mycophenolic-acid and Hemorrhage

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor prognosis. Patients with IPF represent a heterogeneous population with several described clinical phenotypes. More recently, the development of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in IPF patients, with an incidence higher than that in the general population, has drawn attention.. A 64-year-old woman previously diagnosed with IPF presented to the emergency department with hemoptysis and hypoxemic respiratory failure.. High-resolution chest computed tomography revealed bilateral ground-glass opacities associated with areas of consolidation superimposed on the patient's fibrotic background pattern. Diffuse alveolar hemorrhage was confirmed by the presence of hemorrhagic bronchoalveolar lavage fluid. Hematological and biochemical investigations revealed an inflammatory syndrome, moderate anemia, and rapidly progressive glomerulonephritis. Serological analysis revealed perinuclear antineutrophil cytoplasmic antibody positivity and high levels of antimyeloperoxidase antibodies antibodies. The patient underwent kidney biopsy, which revealed necrotizing glomerulonephritis. Clinical and laboratory findings were diagnostic of microscopic polyangiitis with lung and renal involvement.. Cyclophosphamide in combination with methylprednisolone was administered as remission induction therapy. The maintenance therapy consisted of mycophenolate mofetil and prednisone.. The patient achieved clinical, radiological, and serological remission within six weeks of treatment.. The association between IPF and ANCA-associated vasculitis may represent a distinct clinical phenotype. Autoimmune testing for ANCAs should be considered part of the diagnostic work-up and follow-up of patients with IPF because of the clinical and therapeutic implications of developing vasculitis in an already vulnerable patient.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Cyclophosphamide; Female; Hemorrhage; Humans; Idiopathic Pulmonary Fibrosis; Methylprednisolone; Middle Aged; Mycophenolic Acid; Prednisone

Dermatomyositis (DM) is a rare inflammatory disorder affecting the muscle and skin. DM patients can present with spontaneous muscle hemorrhage, a potentially fatal complication. The best practice for management of hemorrhagic myositis in these patients remains unclear. Here we discuss the case of a patient who presented with progressive muscle weakness and intermittent rash that was diagnosed with dermatomyositis. During admission, she developed spontaneous hemorrhagic myositis of the right pectoralis major treated with surgical evacuation. She also developed a spontaneous left anterior thigh hematoma which was treated conservatively. She recovered and showed no evidence of recurrent bleeding at either location. We performed a literature review and identified ten cases of spontaneous hemorrhage in DM patients, with a 60% mortality rate among reported cases. Given the high mortality rate associated with spontaneous hemorrhage in DM patients, it is important for physicians to be aware of the diagnosis, workup, and management strategies.

Topics: Compression Bandages; Conservative Treatment; Dermatomyositis; Drainage; Enzyme Inhibitors; Female; Glucocorticoids; Hematoma; Hemorrhage; Hemostasis, Surgical; Humans; Hypotension; Immunoglobulins, Intravenous; Immunologic Factors; Methylprednisolone; Middle Aged; Mortality; Muscular Diseases; Mycophenolic Acid; Pectoralis Muscles; Prednisone; Quadriceps Muscle

Immune thrombocytopenia is a rare autoimmune disorder with associated bleeding risk and fatigue. Recommended first-line treatment for immune thrombocytopenia is high-dose glucocorticoids, but side effects, variable responses, and high relapse rates are serious drawbacks.. In this multicenter, open-label, randomized, controlled trial conducted in the United Kingdom, we assigned adult patients with immune thrombocytopenia, in a 1:1 ratio, to first-line treatment with a glucocorticoid only (standard care) or combined glucocorticoid and mycophenolate mofetil. The primary efficacy outcome was treatment failure, defined as a platelet count of less than 30×10. A total of 120 patients with immune thrombocytopenia underwent randomization (52.4% male; mean age, 54 years [range 17 to 87]; mean platelet level, 7×10. The addition of mycophenolate mofetil to a glucocorticoid for first-line treatment of immune thrombocytopenia resulted in greater response and a lower risk of refractory or relapsed immune thrombocytopenia, but with somewhat decreased quality of life. (Funded by the U.K. National Institute for Health Research; FLIGHT ClinicalTrials.gov number, NCT03156452; EudraCT number, 2017-001171-23.).

Topics: Adolescent; Adult; Aged; Drug Therapy, Combination; Fatigue; Female; Glucocorticoids; Hemorrhage; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Quality of Life; Young Adult

We report a case of a 56-year-old woman with a history of idiopathic thrombocytopenic purpura (ITP) following splenectomy on mycophenolate mofetil (MMF), who developed moderate bleeding after stopping MMF. Her laboratory testing suggested the presence of an abnormal circulating heparin-like anticoagulant with demonstrable anti-Xa activity. She was initially treated with antifibrinolytic therapy and was subsequently started on MMF alongside intravenous immunoglobulin, which significantly improved her bleeding symptoms. The presence of abnormal circulating heparin-like anticoagulants is a rare cause of coagulopathy. Few cases exist in the literature, with nearly all occurring in the setting of hematologic or solid-organ malignancy. The mechanism by which these endogenous anticoagulants develop is unclear. Clinical manifestations range from mild bleeding and bruising to life-threatening hemorrhage refractory to conventional therapy. Diagnosis of a heparin-like anticoagulant is based on coagulation testing as well as exclusion of other exogenous anticoagulants, acquired inhibitors, and/or factor deficiencies.

Topics: Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Coagulation Tests; Factor Xa Inhibitors; Female; Hemorrhage; Heparin; Humans; Hypothyroidism; Middle Aged; Mycophenolic Acid; Purpura, Thrombocytopenic, Idiopathic; Splenectomy

Diffuse alveolar haemorrhage (DAH) is a rare life-threatening complication of systemic lupus erythematosus (SLE), associated with high mortality rates. It usually occurs in patients with an established diagnosis of SLE. It has been reported as the initial presentation of SLE in 11-20% of cases. It occurs most frequently in females. We describe the case of a child, aged 14 years, with fever, asthenia, haemoptysis, dyspnea, anaemia, increased inflammatory markers, positivity to ANA, nDNA, direct Coombs tests, anticardiolipin antibodies and complement factors consumption. Computed tomography (CTscan) of the chest showed bilateral pulmonary alveolar infiltrates. He also developed renal involvement with nephritis later in the course of the disease. He was started on the treatment approved by the Euro Lupus Protocol for critical patients. After starting Mycophenolate Mofetil the clinical and radiological features were improved as was the survival outcome.

Topics: Adolescent; Drug Therapy, Combination; Hemorrhage; Humans; Lung Diseases; Lupus Erythematosus, Systemic; Male; Mycophenolic Acid; Pulmonary Alveoli; Tomography, X-Ray Computed

Topics: Aged, 80 and over; Animals; Antibodies, Neutralizing; Autoantibodies; Biomarkers, Pharmacological; Blood Coagulation; Factor XIII; Factor XIII Deficiency; Hemorrhage; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Prognosis; Risk

Topics: Adult; Atrioventricular Block; Bone Marrow Transplantation; Bradycardia; Electrocardiography; Female; Graft vs Host Disease; Heart Block; Hemorrhage; Humans; Immunosuppressive Agents; Leukemia, Lymphocytic, Chronic, B-Cell; Liver Diseases; Lung Diseases; Methicillin-Resistant Staphylococcus aureus; Methylprednisolone; Mycophenolic Acid; Pneumonia, Staphylococcal; Skin Diseases; Tacrolimus; Transplantation, Homologous

Acquired haemophilia A (AHA) is a bleeding disorder that results from autoantibodies against factor VIII (FVIII). A 70-year-old man with a history of interstitial lung disease presented with spontaneous bleeding into his thigh. He had undetectable FVIII levels and a high-titre FVIII inhibitor (>2000ââ'¬â€°Bethesda units/mL) and was diagnosed with AHA. He had several relapses, required multiple haemostatic and immunosuppressive treatments but eventually achieved a stable remission after 2ââ'¬â€°years of therapy.Our patient matches the typical elderly male demographic of AHA. His relapsing course with remarkably high and persistent inhibitor titre highlights the need for close monitoring and aggressive upfront treatment. Whereas cyclophosphamide and steroids are often used first line in AHA, rituximab has also shown efficacy in refractory patients with high inhibitor levels. The FVIII and inhibitor concentration on presentation have been associated with treatment response and may be used as prognostic factors to tailor immunosuppressive regimens.

Topics: Aged; Antibiotics, Antineoplastic; Flank Pain; Follow-Up Studies; Hemophilia A; Hemorrhage; Humans; Lung Diseases, Interstitial; Male; Mycophenolic Acid; Remission Induction; Secondary Prevention; Thigh; Time Factors; Treatment Outcome

To uniquely classify children with microscopic polyangiitis (MPA), to describe their demographic characteristics, presenting clinical features, and initial treatments in comparison to patients with granulomatosis with polyangiitis (Wegener's) (GPA).. The European Medicines Agency (EMA) classification algorithm was applied by computation to categorical data from patients recruited to the ARChiVe (A Registry for Childhood Vasculitis: e-entry) cohort, with the data censored to November 2015. The EMA algorithm was used to uniquely distinguish children with MPA from children with GPA, whose diagnoses had been classified according to both adult- and pediatric-specific criteria. Descriptive statistics were used for comparisons.. In total, 231 of 440 patients (64% female) fulfilled the classification criteria for either MPA (n = 48) or GPA (n = 183). The median time to diagnosis was 1.6 months in the MPA group and 2.1 months in the GPA group (ranging to 39 and 73 months, respectively). Patients with MPA were significantly younger than those with GPA (median age 11 years versus 14 years). Constitutional features were equally common between the groups. In patients with MPA compared to those with GPA, pulmonary manifestations were less frequent (44% versus 74%) and less severe (primarily, hemorrhage, requirement for supplemental oxygen, and pulmonary failure). Renal pathologic features were frequently found in both groups (75% of patients with MPA versus 83% of patients with GPA) but tended toward greater severity in those with MPA (primarily, nephrotic-range proteinuria, requirement for dialysis, and end-stage renal disease). Airway/eye involvement was absent among patients with MPA, because these GPA-defining features preclude a diagnosis of MPA within the EMA algorithm. Similar proportions of patients with MPA and those with GPA received combination therapy with corticosteroids plus cyclophosphamide (69% and 78%, respectively) or both drugs in combination with plasmapheresis (19% and 22%, respectively). Other treatments administered, ranging in decreasing frequency from 13% to 3%, were rituximab, methotrexate, azathioprine, and mycophenolate mofetil.. Younger age at disease onset and, perhaps, both gastrointestinal manifestations and more severe kidney disease seem to characterize the clinical profile in children with MPA compared to those with GPA. Delay in diagnosis suggests that recognition of these systemic vasculitides is suboptimal. Compared with adults, initial treatment regimens in children were comparable, but the complete reversal of female-to-male disease prevalence ratios is a provocative finding.

Topics: Adolescent; Adrenal Cortex Hormones; Age Distribution; Antibodies, Antineutrophil Cytoplasmic; Asia; Azathioprine; Canada; Child; Child, Preschool; Cohort Studies; Cyclophosphamide; Drug Therapy, Combination; Europe; Female; Granulomatosis with Polyangiitis; Hemorrhage; Humans; Immunosuppressive Agents; Infant; Kidney Failure, Chronic; Lung Diseases; Male; Methotrexate; Microscopic Polyangiitis; Mycophenolic Acid; Nephrotic Syndrome; Oxygen Inhalation Therapy; Plasmapheresis; Proteinuria; Renal Dialysis; Respiratory Insufficiency; Rituximab; United States

Pretransplant removal of antiblood group ABO antibodies is the cornerstone of all current ABO-incompatible (ABOi) transplantation programmes. In our protocol, plasmapheresis (PP) is performed with a plasmafilter followed by immunoadsorption (IA) of anti-ABO antibodies. The bleeding complications of this technique are not known. We analysed the data of all 65 consecutive ABOi kidney transplantations between March 2006 and October 2013 and compared these with matched 130 ABO-compatible (ABOc) kidney transplantations. Cases differed from controls in the pre-operative regimen, which included IA-PP and rituximab, tacrolimus, mycophenolate mofetil, prednisone and immunoglobulines. Data on platelet count, blood loss and red blood cell (EC) transfusions during 48 h postoperatively were collected. ABOi patients received EC transfusions more frequently than controls (29% vs. 12%, P = 0.005). Intra-operative blood loss was higher (544 vs. 355 ml, P < 0.005) and they experienced more major bleeding (≥3 EC within 24 h, 15% vs. 2%, P < 0.0005). Platelet count decreased by 28% after the pre-operative IA. In a multivariate model, only the number of pre-operative IAs was associated with the number of ECs given (OR per IA 1.9, P < 0.05). ABOi kidney transplant recipients have a high postoperative bleeding risk, correlating with the number of pre-operative IA sessions performed.

Topics: ABO Blood-Group System; Antibodies; Antibodies, Monoclonal, Murine-Derived; Antigens; Blood Group Incompatibility; Case-Control Studies; Cohort Studies; Erythrocyte Transfusion; Female; Hemorrhage; Humans; Immunoglobulins; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Multivariate Analysis; Mycophenolic Acid; Platelet Count; Prednisone; Rituximab; Tacrolimus

Immunosuppressive drugs are an integral part of therapy in organ transplantation. However, they are not without side effects, and although rare, these agents should be considered in the differential diagnosis of pulmonary complications in patients receiving transplants. We present a case of a patient who developed acute respiratory failure 7 days after orthotopic heart transplantation and who had been on both mycophenolate mofetil (MMF) and tacrolimus agents. Lung biopsy revealed features of pulmonary hemorrhage with capillaritis. Considered as a possible etiology, MMF was withdrawn. There was immediate improvement of the patient's symptoms. The temporal relationship between MMF exposure and onset of pulmonary symptoms in the absence of other possible etiologies strongly suggests a causal relationship. Previously published reports of pulmonary toxicity from MMF included interstitial fibrosis. To the best of our knowledge, this is the first reported case of pulmonary hemorrhage with capillaritis because of administration of MMF.

Topics: Heart Transplantation; Hemorrhage; Humans; Immunosuppressive Agents; Lung Diseases; Male; Middle Aged; Mycophenolic Acid; Tacrolimus; Vasculitis

Diffuse alveolar hemorrhage (DAH) is rarely seen in patients with systemic lupus erythematosus (SLE), often associated with a poor outcome. It almost affects young women and it is an unusual initial manifestation of SLE. We report a case of SLE presenting with DAH. The patient was a male. He had no history of photosensitivity, malar rash, discoid rash, arthritis, and oral ulcer. Antinuclear antibody, and anti-double stranded DNA (dsDNA) were positive with very high titers, and serum complement levels (C3, C4) were low. He also had renal dysfunction and pericardial effusion. He was diagnosed as DAH due to SLE. He had to undergo hemodialysis for several weeks. DAH and renal dysfunction were improved with intensive treatment including corticosteroid, cyclophosphamide, and mycophenolate mophetil.

Topics: Cyclophosphamide; Diagnosis, Differential; Glucocorticoids; Hemorrhage; Humans; Immunosuppressive Agents; Lung Diseases; Lupus Erythematosus, Systemic; Male; Mycophenolic Acid; Pulmonary Alveoli; Renal Dialysis; Treatment Outcome; Young Adult

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown etiology with multisystem involvement. A number of pulmonary complications including pleuritis, pneumonitis, infectious pneumonia, and pulmonary hemorrhage, have been reported in patients with SLE. Pulmonary hemorrhage is a major life-threatening manifestation in children and adolescents with SLE. Mycophenolate mofetil is an immunosuppressive agent used in solid organ transplantation, and it may play an increasing role in autoimmune disease. In this report, we present two cases of childhood SLE with recurrent pulmonary hemorrhage, which were unresponsive to treatment with high-dose corticosteroids, cytotoxic therapy, IVIG, plasmaphoresis, and supportive therapy, but responded to IV mycophenolate mofetil. A multimodal therapy including mycophenolate mofetil was effective in treatment of these two children.

Topics: Adolescent; Female; Follow-Up Studies; Hemoptysis; Hemorrhage; Humans; Immunosuppressive Agents; Lung Diseases; Lupus Erythematosus, Systemic; Male; Mycophenolic Acid; Radiography; Time Factors; Treatment Outcome

Systemic lupus erythematosus in infants born to healthy mothers is a rare entity. We describe a male infant who presented at 1 month of age with pulmonary hemorrhage and glomerulonephritis due to systemic lupus erythematosus, confirmed serologically and histologically. He was managed with a combination of prednisone and intermittent cyclophosphamide, but also received mycophenolate mofetil, with a complete serological and clinical remission at 30-month follow-up. This case underscores the importance of a broad approach to the evaluation of pulmonary hemorrhage and glomerulonephritis in the very young and the need for aggressive immunosuppressive therapy to achieve sustained serological and clinical remission.

Topics: Cyclophosphamide; Drug Therapy, Combination; Glomerulonephritis; Glucocorticoids; Hemorrhage; Humans; Immunosuppressive Agents; Infant, Newborn; Kidney; Lung Diseases; Lupus Erythematosus, Systemic; Male; Mycophenolic Acid; Prednisone

Systemic lupus erythematosus is a chronic autoimmune disease of unknown etiology with multisystem involvement. Pulmonary hemorrhage is a major life-threatening manifestation in children and adolescents with systemic lupus erythematosus, as well as in adults. Treatment has traditionally been with high-dose corticosteroids, with or without the addition of cytotoxic agents. We report the response of a patient with childhood systemic lupus erythematosus with recurrent pulmonary hemorrhage to treatment with mycophenolate mofetil.

Topics: Adolescent; Combined Modality Therapy; Disease Progression; Drug Therapy, Combination; Hemorrhage; Humans; Hydroxychloroquine; Immunosuppressive Agents; Infusions, Intravenous; Lung Diseases; Lupus Erythematosus, Systemic; Lupus Nephritis; Male; Methylprednisolone; Mycophenolic Acid; Plasmapheresis; Prednisone; Respiration, Artificial

Topics: Adult; Creatinine; Cyclosporine; Edema; Female; Follow-Up Studies; Hemolytic-Uremic Syndrome; Hemorrhage; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Optic Nerve; Time Factors