Selleng Kathleen, Warkentin Theodore E, Greinacher Andreas
Department of Immunology and Transfusion Medicine, Ernst-Moritz-Arndt Universität, Greifswald, Germany.
Crit Care Med. 2007 Apr;35(4):1165-76. doi: 10.1097/01.CCM.0000259538.02375.A5.
To summarize new information on frequency of heparin-induced thrombocytopenia (HIT) in patients treated in intensive care units (ICU), developments in the interpretation of assays for detecting anti-PF4/heparin antibodies, and treatment of HIT patients.
All data on the frequency of laboratory-confirmed HIT in ICU patients were included; for laboratory testing of HIT and treatment of patients, this review focuses on recent data that became available in 2005 and 2006.
HIT is a potentially life-threatening adverse effect of heparin treatment caused by platelet-activating antibodies of immunoglobulin G class usually recognizing complexes of platelet factor 4 and heparin. HIT is more often caused by unfractionated heparin than low-molecular-weight heparin and is more common in postsurgical than in medical patients. In the ICU setting, HIT is uncommon (0.3-0.5%), whereas thrombocytopenia from other causes is very common (30-50%). For laboratory diagnosis of HIT antibodies, both antigen assays and functional (platelet activation) assays are available. Both tests are very sensitive (high negative predictive value) but specificity is problematic, especially for the antigen assays, which also detect nonpathogenic immunoglobulin M and immunoglobulin A class antibodies. Detection of immunoglobulin M or immunoglobulin A antibodies could potentially lead to adverse events such as bleeding if a false diagnosis of HIT prompts replacement of heparin by an alternative anticoagulant. For treatment of HIT, three alternative anticoagulants are approved: the direct thrombin inhibitors, lepirudin and argatroban, and the heparinoid, danaparoid (not approved in the United States). Recent data indicate that the approved dosing regimens of the direct thrombin inhibitors are too high, especially in ICU patients.
HIT affects <1% of ICU patients even though 30-50% develop thrombocytopenia. The choice of the optimal alternative anticoagulant depends on patient characteristics. Many ICU patients require lower doses of alternative anticoagulant than those recommended by the manufacturer.
总结重症监护病房（ICU）患者中肝素诱导的血小板减少症（HIT）的发生频率的新信息、检测抗PF4/肝素抗体的检测方法的解读进展以及HIT患者的治疗情况。
纳入所有关于ICU患者中实验室确诊的HIT发生频率的数据；对于HIT的实验室检测和患者治疗，本综述重点关注2005年和2006年可得的最新数据。
HIT是肝素治疗的一种潜在危及生命的不良反应，由通常识别血小板因子4和肝素复合物的免疫球蛋白G类血小板激活抗体引起。HIT更多由普通肝素而非低分子量肝素引起，且在外科术后患者中比在内科患者中更常见。在ICU环境中，HIT并不常见（0.3 - 0.5%），而其他原因导致的血小板减少非常常见（30 - 50%）。对于HIT抗体的实验室诊断，有抗原检测和功能（血小板激活）检测两种方法。两种检测都非常敏感（高阴性预测值），但特异性存在问题，尤其是抗原检测，其也会检测到非致病性的免疫球蛋白M和免疫球蛋白A类抗体。如果HIT的误诊促使使用替代抗凝剂替代肝素，免疫球蛋白M或免疫球蛋白A抗体的检测可能会导致诸如出血等不良事件。对于HIT的治疗，有三种替代抗凝剂已获批准：直接凝血酶抑制剂来匹卢定和阿加曲班，以及类肝素药物达那肝素（在美国未获批准）。最新数据表明，直接凝血酶抑制剂的批准给药方案过高，尤其是在ICU患者中。
尽管30 - 50%的患者会出现血小板减少，但HIT影响不到1%的ICU患者。最佳替代抗凝剂的选择取决于患者特征。许多ICU患者需要的替代抗凝剂剂量低于制造商推荐的剂量。
