4,246 results match your criteria Paroxysmal Nocturnal Hemoglobinuria

Author Correction: Mutational landscape and its clinical significance in paroxysmal nocturnal hemoglobinuria.

Blood Cancer J 2021 May 6;11(5):85. Epub 2021 May 6.

Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

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Iron-driven alterations on red blood cell-derived microvesicles amplify coagulation during hemolysis via the intrinsic tenase complex.

Thromb Haemost 2021 May 3. Epub 2021 May 3.

Department of Immunopathology, Sanquin-AMC Landsteiner Laboratory, Amsterdam, Netherlands.

Hemolytic disorders characterized by complement-mediated intravascular hemolysis, such as autoimmune hemolytic anemia and paroxysmal nocturnal hemoglobinuria, are often complicated by life-threatening thromboembolic complications. Severe hemolytic episodes result in the release of red blood cell (RBC)-derived pro-inflammatory and oxidatively reactive mediators (e.g. Read More

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Thrombotic Complications in Patients with Immune-Mediated Hemolysis.

J Clin Med 2021 Apr 18;10(8). Epub 2021 Apr 18.

Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.

Autoimmune hemolytic anemias are rare and heterogeneous disorders characterized by hemolysis, which is a well-recognized risk factor for thrombosis. The most common immune-mediated anemias are represented by autoimmune hemolytic anemia and paroxysmal nocturnal hemoglobinuria, both associated with a high rate of thrombosis. Multiple pathophysiological mechanisms for thrombosis have been proposed, involving hemolysis itself and additional effects of the immune system. Read More

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Predicting response of severe aplastic anemia to immunosuppression combined with eltrombopag.

Haematologica 2021 Apr 29. Epub 2021 Apr 29.

Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health.

Pretreatment blood counts, particularly the absolute reticulocyte count (ARC) ≥25×109/L, correlate with response to immunosuppressive therapy (IST) in severe aplastic anemia (SAA). In recent trials, eltrombopag (EPAG) combined with standard IST yielded superior responses than did IST alone. Our single institution retrospective study aimed to elucidate whether historical response predictors associated with IST plus EPAG. Read More

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Efficacy and Safety of Eculizumab for Paroxysmal Nocturnal Hemoglobinuria: A Systematic Review and Meta-Analysis.

J Pediatr Hematol Oncol 2021 Apr 26. Epub 2021 Apr 26.

Departments of Pharmacy Pediatrics, Peking University First Hospital Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, China.

Background: Eculizumab is indicated for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). This study aimed to evaluate the efficacy and safety of eculizumab in patients with PNH.

Methods: PubMed, EMBASE, The Cochrane Library, and ClinicalTrials. Read More

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Clinico-Hematological Profile of Paroxysmal Nocturnal Hemoglobinuria in Indian Patients: FLAER Flow Cytometry Based Experience from an Indian Tertiary Care Centre.

Indian J Hematol Blood Transfus 2021 Apr 10;37(2):220-225. Epub 2020 Jun 10.

Department of Hematology, All India Institute of Medical Sciences, New Delhi, 110049 India.

PNH is a rare disease with wide spectrum of intra-vascular hemolysis and thrombosis to sub-clinical PNH clones. We aimed to study the clinico-hematological profile and clone size on granulocytes and monocytes of PNH patients classified as per International PNH Interest Group recommendations. A retrospective analysis of clinico-hematological profile of 112 PNH clone positive patients by FLAER based flow cytometry between January and September 2017 done and classified into classical PNH, PNH with aplastic anemia or myelodysplastic syndrome (PNH-AA/MDS) and sub-clinical PNH clones (PNH-sc). Read More

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Markers of Thrombin Generation and Inflammation in Patients with Paroxysmal Nocturnal Hemoglobinuria.

Indian J Hematol Blood Transfus 2021 Apr 26;37(2):204-209. Epub 2019 Nov 26.

Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Paroxysmal nocturnal hemoglobinuria (PNH) presents with intravascular hemolysis, bone marrow failure and thrombosis. Various studies have reported geographic and ethnic variation in prevalence of thrombosis in PNH. There is limited data on thrombosis in PNH from the Indian subcontinent. Read More

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CD52/GPI- T-Cells Are Enriched for Alloreactive Specificity and Predict Acute Graft-Versus-Host-Disease After Stem Cell Transplantation.

Transplant Cell Ther 2021 Feb 25. Epub 2021 Feb 25.

Institute of Immunology and Immunotherapy, College of Medical and Dental Studies, University of Birmingham and Birmingham Health Partners, Birmingham, United Kingdom; Centre for Clinical Haematology, Queen Elizabeth NHS Foundation Trust and Birmingham Health Partners, Birmingham, United Kingdom.

Alemtuzumab is a CD52-specific lympho-depleting antibody. CD52- T cells emerge under alemtuzumab selection pressure. We sought to investigate the phenotype and function of the CD52- T cell fraction and related their presence to clinical outcome. Read More

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February 2021

Eltrombopag in children with severe aplastic anemia.

Pediatr Blood Cancer 2021 Apr 15:e29066. Epub 2021 Apr 15.

Department of Hematology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

Background: Immunosuppressive therapy with horse antithymocyte globulin and cyclosporine currently remains the standard therapy for children with severe aplastic anemia (SAA) who lack human leukocyte antigen (HLA)-identical sibling. The thrombopoietin receptor agonist eltrombopag has been recently approved for SAA patients 2 years and older. However, there are limited data on its safety and efficacy in pediatric cohorts. Read More

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Iron overload after complement inhibitor treatment of Paroxysmal Nocturnal Hemoglobinuria.

Am J Hematol 2021 Apr 12. Epub 2021 Apr 12.

Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

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Advances in Hematopoietic Stem Cell Transplantation for Patients with Paroxysmal Nocturnal Hemoglobinuria.

Yali Du Bing Han

Transplant Cell Ther 2021 Apr 11;27(4):301-307. Epub 2020 Dec 11.

Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences. Electronic address:

In the era of eculizumab, the number of patients with paroxysmal nocturnal hemoglobinuria (PNH) who undergo hematopoietic stem cell transplantation (HSCT) has decreased significantly. However, owing to the possibility of severe aplastic anemia (AA) or a suboptimal response to eculizumab, HSCT still plays an important role in the treatment of patients with PNH combined with AA or recurrent hemolysis-related symptoms despite its high level of risk. Here we review studies involving patients with PNH who underwent HSCT over the past 15 years and conclude that patients with refractory AA/PNH and patients with severe classical PNH are candidates for HSCT in countries where eculizumab is unavailable. Read More

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Difficult Cases of Paroxysmal Nocturnal Hemoglobinuria: Diagnosis and Therapeutic Novelties.

J Clin Med 2021 Mar 1;10(5). Epub 2021 Mar 1.

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, 20122 Milan, Italy.

Paroxysmal nocturnal hemoglobinuria (PNH) is an intriguing disease that can pose many difficulties to physicians, as well as to hematologists, who are unfamiliar with it. Research regarding its pathophysiologic, diagnostic, and therapeutic aspects is still ongoing. In the last ten years, new flow cytometry techniques with high sensitivity enabled us to detect PNH clones as small as <1% of a patient's hematopoiesis, resulting in increasing incidence but more difficult data interpretation. Read More

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Monitoring of patients with paroxysmal nocturnal hemoglobinuria on a complement inhibitor.

Am J Hematol 2021 Mar 29. Epub 2021 Mar 29.

Department of Haematology, Leeds Teaching Hospitals, Leeds, UK.

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Very severe aplastic anemia in an 80-year-old man.

Clin Case Rep 2021 Mar 18;9(3):1330-1333. Epub 2021 Jan 18.

Department of Hematology Ampang Hospital Ampang Malaysia.

Although the patient with very severe aplastic anemia might be a fit elderly receiving standard therapy, there are factors which contribute to an adverse outcome such as severity of pancytopenia, absence of minor paroxysmal nocturnal hemoglobinuria clone and infective complications of therapy. Read More

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Addition of iptacopan, an oral factor B inhibitor, to eculizumab in patients with paroxysmal nocturnal haemoglobinuria and active haemolysis: an open-label, single-arm, phase 2, proof-of-concept trial.

Lancet Haematol 2021 May 23;8(5):e344-e354. Epub 2021 Mar 23.

Hôpital Saint-Louis, Department of Hematology and Bone Marrow Transplant, Paris, France; French Reference Center for Aplastic and Paroxysmal Nocturnal Haemoglobinuria, Paris, France.

Background: The haematological benefit of standard-of-care anti-C5 treatment for haemolytic paroxysmal nocturnal haemoglobinuria is limited by residual intravascular haemolysis or emerging C3-mediated extravascular haemolysis. Therefore, the aim of this phase 2 study was to assess the safety, tolerability, pharmacokinetics and pharmacodynamics, and activity of the new complement factor B inhibitor, iptacopan, in patients with paroxysmal nocturnal haemoglobinuria who have active haemolysis despite anti-C5 therapy.

Methods: In this multicentre, open-label, single-arm, phase 2 trial, we enrolled adult patients (aged 18-80 years) with paroxysmal nocturnal haemoglobinuria who showed signs of active haemolysis despite receiving eculizumab treatment. Read More

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Factor B inhibition for paroxysmal nocturnal haemoglobinuria.

Robert A Brodsky

Lancet Haematol 2021 05 23;8(5):e309-e310. Epub 2021 Mar 23.

Department of Medicine, Division of Hematology, John Hopkins University, Baltimore, MD, USA. Electronic address:

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A Nationwide Analysis of Budd-Chiari Syndrome in the United States.

J Clin Exp Hepatol 2021 Mar-Apr;11(2):181-187. Epub 2020 Aug 15.

Institute of Digestive Health & Liver Diseases, Mercy Medical Center, Baltimore, MD, USA.

Objective: The Budd-Chiari Syndrome (BCS) is a rare disorder characterized by hepatic venous outflow obstruction. The primary objectives of our study were to assess temporal trends in the prevalence of BCS among hospitalized patients in the United States using the National Inpatient Sample (NIS) database and to evaluate demographics, risk factors, and common presentation of BCS.

Methods: Data were extracted from the NIS to identify patients >18 years of age using all listed diagnosis of BCS from 1998 to 2017 and analyzed. Read More

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Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria.

N Engl J Med 2021 03;384(11):1028-1037

From the Department of Haematology, St. James's University Hospital, Leeds (P.H., M.G.), and Lisa Tan Pharma Consulting, Cambridge (L.T.) - both in the United Kingdom; the Department of Clinical Haematology, Peter MacCallum Cancer Center and Royal Melbourne Hospital, Melbourne, VIC, Australia (J.S.); Jane Anne Nohl Division of Hematology, Keck School of Medicine of USC, Los Angeles (I.W.); the Department of Hematology, West German Cancer Center University Hospital Essen, University of Duisburg-Essen, Essen (A. Röth), the Institute of Transfusion Medicine, University of Ulm and Institute of Clinical Transfusion Medicine and Immunogenetics, German Red Cross Blood Transfusion Service and University Hospital Ulm, Ulm (B.H.), and the Department of Oncology, Hematology, Hemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen, Aachen (J.P.) - all in Germany; the Department of Hematology, NTT Medical Center Tokyo, Tokyo (K.U.), and the Department of Hematology and Oncology, Okayama University Hospital, Okayama (H.N.) - both in Japan; Centre d'Investigations Cliniques (J.-J.K.) and the French Reference Center for Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria (R.P.T.), Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Université de Paris, Paris; the Department of Medicine, Division of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, NC (C.C.); Apellis Pharmaceuticals, Waltham, MA (M.H., P.D., C.F., F.G., T.A.); and the Hematology and BMT Unit, AORN San Giuseppe Moscati, Avellino, Italy (A. Risitano).

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired disease characterized by chronic complement-mediated hemolysis. C5 inhibition controls intravascular hemolysis in untreated PNH but cannot address extravascular hemolysis. Pegcetacoplan, a pegylated peptide targeting proximal complement protein C3, potentially inhibits both intravascular and extravascular hemolysis. Read More

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Mutational landscape and its clinical significance in paroxysmal nocturnal hemoglobinuria.

Blood Cancer J 2021 Mar 16;11(3):58. Epub 2021 Mar 16.

Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

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Long Non-coding RNA MALAT1 Contributed to the Proliferation of PNH Clone in Paroxysmal Nocturnal Hemoglobinuria Patients.

Turk J Haematol 2021 Mar 17. Epub 2021 Mar 17.

Department of Hematology, Tianjin Medical University General Hospital, Tianjin, China.

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Atypical Hemolytic Uremic Syndrome: Cancer-Induced or Chemotherapy-Induced?

Cureus 2021 Feb 10;13(2):e13260. Epub 2021 Feb 10.

Oncology, Allegheny Health Network, Pittsburgh, USA.

Atypical hemolytic uremic syndrome (aHUS) is an atypical type of thrombotic microangiopathy (TMA), which is characterized by microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and thrombi in small blood vessels, leading to end-organ damage. aHUS causes an over-activation of the complement pathway. There are many etiologies of aHUS, including inherited and acquired. Read More

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February 2021

JAK2V617F positive polycythemia vera with paroxysmal nocturnal hemoglobinuria and visceral thromboses: a case report and review of the literature.

Thromb J 2021 Mar 10;19(1):16. Epub 2021 Mar 10.

Hematology Unit, First Department of Internal Medicine, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.

Background: Polycythemia vera (PV) is characterized by red cell mass expansion in the peripheral blood and can be complicated with thrombosis, bleeding, evolution to acute myeloid leukemia (AML) or a fibrotic phase. Paroxysmal nocturnal hemoglobinuria (PNH) in an acquired clonal haematopoietic stem cell disorder associated with chronic intravascular hemolysis, venous thrombosis, defective hematopoiesis, frequent episodes of infection and, rarely, leukemic transformation. Herein, we report an interesting case of a patient with coexistence of PNH clones and a JAK2V617F positive PV, with unusual thromboses without hemolysis. Read More

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Therapeutic Targeting of the Complement System: From Rare Diseases to Pandemics.

Pharmacol Rev 2021 04;73(2):792-827

Laboratory of Molecular Medicine, Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark, and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (P.G.); Departments of Molecular Biology and Biochemistry, Neurobiology and Behavior, and Pathology and Laboratory Medicine, University of California, Irvine, California (A.J.T.); and Research Laboratory, Nordland Hospital, Bodø, Norway, Faculty of Health Sciences, K.G. Jebsen TREC, University of Tromsø, Tromsø, Norway (T.E.M.); Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway (T.E.M.); and Department of Immunology, Oslo University Hospital and University of Oslo, Oslo, Norway (T.E.M.)

The complement system was discovered at the end of the 19th century as a heat-labile plasma component that "complemented" the antibodies in killing microbes, hence the name "complement." Complement is also part of the innate immune system, protecting the host by recognition of pathogen-associated molecular patterns. However, complement is multifunctional far beyond infectious defense. Read More

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Nanobodies Provide Insight into the Molecular Mechanisms of the Complement Cascade and Offer New Therapeutic Strategies.

Biomolecules 2021 02 17;11(2). Epub 2021 Feb 17.

Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus, Denmark.

The complement system is part of the innate immune response, where it provides immediate protection from infectious agents and plays a fundamental role in homeostasis. Complement dysregulation occurs in several diseases, where the tightly regulated proteolytic cascade turns offensive. Prominent examples are atypical hemolytic uremic syndrome, paroxysmal nocturnal hemoglobinuria and Alzheimer's disease. Read More

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February 2021

Dynamics of patents, orphan drug designation, licensing, and revenues from drugs for rare diseases: The market expansion of eculizumab.

PLoS One 2021 5;16(3):e0247853. Epub 2021 Mar 5.

Departamento de Política de Medicamentos e Assistência Farmacêutica, Escola Nacional de Saúde Pública Sergio Arouca, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.

Background: This study examines the dynamics of the eculizumab patenting, orphan designation, and marketing authorization process in different countries and regulatory systems and analyzes drug revenues since its first marketing authorization.

Methods: A retrospective case study was conducted. Multiple information sources were used to: determine the status of eculizumab patents; examine the designation of orphan drug status by US, European, Japanese, and Brazilian regulatory authorities to determine registration status and approved clinical indications; estimate the prevalence of associated clinical conditions; investigate the history of the drug manufacturer, Alexion Pharmaceuticals, Inc. Read More

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Treatment of paroxysmal nocturnal hemoglobinuria in pregnancy with eculizumab: A case report.

Case Rep Womens Health 2021 Apr 11;30:e00294. Epub 2021 Feb 11.

Department of Obstetrics and Gynecology, Kaiser Permanente Southern California, Los Angeles Medical Center, 4900 Sunset Blvd 5th Floor, Los Angeles, CA 90027, United States of America.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease caused by mutations in hematopoietic stem cells leading to pancytopenia and a predisposition for thromboembolic events. In pregnancy, these manifestations can be amplified, leading to increased neonatal and maternal morbidity and mortality. Although data are limited, eculizumab has emerged as a potential treatment of PNH in pregnancy. Read More

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Clinical and prognostic significance of small paroxysmal nocturnal hemoglobinuria clones in myelodysplastic syndrome and aplastic anemia.

Leukemia 2021 Mar 4. Epub 2021 Mar 4.

Department of Hematological medicine, King's College Hospital, London, UK.

In this large single-centre study, we report high prevalence (25%) of, small (<10%) and very small (<1%), paroxysmal nocturnal hemoglobinuria (PNH) clones by high-sensitive cytometry among 3085 patients tested. Given PNH association with bone marrow failures, we analyzed 869 myelodysplastic syndromes (MDS) and 531 aplastic anemia (AA) within the cohort. PNH clones were more frequent and larger in AA vs. Read More

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