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Marchiafava Micheli syndrome [keywords]
- [The variation and clinical significance of paroxysmal nocturnal hemoglobinuria clone in patients with aplastic anemia before and after immunosuppressive therapy]. [English Abstract, Journal Article]
- Zhonghua Nei Ke Za Zhi 2013 Jul; 52(7):585-9.
To evaluate the evolution of paroxysmal nocturnal hemoglobinuria (PNH) clone and its clinical significance before and after immunosuppressive therapy (IST) in patients with aplastic anemia (AA).A total of 186 patients diagnosed as AA were enrolled in this study. Among them, 55 patients were diagnosed as severe AA (SAA) and treated with cyclosporine (CsA) plus anti-thymocyteglobulin (ATG), 131 were diagnosed as non SAA (NSAA) and treated with CsA alone. All patients were screened for PNH clone by flow cytometry before treatment and followed up for 18-76 months, with a median time of 22 months.Positive PNH clones were detected in 10 SAA (18.9%) patients, significantly more than that of NSAA group [9 patients (7.4%), t = 5.041, P = 0.025]. The proportions of PNH clones in SAA group at 6, 12, 24 and > 24 months were 13.38%, 14.88%, 20.00% and 18.85%, respectively, also significantly higher than those of NSAA patients (5.67%, 5.31%, 5.47% and 9.08%, all P values < 0.05). Clinical response rates were comparable in both ATG+CsA or CsA alone groups no matter PNH clone was positive or negative.PNH clone are detectable in AA patients either treated with ATG plus CsA or CsA alone, and more significant by ATG plus CsA. Whether PNH clone occurres before or after IST does not affect the therapeutic efficacy.
- Long-term outcome of immunosuppressive therapy for Japanese patients with lower-risk myelodysplastic syndromes. [JOURNAL ARTICLE]
- Int J Hematol 2013 Nov 20.
To investigate the long-term usefulness of immunosuppressive therapy (IST) for Japanese patients with lower-risk myelodysplastic syndromes, we retrospectively analyzed 29 MDS patients who were treated with cyclosporine A alone or with anti-thymocyte globulin at a single institute in Japan. A total of 58.6 % of patients showed hematological response to IST. Overall survival of all patients was 74.5 % at 5 years and 48.3 % at 10 years. The major adverse event was the elevation of creatinine level (grade 1 and 2). Eleven patients were still on IST at the time of analysis with, at least, some clinical benefits. Pneumonia was the most frequent cause of death (eight of 12 deaths), followed by bleeding (three of 12); most of the patients who died were non-responders. The presence of paroxysmal nocturnal hemoglobinuria-type cells was significantly associated with both response to IST and long-term survival by univariate analysis. The 10-year overall survival of responders (72.2 %) was significantly superior to that of non-responders (15.6 %, P < 0.0001). These results suggest that IST using cyclosporine A provides long-term benefit for Japanese patients with lower-risk MDS.
- A prospective multicenter study of paroxysmal nocturnal hemoglobinuria cells in patients with bone marrow failure. [JOURNAL ARTICLE]
- Cytometry B Clin Cytom 2013 Nov 12.
Paroxysmal nocturnal hemoglobinuria (PNH), a rare clonal hematopoietic stem cell disorder, is characterized by chronic, uncontrolled complement activation leading to intravascular hemolysis and an inflammatory prothrombotic state. The EXPLORE study aimed to determine the prevalence of undiagnosed PNH in patients with aplastic anemia (AA), myelodysplastic syndrome (MDS), and/or other bone marrow failure (BMF) syndromes and the effect of PNH clone size on hemolysis.Patients, selected from medical office chart reviews, had blood samples collected for hematologic panel testing and for flow cytometry detection of PNH clones.Granulocyte PNH clones ≥ 1% were detected in 199 of all 5,398 patients (3.7%), 93 of 503 AA patients (18.5%), 50 of 4,401 MDS patients (1.1%), and 3 of 130 other BMF patients (2.3%). Higher-sensitivity analyses detected PNH clones ≥ 0.01% in 167 of 1,746 patients from all groups (9.6%) and in 22 of 1,225 MDS patients (1.8%), 116 of 294 AA patients (39.5%), and four of 54 other BMF patients (7.8%). Among patients with PNH clones ≥ 1%, median clone size was smaller in patients with AA (5.1%) than in those with MDS (17.6%) or other BMF (24.4%), and the percentage of patients with lactate dehydrogenase levels (a marker for intravascular hemolysis) ≥ 1.5 × upper limit of normal was smaller in patients with AA (18.3%) than in those with MDS (42.0%).These results confirm the presence of PNH clones in high-risk patient groups and suggest that screening of such patients may facilitate patient management and care. © 2013 The Authors. Published by Wiley Periodicals, Inc.
- Detection of CD59 Using Flow Cytometry. [Journal Article]
- Methods Mol Biol 2014.:341-6.
CD59 is the single regulator of the terminal complement pathway. It has been implicated in disease such as Paroxysmal nocturnal hemoglobinuria (PMH) and cancer. Expression of CD59 protects normal and malignant cells from the cytotoxic potential of the complement system. Here we describe a method, which allows for studying its expression on the surface of cells.
- Paroxysmal Nocturnal Hemoglobinuria: A Red Clot Syndrome. [JOURNAL ARTICLE]
- Ann Vasc Surg 2013 Nov 4.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, nonmalignant disorder of hematopoietic stem cells characterized by hemolysis, diminished hematopoiesis, and thrombophilia. We describe a 65-year-old woman with known PNH and peripheral arterial disease who presented with critical limb ischemia and a nonhealing left foot ulcer. She underwent surgical bypass of a diffusely diseased left superficial femoral artery with autologous reversed saphenous vein graft. Her postoperative course was complicated by wound sepsis and PNH exacerbation with resultant graft thrombosis requiring an above-knee amputation. This case highlights several key concepts relevant to the management of vascular surgery patients with PNH: (1) their predisposition for arterial and venous thrombosis; (2) hypercoagulability despite standard anticoagulation regimens; (3) the role of eculizumab (a monoclonal antibody that inhibits complement activation used to treat PNH) in reducing thrombotic complications and hemolysis; and (4) complications associated with the immunosuppressive effects of eculizumab. We recommend careful monitoring of hemolysis and immunosuppression, aggressive anticoagulation, frequent graft surveillance, and early consultation with hematology.
- Paroxysmal nocturnal haemoglobinuria. Experience over a 10 years period. [JOURNAL ARTICLE]
- Int J Lab Hematol 2013 Nov 5.
Paroxysmal nocturnal hemoglobinuria (PNH) is a hemolytic, clonal and acquired disorder of the hematopoietic stem cell with a deficiency of all glycophosphatidyl-inositol (GPI) linked proteins. The aim of this retrospective study was to analyse haematological and biochemical data from 152 patients referred to our laboratory for diagnosis of PNH by flow cytometry (FC).Patients and healthy donor (152 and 99 respectively) were studied. Ham, sucrose, lactate dehydrogenase (LDH), Iron, haptoglobin (Hp), blood cell morphology and Kaplow cytochemical stain for leukocyte alkaline phosphatase (LAP) were carried out. GPI-proteins anti-CD55 and CD59 in erythrocytes and the former, plus anti CD16b and CD66b on neutrophils were evaluated by FC.Anemia and/or leukopenia and/or thrombocytopenia, increased reticulocyte count and LDH were observed in patients with PNH clone. Some of them had dacriocytes, schistocytes. LAP was low. On average, we detected 50% CD59 (-) erythrocytes and 29, 83, 78% CD55/59 (-), CD16b (-), CD66b (-) neutrophils, respectively.Paroxysmal nocturnal hemoglobinuria clone was detected in 20/152 patients. Negative population's percentages were high in patients with classic PNH, Hematimetry, LAP and adequate use of CF contribute to PNH clone detection in the laboratory.
- Paroxysmal nocturnal hemoglobinuria and the age of therapeutic complement inhibition. [Journal Article]
- Expert Rev Clin Immunol 2013 Nov; 9(11):1113-24.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease of hematopoietic stem cells due to a mutation in the PIG-A gene leading to a deficiency of GPI-anchored proteins. Lack of two specific GPI-anchored proteins, CD55 and CD59, leads to uncontrolled complement activation that result in both intravascular and extravascular hemolysis. Free hemoglobin leads to nitric oxide depletion that mediates the pathophysiology of some of the common clinical signs of PNH. Clinical symptoms of PNH include evidence of hemolytic anemia, bone marrow failure, smooth muscle dystonias and thromboses. Treatment options for patients with PNH include bone marrow transplantation, a therapy associated with high morbidity and mortality, or treatment with the complement inhibitor eculizumab. Eculizumab is a first-in-class anti-complement drug that in PNH has been shown to block complement-mediated hemolysis, reduce transfusion dependency, reduce thromboembolic complications and improve the quality of life (QoL) of patients.
- Dysplasia Features of Myelodysplastic Syndrome in Ethnically Chinese People. [JOURNAL ARTICLE]
- Acta Haematol 2013 Oct 22; 131(2):126-132.
Objective: It was our aim to study the diagnostic significances of various dysplasia characteristics in myelodysplastic syndrome (MDS). Methods: We analyzed 160 cases of primary MDS and a control group including 28 cases of paroxysmal nocturnal hemoglobinuria (PNH), 104 cases of idiopathic thrombocytopenic purpura (ITP), 53 cases of non-severe aplastic anemia (NSAA), 40 cases of megaloblastic anemia and 50 cases of infectious and autoimmune diseases. Peripheral blood smears and bone marrow morphology were reviewed. Results: There was no significant difference in the occurrence rates of a variety of dysplasias in three lineages among MDS, megaloblastic anemia and PNH; however, changes in qualities and quantities in three lineages between NSAA and MDS were significantly different. ITP and MDS showed statistical differences in multiple changes in myeloid and erythroid cells. Significant differences also existed in multiple changes in erythroid series and megakaryocytes between infectious and autoimmune diseases and MDS. Morphological abnormalities highly related with MDS included multinucleated erythroblasts, ringed sideroblasts, poikilocytosis and gigantocytes, pseudo-Pelger neutrophils, ring-shaped nucleus, and micromegakaryocytes. Conclusions: It is difficult to discriminate megaloblastic anemia and PNH from MDS by means of cell morphology. Different dysplasias of MDS have specific diagnostic values. © 2013 S. Karger AG, Basel.
- Paroxysmal cold hemoglobinuria caused by an IgM-class Donath-Landsteiner antibody. [Journal Article]
- Pediatr Int 2013 Oct; 55(5):664-6.
We report on a 4-year-old boy who developed paroxysmal cold hemoglobinuria (PCH) following the first dose of a seven-valent pneumococcal conjugate vaccine. He was admitted because of dark urine after exposure to cold air. Laboratory tests indicated anemia, increased serum indirect bilirubin and lactate dehydrogenase, and decreased serum haptoglobin. Donath-Landsteiner (D-L) test was positive. The D-L antibody belonged to the IgM class and exhibited anti-P specificity. Symptoms and signs subsided after supportive care without any medication. Although PCH is often associated with viral or bacterial infection and is caused by IgG-class D-L antibodies with anti-P specificity, this case was unique because a D-L antibody of the IgM class with anti-P specificity caused PCH after immunization with a pneumococcal vaccine.
- A Prospective Multicenter Study of Paroxysmal Nocturnal Hemoglobinuria Cells in Patients with Bone Marrow Failure. [JOURNAL ARTICLE]
- Cytometry B Clin Cytom 2013 Oct 11.
Background: Paroxysmal nocturnal hemoglobinuria (PNH), a rare clonal hematopoietic stem cell disorder, is characterized by chronic, uncontrolled complement activation leading to intravascular hemolysis and an inflammatory prothrombotic state. The EXPLORE study aimed to determine the prevalence of undiagnosed PNH in patients with aplastic anemia (AA), myelodysplastic syndrome (MDS), and/or other bone marrow failure (BMF) syndromes and the effect of PNH clone size on hemolysis. Methods: Patients, selected from medical office chart reviews, had blood samples collected for hematologic panel testing and for flow cytometry detection of PNH clones. Results: Granulocyte PNH clones ≥ 1% were detected in 199 of all 5398 patients (3.7%), 93 of 503 AA patients (18.5%), 50 of 4401 MDS patients (1.1%), and 3 of 130 other BMF patients (2.3%). Higher-sensitivity analyses detected PNH clones ≥ 0.01% in 167 of 1746 patients from all groups (9.6%) and in 22 of 1225 MDS patients (1.8%), 116 of 294 AA patients (39.5%), and 4 of 54 other BMF patients (7.8%). Among patients with PNH clones ≥ 1%, median clone size was smaller in patients with AA (5.1%) than in those with MDS (17.6%) or other BMF (24.4%), and the percentage of patients with lactate dehydrogenase levels (a marker for intravascular hemolysis) ≥ 1.5 × upper limit of normal was smaller in patients with AA (18.3%) than in those with MDS (42.0%). Conclusions: These results confirm the presence of PNH clones in high-risk patient groups and suggest that screening of such patients may facilitate patient management and care. © 2013 Clinical Cytometry Society.