Tacrolimus Induced Refractory Immune Thrombocytopenia.

Abstract 1426

Tacrolimus, a calcineurin inhibitor, has become a standard immunosuppressive therapy in solid organ transplantation. It is known to cause a thrombotic microangiopathy, and has been implicated to cause immune thrombocytopenia (IT) in children. Our institution has recognized a delayed onset IT in adult liver transplant patients that appears associated with chronic therapy with Tacrolimus. Between 2007–2009, 4 patients (3 females and one male) between the ages of 28–71 years who were status post orthotopic liver transplant and were on Tacrolimus developed a refractory IT. The onset of the IT was 3–12 years after starting on the Tacrolimus. One of the patients had a history of an autoimmune hemolytic anemia, which occurred one month after transplantation and resolved with IVIG therapy. Two of the patients were diagnosed with Hepatitis C reactivation after transplantation, but were not on therapy before the onset of IT. At presentation, the platelet counts were between 2,000 – 4,000/μL. IT was diagnosed after ruling out other causes of thrombocytopenia. Bone marrow biopsies were done in all four patients, and were consistent with increased platelet destruction. The thrombocytopenia was refractory to conventional IT treatment with steroids and IVIG. Other therapies included Rituximab (3 patients), Vincristine (2 patients), and splenectomy (1 patient), but none of these significantly improved the platelet count. However, switching the Tacrolimus to Cyclosporine in all the patients led to a rise in platelet count within 6 days to two months. These patients have been observed for over 1 year without a recurrence of their IT. One patient requires chronic therapy with Romiplostim, while being treated with Ribavirin and Interferon for his Hepatitis C reactivation. His platelet count has not fallen below 100k/μL. CONCLUSION: Tacrolimus may cause a refractory IT that occurs several years after its initiation as an immunosuppressant. When this situation occurs, discontinuing the Tacrolimus and replacing the immunosuppression with Cyclosporine is the most effective therapeutic approach.