mycophenolic-acid and Purpura--Thrombotic-Thrombocytopenic

Thrombocytopenia develops in 5% to 10% of women during pregnancy or in the immediate postpartum period. A low platelet count is often an incidental feature, but it might also provide a biomarker of a coexisting systemic or gestational disorder and a potential reason for a maternal intervention or treatment that might pose harm to the fetus. This chapter reflects our approach to these issues with an emphasis on advances made over the past 5 to 10 years in understanding and managing the more common causes of thrombocytopenia in pregnancy. Recent trends in the management of immune thrombocytopenia translate into more women contemplating pregnancy while on treatment with thrombopoietin receptor agonists, rituximab, or mycophenylate, which pose known or unknown risks to the fetus. New criteria to diagnose preeclampsia, judicious reliance on measurement of ADAMTS13 to make management decisions in suspected thrombotic thrombocytopenic purpura, new evidence supporting the efficacy and safety of anticomplement therapy for atypical hemolytic uremic syndrome during pregnancy, and implications of thrombotic microangiopathies for subsequent pregnancies are evolving rapidly. The goals of the chapter are to help the hematology consultant work through the differential diagnosis of thrombocytopenia in pregnancy based on trimester of presentation, severity of thrombocytopenia, and coincident clinical and laboratory manifestations, and to provide guidance for dealing with some of the more common and difficult diagnostic and management decisions.

Topics: ADAMTS13 Protein; Female; Humans; Mycophenolic Acid; Postpartum Period; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Hematologic; Purpura, Thrombotic Thrombocytopenic; Receptors, Thrombopoietin; Rituximab

Haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are related conditions with similar clinical features of variable severity. Survival of patients with HUS and TTP has improved greatly over the past two decades with improved supportive care for patients with HUS and by the use of plasma exchange (PE) with fresh frozen plasma (FFP) for patients with TTP. Separate pathogenesis of these two disorders has become more evident, but management overlaps.. To evaluate the benefits and harms of different interventions for HUS and TTP separately, in patients of all ages.. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), conference proceedings, reference lists of articles and text books and contact with investigators were used to identify relevant studies.. Randomised controlled trials (RCTs) evaluating any interventions for HUS or TTP in patients of all ages.. Three authors independently extracted data and evaluated study reporting quality using standard Cochrane criteria. Analysis was undertaken using a random effects model and results expressed as risk ratio (RR) and 95% confidence intervals (CI).. For TTP, we found six RCTs (331 participants) evaluating PE with FFP as the control. Interventions tested included antiplatelet therapy (APT) plus PE with FFP, FFP transfusion and PE with cryosupernatant plasma (CSP). Two studies compared plasma infusion (PI) to PE with FFP and showed a significant increase in failure of remission at two weeks (RR 1.48, 95% 1.12 to 1.96) and all-cause mortality (RR 1.91, 95% 1.09 to 3.33) in the PI group. Seven RCTs were undertaken in children with HUS. None of the assessed interventions used (FFP transfusion, heparin with or without urokinase or dipyridamole, shiga toxin binding protein and steroids) were superior to supportive therapy alone, for all-cause mortality, neurological/extrarenal events, renal biopsy changes, proteinuria or hypertension at the last follow-up visit. Bleeding was significantly higher in those receiving anticoagulation therapy compared to supportive therapy alone (RR 25.89, 95% CI 3.67 to 182.83).. PE with FFP is still the most effective treatment available for TTP. For patients with HUS, supportive therapy including dialysis is still the most effective treatment. All studies in HUS have been conducted in the diarrhoeal form of the disease. There were no RCTs evaluating the effectiveness of any interventions on patients with atypical HUS who have a more chronic and relapsing course.

Topics: Cyclophosphamide; Hemolytic-Uremic Syndrome; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Mycophenolic Acid; Plasma Exchange; Purpura, Thrombotic Thrombocytopenic; Randomized Controlled Trials as Topic

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

Absolute immature platelet counts (A-IPC) aid in diagnosis and treatment follow-up in thrombotic thrombocytopenic purpura (TTP). A-IPC was used to follow a patient on mycophenolate mofetil (MMF) maintenance therapy treated with a prolonged therapeutic plasma exchange (TPE) regimen for relapsing TTP. On admission, the platelet (PLT) count was 95 × 109/L declining to 14 × 109/L in 5 days. Daily TPE was initiated for suspected TTP, and MMF was discontinued. A-IPC and PLT count were 1 × 109/L and 14 × 109/L, respectively, prior to first TPE. A-IPC improved to 3.2 × 109/L with 1 TPE, and on day 5, A-IPC and PLT count were 7.5 × 109/L and 218 × 109/L, respectively. On day 6, A-IPC and PLT count decreased to 4.8 × 109/L and 132 × 109/L further worsening to 0.4 × 109/L and 13 × 109/L, respectively. ADAMTS13 activity remained <5% with an inhibitor; counts did not recover. Initial improvement followed by rapidly declining A-IPC despite therapy suggested production suppression. In TTP, A-IPC may aid in establishing early therapy effects over PLT production.

Topics: ADAMTS13 Protein; Antibiotics, Antineoplastic; Blood Platelets; Humans; Male; Middle Aged; Mycophenolic Acid; Plasma Exchange; Platelet Count; Purpura, Thrombotic Thrombocytopenic; Recurrence

Acute acquired thrombotic thrombocytopenic purpura (TTP) requires prompt recognition and initiation of plasma exchange (PEX) therapy and immunosuppression. When PEX fails, mortality nears 100%, making finding an effective treatment crucial. Primary refractory TTP occurs when initial therapies fail or if exacerbations occur during PEX therapy, both signifying the need for treatment intensification to achieve clinical remission. Rituximab helps treat most of the refractory TTP cases, except those that are severely refractory. A paucity of studies guiding severely refractory TTP makes management arbitrary and individualised, highlighting the value of isolated reports. We present an extremely rare case of primary refractory TTP with an insufficient platelet response to numerous types of treatments, including emerging therapies such as caplacizumab, on the background of repeated PEX and immunosuppressive therapies.

Topics: ADAMTS13 Protein; Dizziness; Drug Resistance; Fibrinolytic Agents; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Neurologic Examination; Plasma Exchange; Platelet Count; Purpura, Thrombotic Thrombocytopenic; Rituximab; Secondary Prevention; Severity of Illness Index; Single-Domain Antibodies; Syncope; Treatment Outcome; von Willebrand Factor

Thrombotic thrombocytopaenic purpura (TTP) is a life-threatening thrombotic microangiopathy characterised by microangiopathic haemolytic anaemia, thrombocytopaenia and organ ischaemia. TTP is caused by a severe functional deficiency of ADAMTS13 activity. We describe a 10-year-old girl presenting anaemia and thrombocytopaenia with schistocytes. Urine protein to creatinine ratio was within nephrotic range. ADAMTS13 activity was 0%, and no anti-ADAMTS13 antibodies were found. A renal biopsy showed deposits of IgG, C3 and C1q in the capillary membrane, compatible with class V lupus nephritis. Therapeutic plasma exchange (TPE) was performed in conjunction with therapy consisting of steroids and mycophenolate mofetil. After 11 months of follow-up, the patient remains in remission with normal ADAMTS13 activity. Although acquired TTP is a rare finding in children, differential diagnosis of thrombotic microangiopathy should include ADAMTS13 and the assay should be performed early. TTP treatment is based on TPE, although the underlying disease must be ruled out to optimise treatment and prevent relapse.

Topics: ADAMTS13 Protein; Biopsy; Child; Diagnosis, Differential; Female; Glucocorticoids; Humans; Kidney; Lupus Nephritis; Mycophenolic Acid; Plasma Exchange; Purpura, Thrombotic Thrombocytopenic; Sequence Analysis, DNA; Treatment Outcome

Topics: ADAMTS13 Protein; Adolescent; Antibiotics, Antineoplastic; Apoptosis; Biomarkers; Caspase 10; Caspase 8; Disease Susceptibility; Female; Humans; Mutation; Mycophenolic Acid; Proteolysis; Purpura, Thrombotic Thrombocytopenic

A case of relapsing and refractory thrombotic thrombocytopenic purpura received mycophenolate mofetil (MMF) to attempt to maintain remission. The possible use of MMF in thrombotic thrombocytopenic purpura is discussed.

Topics: Female; Humans; Immunosuppressive Agents; Middle Aged; Mycophenolic Acid; Purpura, Thrombotic Thrombocytopenic; Treatment Outcome