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Paroxysmal nocturnal haemoglobinuria

Kohei Hosokawa, Sachiko Kajigaya, Keyvan Keyvanfar, Wangmin Qiao, Yanling Xie, Angelique Biancotto, Danielle M Townsley, Xingmin Feng, Neal S Young
The aetiology of paroxysmal nocturnal haemoglobinuria (PNH) is a somatic mutation in the X-linked phosphatidylinositol glycan class A gene (PIGA), resulting in global deficiency of glycosyl phosphatidylinositol-anchored proteins (GPI-APs). This study applied RNA-sequencing to examine functional effects of the PIGA mutation in human granulocytes. CXCR2 expression was increased in GPI-AP(-) compared to GPI-AP(+) granulocytes. Macrophage migration inhibitory factor, a CXCR2 agonist, was significantly higher in plasma of PNH patients...
February 1, 2017: British Journal of Haematology
Marilena Briglia, Maria Antonia Rossi, Caterina Faggio
Prior to senescence, erythrocytes may, experience injury which compromises their integrity and thus triggers suicidal erythrocyte death or eryptosis. This mechanism is characterised by cell shrinkage, cell membrane blebbing, and cell membrane phospholipid scrambling after phosphatidylserine exposure on the cell surface that is identified by macrophages which engulf and degrade the eryptotic cells. The term eryptosis also includes typical mechanisms, which contribute to the triggering of this process. Among them: oxidative stress, Ca2+ entry with an increase in cytosolic Ca2+ activity ([Ca ]i) and the activation of p38 kinase, which is a kinase expressed in human erythrocytes and activated after hyperosmotic shock...
November 18, 2016: Current Medicinal Chemistry
Abdul A Shlebak, Alexia D Katsarou, George Adams, Fiona Fernando
Dysfibrinogenaemias may present in either congenital or acquired form and are disorders of fibrinogen structure which may or may not be associated with abnormal function. More than 100 point mutations with single amino acid substitutions have been identified in over 400 families. These lead to defective DNA in the translated fibrinogen molecule. Such cases have improved our understanding of the fibrinogen-fibrin structure. Six members of a consanguineous family including a female proband, a female sibling, three male siblings and a daughter, with ages between 29 years and 53 years presented with early onset venous and premature arterial thromboembolic disease were investigated for a pro-thrombotic tendency associated with dysfibrinogenaemia...
November 3, 2016: Journal of Thrombosis and Thrombolysis
X Qi, G Han, X Guo, V De Stefano, K Xu, Z Lu, H Xu, A Mancuso, W Zhang, X Han, D C Valla, D Fan
BACKGROUND: China may have the largest number of Budd-Chiari syndrome (BCS) cases in the world (at least 1914 original papers were published, and at least 20 191 BCS patients were reported). Considering the discrepancy in the clinical profiles and preferred treatment selection of primary BCS between the West and China, understanding its aetiology in these two different regions is very important. AIM: To review the data from large cohort studies and meta-analyses to illustrate the epidemiology of risk factors for BCS in the West and China...
December 2016: Alimentary Pharmacology & Therapeutics
Aude Servais, Nadège Devillard, Véronique Frémeaux-Bacchi, Aurélie Hummel, Laurent Salomon, Cécile Contin-Bordes, Hélène Gomer, Christophe Legendre, Yahsou Delmas
BACKGROUND: A therapeutic strategy based on complement blockade by eculizumab is widely used to treat atypical haemolytic uraemic syndrome (aHUS). Recent data are available on the administration of eculizumab during pregnancy in patients treated for paroxysmal nocturnal haemoglobinuria but there are very few data for aHUS patients. METHODS: We analysed the use of eculizumab for the treatment of aHUS during five pregnancies in three patients and studied an additional pregnancy without eculizumab...
December 2016: Nephrology, Dialysis, Transplantation
Chizuru Saito, Ken Ishiyama, Hirohito Yamazaki, Yoshitaka Zaimoku, Shinji Nakao
Patients with mild hypomegakaryocytic thrombocytopenia (HMT) that does not meet the diagnostic criteria for a definite disease entity may potentially progress to aplastic anaemia (AA) that is refractory to therapy. To clarify the clinical picture of HMT, we prospectively followed 25 HMT patients with white blood cell count >3·0 × 10(9) /l, haemoglobin level >100 g/l and platelet count of <100·0 × 10(9) /l in the absence of morphological and karyotypic abnormalities in the bone marrow. Glycosylphosphatidylinositol-anchored protein-deficient blood cells [paroxysmal nocturnal haemoglobinuria (PNH)-type cells] were detected in 7 of the 25 (28%) patients and elevated plasma thrombopoietin (TPO, also termed THPO) levels (>320 pg/ml) were observed in 11 (44%) patients...
June 28, 2016: British Journal of Haematology
G Socié, H Schrezenmeier, P Muus, I Lisukov, A Röth, A Kulasekararaj, J W Lee, D Araten, A Hill, R Brodsky, A Urbano-Ispizua, J Szer, A Wilson, P Hillmen
BACKGROUND: Paroxysmal nocturnal haemoglobinuria (PNH) is a rare disease. Although much progress has been made in the understanding of the pathophysiology of the disease, far less is known with respect to the clinical outcomes of patients with PNH. Few retrospective studies provide survival estimates, and even fewer have explored the clinical heterogeneity of the disease. Haemolytic and aplastic anaemia (AA) forms of the disease have been recognised as main disease categories, with the haemolytic form being associated with the worst prognosis by the largest studied cohort some years ago...
September 2016: Internal Medicine Journal
Dániel Horányi, Andrea Várkonyi, Gyula Richárd Nagy, Imre Bodó, Tamás Masszi
Paroxysmal nocturnal hemoglobinuria is a rare hematological disease. It is associated with increased maternal and fetal complications to such an extent that pregnancy has been considered relatively contraindicated in woman with paroxysmal nocturnal haemoglobinuria. Recently, eculizumab, a monoclonal antibody, has been shown to decrease complications during pregnancies. The highest risk is thromboembolic complication and, therefore, anticoagulant is a standard therapy during pregnancy. In the presented case, a 29-year-old woman with a 5-year history of paroxysmal nocturnal haemoglobinuria had a pregnancy...
June 5, 2016: Orvosi Hetilap
Athina Damianaki, Elias Stagakis, Irene Mavroudi, Michael Spanoudakis, Helen Koutala, Fotios Papadogiannis, Peggy Kanellou, Charalampos Pontikoglou, Helen A Papadaki
Chronic idiopathic neutropenia (CIN) is an acquired disorder of granulopoiesis characterized by increased apoptosis of the bone marrow (BM) granulocytic progenitor cells under the influence of pro-inflammatory mediators and oligoclonal/monoclonal T-lymphocytes. Because patients with immune-mediated BM failure display frequently paroxysmal nocturnal hemoglobinuria (PNH)-type cells in the peripheral blood (PB), we investigated the possible existence of PNH-type cells in 91 patients with CIN using flow cytometry...
December 2016: European Journal of Haematology
J C W Marsh, G J Mufti
Aplastic anaemia (AA) is frequently associated with other disorders of clonal haemopoiesis such as paroxysmal nocturnal haemoglobinuria (PNH), myelodysplastic syndrome (MDS) and T-large granular lymphocytosis. Certain clones may escape the immune attack within the bone marrow environment and proliferate and attain a survival advantage over normal haemopoietic stem cells, such as trisomy 8, loss of heterozygosity of short arm of chromosome 6 and del13q clones. Recently acquired somatic mutations (SM), excluding PNH clones, have been reported in around 20-25 % of patients with AA, which predispose to a higher risk of later malignant transformation to MDS/acute myeloid leukaemia...
August 2016: International Journal of Hematology
Natalia Rompoti, Uwe Hillen, Alexander Rösch, Joachim Dissemond
No abstract text is available yet for this article.
August 1, 2016: European Journal of Dermatology: EJD
Fabio Timeus, Nicoletta Crescenzio, Luiselda Foglia, Alessandra Doria, Paola Saracco
Paroxysmal nocturnal haemoglobinuria (PNH) is very rare in children. The review of the literature shows some peculiarities of paediatric age: high incidence of bone marrow failure at diagnosis, dark urines uncommon, diagnosis often delayed. The thrombosis incidence is variable in the different reports, but in general lower than in adults. The presence of glycosil phosphatidyl-inositol (GPI)-negative populations in acquired aplastic anaemia (AA) at diagnosis has been correlated with a favourable response to immune-suppressive therapy (IST) in adults, whereas the literature data in children are discordant...
April 1, 2016: Current Drug Targets
Matthew Fletcher, Liam Whitby, Alison Whitby, David Barnett
Background Paroxysmal Nocturnal Haemoglobinuria (PNH) is a rare acquired genetic disorder, with an incidence of approximately 1.3 new cases per million population per year. Evidence from the UK National External Quality Assessment Service for Leucocyte Immunophenotyping (UK NEQAS LI) programme suggested major discrepancies on how PNH testing is undertaken. To investigate this we surveyed laboratories in the UK NEQAS LI PNH programme and report here the findings. Method A questionnaire was distributed to all centres registered in UK NEQAS LI flow cytometry programmes (n=1587)...
March 2, 2016: Cytometry. Part B, Clinical Cytometry
Luísa Azevedo, Mariana Reis Costa, Ana Catarina Fonseca, Teresa Pinho e Melo
The authors present a case of a 28-year-old man with a known history of paroxysmal nocturnal haemoglobinuria (PNH), under platelet antiaggregation, admitted following recurrent transitory arterial ischaemic attacks. Concomitant thrombosis of the superior mesenteric artery and bilateral renal infarction was found. Cardioembolism, namely patent foramen ovale, was excluded and anticoagulation added, with no further events on 10-month follow-up. PNH is a rare acquired disorder of haematopoietic stem cells, characterised by haemolytic anaemia, pancytopenia and thrombotic events classically involving the venous system...
February 4, 2016: BMJ Case Reports
Archana Dambal, Naren V Nimbal, Shanmukh T Kalsad, K Pramod, M P Madhavaranga
Paroxysmal Nocturnal Haemoglobinuria (PNH) is a rare type of acquired Haemolytic anaemia that is described as a triad of acquired intravascular Haemolysis, venous thrombosis and anaemia with pancytopenia sometimes due to bone marrow failure. However the classical triad may not be observed at once and fever due to leucocytopenia may confuse the clinical picture. Since this is a rare disease, other epidemiologically common causes may be attributed to the illness. We report a case of PNH with a rare association of malaria due to Falciparum and Vivax species which was undiagnosed for 6 years in a young man...
August 2015: Journal of Clinical and Diagnostic Research: JCDR
P J Lachmann, E Lay, D J Seilly, A Buchberger, W Schwaeble, J Khadake
In this paper we have extended our earlier studies of the action of increasing Factor I concentration on complement activation by using a soluble activator, lipopolysaccharide (LPS) endotoxin, and using human erythrocytes as a source of CR1 - the co-factor needed for the final clip of iC3b to C3dg by Factor I. Using this more physiological system, the results show that we can predict that a quite modest increase in Factor I concentration - 22 µg/ml of extra Factor I - will convert the activity of the highest risk sera to those of the lowest risk...
January 2016: Clinical and Experimental Immunology
Tomoyuki Sasano, Takuji Tomimatsu, Jun-Ichi Nishimura, Itaru Matsumura, Yuzuru Kanakura, Tadashi Kimura
Paroxysmal nocturnal haemoglobinuria (PNH) is a rare acquired disorder of haematopoietic stem cells characterized by intravascular haemolysis, cytopenias and thrombophilia. Thrombophilia is the leading cause of mortality in patients with PNH. As the risk of thrombogenesis further increases during pregnancy and the postpartum period, an anticoagulant therapy is generally recommended for pregnant women with PNH. However, there are no standardized criteria for determining the appropriate dose of anticoagulant therapy...
January 2016: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
Laura Rodriguez-Osorio, Alberto Ortiz
Eculizumab is an anti-C5 antibody that inhibits C5 cleavage and prevents the generation of the terminal complement complex C5b-9. Eculizumab is licensed to treat paroxysmal nocturnal haemoglobinuria or atypical haemolytic uraemic syndrome (aHUS). Clinical trials are ongoing for C3 glomerulopathy. Given the unfamiliarity of physicians with these rare diseases and the variability of clinical presentation, a delayed initiation of eculizumab therapy is common. Thus, the question arises as to what extent improvement of kidney function may be expected when patients have been dialysis dependent for weeks or months already when eculizumab is initiated...
August 2015: Clinical Kidney Journal
Y Schuller, C E M Hollak, M Biegstraaten
An orphan disease is defined in the EU as a disorder affecting less than 1 in 2 000 individuals. The concept of ultra-orphan has been proposed for diseases with a prevalence of less than 1:50 000. Drugs for ultra-orphan diseases are amongst the most expensive medicines on a cost-per-patient basis. The extremely high prices have prompted initiatives to evaluate cost-effectiveness and cost-utility in EU-member states. The objective of this review was to evaluate the quality of cost-effectiveness and cost-utility studies on ultra-orphan drugs...
2015: Orphanet Journal of Rare Diseases
Ozan Salim, Orhan K Yücel, Gülay Karatas, Sevil Alan, Cumhur I Bassorgun, Levent Undar
No abstract text is available yet for this article.
November 2015: British Journal of Haematology
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