Introduction: Immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by destruction of opsonized platelets. The first-line therapy for adult patients with chronic ITP includes steroid, IVIG and anti-D. Splenectomy is reserved for patients not responding to the first-line therapy. However, approximately 20–30% of patients are resistant or relapsed after splenectomy. In this subgroup of patients, more aggressive immunosuppressive therapy is indicated. Methods: This is a case series of patients with chronic resistant ITP receiving multiple immunosuppressive treatments in a tertiary medical referral center. The diagnosis of ITP was established by excluding other thrombocytopenic diseases. Adult patients with chronic resistant ITP presenting with life threatening thrombocytopenia were selected for a therapeutic trial of immunosuppressive therapy. The therapy included azathioprine 100–200 mg daily; cyclosporine 100–200 mg daily; and mycophenolate 1–2 gm daily (triple immunosuppressive therapy). All of these patients failed 1st line therapy; splenectomy; and other immunosuppressive treatments. Patients with uncontrolled hypertension; impaired liver functions; impaired renal functions; and those who have not completed family were excluded from triple immunosuppressive therapy. A response to the therapy was defined as persistent platelet count above 30 without other concurrent treatments. When patients responded to the triple immunosuppressive therapy, the doses of the medications were gradually tapered to minimize the long-term side effects. Results: Since July of 2000, 11 patients with chronic resistant ITP have received triple immunosuppressive therapy for a variable duration (table 1). Five out of these 11 patients (45.5%) achieved a response within 4 to 6 weeks after the initiation of the treatments. One of the five patients eventually had a break-through during the tapering of triple immunosuppressive therapy. This patient was stabilized by further doses of IVIG and prednisone. The treatments were well tolerated. The most common side effects were mildly elevated blood pressure; and mildly impaired liver function tests. None of the patients suffered from serious side effects that resulted in termination of the treatments. Conclusion: Combining low-dose azathioprine, cyclosporin and mycophenolate can induce long-term remission in patients with chronic ITP resistant to steroid, IVIG, splenectomy and other immunosuppressive agents. This combination regimen is safe and well-tolerated. In adult patients with chronic resistant ITP, the immune dysfunction may need multiple immune blockades. Summary of Treatments ID Rx Prior to Triple Rx Concurrent Rx with Triple Rx Mean (mg OD) Mean (mg OD) Mean (gm OD) Response Duration of Triple Rx Triple Rx:Triple Immunosuppressive Therapy; PRD:Prednisone; DAN:Danazol; AnD:Anti-D; SPN:Splenectomy; VCR:Vincristine; CTX:Cyclophosphamide; LUF:Luflunomide 1 PRD, IVIG, DAN, SPN PRD, IVIG 66.7 63.8 1 No 77 2 PRD, IVIG, DAN, SPN, VCR 75 25 0.8 No 20 3 PRD, AnD, SPN, CTX PRD (taper) 75 50 0.9 Yes 91 4 PRD, SPN, DAN, CTX, LUF 100 100 2 No 106 5 PRD, IVIG, SPN, DAN PRD, IVIG 144.2 236.1 1.9 No 217 6 PRD, IVIG, SPN, DAN, VCR IVIG 91.7 120.5 1.4 No 406 7 PRD, IVIG, DAN, SPN, VCR PRD (taper) 140.9 156.6 1.6 Yes 296 8 PRD, IVIG, SPN, DAN, VCR DAN (taper) 150 100 2 Yes 1351 9 PRD, DAN, SPN, AnD, CTX IVIG 100 150 2 No 130 10 PRD, IVIG, SPN, VCR, CTX PRD (taper) 85.6 121.1 1.4 Yes 1456 11 PRD, DAN, IVIG, SPN, AnD IVIG, PRD (taper) 125.6 225 1.9 Yes 875