Rheumatology Unit, Sheba Medical Center, Ramat Gan, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Immunol Res. 2018 Dec;66(6):668-674. doi: 10.1007/s12026-018-9047-y.
To report the temporal association between a series of thromboembolic events and intravenous immunoglobulin infusion in patients with rheumatic diseases, and to review the literature on the subject. The clinical presentation, course, and outcome of thromboembolic events occurring post-immunoglobulin infusion in nine patients is described. A web-based literature review using the PubMed database from 1996 to 2017 was performed, searching for the keywords: thrombosis, thromboembolism, intravenous immunoglobulin, pulmonary embolism, deep vein thrombosis, cerebrovascular event, and acute myocardial infarction. Nine patients who had suffered a thromboembolic event within a week after receiving an intravenous immunoglobulin infusion (Omr-IgG-am™, OMRIX) were identified among our joint cohort. All patients except one were female ranging in age from 22 to 69 years. Five had progressive systemic sclerosis (one of them had progressive systemic sclerosis with antiphospholipid syndrome, and another had an overlap of progressive systemic sclerosis with systemic lupus erythematosus), the sixth had monoclonal IgM autoimmune neuropathy, the seventh had systemic lupus erythematosus with antiphospholipid syndrome, the eighth had granulomatosis with polyangiitis (GPA) and the ninth had overlap autoimmune syndrome. Six of the patients had an arterial thrombosis: an acute myocardial infarction in four, a brachial artery thrombosis in the fifth, and a cerebrovascular attack in the sixth. Three patients sustained a venous thrombosis and/or an acute pulmonary embolism (one of them had a DVT with the PE). Two events occurred during the IVIG infusion, three within an hour after the last infusion of the 5-day course, one occurred a few hours after the initiation of the IVIG therapy, another occurred 3 days after receiving the final infusion of the 10th course, and two events occurred a week after the treatment course has ended. Fifty-five percent of the patients had no thrombogenic risk factors other than their rheumatic condition, and most of them had received numerous, uneventful IVIG treatment courses before sustaining the thromboembolic event. No immediate deaths occurred among this cohort. Thromboembolic events after IVIG infusions, although infrequent, may occur in rheumatic patients, even in the absence of other recognizable risk factors for thromboembolism. The reported events had occurred despite complying with recommended guidelines for IVIG administration, which include a lengthy 8-h infusion and division of the total dose. No correlation was found between the number and frequency of the infusions to the thromboembolic events. Heightened awareness of possible thromboembolic events in rheumatic patients is encouraged for at least a week following IVIG administration.
报告了一系列风湿性疾病患者静脉注射免疫球蛋白输注后血栓栓塞事件的时间关联，并回顾了该主题的文献。描述了 9 例患者在免疫球蛋白输注后发生血栓栓塞事件的临床表现、病程和转归。使用 PubMed 数据库从 1996 年到 2017 年进行了基于网络的文献回顾，搜索了以下关键词：血栓形成、血栓栓塞、静脉注射免疫球蛋白、肺栓塞、深静脉血栓形成、脑血管事件和急性心肌梗死。在我们的联合队列中，发现了 9 例在接受静脉免疫球蛋白输注（Omr-IgG-am™，OMRIX）后一周内发生血栓栓塞事件的患者。除 1 例外，所有患者均为女性，年龄 22 至 69 岁。其中 5 例患有进行性系统性硬化症（1 例为进行性系统性硬化症伴抗磷脂综合征，另 1 例为进行性系统性硬化症伴系统性红斑狼疮重叠），第 6 例患有单克隆 IgM 自身免疫性神经病，第 7 例患有系统性红斑狼疮伴抗磷脂综合征，第 8 例患有肉芽肿性多血管炎（GPA），第 9 例患有重叠自身免疫综合征。其中 6 例为动脉血栓形成：4 例急性心肌梗死，5 例肱动脉血栓形成，6 例脑血管攻击。3 例患者发生静脉血栓形成和/或急性肺栓塞（其中 1 例为 DVT 伴 PE）。2 例事件发生在 IVIG 输注过程中，3 例发生在 5 天疗程最后一次输注后 1 小时内，1 例发生在 IVIG 治疗开始数小时后，另 1 例发生在第 10 次疗程最后一次输注后 3 天，2 例发生在治疗疗程结束后 1 周。除风湿性疾病外，55%的患者无其他血栓形成危险因素，且大多数患者在发生血栓栓塞事件前曾接受过多次无并发症的 IVIG 治疗。该队列中无即时死亡病例。尽管遵循了静脉注射免疫球蛋白给药的推荐指南，包括 8 小时的长时间输注和总剂量的分配，但风湿性疾病患者仍可能发生静脉注射免疫球蛋白输注后的血栓栓塞事件，即使没有其他可识别的血栓栓塞危险因素。报告的事件发生在遵守静脉注射免疫球蛋白给药建议指南的情况下，并未发现输注次数和频率与血栓栓塞事件之间存在相关性。建议在静脉注射免疫球蛋白给药后至少一周内提高对风湿性疾病患者发生血栓栓塞事件的认识。
