Treatment of Refractory Immune Thrombocytopenia

Definition and Diagnosis

Refractory Immune Thrombocytopenia is defined as failure to respond to corticosteroids after 6-8 weeks of treatment, or requiring continuous corticosteroid therapy to maintain safe platelet counts, according to the American Society of Hematology 1, 2
Patients requiring on-demand corticosteroid administration after completing first-line induction should be considered non-responders and switched promptly to alternative therapy, as recommended by the American Society of Hematology 2

The American Society of Hematology suggests thrombopoietin receptor agonists (TPO-RAs) over both rituximab and splenectomy for patients who are corticosteroid-dependent or unresponsive 1
TPO-RAs, such as eltrombopag or romiplostim, achieve platelet responses in 70-80% of patients and allow 53-62% of patients to reduce or discontinue concomitant corticosteroids, according to the American Society of Hematology 1, 4
Rituximab achieves short-term responses in 50-60% of patients, with long-term responses in 20-30%, but has critical safety concerns, including risk of hepatitis B reactivation, multifocal leukoencephalopathy, hypogammaglobulinemia, and reduced vaccine efficacy, as reported by the American Journal of Hematology 2, 5
Splenectomy has an initial response rate of 80-85% with sustained long-term responses in 60-66% of patients, but requires mandatory pre-operative vaccines and has lifelong risks, including increased risk of septicemia, pulmonary embolism, and venous thromboembolism, according to the American Society of Hematology 2, 4

The 2019 American Society of Hematology guidelines provide conditional recommendations suggesting TPO-RAs over rituximab, rituximab over splenectomy, and TPO-RAs or splenectomy as equivalent options, based on patient values and preferences 1
Decision factors favoring each option include patient requirements for ongoing medication management, wishes to avoid surgery, needs for sustained platelet response, or failure of previous therapies, as recommended by the American Society of Hematology 1, 4

Excessive corticosteroid duration should be avoided, as it can lead to cumulative toxicity, including weight gain, diabetes, osteoporosis, and infections, according to the American Society of Hematology and the American Journal of Hematology 1, 2, 5
Premature splenectomy should be avoided, unless severe bleeding is unresponsive to medical therapies, as spontaneous remissions can occur, as reported by the American Journal of Hematology 1, 5
Underuse of TPO-RAs should be avoided, as they have superior efficacy and safety profiles, according to the American Journal of Hematology 5