An Individual Platelet Count Set-Point in ITP: A Concept Learned from Patients with Mild Thrombocytopenia and a Good Response to IVIg or Corticosteroids.

Abstract Background: Immune thrombocytopenic purpura (ITP) is a heterogeneous disease caused by both increased platelet destruction and decreased platelet production. Thrombocytopenia is typically severe, and in the absence of a sensitive and specific test, a platelet count response to intravenous immune globulin (IVIg) or corticosteroids is diagnostic. Patients with mild thrombocytopenia (platelets 50 – 150 × 109/L) may have ITP, non-immune thrombocytopenia or a low-normal platelet count. The diagnostic value of platelet autoantibodies for such patients is not known. Methods: We studied the platelet count responses of 6 patients with mild thrombocytopenia who were treated with either IVIg or corticosteroids. Baseline platelet count was defined as the mean of the 2 lowest, consecutive platelet counts that were within 15% of each other. The peak platelet count was the highest recorded platelet count measured within 1 month of treatment. For most patients, the dose of IVIg was 1g/kg ×1, and the dose of prednisone was 1mg/kg for 2 – 4 weeks. Complete response was defined as a peak platelet count that was at least 2x baseline; a partial response was defined as a peak platelet count 1.5 – 2x baseline; below that was not considered a response. Platelet glycoprotein IIb/IIIa and Ib/IX autoantibodies were determined by the antigen capture assay using platelet lysates prepared from samples collected prior to treatment. An OD >0.4 was considered positive. Results: Five patients with mild thrombocytopenia received 5 treatments with IVIg and 2 treatments with corticosteroid (2 patients received IVIg on 2 separate occasions). The indications for treatment were: planned invasive procedure (n=5), pregnancy/delivery (n=1), and treatment of multiple sclerosis (n=1). Patients were followed for a median of 1.6 years (range 0.6 – 3 years). Median baseline platelet count prior to treatment was 70 ×109/L (range 57 – 79 ×109/L). A platelet count response was observed following all 7 treatments; including 5 complete responses and 2 partial responses. Median peak platelet count was 180 ×109/L (range 115 – 297 ×109/L). Post-treatment platelet counts returned to within 15% of pre-treatment values following 6 of 7 treatments after a median of 3 months (range 1 week – 5 months). Of the 3 patient tested, none had anti-GP IIb/IIIa or anti-Ib/IX autoantibodies. Interpretation: A good response to IVIg (or steroid) treatment confirmed the immune nature of mild thrombocytopenia in this cohort and should be used as the gold standard to evaluate the test characteristics of platelet autoantibodies. We observed that some patients with mild ITP have an individual platelet count “set-point” which remained relatively stable over time. Although further testing is required, this concept implies that in some patients, there is a regulated balance between platelet destruction and underproduction.