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接受血液透析的慢性肾衰竭患者中肝素诱导抗体的患病率。

Prevalence of heparin-induced antibodies in patients with chronic renal failure undergoing hemodialysis.

作者信息

Palomo Iván, Pereira Jaime, Alarcón Marcelo, Díaz Gonzalo, Hidalgo Patricia, Pizarro Isabel, Jara Eric, Rojas Patricio, Quiroga Guillermo, Moore-Carrasco Rodrigo

机构信息

Department of Clinical Biochemistry and Immunohematology, Faculty of Health Science, Universidad de Talca, Talca, Chile.

出版信息

J Clin Lab Anal. 2005;19(5):189-95. doi: 10.1002/jcla.20076.

Abstract

Heparin-induced thrombocytopenia (HIT) type II is a serious complication of heparin therapy. It presents initially as thrombocytopenia, and is associated with thrombosis in 20-50% of the cases. HIT is related to the presence of heparin-induced antibodies (HIA), which show specificity for the PF4-heparin (PF4-H) complex. The FcgammaRIIa receptor has been suggested to participate in the pathogenic mechanism of HIA. Since patients undergoing chronic hemodialysis (HD) are exposed repeatedly to heparin, we studied the prevalence of HIA and their eventual relationship with thrombocytopenia and/or thrombosis, and the possible participation of the FcgammaRIIa polymorphism. We studied 207 patients with chronic renal failure (CRF) undergoing HD. As a control we included 130 blood donors and 28 patients with CRF without HD. The HIA patients were studied with the use of a PF4-H ELISA. Additionally, in some positive cases for the previous test, a 14C- serotonin release assay (14C-SRA) was performed. The polymorphism FcgammaRIIa H/R131 was studied by polymerase chain reaction (PCR) with allele-specific primers. Thirty-seven patients (17.9%) undergoing HD presented with HIA. The majority of these antibodies were IgG, IgM, and IgA. The HIA investigated presented specificity against the PF4-H complex, but not against PF4 alone (P<0.001). Twelve out of 22 (54.5%) PF4-H antibodies were positive when tested with the 14C-SRA. The distribution of the FcgammaRIIa polymorphism in patients and healthy controls was 42.6% and 41.6% for H/H131, 41% and 48.9% for the H/R131 isoform, and 16.4% and 9.5% for the R/R131 isoform, respectively. No statistically significant difference in the FcgammaRIIa isoform distribution was found. Twenty-nine out of 156 patients (18.5%) presented thrombocytopenia, and 21/207 (12.4%) had thrombosis of the native vein arterio-venous fistula (AVF). We did not find any statistically significant between HIA and thrombocytopenia or thrombosis. An important proportion of patients with CRF undergoing HD developed HIA, but these cases were not associated with thrombocytopenia or thrombosis of AVF. The frequency of the FcgammaRIIa polymorphism did not statistically differ between HIT type II and normal controls.

摘要

II型肝素诱导的血小板减少症(HIT)是肝素治疗的一种严重并发症。它最初表现为血小板减少症,20%-50%的病例与血栓形成有关。HIT与肝素诱导的抗体(HIA)的存在有关,这些抗体对PF4-肝素(PF4-H)复合物具有特异性。已表明FcγRIIa受体参与HIA的致病机制。由于接受慢性血液透析(HD)的患者反复接触肝素,我们研究了HIA的患病率及其与血小板减少症和/或血栓形成的最终关系,以及FcγRIIa多态性的可能参与情况。我们研究了207例接受HD的慢性肾衰竭(CRF)患者。作为对照,我们纳入了130名献血者和28例未接受HD的CRF患者。使用PF4-H ELISA对HIA患者进行研究。此外,在先前检测呈阳性的一些病例中,进行了14C-5-羟色胺释放试验(14C-SRA)。通过使用等位基因特异性引物的聚合酶链反应(PCR)研究FcγRIIa H/R131多态性。37例(17.9%)接受HD的患者出现HIA。这些抗体大多数为IgG、IgM和IgA。所研究的HIA对PF4-H复合物具有特异性,但对单独的PF4无特异性(P<0.001)。22例PF4-H抗体中有12例(54.5%)在进行14C-SRA检测时呈阳性。患者和健康对照中FcγRIIa多态性的分布,H/H131分别为42.6%和41.6%,H/R131异构体分别为41%和48.9%,R/R131异构体分别为16.4%和9.5%。未发现FcγRIIa异构体分布有统计学显著差异。156例患者中有29例(18.5%)出现血小板减少症,207例中有21例(12.4%)出现自体动静脉内瘘(AVF)血栓形成。我们未发现HIA与血小板减少症或血栓形成之间有任何统计学显著差异。接受HD的CRF患者中有相当比例发生HIA,但这些病例与AVF的血小板减少症或血栓形成无关。II型HIT与正常对照之间FcγRIIa多态性的频率在统计学上无差异。

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