Maeda Takuma, Nakagawa Katsura, Murata Kuniko, Kanaumi Yoshiaki, Seguchi Shu, Kawamura Shiori, Kodama Mayumi, Kawai Takeshi, Kakutani Isami, Ohnishi Yoshihiko, Kokame Koichi, Okazaki Hitoshi, Miyata Shigeki
Shigeki Miyata MD, PhD, Division of Transfusion Medicine, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita-city, Osaka 565-8565, Japan, Tel.: +81 6 6833 5012 ext. 2294, Fax: +81 6 6872 8175, E-mail:
Thromb Haemost. 2017 Jan 5;117(1):127-138. doi: 10.1160/TH16-06-0482. Epub 2016 Oct 13.
To diagnose heparin-induced thrombocytopenia (HIT), detection of platelet-activating antibodies (HIT antibodies) is crucial. However, serum platelet activation profiles vary across patients and depend on test conditions. We evaluated the association between clinical outcomes and platelet-activating profiles assessed by a platelet microparticle assay (PMA), which detects activation of washed platelets induced by HIT antibodies, in 401 consecutive patients clinically suspected of having HIT. We made modifications to the assay, such as donor selection for washed platelets that increased sensitivity. Serum that activated platelets at a therapeutic (but not high) heparin concentration was defined as positive. Of these, serum that activated platelets within 30 minutes or in the absence of heparin was defined as strongly positive. The remaining samples were considered weakly positive. As a result, 97 % and 93 % of patients who tested strongly and weakly positive had clinical profiles consistent with HIT, respectively. The incidence of thromboembolic events (TEEs) after heparin exposure in patients who tested strongly positive, weakly positive, and negative was 61 %, 40 %, and 29 %, respectively. Among patients who did not experience a TEE on the day HIT was suspected, there was no significant difference in the cumulative incidence of subsequent TEEs between patients who tested strongly and weakly positive when argatroban was initiated on the same day (19.0 % vs 7.1 %, p=0.313), but there was a significant difference when argatroban therapy was delayed by one or more days (61.1 % vs 17.6 %, p=0.007). The modified PMA is effective in diagnosing HIT and identifying patients at high risk for HIT-associated TEEs.
要诊断肝素诱导的血小板减少症（HIT），检测血小板激活抗体（HIT抗体）至关重要。然而，不同患者的血清血小板激活情况各不相同，且取决于检测条件。我们评估了401例临床疑似HIT患者的临床结局与通过血小板微粒分析（PMA）评估的血小板激活情况之间的关联，该分析可检测由HIT抗体诱导的洗涤血小板的激活。我们对该分析进行了改进，例如选择洗涤血小板的供体以提高灵敏度。在治疗性（而非高剂量）肝素浓度下激活血小板的血清被定义为阳性。其中，在30分钟内或无肝素情况下激活血小板的血清被定义为强阳性。其余样本被视为弱阳性。结果，分别有97%和93%的强阳性和弱阳性检测患者具有与HIT一致的临床特征。肝素暴露后，强阳性、弱阳性和阴性检测患者的血栓栓塞事件（TEE）发生率分别为61%、40%和29%。在疑似HIT当天未发生TEE的患者中，当同一天开始使用阿加曲班时，强阳性和弱阳性检测患者后续TEE的累积发生率无显著差异（19.0%对7.1%，p = 0.313），但当阿加曲班治疗延迟一天或更多天时，存在显著差异（61.1%对17.6%，p = 0.007）。改良的PMA在诊断HIT和识别HIT相关TEE高危患者方面有效。
