Hematologic abnormalities in children and young adults receiving tacrolimus‐based immunosuppression following cardiothoracic transplantation

Abstract

To define the incidence, course, and etiology of hematologic abnormalities in children on tacrolimus-based immunosuppression, we reviewed records of 106 transplant patients (70 heart, 16 heart and lung, 20 double lung), 0-21 yr of age, who were transplanted at the Children's Hospital of Pittsburgh from 1989 to 1997. Fifty-four of the 106 patients (51%) developed 65 abnormal hematologic episodes (32 anemia, nine neutropenia, nine thrombocytopenia, 15 simultaneous anemia and neutropenia with or without thrombocytopenia). Common etiologies included: infections, post-transplant lymphoproliferative disease, and medications. Eleven episodes (seven anemia, one neutropenia, and three simultaneous anemia and neutropenia) had unclear etiologies and process of elimination suggested an association with tacrolimus. Interventions included filgrastim (effective in 15 of 15 patients, with resolution of neutropenia in a median of 5 days) and epoetin alfa (effective in five of 16 patients, including four of four patients with anemia possibly related to tacrolimus). Five patients (two with neutropenia and three with simultaneous neutropenia and anemia) were switched to cyclosporin A (CsA); rapid resolution occurred in four of the five patients, suggesting a possible association of the hematologic abnormalities with tacrolimus. In summary, hematologic abnormalities are common in children on tacrolimus-based immunosuppression. Most of these hematologic abnormalities are caused by common etiologies; however, a sub-population exists where tacrolimus may be the etiologic agent. Anemia and neutropenia respond to treatment with epoetin alfa and filgrastim. After thorough investigation, a trial switch to CsA may be warranted.

Effect of oral tacrolimus (FK 506) on steroid‐refractory moderate/severe ulcerative colitis

“…Thrombopenia due to tacrolimus is a rare but well documented side-effect. 31 In our case the pathogenesis of thrombopenia could not be clarified. Considering the hyperplastic megakaryopoesis, we hypothesize that an unknown mechanism led to increased consumption of thrombocytes.…”

“…The high rate of side-effects might in part be explained by the concomitant immunosuppression with azathioprine and corticosteroids. For example bicytopenia (anemia and leukopenia) can be induced by azathioprine and by tacrolimus, 31 and both drugs were initiated within a short period of time in our patient with this complication. The anemia was presumably due to intestinal blood loss in activated colitis.…”

Tacrolimus-Induced Neutropenia in Renal Transplant Recipients

“…However, the immunosuppressive activity of tacrolimus seems to be stronger compared with cyclosporine, leading to improved kidney graft survival and prevention of rejection at 1 year (3). Although the association between tacrolimus and myelosuppression, in particular leucopenia, has been suspected for a long time, the exact mechanisms have not been elucidated yet (4). However, multiple hypotheses have been proposed and examined during the last few years.…”

Incidence, Risk Factors and Clinical Consequences of Neutropenia Following Kidney Transplantation: A Retrospective Study

“…, tacrolimus (5), sirolimus (6), cotrimoxazole (7), omeprazole (8), rituximab (9) and angiotensin converting enzyme inhibitors (10). Drug imputability often remains difficult to establish directly, and regression of neutropenia after drug discontinuation can be used as indirect evidence.…”