Download the Free Unbound MEDLINE PubMed App to your smartphone or tablet.
Available for iPhone, iPad, iPod touch, and Android.
Marchiafava Micheli syndrome [keywords]
- [The evaluation and comparative characteristic of detection of clone of paroxysmal nocturnal hemoglobinuria on reticulocytes using the technique of flow cytometry]. [English Abstract, Journal Article]
- Klin Lab Diagn 2014 Jul; 59(7):25-8, 40.
The paroxysmal nocturnal hemoglobinuria is a rare clonal disease characterized by somatic mutation of gene PIG-A at the level of stem hematopoietic cell. This process results in disorder of synthesis of glycosil phosphatidyl innozitol (GPI) anchor fixing numerous molecules on membrane of blood cells which protect blood cells from impact of complement. The international society of clinical cytometry (2010) proposed the guidelines of detection of clone of paroxysmal nocturnal hemoglobinuria among erythrocytes, granulocytes and monocytes. The original technique is proposed to evaluate the clone of paroxysmal nocturnal hemoglobinuria in reticulocyte population of blood using method of flow cytofluorometry. The sampling of 160 samples of blood of patients with clinical symptoms of paroxysmal nocturnal hemoglobinuria and anemia was analyzed. Two modes of gatedrawing were applied--using monoclonal antibodies to CD71 (receptor to transferrin) and reagent BD ReticCount. The high correlation was established between size of reticulocytic clone of paroxysmal nocturnal hemoglobinuria evaluated by CD71 and size of granulocytic and monocytic clone of paroxysmal nocturnal hemoglobinuria. The developed panel (CD71/CD235a/CD59) can be applied for screening and monitoring of paroxysmal nocturnal hemoglobinuria.
- Biomechanical properties of red blood cells in health and disease towards microfluidics. [Journal Article, Review]
- Biomicrofluidics 2014 Sep; 8(5):051501.
Red blood cells (RBCs) possess a unique capacity for undergoing cellular deformation to navigate across various human microcirculation vessels, enabling them to pass through capillaries that are smaller than their diameter and to carry out their role as gas carriers between blood and tissues. Since there is growing evidence that red blood cell deformability is impaired in some pathological conditions, measurement of RBC deformability has been the focus of numerous studies over the past decades. Nevertheless, reports on healthy and pathological RBCs are currently limited and, in many cases, are not expressed in terms of well-defined cell membrane parameters such as elasticity and viscosity. Hence, it is often difficult to integrate these results into the basic understanding of RBC behaviour, as well as into clinical applications. The aim of this review is to summarize currently available reports on RBC deformability and to highlight its association with various human diseases such as hereditary disorders (e.g., spherocytosis, elliptocytosis, ovalocytosis, and stomatocytosis), metabolic disorders (e.g., diabetes, hypercholesterolemia, obesity), adenosine triphosphate-induced membrane changes, oxidative stress, and paroxysmal nocturnal hemoglobinuria. Microfluidic techniques have been identified as the key to develop state-of-the-art dynamic experimental models for elucidating the significance of RBC membrane alterations in pathological conditions and the role that such alterations play in the microvasculature flow dynamics.
- A paroxysmal nocturnal haemoglobinuria progress with waldenström macroglobulinemia along with T cell monoclonal expansion. [Journal Article]
- Indian J Hematol Blood Transfus 2014 Sep; 30(Suppl 1):227-31.
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem cell clinical disease, which has been reported associated with T cell monoclonal expansion and plasma cell dyscrasias. There we reported a case with a 20-year clinical history of PNH. Lately diagnosis of Waldenström macroglobulinemia with the offered evidences of bone marrow examination, flow cytometry and immunofixation electrophoresis. T cell monoclonal expansion was established by polymerase chain reaction. Meanwhile the decreased expression of CD55 and CD59 on neutrophils and erythrocyte were obvious observed. Here we describe the diagnostic evaluation of this patient and provide a brief review of such clonal disorder.
- Hematopoietic stem cell transplantation for aplastic anemia and paroxysmal nocturnal hemoglobinuria: current evidence and recommendations. [JOURNAL ARTICLE]
- Expert Rev Hematol 2014 Oct 21.:1-15.
Aplastic anemia (AA) is a bone marrow failure syndrome characterized by pancytopenia and an empty bone marrow. Standard treatments for AA include immunosuppressive therapy and bone marrow transplantation (BMT). BMT is the preferred option for young AA patients with a sibling donor, whereas in older patients or in those to be grafted from an unrelated donor BMT is exploited as second-line treatment. Current results of BMT for AA demonstrate cure rates up to 80 and 70% in BMT from HLA-matched siblings and unrelated donor, respectively, with age and stem cell source largely affecting the outcome. BMT is also a potential treatment option for paroxysmal nocturnal hemoglobinuria, a rare hematological disorder characterized by complement-mediated intravascular hemolytic anemia, thrombophilia and bone marrow failure.
- First-Line Immunosuppressive Treatment in Children with Aplastic Anemia: Rabbit Antithymocyte Globulin. [JOURNAL ARTICLE]
- Adv Exp Med Biol 2014 Oct 14.
Immunosuppressive therapy is the treatment of choice in children with acquired severe aplastic anemia (AA) and no HLA-matched family donor. The paper presents results of a multicenter study of 63 children with AA treated with rabbit antithymocyte globulin (r-ATG) and cyclosporine A as the first line treatment in the years 1996-2012. Therapeutic effects were evaluated at Days 112, 180, and 360. At Day 112, remission was achieved in 28 out of the 63 patients (44.4 %), complete remission in 10 patients (15.9 %), and partial remission in 18 (28.5 %). At Day 180, 31 patients (49.2 %) were in remission including 15 cases in complete (23.8 %), and 16 cases in partial remission (25.4 %). One year after therapy onset, 34 patients (64.9 %) were in remission including 24 patients (38.0 %) in complete and 10 (15.9 %) in partial remission. Relapse occurred in 4 patients, from 8 months up to 2 years and 2 months after remission. One child, 5 years after remission, was diagnosed with paroxysmal nocturnal hemoglobinuria. The estimated 10-year overall survival rate and 10-year event-free survival rate were 67 % and 57 %, respectively.
- [C5: eculizumab]. [English Abstract, Journal Article]
- Brain Nerve 2014 Oct; 66(10):1191-9.
Abstract Eculizumab is a recombinant humanized monoclonal antibody that specifically binds to a C5 terminal complement and inhibits the cleavage of C5 to C5a and C5b through complement activation. Eculizumab has been used clinically for paroxysmal nocturnal hemoglobinuria. Clinical studies have been initiated for neurological disorders, such as, optic neuromyelitis and myasthenia gravis, mediated by the complement system. In addition, eculizumab is expected to be useful for the treatment of intractable neurological diseases.
- Treatment of autoimmune hemolytic anemias. [REVIEW]
- Haematologica 2014 Oct; 99(10):1547-1554.
Autoimmune hemolytic anemia (AIHA) is a relatively uncommon disorder caused by autoantibodies directed against self red blood cells. It can be idiopathic or secondary, and classified as warm, cold (cold hemagglutinin disease (CAD) and paroxysmal cold hemoglobinuria) or mixed, according to the thermal range of the autoantibody. AIHA may develop gradually, or have a fulminant onset with life-threatening anemia. The treatment of AIHA is still not evidence-based. The first-line therapy for warm AIHA are corticosteroids, which are effective in 70-85% of patients and should be slowly tapered over a time period of 6-12 months. For refractory/relapsed cases, the current sequence of second-line therapy is splenectomy (effective approx. in 2 out of 3 cases but with a presumed cure rate of up to 20%), rituximab (effective in approx. 80-90% of cases), and thereafter any of the immunosuppressive drugs (azathioprine, cyclophosphamide, cyclosporin, mycophenolate mofetil). Additional therapies are intravenous immunoglobulins, danazol, plasma-exchange, and alemtuzumab and high-dose cyclophosphamide as last resort option. As the experience with rituximab evolves, it is likely that this drug will be located at an earlier point in therapy of warm AIHA, before more toxic immunosuppressants, and in place of splenectomy in some cases. In CAD, rituximab is now recommended as first-line treatment.
- Deep sequencing reveals stepwise mutation acquisition in paroxysmal nocturnal hemoglobinuria. [JOURNAL ARTICLE]
- J Clin Invest 2014 Sep 17.
Paroxysmal nocturnal hemoglobinuria (PNH) is a nonmalignant clonal disease of hematopoietic stem cells that is associated with hemolysis, marrow failure, and thrombophilia. PNH has been considered a monogenic disease that results from somatic mutations in the gene encoding PIGA, which is required for biosynthesis of glycosylphosphatidylinisotol-anchored (GPI-anchored) proteins. The loss of certain GPI-anchored proteins is hypothesized to provide the mutant clone with an extrinsic growth advantage, but some features of PNH argue that there are intrinsic drivers of clonal expansion. Here, we performed whole-exome sequencing of paired PNH+ and PNH- fractions on samples taken from 12 patients as well as targeted deep sequencing of an additional 36 PNH patients. We identified additional somatic mutations that resulted in a complex hierarchical clonal architecture, similar to that observed in myeloid neoplasms. In addition to mutations in PIGA, mutations were found in genes known to be involved in myeloid neoplasm pathogenesis, including TET2, SUZ12, U2AF1, and JAK2. Clonal analysis indicated that these additional mutations arose either as a subclone within the PIGA-mutant population, or prior to PIGA mutation. Together, our data indicate that in addition to PIGA mutations, accessory genetic events are frequent in PNH, suggesting a stepwise clonal evolution derived from a singular stem cell clone.
- The mutational landscape of paroxysmal nocturnal hemoglobinuria revealed: new insights into clonal dominance. [JOURNAL ARTICLE]
- J Clin Invest 2014 Sep 17.:1-4.
Paroxysmal nocturnal hemoglobinuria (PNH) is a disorder of hematopoietic stem cells that has largely been considered a monogenic disorder due to acquisition of mutations in the gene encoding PIGA, which is required for glycosylphosphatidylinositol (GPI) anchor biosynthesis. In this issue of the JCI, Shen et al. discovered that PNH is in fact a complex genetic disorder orchestrated by many genetic alterations in addition to PIGA mutations. Some of these mutations predate the acquisition of PIGA mutations, while others occur later. Surprisingly, this work indicates that PNH has a clonal evolution and architecture strikingly similar to that of other myeloid neoplasms, highlighting a potentially broader mechanism of disease pathogenesis in this disorder.