Use of intravenous immunoglobulin G to treat spontaneous heparin-induced thrombocytopenia
Use of intravenous immunoglobulin G to treat spontaneous heparin-induced thrombocytopenia
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DOI：
10.1111/trf.15105
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发表时间：
2019-03-01
期刊：
影响因子：
2.9
通讯作者：
Padmanabhan, Anand
中科院分区：
文献类型：
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作者：
Irani, Mehraboon;Siegal, Eric;Padmanabhan, Anand
背景自发性肝素诱导的血小板减少症(HIT)是一种罕见但严重的血栓前综合征，在无肝素暴露的情况下，以血栓形成、血小板减少和强大的血小板激活HIT抗体为特征，通常对标准治疗的反应不佳。在这里，我们提出了第一个报告静脉注射免疫球蛋白G(IVIG)的自发性打击患者。研究设计和方法从电子病历中获取患者信息，包括人口统计学、临床和实验室结果。采用5-羟色胺释放试验、血小板第4因子(PF4)依赖的P-选择素表达试验和PF4/聚乙烯基磺酸盐酶联免疫吸附试验研究IVIG对HIT抗体介导的血小板活化的影响。这名患者还进行了血小板上Ig G受体基因多态Fc Gamma RIIA的基因分型，位于第131位氨基酸。结果1例30岁男性患者在未使用肝素的情况下，有血栓性中风和血小板减少症，并有较强的HIT血清。直接的凝血酶抑制剂治疗与快速反应无关。由于血栓形成的严重程度和程度以及持续性的血小板减少，他接受了大剂量静脉注射免疫球蛋白的治疗。这种治疗与快速和持续的血小板计数正常化和血栓并发症的逐渐改善有关。IVIG治疗后，在PF4依赖的P-选择素表达分析(Low PF4)中，HIT抗体诱导的血小板活化明显降低，与血小板升高有很好的相关性。与血栓形成的严重程度一致，患者被发现具有Fc-Gamma RIIA的131HR多态。结论IVIG可作为自发性HIT的一种有效辅助治疗方法。
BACKGROUND Spontaneous heparin-induced thrombocytopenia (HIT) is a rare but serious prothrombotic syndrome characterized by thrombosis, thrombocytopenia, and strong platelet-activating HIT antibodies in the absence of heparin exposure, and is frequently characterized by a suboptimal response to standard therapies. Here, we present the first report of intravenous immunoglobulin G (IVIG) use in a patient with spontaneous HIT. STUDY DESIGN AND METHODS Patient information, including demographic, clinical, and laboratory results, were obtained from the electronic medical record. Laboratory testing was performed in the serotonin release assay, platelet factor 4 (PF4)-dependent P-selectin expression assay, and PF4/polyvinylsulfonate enzyme-linked immunosorbent assay to study the impact of IVIG on HIT antibody-mediated platelet activation. The patient was also genotyped for a polymorphism in the IgG receptor on platelets, Fc gamma RIIa, at amino acid position 131. RESULTS A 30-year-old man had a thrombotic stroke and thrombocytopenia and strong HIT serologies in the absence of proximate heparin use. Direct thrombin inhibitor therapy was not associated with a prompt response. Due to severity and extent of thrombosis and persistent thrombocytopenia, he was treated with high-dose IVIG. This treatment was associated with rapid and sustained normalization of platelet counts and a gradual improvement in thrombotic complications. Platelet activation induced by HIT antibodies in the PF4-dependent P-selectin expression assay (low PF4) was significantly lower after IVIG treatment, correlating well with platelet rise. Consistent with the severity of thrombosis, the patient was found to possess the 131HR polymorphism in Fc gamma RIIa. CONCLUSION These results suggest that IVIG may be a useful adjunctive therapy in spontaneous HIT.