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Abstract Background 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. Methods 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. Results 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

Romiplostim was effective, safe, and well-tolerated over 6–12 months of continuous treatment in Phase 3 trials in patients with immune thrombocytopenia (ITP). This report describes up to 5 years of weekly treatment with romiplostim in 292 adult ITP patients in a long-term, single-arm, open-label study. Outcome measures included adverse events (including bleeding, thrombosis, malignancy, and reticulin / fibrosis), platelet response (platelet count >50 × 109 per litre), and the proportion of patients requiring rescue treatments. Treatment – related serious adverse events were infrequent and did not increase with longer treatment. No new classes of adverse events emerged. Thrombotic events occurred in 6.5 % of patients and were not associated with platelet count. Median platelet counts of 50–200 × 109 per litre were maintainedwith stable doses of romiplostim (mean 5–8 μg / kg; generally self-administered at home) throughout the study. A platelet response was achieved at least once by 95 % of patients, with a platelet response maintained by all patients on a median 92 % of study visits. There was a low rate of bleeding and infrequent need for rescue treatments. In conclusion, this study demonstrated that romiplostim was safe and welltolerated over 614 patient-years of exposure in ITP patients, and that efficacy was maintained with stable dosing for up to 5 years of continuous treatment.