Mechanism of Action: How Steroids Treat ITP
Corticosteroids treat ITP by suppressing the autoimmune destruction of platelets through multiple mechanisms: they reduce autoantibody production against platelets, decrease macrophage-mediated phagocytosis of antibody-coated platelets in the spleen and liver, and may directly stabilize blood vessel walls to reduce bleeding independent of platelet count increases. 1
Primary Immunosuppressive Mechanisms
Reduction of Autoantibody Production
- Corticosteroids suppress B-cell and plasma cell function, thereby decreasing the production of anti-platelet autoantibodies that target platelet surface glycoproteins (primarily GPIIb/IIIa and GPIb/IX) 2
- This immunosuppressive effect reduces the immune system's attack on the patient's own platelets 3
Inhibition of Macrophage-Mediated Platelet Destruction
- Corticosteroids impair the function of macrophages in the spleen and liver, which are responsible for recognizing and destroying antibody-coated platelets 4, 2
- By reducing macrophage activity, steroids create a "partial splenic dysfunction" that allows antibody-coated platelets to survive longer in circulation 5
- This mechanism explains why corticosteroids can work synergistically with IVIG, which also blocks macrophage Fc receptors through different pathways 5
Additional Therapeutic Effects
Direct Vascular Stabilization
- Corticosteroids may reduce bleeding through direct effects on blood vessel integrity, independent of their effect on platelet counts 1
- This vascular stabilization can provide clinical benefit even before platelet counts rise significantly 1
Clinical Response Patterns
Expected Timeline and Efficacy
- Initial response rates with corticosteroids range from 70-90% depending on the regimen used 6, 1
- Time to response typically ranges from several days to several weeks 1
- However, sustained long-term responses occur in only 20-40% of patients after corticosteroid discontinuation, as the underlying autoimmune process often recurs once immunosuppression is withdrawn 7
Common Pitfalls
- The temporary nature of corticosteroid-induced immunosuppression means that many patients relapse after tapering, requiring either prolonged therapy (which carries significant toxicity) or transition to second-line treatments 7
- The American Society of Hematology strongly recommends against prolonged courses exceeding 6-8 weeks due to substantial morbidity including osteoporosis, diabetes, hypertension, avascular necrosis, and opportunistic infections 7, 6, 1