Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.
University of Washington School of Medicine, Seattle, WA.
Chest. 2011 Aug;140(2):366-373. doi: 10.1378/chest.10-1599. Epub 2011 Mar 10.
Some patients with acute VTE who may previously have been exposed to heparin products have unrecognized antibodies implicated in heparin-induced thrombocytopenia (HIT). Antibody prevalence and patient consequences upon exposure to heparin, low-molecular-weight heparin, and fondaparinux are uncertain.
In this secondary analysis, we tested patients in the Matisse VTE studies at study entry for heparin-dependent antibodies and further tested patients with enzyme-linked immunosorbent assay (ELISA)-positive results for platelet-activating antibodies. We compared the risk of HIT (> 50% fall in platelet count, heparin-dependent antibodies, no contradicting features) between patients treated with heparin (either unfractionated or low molecular weight [enoxaparin]) vs those who received fondaparinux. Comparison groups for thrombocytopenia occurrence comprised patients with ELISA-positive, platelet-activating, antibody-positive results; ELISA-positive, but platelet-activating antibody-negative results; and randomly selected antibody-negative results.
A total of 127 of 3,994 patients (3.2%) had ELISA-positive results at baseline, but only 14 (0.4%; 95% CI, 0.2%-0.6%) had platelet-activating antibodies. Among these 14, four treated with unfractionated or low-molecular-weight heparin developed HIT compared with zero of 10 fondaparinux-treated patients (OR, 95; 95% CI, 8-1,123; P < .001). This frequency (four of four, 100%) significantly differed from that of both heparin-treated patients whose results were ELISA positive but platelet-activating antibody negative and from heparin-treated antibody-negative control subjects (zero of 15 and zero of 27, respectively; P < .001 for both).
Of patients with VTE, 0.4% had pathologic platelet-activating heparin-dependent antibodies rather than the 3.2% detected by the recommended cutoff of the commercial ELISA. Among study patients with acute VTE who had platelet-activating antibodies, treatment with fondaparinux reduced the risk of precipitating rapid-onset HIT.
一些可能曾接触过肝素制品的急性 VTE 患者存在与肝素诱导的血小板减少症（HIT）相关的未被识别的抗体。肝素、低分子肝素和磺达肝素钠暴露后抗体的流行率和患者的后果尚不确定。
在这项次要分析中，我们在 Matisse VTE 研究的入组时对患者进行了肝素依赖性抗体检测，并对酶联免疫吸附试验（ELISA）阳性结果的患者进一步进行了血小板激活抗体检测。我们比较了接受肝素（未分馏或低分子质量[依诺肝素]）治疗与接受磺达肝素钠治疗的患者之间发生 HIT（血小板计数下降>50%、肝素依赖性抗体、无矛盾特征）的风险。血小板减少症发生的对照组包括 ELISA 阳性、血小板激活抗体阳性的患者；ELISA 阳性但血小板激活抗体阴性的患者；以及随机选择的抗体阴性的患者。
共有 3994 名患者中的 127 名（3.2%）在基线时 ELISA 结果阳性，但只有 14 名（0.4%；95%CI，0.2%-0.6%）有血小板激活抗体。在这 14 名患者中，4 名接受未分馏或低分子质量肝素治疗的患者发生了 HIT，而 10 名接受磺达肝素钠治疗的患者无一例发生（OR，95%CI，8-1123；P<.001）。这一频率（4 例中的 4 例，100%）与接受肝素治疗的患者的 ELISA 阳性但血小板激活抗体阴性的患者以及接受肝素治疗的抗体阴性对照患者（分别为 15 例中的 0 例和 27 例中的 0 例；均 P<.001）显著不同。
在 VTE 患者中，有 0.4%的患者存在病理性的血小板激活的肝素依赖性抗体，而不是推荐的商业 ELISA 截断值检测到的 3.2%。在急性 VTE 患者中有血小板激活抗体的患者中，磺达肝素钠治疗降低了快速发作的 HIT 的风险。
