Tacrolimus-Induced Refractory Immune Thrombocytopenia In Solid Organ Transplant Patients

Immune thrombocytopenia (IT) is an uncommon complication in patients who have undergone solid organ transplantation. A few case reports have suggested a role for tacrolimus in inducing IT in such patients.

A retrospective chart review was conducted in two major academic institutions with a high volume of transplant surgeries. We identified cases of refractory IT in solid organ transplant patients who were on tacrolimus as their graft-rejection immunosuppressant, in whom platelet counts recovered after discontinuation of the medication. Retrospective chart review was performed. All other etiologies for thrombocytopenia were excluded. Finally, descriptive statistical analysis was performed.

Ten patients were identified of which five each were renal and liver transplantations. Median age was 48 years. The median time from transplantation to onset of IT was 5.9 years (range 2.1-20 years) (table 1). In all but one case, the nadir platelet count was less than 5000/μL. Multiple therapeutic strategies including intravenous immunoglobulin, steroids, chemotherapy, rituximab, splenectomy, and romiplostim were attempted without any response. Bone marrow biopsy was consistent with IT in 9 of these patients; one patient did not undergo the procedure. Two patients were treated for H.pylori IgG positivity without any platelet recovery response. After tacrolimus was discontinued, median time to platelet recovery to greater than 50,000/μL was 8.5 days (range 5-81; n=8) (table 2). Median time to platelet count recovery to greater than 100,000/μL was 14 days (range 5-88 days; n=10). Median follow-up duration after platelet recovery of greater than 100,000/μL was 30 months (range 2-60; n=10). One patient, who recovered counts after nearly 3 months of discontinuation of tacrolimus, was on romiplostim for 2 years. If this patient is excluded from the analysis, the median time to platelet count recovery of greater than 100,000/μL was 13 days (range 5-35; n=9). Of note, 6 patients were on a steroid taper at the time of discontinuation of the medication. All except one patient was transitioned to immunosuppression using cyclosporine A; one patient was safely taken off immunosuppression.

Tacrolimus appears to occasionally cause a refractory IT in solid organ transplant recipients, which only appears to resolve with cessation of the drug. The onset of the IT usually occurs after at least two years of taking the medication. A trial of tacrolimus discontinuation for at least a 3 month period, substituted by another immunosuppressant such as cyclosporine A, should be attempted when seeing these patients, especially if there is consideration to perform a more invasive procedure such as a splenectomy or splenic artery embolization.

No relevant conflicts of interest to declare.