Historical data on high splenectomy success rates in ITP is outdated. For modern patients who have already failed multiple lines of therapy (e.g., corticosteroids and a TPORA), the likelihood of a curative response from splenectomy falls to around 40-45%, making it a less appealing option.

ITP caused by immune checkpoint inhibitors (ICIs) is rare (0.25% incidence) but generally has a good prognosis. Most patients respond to standard first-line ITP therapies, and approximately 70% of those re-challenged with the ICI can continue treatment without a recurrence of ITP.

The VEHIT2 trial protocol, combining yanalumab and eltrombopag shortly after steroid failure, represents a paradigm shift. It moves beyond sequential single-agent therapy to explore if early, potent intervention can fundamentally reduce the long-term severity and chronic nature of ITP.

Contrary to common assumptions, standard initial steroid therapy is ineffective for the vast majority of adult ITP patients. Approximately 80% progress to chronic disease, highlighting the urgent need for more effective first- and second-line therapies to alter the disease course.

The treatment paradigm for ITP is shifting towards early combination therapy. Recent clinical trials are investigating augmented first- and second-line regimens, such as combining dexamethasone with rituximab or romiplostim, to achieve more durable, treatment-free responses than monotherapy.

Patients with ITP who fail or are intolerant to one TPO receptor agonist (e.g., eltrombopag) should not be considered a class failure. Switching to another TPO agent is a viable strategy that can induce a response in nearly half of these cases, particularly for intolerance.

To minimize steroid toxicity, a thrombopoietin receptor agonist (TPORA) should be the immediate second-line therapy for ITP patients who fail their initial course of corticosteroids. There is no need to trial multiple other therapies before considering a TPORA.

The LUNA-three trial demonstrated that ITP patients on rilzabrutinib showed improved fatigue. Notably, even patients whose platelet counts did not respond to the drug still had better fatigue outcomes than the placebo group, suggesting a separate anti-inflammatory benefit on quality of life.

When imaging is ambiguous between radiation necrosis and tumor progression in the brain, a short course of high-dose dexamethasone can serve as a diagnostic tool. Imaging improvement after steroids strongly suggests radionecrosis, potentially avoiding an invasive biopsy.