Patients with refractory immune thrombocytopenia have additional burdens that need to be considered. This patient burden includes an impaired health-related quality of life, additional side effect concerns related to second- and third-line treatments, anxiety about the long-term course of the disease, fears related to family planning, and it is hypothesized that fatigue is more pronounced in patients with refractory disease. The burden of disease therefore should be carefully assessed and considered in these patients. There is a need to standardize assessment using either disease-specific or generic instruments that can be easily implemented in routine clinical practice.

The management of multirefractory immune thrombocytopenia remains a challenge. Advances in knowledge about the complications of splenectomy, particularly severe late infections and deep vein thrombosis, and the inability to reliably predict its efficacy, may explain why most physicians hesitate to offer it to refractory patients. However, recent data suggest that splenectomy remains an effective treatment, even in patients who have failed to respond to rituximab and available TPO-RAs. In CVID and CLL, splenectomy is possible even if the risk of infection is a concern. In the case of SLE and anti-phospholipid syndrome, the potential increased risk of thrombosis must be discussed on a case-by-case basis. In the elderly, splenectomy is not strictly contraindicated, but depends on comorbidities. Note: the figure was created in BioRender.com.

Evidence-based markers of refractoriness to ‘second-line’ marketed ITP treatments. ITP, immune thrombocytopenia; TPO, thrombopoietin. TPO-RA, thrombopoietin receptor agonist.

Immunomodulation pathways with TPO-RAs in ITP.