HIT-risk (4Ts score ≥4 points), and received treatment with ≥1 dose of the aforementioned anticoagulants were included. Main outcome measures were the incidences of HIT-specific complications (thromboembolic venous/arterial events, amputations, recurrent/persistent thrombocytopenia, skin lesions) and bleedings.
Of 195 patients, 46 (23.6%), 4 (2.1%), 61 (31.3%), and 84 (43.1%) had been treated first-line with argatroban, lepirudin, danaparoid, and fondaparinux, respectively. The composite endpoint of HIT-specific complications (thromboembolic events, amputation, skin necrosis) occurred in 11.7% of patients treated with approved alternative anticoagulation and in 0.0% of fondaparinux-treated patients. The all-cause in-hospital mortality rates were 14.4% during approved alternative anticoagulation and 0.0% during fondaparinux treatment. Bleeding complications occurred in alternatively anticoagulated patients and in fondaparinux-treated patients in 6.3% and 4.8%, respectively. Post hoc analysis of clinical and laboratory features confirmed "true" HIT in at least 74 of 195 (38.0%) patients; 35 of 74 (47.3%) were treated with fondaparinux.
Fondaparinux is effective and safe in suspected acute HIT; no HIT-specific complications occurred in the fondaparinux-treated patients, even among those with a high clinical HIT probability. Further data from randomized controlled trials are urgently needed because lepirudin was recalled from the market; danaparoid access has been limited and is not approved in the United States; and argatroban is contraindicated in patients with impaired liver function, and activated partial thromboplastin time confounding may interfere with monitoring. (Retrospective Registry of Patients With Acute Heparin-induced Thrombocytopenia Type II; NCT01304238).
危及生命的肝素诱导的血小板减少症（HIT）的治疗方法是使用替代非肝素抗凝剂，如阿加曲班、来匹卢定或达那肝素。戊多糖磺达肝癸钠经常被超适应证使用。
作者旨在研究不同抗凝剂治疗 HIT 的安全性和疗效。
在一项全国性的多中心注册研究中，纳入了至少有中等临床 HIT 风险（4Ts 评分≥4 分）、接受过上述抗凝剂至少一剂治疗的 HIT 确诊住院患者。主要观察终点是 HIT 特异性并发症（血栓栓塞性静脉/动脉事件、截肢、复发性/持续性血小板减少、皮肤损伤）和出血的发生率。
195 例患者中，46 例（23.6%）、4 例（2.1%）、61 例（31.3%）和 84 例（43.1%）一线分别接受了阿加曲班、来匹卢定、达那肝素和磺达肝癸钠治疗。在接受批准的替代抗凝治疗的患者中，HIT 特异性并发症（血栓栓塞事件、截肢、皮肤坏死）的复合终点发生率为 11.7%，而接受磺达肝癸钠治疗的患者中则为 0.0%。在接受批准的替代抗凝治疗的患者中，全因住院死亡率为 14.4%，而接受磺达肝癸钠治疗的患者中则为 0.0%。在接受替代抗凝治疗的患者和接受磺达肝癸钠治疗的患者中，出血并发症的发生率分别为 6.3%和 4.8%。对临床和实验室特征的事后分析证实，至少有 74 例（47.3%）患者存在“真正”的 HIT；其中 35 例接受了磺达肝癸钠治疗。
磺达肝癸钠在疑似急性 HIT 中有效且安全；在接受磺达肝癸钠治疗的患者中，没有发生 HIT 特异性并发症，即使在临床 HIT 概率较高的患者中也是如此。由于来匹卢定已被召回市场，因此急需来自随机对照试验的进一步数据；达那肝素的使用受到限制，且未在美国获得批准；而阿加曲班禁用于肝功能受损的患者，且激活部分凝血活酶时间的干扰可能会影响监测。（肝素诱导的血小板减少症 II 型急性患者的回顾性登记研究；NCT01304238）
