mycophenolic-acid and Anemia--Hemolytic--Autoimmune

Clinical heterogeneity, unpredictable course and flares are characteristics of systemic lupus erythematosus (SLE). Although SLE is-by and large-a systemic disease, occasionally it can be organ-dominant, posing diagnostic challenges. To date, diagnosis of SLE remains clinical with a few cases being negative for serologic tests. Diagnostic criteria are not available and classification criteria are often used for diagnosis, yet with significant caveats. Newer sets of criteria (European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019) enable earlier and more accurate classification of SLE. Several disease endotypes have been recognised over the years. There is increased recognition of milder cases at presentation, but almost half of them progress overtime to more severe disease. Approximately 70% of patients follow a relapsing-remitting course, the remaining divided equally between a prolonged remission and a persistently active disease. Treatment goals include long-term patient survival, prevention of flares and organ damage, and optimisation of health-related quality of life. For organ-threatening or life-threatening SLE, treatment usually includes an initial period of high-intensity immunosuppressive therapy to control disease activity, followed by a longer period of less intensive therapy to consolidate response and prevent relapses. Management of disease-related and treatment-related comorbidities, especially infections and atherosclerosis, is of paramount importance. New disease-modifying conventional and biologic agents-used alone, in combination or sequentially-have improved rates of achieving both short-term and long-term treatment goals, including minimisation of glucocorticoid use.

Topics: Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal, Humanized; Autoantibodies; Azathioprine; Calcineurin Inhibitors; Cardiovascular Diseases; Cyclophosphamide; Disease Management; Female; Glucocorticoids; Heart Valve Diseases; Humans; Hydroxychloroquine; Hypertension, Pulmonary; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lupus Nephritis; Lupus Vasculitis, Central Nervous System; Macrophage Activation Syndrome; Methotrexate; Mycophenolic Acid; Myocarditis; Outcome Assessment, Health Care; Pericarditis; Phenotype; Pregnancy; Pregnancy Complications; Prognosis; Purpura, Thrombocytopenic, Idiopathic; Quality of Life; Recurrence; Rituximab; Severity of Illness Index; Survival Rate; Uterine Cervical Neoplasms

Immune-mediated hemolytic anemia is a common hematologic disorder in dogs. Disease management involves immunosuppression using glucocorticoids, potentially in combination with other medications such as azathioprine, cyclosporine, or mycophenolate mofetil. Therapeutic drug monitoring may enhance the utility and maximize the safety of cyclosporine and mycophenolate mofetil. The disease is proinflammatory and prothrombotic. Antithrombotic drug administration is therefore essential, and anticoagulant therapy should be initiated at the time of diagnosis. Additional therapies include red blood cell transfusion to support blood oxygen content. Future therapies may include therapeutic plasma exchange, anti-CD20 monoclonal antibodies, and complement inhibitors.

Topics: Anemia, Hemolytic, Autoimmune; Animals; Cyclosporine; Dog Diseases; Dogs; Enzyme Inhibitors; Immunosuppressive Agents; Mycophenolic Acid; Plasma Exchange

The management of Evans Syndrome in children is challenging due to the lack of evidence-based data on treatment. Steroids, the first-choice therapy, are successful in about 80% of cases. For children who are resistant, relapse or become steroid-dependent, rituximab is considered a valid second-line treatment, with the exception of those with an underlying diagnosis of autoimmune lymphoproliferative syndrome who may benefit from other options such as mycophenolate mofetil and sirolimus. Better knowledge of the immunological mechanisms underlying cytopenias and the availability of new immunosuppressive drugs can be helpful in the choice of more targeted therapies that would enable the reduction of the use of long-term steroid administration or other more aggressive options, such as splenectomy or stem cell transplantation. This manuscript provides an overview of the pathogenic background of the disease, and suggests a clinical approach to diagnosis and treatment with a particular focus on the management of relapsing/resistant disease.

Topics: Alemtuzumab; Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal, Humanized; Bortezomib; Child; Cyclophosphamide; Cyclosporine; Drug Resistance; Erythrocyte Transfusion; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Immunosuppressive Agents; Mycophenolic Acid; Recurrence; Rituximab; Sirolimus; Splenectomy; Stem Cell Transplantation; Steroids; Thrombocytopenia

Mycophenolate mofetil (MMF) has been shown to be effective in children with immune thrombocytopenia (ITP) and Evans syndrome (ES), but data from larger series and details on the timing of the response are lacking. We evaluated 56 children treated with MMF for ITP (n = 40) or ES (n = 16), which was primary or secondary to autoimmune lymphoproliferative syndrome -related syndrome (ARS). Thirty-five of the 54 evaluable patients (65%) achieved a partial (18%) or complete (46%) response after a median (range) of 20 (7-137) and 37 (7-192) d, respectively. ITP and ES patients responded in 58% and 81% of cases (P = not significant, ns), with complete response in 32% and 81% (P = 0·01), respectively. 60% and 73% of children with primary disease and ARS responded (P = ns) with complete response in 34% and 68% of cases (P = 0·01), respectively. Six of 35 (17%) children relapsed after a median of 283 d (range 189-1036). Limited toxicity was observed in four patients. The median durations of treatment and follow-up were seven and 12·7 months, respectively. This is the largest reported cohort of patients treated with MMF for ITP/ES. The results show that MMF is effective and safe and provides a relatively quick response, suggesting that it has a potential role as an alternative to more aggressive and expensive second/further-line treatments.

Topics: Adolescent; Anemia, Hemolytic, Autoimmune; Antibiotics, Antineoplastic; Child; Child, Preschool; Disease Progression; Female; Humans; Infant; Italy; Male; Mycophenolic Acid; Odds Ratio; Purpura, Thrombocytopenic, Idiopathic; Recurrence; Retreatment; Retrospective Studies; Thrombocytopenia; Treatment Outcome

Evans syndrome is a rare disorder characterized by combined autoimmune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Standard treatments consist of transfusions, corticosteroids, splenectomy, IVIG, anabolic steroids, vincristine, alkylating agents, or cyclosporine. In a patient with refractory disease, an allogeneic hematopoietic stem cell transplant (HSCT) resulted in complete clinical and serologic remission for more than 30 months. Allogeneic HSCT may be the only current curative therapy for Evans syndrome but may also be complicated by significant toxicities.

Topics: Adrenal Cortex Hormones; Adult; Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal; Autoimmune Diseases; Combined Modality Therapy; Danazol; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Infliximab; Male; Mycophenolic Acid; Opportunistic Infections; Prednisone; Purpura, Thrombotic Thrombocytopenic; Remission Induction; Salvage Therapy; Splenectomy; Syndrome; Thrombocytopenia; Transplantation Conditioning; Transplantation, Homologous; Vincristine

Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of apoptosis associated most often with heritable FAS mutations leading to lymphadenopathy, hypersplenism and chronic refractory autoimmune cytopenias. Mycophenolate mofetil (MMF) was used to treat cytopenias in 13 ALPS patients aged 9 months to 17 years from a cohort of 118 children (aged < 18 years) and 82 adults. Twelve responded for a median follow-up of 49 weeks (range 38-240 weeks), defined by maintenance of adequate blood counts and reduction in dosage or cessation of other immunosuppressive agents. This preliminary experience suggests that MMF may spare steroid usage in patients with ALPS-associated cytopenias.

Topics: Adolescent; Anemia, Hemolytic, Autoimmune; Autoimmune Diseases; Child; Child, Preschool; Follow-Up Studies; Humans; Immunosuppressive Agents; Infant; Leukocyte Count; Lymphoproliferative Disorders; Male; Mycophenolic Acid; Neutropenia; Pain; Prodrugs; Thrombocytopenia

A 9-year-old castrated male poodle dog was presented with icterus, anorexia, and lethargy. The dog was diagnosed with hypothyroidism 1 month before and was treated with levothyroxine. Severe anaemia with spherocytes, positive saline agglutination test, and hyperbilirubinemia indicated immune-mediated haemolytic anaemia (IMHA). Therefore, immunosuppressive therapy with prednisolone, mycophenolate mofetil, and danazol was started. Although the IMHA was well controlled, during tapering of prednisolone, acute multiple joint swelling and oedema suspected immune-mediated polyarthritis occurred twice. First, clinical symptoms improved as the dosage of prednisolone increased. However, the dog showed severe adverse effects to the steroid. Second time, we added leflunomide as another immunosuppressant, and clinical signs of arthritis disappeared. About 3 weeks later, despite the immunosuppressive therapy, skin lesions resembling an autoimmune dermatologic disorder spread throughout the body. Addition of cyclosporine resolved the skin lesions. This is a case report of a dog showing several sporadic clinical signs related to multiple autoimmune syndromes and their management using different immunosuppressant drugs.

Topics: Anemia, Hemolytic, Autoimmune; Animals; Dog Diseases; Dogs; Immunosuppressive Agents; Male; Mycophenolic Acid; Prednisolone; Syndrome

Large clinical trials have demonstrated the overall safety of vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, reports have emerged of autoimmune phenomena, including vaccine-associated myocarditis, immune thrombocytopenia, and immune thrombotic thrombocytopenia.. Here we present a novel case of a young woman who developed life-threatening autoimmune hemolytic anemia (AIHA) after her first dose of a SARS-CoV-2 mRNA vaccine. Notably, initial direct antiglobulin testing was negative using standard anti-IgG reagents, which are "blind" to certain immunoglobulin (IgG) isotypes. Further testing using an antiglobulin reagent that detects all IgG isotypes was strongly positive and confirmed the diagnosis of AIHA. The patient required transfusion with 13 units of red blood cells, as well as treatment with corticosteroids, rituximab, mycophenolate mofetil, and immune globulin.. As efforts to administer SARS-CoV-2 vaccines continue globally, clinicians must be aware of potential autoimmune sequelae of these therapies.

Topics: Adrenal Cortex Hormones; Adult; Anemia, Hemolytic, Autoimmune; Autoantibodies; COVID-19; COVID-19 Vaccines; Erythrocyte Transfusion; Female; Humans; Immunoglobulin G; Immunoglobulins; Mycophenolic Acid; Rituximab; SARS-CoV-2

Immune mediated hemolytic anemia (IMHA) is a life-threatening disease with severe, acute hemolysis as a result of an autoimmune response directed against erythrocyte surface antigens. In veterinary medicine, IMHA is usually treated with immunosuppressants and often multiple blood transfusions. In human medicine, immunoadsorption (IA) is an established therapy for antibody removal in immune-mediated diseases. A female, spayed, five-year-old, 28 kg Entlebucher Mountain dog was presented with regenerative anemia and positive autoagglutination diagnosed as immune-mediated hemolytic anemia to the veterinary emergency service. Conventional treatment consisting immunosuppression with prednisolone and mycophenolate failed to improve hemolysis. As hematocrit dropped daily, multiple blood transfusions of blood group DEA 1 negative were required. IA was initiated at day 3 with COM.TEC and ADAsorb platforms and a LIGASORBstaphylococcus antitoxin A column. IA with citrate anticoagulation was performed over the treatment time of 77 minutes with a blood flow of 50 mL/min. Total plasma volume of 1.6 L was processed. Complications consisted of vomitus and lid swelling, shivering, excessive clotting in the tubing after a calcium bolus and hypotension. After IA, hemolysis stopped immediately, plasma concentrations of immunoglobulin G, immunoglobulin M and bilirubin decreased, and hematocrit remained stable. The dog was discharged without further hemolysis 4 days after immunoadsorption with immunosuppressive therapy. IA is a promising adjunctive therapy in severe cases of canine IMHA, but it cannot be concluded to which degree IA or concurrent immunosuppression contributed to cessation of hemolysis in the present case.

Topics: Adsorption; Anemia, Hemolytic, Autoimmune; Animals; Dogs; Erythrocytes; Female; Hematocrit; Hemolysis; Immunoglobulin G; Immunosuppression Therapy; Immunosuppressive Agents; Mycophenolic Acid; Prednisolone

Information regarding adverse events (AEs) of mycophenolate mofetil (MMF) is limited.. To evaluate the types and frequency of potential AEs of MMF in dogs with immune-mediated disease.. One hundred thirty-one dogs treated with MMF for management of suspected immune-mediated disease.. Retrospective study. Medical records were reviewed to find and group suspect AEs in gastrointestinal (GI), hematologic, and other categories. Age, dosage, body weight, and sex were analyzed between dogs with and without AEs by using the Mann-Whitney U-test and chi-squared test.. The median starting dosage of MMF was 17.5 mg/kg/day (interquartile range [IQR] = 15.1-20.6 mg/kg/day) and the median treatment duration was 56 days (IQR = 14-236 days). Mycophenolate mofetil was prescribed for immune-mediated hemolytic anemia (n = 31), immune-mediated thrombocytopenia (n = 31), pemphigus foliaceus (n = 15), immune-mediated polyarthritis (n = 12), and others (n = 42). Overall, potential AEs of MMF were observed in 34 of 131 dogs (GI 24.4% [31/127], neutropenia 4% [3/76], anemia 4% [1/25], thrombocytopenia 4.0% [1/25], and dermatologic 1.5% [2/131]). There were no significant differences among dogs with (n = 37) or without potential AEs (n = 94) in regards to sex, age, body weight, or dosage of MMF (P = .06, .13, .24, and .26, respectively).. In the dogs administered MMF, GI AEs were most common. Since potential hematologic and dermatologic AEs developed in a few dogs, clinicians should be aware of these when prescribing MMF to dogs with immune-mediated disease.

Topics: Anemia, Hemolytic, Autoimmune; Animals; Dog Diseases; Dogs; Immunosuppressive Agents; Mycophenolic Acid; Retrospective Studies; Thrombocytopenia

Topics: Adolescent; Adrenal Cortex Hormones; Anemia, Hemolytic, Autoimmune; Benzoates; Betacoronavirus; Coronavirus Infections; COVID-19; Erythrocyte Transfusion; Humans; Hydrazines; Male; Mycophenolic Acid; Oxygen; Pandemics; Pneumonia, Viral; Pyrazoles; SARS-CoV-2

Topics: Anemia, Hemolytic, Autoimmune; Antiviral Agents; Computed Tomography Angiography; Dysarthria; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Paresis; Stroke; Varicella Zoster Virus Infection; Vasculitis, Central Nervous System

Idiopathic immune-mediated haemolytic anaemia (IMHA) is one of the most common immune-mediated diseases in dogs with a high mortality rate. In this retrospective study, we examined the effect of mycophenolate- mofetil (MMF) and human intravenous immunoglobulin (hIVIG) in combination with glucocorticoids on canine IMHA patients. Six dogs were treated with prednisolone and MMF (hIVIG-) and in 15 patients hIVIG was added (hIVIG+). There was no significant difference between the groups regarding age, weight, number of blood transfusions or hematocrit on the day of diagnosis. The hIVIG+ group showed a significantly faster recovery of the hematocrit, but this difference was only short-lived. The survival in the first year was similar in both groups and was with 71.5% somewhat higher than in other published studies. The addition of MMF to prednisolone for the treatment of dogs with acute IMHA was well tolerated and seemed to positively affect the course of the disease. Randomized studies are necessary to confirm this observation. Human immunoglobulin had only minimal clinical advantages and no effect on mortality.. Eine idiopathische immunvermittelte hämolytische Anämie (IMHA) beim Hund zählt zu den häufigsten immunbedingten Erkrankungen mit einer hohen Mortalität. In dieser retrospektiven Studie untersuchten wir die Wirkung von Mycophenolate-Mofetil (MMF) und humanem intravenösem Immunglobulin (hIVIG) in Kombination mit Glukokortikoiden bei caninen IMHA–Patienten. Sechs Hunde wurden mit der Kombination Prednisolon/MMF behandelt (hIVIG–), bei 15 Patienten wurde zusätzlich hIVIG eingesetzt (hIVIG+). Die beiden Gruppen unterschieden sich nicht signifikant bezüglich Alter, Gewicht, Anzahl Bluttransfusionen oder Hämatokrit am Tag der Diagnose. Die Patienten der Gruppe hIVIG+ wiesen eine signifikant schnellere aber nur kurzfristige Erholung der Hämatokrit-Werte auf. Die 1-Jahr Überlebensrate war in beiden Gruppen ähnlich und lag mit 71.5% etwas höher als in anderen Studien. Die Zugabe von MMF zu Prednisolon bei der Behandlung von Hunden mit akuter IMHA war gut verträglich und schien den Krankheitsverlauf bei IMHA positiv zu beeinflussen. Randomisierte Studien zur Bestätigung dieser Beobachtung sind notwendig. Humanes Immunoglobulin hatte nur einen geringen klinischen Nutzen und keinen Einfluss auf die Mortalität.. Une anémie hémolytique auto-immune idiopathique (IMHA) compte chez le chien au nombre des affections auto-immunes les plus fréquentes avec un taux de mortalité élevé. Dans le cadre de la présente étude rétrospective, nous avons examiné l’effet du mycophénolate mofétil (MMF) et des globulines humaines par voie intraveineuse (hIVIG) en combinaison avec des glucocorticoïdes sur des chiens souffrant d’IMHA. Six chiens ont été traités au moyen d’une combinaison prédnisolone/ MMF (hIVIG–) et chez 15 patients on a en plus utilisé des hlVIG (hIVIG+). Les deux groupes ne se différenciaient pas de façon significative en ce qui concerne l’âge, le poids, le nombre de transfusions sanguines ou l’hématocrite lors du diagnostic. Les patients du groupe hIVIG+ ont montré une normalisation significativement plus rapide mais de courte durée de l’hématocrite. Le taux de survie à une année était similaire dans les deux groupes avec 71,5%, ce qui est un peu plus élevé que dans d’autres études. L’ajout de MMF à la prédnisolone dans le traitement de chiens atteints d’IMHA est bien supporté et semble influencer le cours de la maladie de façon positive. Des études randomisées sont nécessaires pour confirmer ces observations. Les immunoglobulines humaines n’ont eu qu’un effet limité et pas d’influence sur la mortalité.. L’idiopatica anemia emolitica immuno-mediata (IMHA) nei cani è una delle malattie immuno-correlate più frequenti con un alto tasso di mortalità. In questo studio retrospettivo si è studiato l’effetto del micofenolato mofetile (MMF) e delle immunoglobuline umane somministrate per via endovenosa (hIVIG) in combinazione con glucocorticoidi in cani affetti da IMHA. Sei cani sono stati trattati con la combinazione di prednisolone/ MMF (hIVIG-) e a 15 cani è stato aggiunto hIVIG (HIVIG+). Entrambi i gruppi non differivano significativamente per età, peso, numero di trasfusioni sanguigne o ematocrito al momento della diagnosi. I valori dell’ematocrito nei pazienti nel gruppo HIVIG+ miglioravano in modo significativo più rapidamente ma per breve tempo. Il tasso di sopravvivenza di 1 anno era simile in entrambi i gruppi ma risultava di poco più alto (71.5%) comparato ad altri studi. L’aggiunta di MMF al prednisolone per il trattamento dei cani afftetti da IMHA acuta è stato ben tollerato ed è apparso che influenzava positivamente il corso della malattia IMHA. Ulteriori studi randomizzati sono necessari per confermare questa osservazione. L’immunoglobulina umana dava poco beneficio clinico e nessun’influenza sulla mortalità.

Topics: Anemia, Hemolytic, Autoimmune; Animals; Dog Diseases; Dogs; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Mycophenolic Acid; Prednisolone; Retrospective Studies

Successful treatment of both pediatric autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP), specifically those that are refractory to first-line therapies, remains unsatisfactory in terms of long-term remission and medication side effects. Here, we propose a novel combination therapy of mycophenolate mofetil (MMF), an adjunct immunosuppressive, and short-term corticosteroids for the treatment of persistent or chronic autoimmune cytopenias in children. This combination may allow for rapid decrease of steroid usage as well as prolonged count stabilization with minimal toxicity to the patient.. Prospective case series of nine patients, six with persistent or chronic ITP and three with persistent or chronic AIHA, between the ages of 5 and 19 years who are being treated with combination therapy consisting of corticosteroids and MMF.. Our results are very promising, as MMF appears to be an effective and well-tolerated adjunct immunosuppressant that allows for rapid weaning of steroid usage, minimal adverse side effects to the patients, and long-term stabilization of counts, a goal that has not been achieved successfully with other secondary treatment modalities. Therefore, this novel combination therapy may be an excellent alternative for the treatment of persistent or chronic autoimmune cytopenias in the pediatric population.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Anemia, Hemolytic, Autoimmune; Antibiotics, Antineoplastic; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Immunomodulation; Male; Mycophenolic Acid; Prognosis; Prospective Studies; Purpura, Thrombocytopenic, Idiopathic; Remission Induction; Young Adult

Systemic lupus erythematosus-related hepatitis, known as lupus hepatitis, is a rare manifestation of systemic lupus erythematosus, and is usually subclinical with mild abnormalities of serum liver enzymes. While cases with clinically significant and refractory lupus hepatitis are uncommon, treatment options for lupus hepatitis are to be established. Here, we report the case of a 45-year-old man with progressive lupus hepatitis accompanied by autoimmune haemolytic anaemia. Lupus hepatitis of this patient was refractory to tacrolimus, azathioprine and cyclophosphamide, but was successfully treated by mycophenolate mofetil. Mycophenolate mofetil might be an effective therapeutic option for refractory lupus hepatitis.

Topics: Anemia, Hemolytic, Autoimmune; Biopsy; Diagnosis, Differential; Drug Resistance; Drug Substitution; Hepatitis; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Liver Function Tests; Lupus Erythematosus, Systemic; Male; Middle Aged; Mycophenolic Acid; Predictive Value of Tests; Remission Induction; Treatment Outcome

AIHA following allogeneic HSCT is appearing more frequently in the literature. It occurs as a result of donor cell-derived antibodies targeting donor red cell antigens. Little guidance exists on the management of such patients, particularly in the pediatric setting. First-line conventional treatment is corticosteroids and/or immunoglobulin therapy with monoclonal antibody therapy reserved for treatment failure. We report our experience of a child refractory to immunoglobulin and steroid therapy who required several infusions of rituximab and immunomodulatory therapy to obtain a clinically significant response.

Topics: Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal, Murine-Derived; Child, Preschool; Dyskeratosis Congenita; Hematopoietic Stem Cell Transplantation; Humans; Immunologic Factors; Immunosuppressive Agents; Male; Mutation; Mycophenolic Acid; Rituximab; Telomere-Binding Proteins; Treatment Outcome

To compare short-term outcome and frequency of adverse events for dogs with idiopathic immune-mediated haemolytic anaemia treated with glucocorticoids and mycophenolate mofetil vs alternate immunosuppressive protocols.. A retrospective study of medical case records of dogs with immune-mediated haemolytic anaemia was conducted. Data collected included signalment, clinicopathological data, medications administered, duration of hospitalization, short-term survival and adverse events. Variables were compared between dogs treated with glucocorticoids and mycophenolate mofetil (mycophenolate mofetil group) vs dogs treated with other two-drug immunosuppressive protocols (combined group).. Sixty-four cases of idiopathic immune-mediated haemolytic anaemia were identified. Two dogs were euthanased without treatment, three received glucocorticoids alone, and seven received two additional drugs. Fifty-two dogs received glucocorticoids and additional immunosuppressive medications: 30 mycophenolate mofetil, 15 cyclosporine, 6 azathioprine and 1 human immunoglobulin. There was no significant difference between the discharge rate, 30-day or 60-day survival rates between the mycophenolate mofetil and the combined groups (Fisher's exact; P=0·272, 0·518, 1·000, respectively). The sole adverse event observed in the mycophenolate mofetil group was diarrhoea (n=5).. Administration of mycophenolate mofetil appears safe in dogs with idiopathic immune-mediated haemolytic anaemia. The combination of glucocorticoids and mycophenolate mofetil has similar efficacy to alternate immunosuppressive protocols used to treat this disease.

Topics: Anemia, Hemolytic, Autoimmune; Animals; Anti-Inflammatory Agents, Non-Steroidal; Azathioprine; Cyclosporine; Diarrhea; Dog Diseases; Dogs; Drug Therapy, Combination; Female; Glucocorticoids; Immunoglobulins; Immunosuppressive Agents; Male; Mycophenolic Acid; Retrospective Studies

Topics: Anemia, Hemolytic, Autoimmune; Child; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid

To describe the use of oral mycophenolate mofetil (MMF) as an adjunctive therapy in 2 cats with primary immune-mediated hemolytic anemia.. Two cats suffering from presumptive primary immune mediated hemolytic were treated with MMF as part of their treatment regimens. Both cats had improved complete blood counts following therapy.. This is the first reported use of oral MMF as adjunctive treatment for cats with immune-mediated hemolytic anemia. Outcome was favorable in both cats and no adverse effects were noted from the MMF.

Topics: Anemia, Hemolytic, Autoimmune; Animals; Cat Diseases; Cats; Female; Immunosuppressive Agents; Mycophenolic Acid; Treatment Outcome

A 32-yr-old male diagnosed with myelodysplastic syndrome underwent an unmanipulated, unrelated, HLA matched, peripheral blood stem cell transplantation. The patient and donor were both blood type O, CcDEe. Twelve weeks post-transplantation, he developed acute autoimmune hemolytic anemia (AIHA). He was transfused multiple times with washed O red cells. High-dose steroid therapy was initiated and he underwent splenectomy; however, AIHA was refractory to therapy. The patient was further treated with combined treatment modalities including immunosuppressive therapy with mycophenolate mofetil and cyclosporine and three cycles of plasma exchange, and AIHA responded to treatment. This is the third case of AIHA complicating hematopoietic stem cell transplantation reported in Korea. Since AIHA is relatively common after hematopoietic stem cell transplantation, accurate and timely diagnosis of the disease and treatment strategies with multiple modalities are necessary.

Topics: Adult; Anemia, Hemolytic, Autoimmune; Combined Modality Therapy; Cyclosporine; Hematopoietic Stem Cell Transplantation; Humans; Male; Mycophenolic Acid; Myelodysplastic Syndromes; Plasma Exchange

Heparin is commonly used as an anticoagulant but its many other pharmacologic properties are less well known. It has an important effect on complement regulation and has been shown in vitro to inhibit complement-mediated lysis of red cells. Although the beneficial effects of heparin for treatment of haemolytic anaemia were described many decades ago, its use in this scenario is not standard practice. Here we report a case where the use of heparin had a beneficial effect on a life-threatening episode of intravascular haemolysis. We also show unfractionated heparin to be more beneficial than low molecular weight heparin. We suggest that heparin has an important role to play in the management of complement-mediated haemolytic episodes.

Topics: 3' Untranslated Regions; Acute Disease; Adult; Anemia, Hemolytic, Autoimmune; Azathioprine; Combined Modality Therapy; Complement Activation; Enoxaparin; Female; Hemolysis; Heparin; Humans; Immunosuppressive Agents; Mycophenolic Acid; Plasma Exchange; Prednisolone; Prothrombin; Splenectomy; Thrombophilia; Venous Thrombosis

Splenic marginal zone lymphomas (SMZL) constitute about 20% of primary splenic NHLs. We report a case of primary SMZL with a florid granulomatous reaction which obscured the underlying lymphoma. Although granulomas have been described in splenic non-Hodgkin lymphoma, it can be extensive and mask the underlying lymphoma. A careful search for the cytoarchitectural features of SMZL is warranted in such a case.

Topics: Adrenal Cortex Hormones; Anemia, Hemolytic, Autoimmune; Enzyme Inhibitors; Granuloma; Humans; Immunohistochemistry; Immunosuppressive Agents; Lymphoma, Non-Hodgkin; Male; Middle Aged; Mycophenolic Acid; Splenectomy; Splenic Neoplasms

Acquired red cell aplasia (RCA) is a rare disorder and can be either idiopathic or associated with certain diseases, pregnancy, or drugs. In exceptionally rare cases, it has been reported to co-exist with other autoimmune cytopenias. We report a high incidence of RCA and autoimmune hemolytic anemia (AIHA) in pancreas transplant recipients on alemtuzumab-based maintenance therapy.. Between February 2003 and July 2005, 357 pancreas transplant recipients were treated with immunosuppressive regimens containing the lymphocyte-depleting antibody alemtuzumab, the T-cell activation inhibitor daclizumab, and the anti-metabolite mycophenolate mofetil (MMF). We retrospectively reviewed medical records, blood bank data and bone marrow biopsy specimens of patients with a Transplant Information Services database diagnosis of RCA and AIHA from February 2003 to November 2005.. Severe RCA, AIHA, and idiopathic thrombocytopenic purpura (ITP) occurred independently or in combination, in 20 out of 357 (5.6%) pancreas transplant recipients, 12 to 24 months following the initiation of the aforementioned immunosuppressive regimens. Severe opportunistic infections developed late in 14/20 (70%) of these patients. Atypical morphologic features, including variable dysgranulopoiesis, variable megakaryocytic hyperplasia with normal or low peripheral platelet counts, and atypical lymphoid aggregates were found in bone marrow trephine sections of 11 patients in whom the diagnosis of RCA was made.. We hypothesize that the combination of alemtuzumab, daclizumab and MMF can result in immune dysregulation thereby permitting autoantibody formation. Because the use of these three immune suppressants is becoming increasingly common, it is important to recognize the severe hematologic complications that can arise.

Topics: Adult; Alemtuzumab; Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Autoimmune Diseases; Bone Marrow; Daclizumab; Female; Humans; Immunoglobulin G; Immunosuppressive Agents; Incidence; Kidney Transplantation; Lymphocyte Activation; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Pancreas Transplantation; Pilot Projects; Postoperative Complications; Purpura, Thrombocytopenic, Idiopathic; Red-Cell Aplasia, Pure; Retrospective Studies; T-Lymphocytes

Topics: Alemtuzumab; Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antibodies, Neoplasm; Antineoplastic Agents; Azathioprine; Biopsy; Celiac Disease; Child, Preschool; Coombs Test; Cyclosporine; Diagnosis, Differential; Follow-Up Studies; Glucocorticoids; Hepatitis; Humans; Immunologic Factors; Immunosuppressive Agents; Infant; Liver; Liver Function Tests; Male; Methylprednisolone; Mycophenolic Acid; Prednisone; Rare Diseases; Remission Induction; Rituximab

Topics: Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antigens, CD20; Biological Factors; Bone Marrow Transplantation; Child; Chronic Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Erythrocyte Membrane; Follow-Up Studies; Humans; Immunosuppressive Agents; IMP Dehydrogenase; Mycophenolic Acid; Rituximab

Unresponsive autoimmune haemolytic anaemia (AIHA) may require therapy with second-line drugs. There is no consensus that any one of these agents is more effective than another. Mycophenolate mofetil (MMF) is an immunosuppressive drug proven to be effective in reducing renal allograft rejection as well as being used in autoimmune diseases including systemic lupus erythematosus (SLE). We describe its use in two patients who were treated with MMF for AIHA in the context of underlying SLE and antiphospholipid syndrome (APS). The patients showed a good response to treatment with MMF, suggesting a possible role in the treatment of AIHA.

Topics: Adult; Anemia, Hemolytic, Autoimmune; Antiphospholipid Syndrome; Antirheumatic Agents; Female; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Middle Aged; Mycophenolic Acid

Autoimmune hemolytic anemia (AIHA) rarely occurs in myelodysplastic syndrome (MDS). A 36-year-old Asian female was diagnosed with MDS (refractory cytopenia with multilineage dysplasia, RCMD) and complicated by AIHA 7 months later. Secondary myelofibrosis developed at the same time. Steroid therapy was ineffective and cyclosporin A (CsA) was discontinued due to its neurotoxicity with the development of leukoencephalopathy. However, the patient achieved a good hematological response after the use of mycophenolate mofetil (MMF, CellCept) with a dose of 1 g/day and prednisolone (15 mg/day). Prednisolone was tapered off over the next 3 weeks. The patient did not require any blood support 4 weeks after the use of MMF and has been hematologically stable for 4 months. To our knowledge, this is the first report of using MMF in treating MDS complicated by AIHA. MMF might be considered as a salvage therapy for patients with refractory anemia complicated by AIHA.

Topics: Adult; Anemia, Hemolytic, Autoimmune; Anemia, Refractory; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Mycophenolic Acid; Myelodysplastic Syndromes; Prednisolone; Primary Myelofibrosis; Remission Induction; Salvage Therapy

The treatment of both auto-immune haemolytic anaemia (AIHA) and auto-immune thromobocytopenic purpura (AITP) remains unsatisfactory in those refractory to first-line management. Mycophenolate mofetil (MMF) is an immunosuppressive agent originally used to prevent acute rejection of solid organ transplants and used more recently in the management of auto-immune conditions. We report its use in four patients with AIHA and six patients with AITP. All four patients with AIHA and five of the six patients with AITP showed a complete or good partial response to treatment with MMF, confirming a possible role in the treatment of these conditions.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Hemolytic, Autoimmune; Female; Hemoglobins; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Purpura, Thrombocytopenic, Idiopathic

Topics: 2-Chloroadenosine; Aged; Aged, 80 and over; Anemia, Hemolytic, Autoimmune; Antimetabolites, Antineoplastic; Deoxyadenosines; Humans; Immunosuppressive Agents; IMP Dehydrogenase; Male; Middle Aged; Mycophenolic Acid