mycophenolic-acid and Anemia--Hemolytic

Topics: Adrenal Cortex Hormones; Anemia, Hemolytic; Anti-Inflammatory Agents, Non-Steroidal; Azathioprine; Cyclophosphamide; Cyclosporine; Hypertension, Pulmonary; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lupus Nephritis; Mycophenolic Acid; Plasma Exchange

Thrombotic microangiopathy (TMA) is generally diagnosed through clinical features characterized as microangiopathic hemolytic anemia, thrombocytopenia, and multiple organ injury, as well as by pathological findings such as vascular damage and endothelial cell injury. Rheumatic and autoimmune diseases could be accompanied by secondary TMA; in fact, systemic lupus erythematosus (SLE) is a common disease associated with secondary TMA, and SLE complicated with TMA has been reported to have a poor prognosis. Although TMA occurs rarely in pediatric SLE patients, it often leads to severe clinical conditions. Here, we report a rare case of severe juvenile-onset SLE complicated with TMA and kidney injury. The 5-year-old patient showed renal dysfunction, thrombocytopenia, hemolytic anemia, nephrotic syndrome, hypocomplementemia, and elevation of anti-dsDNA IgG levels. Kidney biopsy revealed mesangial proliferation and endocapillary proliferation, as well as plumped endothelial cells, with full-house pattern deposits in immunofluorescence study. Combination treatment of methylprednisolone pulse therapy followed by oral prednisolone, mycophenolate mofetil, and plasma exchange was effective, whereas eculizumab did not show therapeutic effects. The patient further showed recurrent deterioration, and we initiated intravenous cyclophosphamide in addition to combination treatment and eventually succeeded in controlling the disease. Genome analysis by whole-exome sequencing revealed no particular gene mutation related to either complement disorders or type-1 interferon. Further elucidations concerning the pathogenic mechanisms causing juvenile-onset SLE are needed to establish an efficient treatment strategy for TMA with SLE.

Topics: Adrenal Cortex Hormones; Anemia, Hemolytic; Antibodies, Antinuclear; Antirheumatic Agents; Biopsy; Child, Preschool; Combined Modality Therapy; Complement Hemolytic Activity Assay; Cyclophosphamide; Enzyme Inhibitors; Humans; Kidney; Lupus Erythematosus, Systemic; Mycophenolic Acid; Nephrotic Syndrome; Plasma Exchange; Recurrence; Thrombocytopenia; Thrombotic Microangiopathies; Treatment Outcome

Ribavirin is ineffective against hepatitis C virus as mono-therapy but is critical in attaining both early virologic response and sustained virologic response when combined with pegylated interferon. Ribavirin has significant dose-limiting toxicities, the most important of which is hemolytic anemia. Taribavirin is a ribavirin pro-drug, which targets the liver and has less incidence of anemia, and it may be a promising alternative to ribavirin in the future.

Topics: Anemia, Hemolytic; Antiviral Agents; Carbamates; Hepacivirus; Hepatitis C; Humans; IMP Dehydrogenase; Mycophenolic Acid; Phenylurea Compounds; Ribavirin

Graft-versus-host-disease (GVHD) is a complication of solid organ transplantation, most commonly of the small bowel or liver. Herein, we have presented a case of GVHD in a 27-year-old man who underwent an human leukocyte antigen (HLA) minor mismatch renal transplantation from his father. After the procedure, the patient presented with a fever, skin rash, and watery diarrhea. An allograft kidney biopsy demonstrated no sign of rejection; however, anti-A antibody was detected in plasma and progressive anemia was attributed to hemolytic anemia owing to a passenger lymphocyte syndrome. From those findings, we suspected that the clinical symptoms were caused by acute GVHD. An endoscopic biopsy of the colon revealed apoptotic cells consistent with the disease. We found reports of only 5 other GVHD cases after kidney transplantation. Several risk factors are associated with GVHD, such as transfer of graft lymphocytes, donor HLA homozygosity, and a relationship between recipient immunogenicity and immunosuppression. In this case, detection led to early diagnosis of donor-derived GVHD due to passenger lymphocyte syndrome. It is important keep GVHD in mind and to understand its risk factors as the mortality rate is high.

Topics: Acute Disease; Adult; Anemia, Hemolytic; Anti-Bacterial Agents; Anti-Inflammatory Agents; Bacterial Infections; Female; Graft vs Host Disease; HLA Antigens; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Methylprednisolone Hemisuccinate; Mycophenolic Acid; Pancreas Transplantation; Reoperation; Treatment Outcome

The aim of the study was to demonstrate clinical course of the first reported cases of PLS in pediatric kidney transplantation and therapeutic outcome for such condition using a combination of high-dose corticosteroid and tacrolimus. We report a single case (a nine-year-old Thai boy) with end-stage kidney disease secondary to obstructive uropathy developed immune-mediated hemolytic anemia from the PLS at second week after a pre-emptive living-related kidney transplantation. The alloimmune hemolysis was a result of anti-B antibodies, derived from blood group O-donor lymphocytes. Using a combination of high-dose corticosteroid and a substitution of cyclosporin with tacrolimus, there was no further hemolysis although the anti-B antibodies remained detectable until the eighth week post-transplantation. An impairment of the graft function because of hemoglobinuria was resolved after the hemolysis was stopped. The alloimmune hemolysis caused by PLS in pediatric kidney transplantation could be controlled with a combination of high-dose corticosteroid and tacrolimus.

Topics: Anemia, Hemolytic; Child; Cyclosporine; Glucocorticoids; Humans; Kidney Transplantation; Living Donors; Male; Methylprednisolone; Mycophenolic Acid; Prednisolone; Tacrolimus

Topics: ABO Blood-Group System; Anemia, Hemolytic; Blood Group Incompatibility; Child, Preschool; Graft vs Host Reaction; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Mycophenolic Acid; Time Factors; Tissue Donors

Mycophenolate mofetil (MMF) has been increasingly used in patients with systemic lupus erythematosus (SLE). While most information concentrates on lupus nephritis, its efficacy in nonrenal manifestations of SLE has not been systematically studied. We describe the successful use of MMF in a patient with SLE-related hemolytic anemia that was refractory to cyclophosphamide, pulse methylprednisolone, intravenous immunoglobulin and cyclosporine. The mechanisms of action of MMF are briefly reviewed.

Topics: Adult; Anemia, Hemolytic; Anemia, Refractory; Dose-Response Relationship, Drug; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Mycophenolic Acid; Treatment Outcome

Hemolysis due to D incompatibility in the setting of liver transplantation is less frequent than that associated with ABO incompatibility, but can represent an equally adverse event. Approximately 10 percent of ABO-compatible liver transplants involve a D- donor and a D+ recipient.. A case of severe D incompatibility resulting from liver transplantation in a 50-year-old O Rh+ man with end-stage liver disease who received an O Rh- liver allograft is reported. A declining hemoglobin level complicated the patient's postoperative course with laboratory evidence of anti-D-mediated hemolysis. Investigations revealed that the transplanted liver was from a female O Rh- donor with detectable antibodies against D, C, and K. The severity of the hemolytic anemia was such that the patient required two separate red blood cell (RBC) exchanges and intermittent RBC transfusions over the course of almost a year. In addition to the use of RBCs negative for D, C, and K, the patient underwent a variety of B-cell suppressive therapies including glucocorticosteroids, mycophenolate mofetil, and rituximab. A normalization of hemoglobin levels and a decrease in serum bilirubin did not occur until after a splenectomy on postoperative Day 321.. This represents the sixth and most severe case reported of hemolysis resulting from D incompatibility in liver transplantation. When unexpected serologic findings are identified in a transplant recipient, obtaining more information on the donor may help guide transfusion support.

Topics: ABO Blood-Group System; Anemia, Hemolytic; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Bilirubin; Blood Group Incompatibility; Blood Grouping and Crossmatching; Erythrocyte Transfusion; Glucocorticoids; Hemoglobins; Humans; Immunosuppressive Agents; Isoantibodies; Liver Transplantation; Male; Middle Aged; Mycophenolic Acid; Rh-Hr Blood-Group System; Rituximab; Splenectomy

We report two cases of hepatitis C virus (HCV) associated autoimmune haematological disorders successfully treated with an unusual protocol (mycophenolate mofetil: MMF). The first case was a male patient with chronic HCV infection who developed, during interferon (IFN)/ribavirin therapy, severe autoimmune thrombocytopenia unresponsive to steroids. MMF was then administered and, simultaneously, the steroid dose was gradually reduced until withdrawal. Following this strategy, a progressive increase in platelet count and complete negativity of anti-PLT antibodies were achieved without changes in HCV-RNA quantitative determination. The second case was a woman with HCV liver cirrhosis with severe anaemia and Coombs test positivity partially responsive to continuous administration of steroid high doses. However, this treatment unmasked a severely painful vertebral osteoporosis. For this reason we introduced MMF and simultaneously steroid therapy was progressively reduced until withdrawal. Haemoglobin reached a normal value and the Coombs test became negative within 60 days. These case reports suggest that MMF may represent an interesting therapeutic approach for autoimmune HCV associated haematological disorders.

Topics: Aged; Anemia, Hemolytic; Anti-Inflammatory Agents, Non-Steroidal; Antiviral Agents; Autoimmune Diseases; Drug Resistance; Female; Glucocorticoids; Hepatitis C, Chronic; Humans; Immunosuppressive Agents; Interferons; Male; Methylprednisolone; Middle Aged; Mycophenolic Acid; Thrombocytopenia; Withholding Treatment

Mycophenolate mofetil is a novel immunosuppressive drug already established in transplantation medicine. Recently, results of three open clinical trials on mycophenolate mofetil in myasthenia gravis have been reported. Mycophenolate mofetil in a dose of 1.0-2.0 g/day was given in 2 patients with severe refractory myasthenia gravis and in 1 patient with myasthenia gravis-polymyositis syndrome. Apart from dose-dependent reversible hemolytic anemia in 1 patient, no severe side effects occurred. Considerable improvement of myasthenic symptoms was seen in all patients within 3-6 months after the initiation of this therapy. Mycophenolate mofetil may be considered as a useful alternative in the treatment of severe myasthenia gravis when standard therapeutic regimens fail. It is usually well tolerated and its application is simple.

Topics: Aged; Anemia, Hemolytic; Autoantibodies; Dose-Response Relationship, Drug; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myasthenia Gravis; Mycophenolic Acid; Neurologic Examination; Receptors, Cholinergic; Treatment Outcome