Is IVIG use in ITP associated with increased risk of thrombosis?¶
Answer: IVIG has generally been associated with thrombosis (venous and arterial), but ITP itself carries a baseline thrombotic risk, and treating the ITP — including with IVIG — likely lowers overall risk. Bottom line: treat the ITP.
- ITP itself raises thrombotic risk vs. the general population:
The annualized incidence was 0.41-0.67 for venous thromboembolism (VTE) and 0.96-1.15 for arterial thrombosis (AT), whereas the control populations had 0.28-0.42 and 0.67-0.91, respectively, showing a slightly but statistically significantly higher risk of VTE and possibly AT in ITP patients
— Ghanima et al., Thrombopoietin receptor agonists: ten years later (Haematologica 2019)
The incidence rate of thrombosis was 2.71 (95% CI, 1.97-3.72) (0.66 [95% CI, 0.33-1.26] for arterial thromboembolism and 2.05 [95% CI, 1.42-2.95] for VTE) per 100 person-years.
— Thrombosis in patients with immune thrombocytopenia: incidence, risk, and clinical outcomes
- TPO-receptor agonists add further risk:
The incidence per 100 patient-years (censoring after first TEE) ranged from 3.1 to 4.2 with romiplostim and was 2.9 in the single eltrombopag study. Without censoring after first event, the incidence ranged from 4.1 to 7.5 with romiplostim and 3.4 with eltrombopag. In a pooled analysis of romiplostim studies, an incidence rate per 100 patient-years of 5.5 was reported for both patients exposed to romiplostim or to placebo/SoC.
The TEE events were neither associated with thrombocytosis nor with a higher dose of TPO-RA. At least 30-50% of cases occurred in patients with lower than normal platelet counts. In general, TEE events tended to happen in the first year of treatment, creating a trend towards lower incidence figures with more prolonged exposure time.
— both from Ghanima et al. (Haematologica 2019)
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In summary, although they have not been substantiated in properly designed trials, the annualized thrombosis rates in adults appear to be 2-3 times higher (annualized incidence rate of TEE of 4-7%) with TPO-RA treatment than in an ITP population not treated with TPO-RA, and even higher if compared to non-ITP control populations.
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IVIG: IVIG use has generally been associated with an increased risk of thrombosis, both venous and arterial. The risk is probably not additive — TPO agonists raise risk but likely don't compound the inherent risk of ITP itself (clinical judgment).
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Treating ITP likely lowers thrombotic risk: a large retrospective review (~56,000 ITP hospitalizations) found IVIG lowered the risk of thrombosis — Sanjeevi et al., Impact of IVIG on VTE/PE in ITP — an NIS 2020 Database Analysis (Blood 2024).
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Bottom line: treat the ITP.