Kappers-Klunne M C, Boon D M, Hop W C, Michiels J J, Stibbe J, van der Zwaan C, Koudstaal P J, van Vliet H H
Department of Haematology, University Hospital Rotterdam, The Netherlands.
Br J Haematol. 1997 Mar;96(3):442-6. doi: 10.1046/j.1365-2141.1997.d01-2056.x.
Heparin-induced thrombocytopenia and/or thrombosis (HITT) are serious complications of heparin treatment. The incidence, as previously reported, varies widely and, in consequence, is not precisely known. Moreover, most reports only concern clinically defined heparin-induced thrombocytopenia. Therefore we carried out a prospective study of the incidence of serologically confirmed HITT. All patients admitted to the Departments of Cardiology and Neurology of our institution with an indication for treatment with therapeutic-dose intravenous unfractionated heparin were enrolled in the study. The patients were examined daily for the occurrence of thromboembolic complications. Regular platelet counts and tests for the presence of heparin-dependent antibodies were carried out using two different tests: a quantitative platelet factor 4/ heparin (PF4/hep) Elisa, and a functional test, the heparin-induced platelet activation assay (HIPAA). HITT was defined as a rapidly occurring (within 5 d) decrease of the platelet count from normal values of > 120 x 10(9)/l to < 60 x 10(9)/l or to < 100 x 10(9)/l if there was a rapid fall of >50% of starting value or >30% with concomitant acute thrombosis. The observed incidence of HITT was 1/358 patients (0.3%, 95% confidence limits 0.01-1.5%). However, Elisa PF4/hep specific IgG antibodies were demonstrated in nine (2.5%) and IgM antibodies in seven (2.0%) of 358 patients. 30/358 patients (8.4%) had platelet activating antibodies in the HIPAA. We conclude that the incidence of serologically confirmed HITT in this study is very low (0.3%) in patients with cardiac and neurologic diseases treated with intravenous unfractionated heparin. The frequency of heparin-dependent antibodies without concomitant occurrence of thrombocytopenia is much higher.
肝素诱导的血小板减少症和/或血栓形成（HITT）是肝素治疗的严重并发症。如先前报道，其发病率差异很大，因此确切数字尚不清楚。此外，大多数报告仅涉及临床定义的肝素诱导的血小板减少症。因此，我们对血清学确诊的HITT发病率进行了一项前瞻性研究。我们机构心内科和神经内科收治的所有有治疗指征需静脉注射普通肝素的患者均纳入本研究。每天检查患者是否发生血栓栓塞并发症。使用两种不同的检测方法定期进行血小板计数和检测是否存在肝素依赖性抗体：定量血小板因子4/肝素（PF4/hep）酶联免疫吸附测定（ELISA）和功能检测——肝素诱导的血小板活化试验（HIPAA）。HITT定义为血小板计数迅速下降（5天内），从正常水平>120×10⁹/L降至<60×10⁹/L，或若起始值迅速下降>50%或伴有急性血栓形成时下降>30%，则降至<100×10⁹/L。观察到的HITT发病率为1/358例患者（0.3%，95%置信区间0.01 - 1.5%）。然而，在358例患者中，有9例（2.5%）检测到ELISA PF4/hep特异性IgG抗体，7例（2.0%）检测到IgM抗体。30/358例患者（8.4%）在HIPAA中有血小板活化抗体。我们得出结论，在本研究中，接受静脉普通肝素治疗的心脏和神经疾病患者中，血清学确诊的HITT发病率非常低（0.3%）。不伴有血小板减少症的肝素依赖性抗体的频率要高得多。
