Dong Yu, Xia Zhinan, Zhou Jie, Hu Yutao, Yue Ming, Wang Yuyong, Hu Mengjiao
Department of the Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
Department of Urology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, China.
Thromb J. 2023 Jun 23;21(1):69. doi: 10.1186/s12959-023-00509-z.
Immune thrombocytopenia (ITP), which is a well-known hemorrhagic disorder characterized by low platelet counts, has been shown to be associated with the risk of thrombosis. Thrombopoietic agents (TAs) are extensively used as second-line treatments for ITP, effectively reducing the risk of hemorrhage. However, thrombosis, a potential adverse effect of TAs, raises clinical challenges.
The MEDLINE(PubMed), Embase, and the Cochrane Library databases were systematically searched for relevant studies, including both single-arm trials and randomized controlled trials (RCTs), without language restrictions.
A total of 17 RCTs comprising 2,105 patients and 29 single-arm trials comprising 3,227 patients were included. In the single-arm meta-analysis, the pooled rate of overall thrombotic events in ITP patients receiving TAs was 2.2% (95% CI 1.0% - 3.7%). In RCTs, a higher incidence of thrombosis (33/1425 vs. 4/680) and higher risk ratios (RR) of overall, arterial, and venous thrombotic events (1.73, 95% CI [0.88, 3.39], P = 0.113; RR 1.98, 95% CI [0.80, 4.92], P = 0.141; RR 1.06, 95% CI [0.46, 2.41], P = 0.895, respectively) were observed in the TAs group than in the control group, although the differences were not significant. Subgroup analysis demonstrated that hetrombopag was the only TA with no increased thrombotic risk (rate 0.3% 95% CI [0.0 - 1.5%]; RR 0.76, 95% CI [0.03, 18.41], P = 0.864) compared to eltrombopag, avatrombopag, romiplostim, and rhTPO. Subgroup analyses also revealed that ITP patients with advanced age (3.7% vs. 1.3%, P = 0.132) or with a thrombotic history (3.0% vs. 1.4%, P = 0.257), and patients who received TAs therapy for a long duration (4.7% vs. 0.1%, P < 0.001) had an increased risk of thrombosis.
Our findings suggest ITP patients treated with TAs have a nonsignificantly higher risk of overall, arterial, and venous thrombotic events. Furthermore, hetrombopag is the recommended TA to avoid thrombophilia. Patients receiving long-term TAs, as well as elderly ITP patients or those with a history of thrombosis, face an increased thrombotic risk. In general, clinicians should consider potential thrombotic risks, address underlying risk factors, and ensure ongoing monitoring and follow-up when treating ITP patients with TAs.
免疫性血小板减少症（ITP）是一种以血小板计数低为特征的常见出血性疾病，已被证明与血栓形成风险相关。促血小板生成剂（TAs）被广泛用作ITP的二线治疗药物，可有效降低出血风险。然而，血栓形成作为TAs的一种潜在不良反应，带来了临床挑战。
系统检索MEDLINE（PubMed）、Embase和Cochrane图书馆数据库中的相关研究，包括单臂试验和随机对照试验（RCT），无语言限制。
共纳入17项RCT（2105例患者）和29项单臂试验（3227例患者）。在单臂荟萃分析中，接受TAs治疗的ITP患者总体血栓事件合并发生率为2.2%（95%CI 1.0% - 3.7%）。在RCT中，TAs组的血栓形成发生率较高（33/1425 vs. 4/680），总体、动脉和静脉血栓事件的风险比（RR）也较高（分别为1.73，95%CI [0.88, 3.39]，P = 0.113；RR 1.98，95%CI [0.80, 4.92]，P = 0.141；RR 1.06，95%CI [0.46, 2.41]，P = 0.895），尽管差异不显著。亚组分析表明，与艾曲泊帕、阿伐曲泊帕、罗米司亭和重组人血小板生成素相比，海曲泊帕是唯一血栓形成风险未增加的TAs（发生率0.3%，95%CI [0.0 - 1.5%]；RR 0.76，95%CI [0.03, 18.41]，P = 0.864）。亚组分析还显示，年龄较大（3.7% vs. 1.3%，P = 0.132）或有血栓形成病史（3.0% vs. 1.4%，P = 0.257）的ITP患者，以及接受TAs治疗时间较长的患者（4.7% vs. 0.1%，P < 0.001），血栓形成风险增加。
我们的研究结果表明，接受TAs治疗的ITP患者总体、动脉和静脉血栓事件风险略高。此外，海曲泊帕是推荐用于避免血栓形成倾向的TAs。接受长期TAs治疗的患者，以及老年ITP患者或有血栓形成病史的患者，面临的血栓形成风险增加。总体而言，临床医生在使用TAs治疗ITP患者时，应考虑潜在的血栓形成风险，处理潜在的风险因素，并确保持续监测和随访。
