tacrolimus and Red-Cell-Aplasia--Pure

Severe anemia requiring multiple blood transfusions in the posttransplant period can trigger rejection. The evaluation of anemia among transplant recipients is a challenging task. Awareness should be continued for tacrolimus to manage pure red cell aplasia, but further evidence is needed to prove whether tacrolimus is a real cause of posttransplant anemia. Our case patient, a 66-year-old male patient with end-stage renal disease due to diabetic nephropathy, underwent a preemptive living donor renal transplant in September 2018. He had received a coronary artery bypass graft with transcatheter aortic valve implantation 3 years before renal transplant. Initially, he was maintained on prednisolone, mycophenolate mofetil, and tacrolimus after basiliximab induction. One month later, he presented with low cardiac output symptoms. His complete blood count showed normocytic normochromic anemia with reticulocytopenia (his hemoglobin level dropped from 112 to 69 g/L), which necessitated regular blood transfusions. His iron profile, serum folate, and vitamin B12 were within normal limits, and he had negative hemolytic and autoimmune screening tests. A bone marrow biopsy revealed acquired pure red cell aplasia, which was most likely drug induced as viral profiles were negative for parvovirus B19, cytomegalovirus, and Epstein-Barr virus. The patient was managed by discontinuing mycophenolate mofetil, and the steroid dose was increased up to 20 mg/day but without improvement. With tacrolimus then considered, 3 weeks after presentation, we replaced tacrolimus with cyclosporine. Complete blood count follow-up showed improvement without any need for further blood transfusions. After 1 month of cyclosporine maintenance, mycophenolate mofetil was resumed with a steady increase of hemoglobin up to 150 g/L and serum creatinine of 122 μmol/L. Pure red cell aplasia is a rare disorder among renal transplant recipients, which could be induced by maintenance tacrolimus therapy.

Topics: Aged; Anemia; Cyclosporine; Epstein-Barr Virus Infections; Graft Rejection; Herpesvirus 4, Human; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Mycophenolic Acid; Red-Cell Aplasia, Pure; Tacrolimus; Transplant Recipients; Treatment Outcome

We report an unexplained anemia that persisted for 4 months in a renal transplant patient who was receiving immunosuppression therapy that included prednisolone, tacrolimus and azathioprine. A bone marrow biopsy demonstrated pure erythroid hypoplasia and occasional giant pronormoblasts with intranuclear inclusions, characteristic of a parvovirus B19 infection. Both the serum and bone marrow cells were positive by parvovirus B19 DNA PCR. The anemia resolved 6 weeks after the administration of intravenous immunoglobulin (IVIG). Four months later, anemia redeveloped and IVIG was infused again. Hemoglobin levels were, however, still subnormal after 1 month of treatment and tacrolimus was then switched to cyclosporin A, resulting in a clear improvement. A parvovirus B19 infection should be included in the differential diagnosis of renal transplant recipients who present with anemia associated with a low reticulocyte count. Tacrolimus may possibly impair the clearance of a parvovirus B19 infection.

Topics: Adolescent; Adult; Child; Cyclosporine; Female; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Parvoviridae Infections; Parvovirus B19, Human; Red-Cell Aplasia, Pure; Tacrolimus

Parvovirus B19 infection is known to cause chronic anemia in immunocompromised hosts, including organ transplant recipients. Most reported cases of parvovirus B19-associated aplastic anemia in renal transplant recipients responded to intravenous immunoglobulin (IVIG) infusion. Tacrolimus is of special interest; it was proposed to be associated with pure red cell aplasia (PRCA) on its own because resolution of anemia on withdrawal of tacrolimus was previously observed. Interaction between parvovirus B19 infection and tacrolimus has not been reported. We report a case of parvovirus B19-associated PRCA in a renal transplant recipient treated with tacrolimus who failed to clear the virus despite repeated courses of IVIG. She showed complete recovery promptly after tacrolimus was switched to cyclosporine A. A well-documented concomitant decrease in serum parvovirus DNA polymerase chain reaction titer was also observed. This shows another mechanism by which tacrolimus can aggravate PRCA because of impaired clearance of parvovirus B19 infection in transplant recipients. For those patients receiving tacrolimus who have parvovirus B19 infection with refractory anemia and who fail to recover with IVIG, replacement of tacrolimus with cyclosporine A can be considered.

Topics: Adult; Female; Humans; Immunocompromised Host; Immunoglobulins, Intravenous; Immunosuppressive Agents; Kidney Transplantation; Parvoviridae Infections; Parvovirus B19, Human; Red-Cell Aplasia, Pure; Tacrolimus

Human parvovirus B19 disease is an infrequent but recognized rare cause of anemia in immunocompromised patients. A few cases of parvovirus B19 infections have been reported in transplant recipients, of those only four patients underwent renal transplantation. The primary immunosuppressive therapy in these patients included prednisone with either cyclosporine or tacrolimus. In one patient the disease was self-limiting, while in three others the hematocrit improved following 10-15 d of treatment with commercial intravenous immunoglobulin (IVIG). Herein, we report the fifth case of pure red cell aplasia due to parvovirus B19 infection in a renal transplant recipient who responded to a 5-d course of IVIG. To our knowledge, this is the first case of parvovirus B19 infection in a patient with solid-organ transplantation whose immunosuppressive regimen included both mycophenolate mofetil and tacrolimus and in whom an excellent clinical response was achieved with a short course of IVIG infusion.

Topics: Adult; Anti-Inflammatory Agents; Cadaver; Cyclosporine; DNA, Viral; Hematocrit; Humans; Immunoblotting; Immunocompromised Host; Immunoglobulins, Intravenous; Immunosuppressive Agents; Infusions, Intravenous; Kidney Transplantation; Male; Mycophenolic Acid; Parvoviridae Infections; Parvovirus B19, Human; Polymerase Chain Reaction; Prednisone; Red-Cell Aplasia, Pure; Remission Induction; Tacrolimus

BACKGROUND Pure red cell aplasia (PRCA) is an uncommon cause of anemia in end-stage kidney disease (ESKD). It is attributed to recombinant human erythropoietin (rHuEPO) administration. Although immunosuppression is the mainstay therapy, its effectiveness varies from 30% to 70%. PRCA in ESKD has been reported to improve following kidney transplantation. CASE REPORT A 46-year-old woman with ESKD secondary to lupus nephritis was treated for uremia at our center. She developed severe anemia. Bone marrow aspiration and biopsy revealed a reduction of erythroid precursors, consistent with PRCA. Because she had no sibling's blood group matched with her, ABO-incompatible kidney transplantation was an option for treatment. She underwent a desensitization protocol consisting of rituximab 375 mg/m2, tacrolimus, mycophenolate mofetil, and prednisolone 4 weeks before surgery, in addition to 3 sessions of double-filtration plasmapheresis (DFPP) every other day followed by intravenous immunoglobulin (IVIG) and 1 session of specific immunoadsorption (Glycosorb® B column) at pre-transplant day -1. She also received low-dose rabbit anti-thymocyte globulin (rATG) (Thymoglobulin®) (total 2.0 mg/kg). Maintenance therapy included tacrolimus, mycophenolate mofetil, and prednisolone. Allograft function normalized a few days after transplantation and her Hb gradually increased. CONCLUSIONS We report a rare case of PRCA in a patient with ESKD undergoing ABO-incompatible kidney transplantation. The outcome was satisfactory, with complete correction of anemia and kidney function.

Topics: ABO Blood-Group System; Blood Group Incompatibility; Erythropoietin; Female; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Middle Aged; Mycophenolic Acid; Prednisolone; Red-Cell Aplasia, Pure; Renal Dialysis; Tacrolimus; Thailand

Pure red cell aplasia is a relatively rare disease characterized by suppression or absence of erythroid precursors while other cell lineages are normal in the bone marrow. The disease could be secondary to other diseases or an adverse side effect of certain drugs. Tacrolimus is widely used as an immunosuppressive agent in solid-organ transplant without significant myelosuppressive effects. However, several tacrolimus-related pure red cell aplasia cases have been reported to date. Here, we report a case of a renal transplant recipient who developed tacrolimus-associated pure red cell aplasia in the posttransplant period and recovered dramatically after switching from tacrolimus to cyclosporine. Early diagnosis of pure red cell aplasia, which generally requires multiple blood transfusions, is very important because an increased number of blood transfusions can cause immunogenic effects and increased risk for allograft survival. Tacrolimus is a prominent drug for immunosuppression and is suspected to cause pure red cell aplasia during the posttransplant period; therefore, clinicians should consider a switch from tacrolimus to another immunosuppressive agent.

Topics: Cyclosporine; Humans; Immunosuppressive Agents; Kidney Transplantation; Red-Cell Aplasia, Pure; Tacrolimus

Pure red cell aplasia is a relatively rare disease characterized by selective suppression of erythroid precursors in the bone marrow. This disease can also develop secondary to several other diseases and as a side effect of certain drugs. Tacrolimus, a potent immunosuppressant, is widely used in organ transplant. Several cases of pure red cell aplasia due to tacrolimus administration in organ transplant recipients have been reported.Here, we report a case of reversible pure red cell aplasia that developed during tacrolimus therapy following living-donor liver transplant. The patient, a 1-year-old girl diagnosed with progressive familial intrahepatic cholestasis type II, underwent living-donor liver transplant when she was 10 months old. She was started on 3 immunosuppressants posttransplant: tacrolimus (0.1 mg/kg/day twice daily), mycophenolate mofetil, and prednisolone (0.2 mg/kg/day). One year after transplant, she developed severe progressive anemia. Her hemoglobin concentration was extremely low (5.4 g/dL). A bone marrow biopsy revealed severe hypoplasia of the erythroblasts with no abnormality of other myelocytes. These findings were suggestive of pure red cell aplasia; we suspected that tacrolimus had caused this based on similar previous cases of tacrolimus-associated pure red cell aplasia. Accordingly, tacrolimus was switched to cyclosporine after this diagnosis. One week after this switch, the patient's red blood cell counts, reticulocytes, and hemoglobin concentration increased. Although tacrolimus is considered to have no significant potential for myelosuppression, cases of tacrolimus-related pure red cell aplasia have occurred. In patients who develop pure red cell aplasia during tacrolimus treatment following living-donor liver transplant, clinicians should consider switching from tacrolimus to another immunosuppressant.

Topics: Cholestasis, Intrahepatic; Cyclosporine; Drug Substitution; Female; Humans; Immunosuppressive Agents; Infant; Liver Transplantation; Living Donors; Red-Cell Aplasia, Pure; Tacrolimus; Treatment Outcome

Acquired pure red cell aplasia (PRCA) and autoimmune hemolytic anemia (AIHA) are rare complications of immunosuppression in pediatric solid organ transplant patients. We report a 14-month-old female child who developed Coombs positive hemolytic anemia and reticulocytopenia while on tacrolimus after cardiac transplantation. She was successfully treated with rituximab after failing treatment with corticosteroids and intravenous immunoglobulins. Clinicians should consider PRCA differential diagnosis in a patient presenting with reticulocytopenia and hemolysis. In addition, the coexistence of PRCA with AIHA, and the response to therapy with rituximab, supports a common immune-mediated pathogenesis for both disorders.

Topics: Anemia, Hemolytic, Autoimmune; Female; Heart Transplantation; Humans; Immunosuppressive Agents; Infant; Red-Cell Aplasia, Pure; Rituximab; Tacrolimus

Parvovirus B19 infection should be contemplated as one of the differential diagnoses of persistent anemia in transplanted patients. There must be high index of suspicion of Parvovirus B19, when post-transplant patients present with refractory and severe anemia with reticulocytopenia and all the other common causes of anemia such as blood loss, adverse effects of immunosuppressant agents and graft dysfunction has been ruled out. In suspected patients, diagnosis is confirmed by serological tests (IgM and IgG), PCR from blood and/or bone marrow and by bone marrow biopsy finding of pure red cell aplasia. Intravenous immunoglobulin (IVIG) is the treatment of choice and highly rewarding. Here we are reporting two cases of post-transplant Parvovirusinfection, one in an adult lady and second in an adult man who underwent live renal transplantation recently.

Topics: Adult; Anemia; Female; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Kidney Transplantation; Male; Parvoviridae Infections; Parvovirus B19, Human; Polymerase Chain Reaction; Postoperative Complications; Red-Cell Aplasia, Pure; Tacrolimus; Transplant Recipients; Treatment Outcome

Anti-erythropoietin (anti-EPO) antibody-related pure red cell aplasia (PRCA) is a rare but serious complication that can occur during the administration of erythropoiesis-stimulating agents. Treatment with the calcineurin inhibitor cyclosporine has shown benefits in patients with anti-EPO PRCA. The efficacy of tacrolimus, another calcineurin inhibitor, in patients with anti-EPO PRCA has not been determined. The present report is the first our knowledge to describe the successful treatment of a patient with anti-EPO PRCA using tacrolimus. A 73-year-old man was markedly anemic 8 months after starting epoetin beta treatment. He was diagnosed with anti-EPO PRCA. Cyclosporine was started, but he experienced side effects. He was switched from cyclosporine to tacrolimus. No side effects were observed, and his anti-EPO PRCA was improved 6 months later, despite the persistence of anti-EPO antibodies. Tacrolimus was continued until the disappearance of the antibodies. Following the cessation of tacrolimus, PRCA did not relapse. Antibody remained detectable at the time of clinical remission, indicating that immunosuppressive therapy should be continued while monitoring the antibody titer. When the antibody titer decreases to the negative range, cessation of the immunosuppressive therapy does not result in disease relapse.

Topics: Aged; Antibodies; Erythropoietin; Hematinics; Humans; Immunosuppressive Agents; Male; Red-Cell Aplasia, Pure; Tacrolimus

Acquired pure red-cell aplasia is a rare disorder that can be either idiopathic or associated with certain autoimmune diseases, pregnancy, lymphoproliferative disorders, nutritional deficiencies, or medicines. We present a deceased-donor renal transplant patient who developed pure red-cell aplasia associated with mycophenolate mofetil or tacrolimus and was treated with cyclosporine. A 20-year-old woman was transplanted from a deceased donor 1 month earlier and presented to us with symptoms of fatigue, prostration, and palpitation. The results of a laboratory examination revealed anemia. A diagnostic work-up resulted in a diagnosis of pure red-cell aplasia. Mycophenolate mofetil was discontinued. Tacrolimus also was replaced with cyclosporine 2 months after mycophenolate mofetil was halted because of a lack of improvement in anemia. Three months later, her anemia improved with cyclosporine. Starting cyclosporine instead of tacrolimus or mycophenolate mofetil showed good improvement in our patient within 6 months of therapy.

Topics: Cyclosporine; Female; Humans; Immunosuppressive Agents; Kidney; Kidney Diseases; Kidney Transplantation; Mycophenolic Acid; Red-Cell Aplasia, Pure; Tacrolimus; Treatment Outcome; Withholding Treatment; Young Adult

After liver transplantation, reinfection of the newly engrafted liver with hepatitis C virus is essentially universal in patients who are viremic at the time of transplantation. Treatment with interferon preparations with or without ribavirin is recommended in patients with marked histologic injury; however, hematologic toxicity associated with therapy has been reported, which is usually treated with growth factor support, including erythropoietin analogues. We present the first reported case of anti-erythropoietin antibody-mediated pure red cell aplasia arising in the setting of hepatitis C virus therapy in a patient who underwent living donor liver transplantation.

Topics: Anemia; Antibodies; Antiviral Agents; Epoetin Alfa; Erythropoietin; Graft Rejection; Hematinics; Hepatitis C; Humans; Immunocompromised Host; Immunosuppressive Agents; Interferon alpha-2; Interferon-alpha; Liver Transplantation; Living Donors; Male; Middle Aged; Mycophenolic Acid; Polyethylene Glycols; Prednisone; Recombinant Proteins; Red-Cell Aplasia, Pure; Ribavirin; Secondary Prevention; Tacrolimus

Topics: Adult; Cyclosporine; Humans; Immunosuppressive Agents; Male; Myasthenia Gravis; Pleural Neoplasms; Red-Cell Aplasia, Pure; Tacrolimus; Thymectomy; Thymoma; Thymus Neoplasms

Despite the well-known association between thymoma and PRCA, the role of thymoma remains uncertain. There is accumulating evidence that clonal T cells are involved in acquired PRCA. We examined T cell receptor repertoires in blood and thymus from a patient with PRCA associated with thymoma and myasthenia gravis. Oligoclonal expansions of Vdelta1- and Vbeta1-expressing T cells were found in peripheral blood, whereas the repertoires of Vdelta1+ and Vbeta1+ T cells in thymoma were not skewed. Oligoclonal expansion of Vdelta1-expressing T cells remained unchanged after thymectomy. Thymus may not be the site of clonal T cell expansion in thymoma-associated PRCA.

Topics: Clone Cells; Cyclosporine; Female; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; Humans; Immunosuppressive Agents; Middle Aged; Myasthenia Gravis; Prednisolone; Red-Cell Aplasia, Pure; T-Lymphocyte Subsets; Tacrolimus; Thymectomy; Thymoma; Thymus Neoplasms

Topics: Adult; Cyclosporine; Female; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Lupus Erythematosus, Systemic; Male; Mycophenolic Acid; Red-Cell Aplasia, Pure; Tacrolimus

A 78-year-old woman has suffered from pure red-cell aplasia (PRCA) associated with generalized myasthenia gravis and thymoma. Cyclosporin A (CyA) with corticosteroid increased numbers of erythroid cells in her bone marrow cells but she required monthly blood transfusions. Administration of tacrolimus as a substitution for CyA inhibited progression of anemia without the need for further blood transfusion. No serious side effects were observed. This case demonstrates that tacrolimus is another option of treatment for PRCA in patients who fail to respond to CyA.

Topics: Aged; Anemia; Cyclosporine; Disease Progression; Erythrocyte Transfusion; Female; Humans; Kidney; Myasthenia Gravis; Red-Cell Aplasia, Pure; Remission Induction; Tacrolimus; Thymoma

Hematological toxicity of tacrolimus has been rarely reported. We report two pediatric recipients of liver transplantation with anemia. They were treated with tacrolimus for 8 and 47 months, respectively, before developing pure red cell aplasia (PRCA) confirmed by bone marrow biopsy. The children recovered quickly on withdrawal of tacrolimus. The clinical profile of these children is compared with the only other patient reported in the literature with PRCA due to tacrolimus. All three patients had similar hematological findings. However, the mechanism of the tacrolimus-induced PRCA in these children appears to be different from that reported in the adult patient.

Topics: Adult; Blood Transfusion; Bone Marrow; Follow-Up Studies; Humans; Immunosuppressive Agents; Infant; Liver Transplantation; Red-Cell Aplasia, Pure; Tacrolimus; Time Factors

Topics: Adult; Humans; Immunosuppressive Agents; Male; Red-Cell Aplasia, Pure; Tacrolimus