3,913 results match your criteria Paroxysmal Nocturnal Hemoglobinuria


Pharmacology, Pharmacokinetics and Pharmacodynamics of Eculizumab, and Possibilities for an Individualized Approach to Eculizumab.

Clin Pharmacokinet 2019 Feb 13. Epub 2019 Feb 13.

Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands.

Eculizumab is the first drug approved for the treatment of complement-mediated diseases, and current dosage schedules result in large interindividual drug concentrations. This review provides insight into the pharmacokinetic and pharmacodynamic properties of eculizumab, both for reported on-label (paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, generalized myasthenia gravis) and off-label (hematopoietic stem cell transplantation-associated thrombotic microangiopathy) indications. Furthermore, we discuss the potential of therapeutic drug monitoring to individualize treatment and reduce costs. Read More

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http://dx.doi.org/10.1007/s40262-019-00742-8DOI Listing
February 2019

Hematopoietic Cell Transplantation for Paroxysmal Nocturnal Hemoglobinuria in the Age of Eculizumab.

Biol Blood Marrow Transplant 2019 Jan 31. Epub 2019 Jan 31.

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Medical Oncology, Department of Medicine. Electronic address:

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired clonal hematopoietic cell disease characterized by destruction of hematopoietic cells through the activation of the complement system with manifestations that can be life threatening including hemolysis, thrombosis, and marrow failure. Allogeneic hematopoietic cell transplantation (HCT) remains the only cure for PNH, but eculizumab, a terminal complement inhibitor of C5, has been used to prevent complement mediated hemolysis in PNH since its FDA approval in 2007. We examined outcomes of HCT in PNH patients to evaluate the effects of disease subtype, conditioning intensity, and eculizumab use either pre- or post-HCT. Read More

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http://dx.doi.org/10.1016/j.bbmt.2019.01.033DOI Listing
January 2019
2 Reads

Post-allogeneic eculizumab as prophylaxis against hemolysis and thrombosis for patients with hematologic disorders associated with PNH clones.

Biol Blood Marrow Transplant 2019 Jan 29. Epub 2019 Jan 29.

Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA; Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope, Duarte, CA.

Paroxysmal nocturnal hemoglobinuria (PNH) is frequently seen in the context of other aplastic anemia and myelodysplastic syndrome and is associated with hemolysis and increased thromboembolic events. Allogeneic hematopoietic stem cell transplantation (alloHCT) is the only curative treatment but is associated with significant morbidity. The terminal complement inhibitor eculizumab reduces hemolysis and thromboembolic events and is the only FDA-approved therapy for PNH. Read More

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http://dx.doi.org/10.1016/j.bbmt.2019.01.025DOI Listing
January 2019
1 Read

Hematopoietic stem cell transplantation with alpha/beta T-lymphocyte depletion and short course of eculizumab in adolescents and young adults with paroxysmal nocturnal hemoglobinuria.

Ter Arkh 2018 Aug;90(7):57-64

Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Department of optimization treatment and prevention of complications of hematopoietic stem cell transplantation, Moscow, Russia.

Aim: The main goal is to optimize hematopoietic stem cell transplantation (HSCT) approach among adolescents and young adults with paroxysmal nocturnal hemoglobinuria (PNH) by means of Graft-versus-host disease (GVHD) and post-transplant complications risk lowering.

Materials And Methods: We report our experience of HSCT from HLA-matched unrelated donors using TCR alfa/beta and CD19 depletion in 5 pts (1M/4F) with PNH, developed after successful immunosuppressive therapy (IST) of acquired aplastic anemia (AA). Median age of pts at the moment of transplantation was 17,8 years (range 14,5-22,7), median interval from IST to PNH was 4 years (5mo - 6,5 y). Read More

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http://dx.doi.org/10.26442/terarkh201890757-64DOI Listing
August 2018
4 Reads

Abdominal pain in combination with an unexplained hemolytic anemia are crucial signs to test for paroxysmal nocturnal hemoglobinuria: A case report.

Clin Case Rep 2019 Jan 4;7(1):175-179. Epub 2018 Dec 4.

Department of Clinical Chemistry Albert Schweitzer Hospital Dordrecht The Netherlands.

Paroxysmal nocturnal hemoglobinuria (PNH), a rare benign hematological disorder, presents with a wide variety of clinical symptoms. A direct Coombs-negative hemolytic anemia combined with an increased LDH = Lactate dehydrogenase level are signs to test for PNH. Follow-up does not need any microscopic review's only flow cytometric PNH clone size. Read More

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http://dx.doi.org/10.1002/ccr3.1771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6333074PMC
January 2019
1 Read

Fatigue, symptom burden, and health-related quality of life in patients with myelodysplastic syndrome, aplastic anemia, and paroxysmal nocturnal hemoglobinuria.

Cancer Med 2019 Jan 11. Epub 2019 Jan 11.

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: Fatigue is distressing and affects quality of life (QoL) among patients with myelodysplastic syndrome (MDS), aplastic anemia (AA), and paroxysmal nocturnal hemoglobinuria (PNH). Limited data exist on the impact of fatigue, QoL, and related symptoms in these patients.

Objective: Prospectively assess fatigue (functional assessment of cancer therapy-anemia [FACT-An]); QoL (FACT-An subscales); pain (brief pain inventory); and depression, anxiety, and stress (depression anxiety stress scale-21) and strategies used to manage these symptoms in patients with MDS, AA, and PNH. Read More

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http://doi.wiley.com/10.1002/cam4.1953
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http://dx.doi.org/10.1002/cam4.1953DOI Listing
January 2019
5 Reads

Detection of paroxysmal nocturnal hemoglobinuria (PNH) in bone marrow aspirates.

Semin Hematol 2019 Jan 27;56(1):65-68. Epub 2018 May 27.

Department of Laboratory Medicine, Hematology Section, National Institutes of Health Clinical Center, Bethesda, MD.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired condition in which, due to a mutation of the phosphatidylinositol glycan class A gene, hematopoietic cells lack proteins that are normally anchored to the cell surface by glycosylphosphatidylinositol (GPI). Thus, PNH cells show poor expression of surface proteins, such as CD55 and CD59, and dim or absent binding of fluorescently labeled modified aerolysin (FLAER). In clinical diagnostic laboratories, the detection and quantitation of PNH is currently performed by flow cytometry (FC) analysis of peripheral blood (PB) samples. Read More

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http://dx.doi.org/10.1053/j.seminhematol.2018.05.011DOI Listing
January 2019
2 Reads

CHAPLE syndrome uncovers the primary role of complement in a familial form of Waldmann's disease.

Authors:
Ahmet Ozen

Immunol Rev 2019 Jan;287(1):20-32

Division of Allergy and Immunology, Marmara University School of Medicine, Istanbul, Turkey.

Primary intestinal lymphangiectasia (PIL) or Waldmann's disease was described in 1961 as an important cause of protein-losing enteropathy (PLE). PIL can be the sole finding in rare individuals or occur as part of a multisystemic genetic syndrome. Although genetic etiologies of many lymphatic dysplasia syndromes associated with PIL have been identified, the pathogenesis of isolated PIL (with no associated syndromic features) remains unknown. Read More

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http://dx.doi.org/10.1111/imr.12715DOI Listing
January 2019
1 Read

A Single-Domain Antibody Targeting Complement Component C5 Acts as a Selective Inhibitor of the Terminal Pathway of the Complement System and Thus Functionally Mimicks the C-Terminal Domain of the SSL7 Protein.

Front Immunol 2018 29;9:2822. Epub 2018 Nov 29.

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

The complement system is an efficient anti-microbial effector mechanism. On the other hand abnormal complement activation is involved in the pathogenesis of multiple inflammatory and hemolytic diseases. As general inhibition of the complement system may jeopardize patient health due to increased susceptibility to infections, the development of pathway-specific complement therapeutics has been a long-lasting goal over the last decades. Read More

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http://dx.doi.org/10.3389/fimmu.2018.02822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281825PMC
November 2018
2 Reads

Paroxysmal Cold Hemoglobinuria in an Adult with Respiratory Syncytial Virus.

Case Rep Hematol 2018 13;2018:7586719. Epub 2018 Nov 13.

Division of Hematology and Medical Oncology, Department of Medicine, Mount Sinai Beth Israel, Mount Sinai Hospital, New York, NY, USA.

Paroxysmal cold hemoglobinuria (PCH) is a rare form of cold autoimmune hemolytic anemia first discovered in the early 20th century in adults with tertiary syphilis. Today, it is more commonly seen in children as a life-threatening anemia during a viral upper respiratory tract infection (URI). Although respiratory syncytial virus (RSV) has previously been reported to cause PCH in a child, herein we present the first documented case in an adult. Read More

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http://dx.doi.org/10.1155/2018/7586719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6257899PMC
November 2018
6 Reads

A brief, but comprehensive, guide to clonal evolution in aplastic anemia.

Authors:
Daria V Babushok

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):457-466

Division of Hematology-Oncology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA; and.

Acquired aplastic anemia (AA) is an immune-mediated bone marrow aplasia that is strongly associated with clonal hematopoiesis upon marrow recovery. More than 70% of AA patients develop somatic mutations in their hematopoietic cells. In contrast to other conditions linked to clonal hematopoiesis, such as myelodysplastic syndrome (MDS) or clonal hematopoiesis of indeterminate potential in the elderly, the top alterations in AA are closely related to its immune pathogenesis. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245980PMC
November 2018
12 Reads

Anticoagulating patients with high-risk acquired thrombophilias.

Authors:
Leslie Skeith

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):439-449

Division of Hematology and Hematological Malignancies, Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Canada; and Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada.

Antiphospholipid syndrome (APS), heparin-induced thrombocytopenia, and paroxysmal nocturnal hemoglobinuria are 3 acquired thrombophilias that carry a high risk of venous and arterial thromboembolism. Management of these conditions has largely included anticoagulation with a vitamin K antagonist after an initial period of a parenteral anticoagulant, for as long as the thrombotic risk is still present. The available evidence for the use of direct oral anticoagulants (DOACs) is limited and primarily consists of case series and cohort studies, which are summarized in this chapter. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246016PMC
November 2018
2 Reads

Complement-driven anemia: more than just paroxysmal nocturnal hemoglobinuria.

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):371-376

Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.

Atypical hemolytic uremic syndrome (aHUS); hemolysis, elevated liver function tests, and low platelets syndrome; and transplant-associated thrombotic microangiopathy are related conditions, in that many patients harbor germline heterozygous mutations in genes that regulate the alternative pathway of complement (APC). Penetrance is variable because development of clinically significant disease appears to require supervention of a process such as inflammation. Complement activation on the endothelial surfaces leads to endothelial damage, platelet consumption, microthrombi, and a mechanical hemolytic anemia with schistocytes. Read More

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http://dx.doi.org/10.1182/asheducation-2018.1.371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245985PMC
November 2018
2 Reads

Moyamoya Syndrome Caused by Paroxysmal Nocturnal Hemoglobinuria.

Chin Med J (Engl) 2018 Dec;131(23):2874-2876

Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.

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http://dx.doi.org/10.4103/0366-6999.246065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278181PMC
December 2018
1 Read

Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study.

Blood 2019 Feb 3;133(6):530-539. Epub 2018 Dec 3.

Department of Haematology, Leeds Teaching Hospitals, Leeds, United Kingdom.

Ravulizumab (ALXN1210), a new complement C5 inhibitor, provides immediate, complete, and sustained C5 inhibition. This phase 3, open-label study assessed the noninferiority of ravulizumab to eculizumab in complement inhibitor-naive adults with paroxysmal nocturnal hemoglobinuria (PNH). Patients with lactate dehydrogenase (LDH) ≥1. Read More

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http://dx.doi.org/10.1182/blood-2018-09-876136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367644PMC
February 2019
3 Reads

Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study.

Blood 2019 Feb 3;133(6):540-549. Epub 2018 Dec 3.

Bone Marrow Transplantation Unit, Saint Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.

Ravulizumab, a new complement component C5 inhibitor administered every 8 weeks, was noninferior to eculizumab administered every 2 weeks in complement-inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria (PNH). This study assessed noninferiority of ravulizumab to eculizumab in clinically stable PNH patients during previous eculizumab therapy. In this phase 3, open-label, multicenter study, 195 PNH patients on labeled-dose (900 mg every 2 weeks) eculizumab for >6 months were randomly assigned 1:1 to switch to ravulizumab (n = 97) or continue eculizumab (n = 98). Read More

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http://dx.doi.org/10.1182/blood-2018-09-876805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368201PMC
February 2019
7 Reads

[Purpura fulminans related to paroxysmal nocturnal haemoglobinuria: a case report and literatures review].

Zhonghua Xue Ye Xue Za Zhi 2018 Nov;39(11):921-926

Department of Hematology, Peking Union Medical College Hospital, CAMS & PUMC, Beijing 100730, China.

To improve the understanding of the rare clinical presentation and management of purpura fulminans (PF) in patients with paroxysmal nocturnal haemoglobinuria (PNH). A case of PF occurring in PNH is reported, while the related literature review is conducted. A 49-year-old male patient suffered from one-week history of fever, greenish-brown colour urine, multiple well demarcated and painful purpura of the head and neck. Read More

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http://dx.doi.org/10.3760/cma.j.issn.0253-2727.2018.11.010DOI Listing
November 2018
1 Read

[Efficacy and safety of haploidentical hematopoietic stem cell transplantation for 17 patients with paroxysmal nocturnal hemamoglobinuria].

Zhonghua Xue Ye Xue Za Zhi 2018 Nov;39(11):904-907

Jiangsu Institute of Hematology, Department of Hematology, the First Affiliated Hospital of Soochow University, Key Lab of Thrombosis and Hemostasis of Ministry of Health, Suzhou 215006, China.

To explore the efficacy and safety of haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) for paroxysmal nocturnal hemoglobinuria (PNH). A total of 17 patients with PNH who received Haplo-HSCT from January 2013 to September 2017 were analyzed retrospectively. Of them, 4 patients had de novo PNH, 13 patients had aplastic anemia-PNH syndrome (AA-PNH). Read More

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http://dx.doi.org/10.3760/cma.j.issn.0253-2727.2018.11.006DOI Listing
November 2018
3 Reads

[How I diagnose and treat paroxysmal nocturnal hemoglobinuria].

Authors:
R Fu

Zhonghua Xue Ye Xue Za Zhi 2018 Nov;39(11):887-891

Tianjin Medical University General Hospital, Tianjin 300052, China.

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http://dx.doi.org/10.3760/cma.j.issn.0253-2727.2018.11.002DOI Listing
November 2018
1 Read

Paroxysmal nocturnal hemoglobinuria testing in patients with myelodysplastic syndrome in clinical practice-frequency and indications.

Curr Oncol 2018 Oct 31;25(5):e391-e397. Epub 2018 Oct 31.

Division of Hematology, St. Paul's Hospital and the University of British Columbia, Vancouver, BC.

Background: Myelodysplastic syndrome (mds) is characterized by peripheral blood cytopenias, with most patients developing significant anemia and dependence on red blood cell (rbc) transfusion. In paroxysmal nocturnal hemoglobinuria (pnh), mutations in the gene lead to lack of cell-surface glycosylphosphatidylinositol, allowing complement-mediated lysis to occur. Paroxysmal nocturnal hemoglobinuria results in direct antiglobulin test-negative hemolysis and cytopenias, and up to 50% of patients with mds test positive for pnh cells. Read More

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http://dx.doi.org/10.3747/co.25.4018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209566PMC
October 2018
9 Reads

Anticoagulating patients with high-risk acquired thrombophilias.

Authors:
Leslie Skeith

Blood 2018 Nov;132(21):2219-2229

Division of Hematology and Hematological Malignancies, Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Canada; and Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada.

Antiphospholipid syndrome (APS), heparin-induced thrombocytopenia, and paroxysmal nocturnal hemoglobinuria are 3 acquired thrombophilias that carry a high risk of venous and arterial thromboembolism. Management of these conditions has largely included anticoagulation with a vitamin K antagonist after an initial period of a parenteral anticoagulant, for as long as the thrombotic risk is still present. The available evidence for the use of direct oral anticoagulants (DOACs) is limited and primarily consists of case series and cohort studies, which are summarized in this chapter. Read More

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http://dx.doi.org/10.1182/blood-2018-05-848697DOI Listing
November 2018
1 Read

Comparison of High Sensitivity and Conventional Flow Cytometry for Diagnosing Overt Paroxysmal Nocturnal Hemoglobinuria and Detecting Minor Paroxysmal Nocturnal Hemoglobinuria Clones.

Ann Lab Med 2019 Mar;39(2):150-157

Department of Laboratory Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Korea.

Background: High sensitivity flow cytometry (HS-FCM) was recently developed for diagnosing paroxysmal nocturnal hemoglobinuria (PNH). We compared its performance with conventional flow cytometry (C-FCM) for diagnosing overt PNH and detecting minor (0.1-1%) PNH clones in aplastic anemia (AA)/low-grade myelodysplastic syndrome (MDS) patients. Read More

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http://dx.doi.org/10.3343/alm.2019.39.2.150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240522PMC
March 2019
1 Read

The economic burden of malignant and premalignant hematological diseases in Southern Nigeria.

Niger J Clin Pract 2018 Nov;21(11):1396-1402

Department of Haematology, Chukwuemeka Odumegwu Ojukwu Teaching Hospital, Awka, Anambra, Nigeria.

Background: Hematological malignancies are a significant cause of morbidity and mortality. They constitute an economic burden for the patients, their relatives, and the society because of the cost associated with their management, which is usually long term. We aimed to determine the total direct cost of managing patients with premalignant hematological disorders (PMHDs) and malignant hematological disorders (MHDs). Read More

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http://dx.doi.org/10.4103/njcp.njcp_278_18DOI Listing
November 2018
11 Reads

Hemosiderin tubulopathy-induced acute kidney injury - A rare initial manifestation of paroxysmal nocturnal hemoglobinuria.

Saudi J Kidney Dis Transpl 2018 Sep-Oct;29(5):1232-1236

Department of Pathology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Udupi, Karnataka, India.

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by episodes of intravascular hemolysis, infections, and thromboembolic complications. Renal abnormalities are rare which occur either due to hemolytic crisis or repeated thrombotic episodes involving small venules. Acute kidney injury (AKI) requiring hemodialysis due to toxic effects of hemoglobinuria, with a stable disease is exceptional. Read More

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http://dx.doi.org/10.4103/1319-2442.243958DOI Listing
November 2018
11 Reads

Effectiveness of eculizumab in patients with paroxysmal nocturnal hemoglobinuria (PNH) with or without aplastic anemia in the International PNH Registry.

Am J Hematol 2019 Jan 25;94(1):E37-E41. Epub 2018 Nov 25.

Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio.

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http://doi.wiley.com/10.1002/ajh.25334
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http://dx.doi.org/10.1002/ajh.25334DOI Listing
January 2019
18 Reads

[Network references for rare diseases: state of the art for the paroxysmal nocturnal hemoglobinuria].

Epidemiol Prev 2018 Sep-Dec;42(5-6):333-343

Dipartimento di sanità pubblica, Azienda ospedaliero-universitaria "Federico II", Napoli;

Background: recently, healthcare network models have been proposed to improve general awareness of rare diseases for patients and specific knowledge about diagnosis, treatment, and management for healthcare services. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare haematological disease that still has no framing in an official network.

Objectives: to describe the use of network models in diagnosis, treatment, and management of PNH patients both in Italy and abroad and its impact on patients and healthcare service. Read More

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http://dx.doi.org/10.19191/EP18.5-6.P333.102DOI Listing
October 2018
3 Reads

Complement activation by human red blood cell antibodies: hemolytic potential of antibodies and efficacy of complement inhibitors assessed by a sensitive flow cytometric assay.

Transfusion 2018 Dec 27;58(12):2992-3002. Epub 2018 Oct 27.

Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Service Baden-Württemberg - Hessen and University Hospital, Ulm, Germany.

Background: Therapeutic intervention strategies in complement-mediated hemolytic diseases are still inappropriate, and lethal events cannot be reliably prevented. As an in vitro model of intravascular hemolysis, a sensitive flow cytometric assay was designed using red blood cells (RBCs) of patients with paroxysmal nocturnal hemoglobinuria (PNH) as target cells. Complement activation by human allo- and autoantibodies directed against RBC antigens and the effect of different complement inhibitors were studied. Read More

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http://doi.wiley.com/10.1111/trf.14893
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http://dx.doi.org/10.1111/trf.14893DOI Listing
December 2018
10 Reads

Frequent mutations in CD8 T cells from patients with pure red cell aplasia.

Blood Adv 2018 Oct;2(20):2704-2712

Division of Hematology, Department of Internal Medicine, School of Medicine.

Dysregulation of T-cell-mediated immunity is responsible for acquired pure red cell aplasia (PRCA). Although mutations are frequently detected in patients with T-cell large granular lymphocytic leukemia (T-LGLL), which is often complicated by PRCA and which is also reported to be associated with acquired aplastic anemia (AA) and myelodysplastic syndrome (MDS), whether -mutated T cells are involved in the pathophysiology of PRCA and other types of bone marrow failure remains unknown. We performed mutation analyses of the peripheral blood mononuclear cells from PRCA patients (n = 42), AA (n = 54), AA-paroxysmal nocturnal hemoglobinuria (AA-PNH; n = 7), and MDS (n = 21) using an allele-specific polymerase chain reaction and amplicon sequencing. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018022723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199660PMC
October 2018
14 Reads

Iron Deficiency in Patients with Paroxysmal Nocturnal Hemoglobinuria: A Cross-Sectional Survey from a Single Institution in China.

Med Sci Monit 2018 Oct 11;24:7256-7263. Epub 2018 Oct 11.

Anemia Therapy Center, Institute of Hematology and Blood Diseases Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences (PUMC and CAMS), Tianjin, China (mainland).

BACKGROUND Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic disorder that often manifests with chronic intravascular hemolysis. Iron deficiency in patients with PNH is most often due to urinary losses of iron secondary to chronic intravascular hemolysis. MATERIAL AND METHODS This cross-sectional survey assessed the prevalence of iron deficiency in a Chinese population of PNH patients who were enrolled between May 2012 and October 2014. Read More

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https://www.medscimonit.com/abstract/index/idArt/910614
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http://dx.doi.org/10.12659/MSM.910614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194753PMC
October 2018
7 Reads

Ecthyma Gangrenosum in Paroxysmal Nocturnal Hemoglobinuria.

Acta Haematol 2018 9;140(3):166-168. Epub 2018 Oct 9.

Department of Dermatology, Hospital Universitario de La Princesa, Madrid, Spain.

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https://www.karger.com/Article/FullText/492739
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http://dx.doi.org/10.1159/000492739DOI Listing
October 2018
11 Reads

Recurrent aseptic meningitis with mutations: a novel pathogenesis of recurrent meningitis successfully treated by eculizumab.

BMJ Case Rep 2018 Sep 27;2018. Epub 2018 Sep 27.

Department of Neurology, Kobe City Medical Center General Hospital, Kobe, Japan.

We report the case of a patient with mutations who experienced recurrent aseptic meningitis 121 times over 16 years before developing paroxysmal nocturnal haemoglobinuria (PNH). Each episode was preceded by urticaria and arthralgia. After developing PNH, haemolysis occurred prior to meningitis. Read More

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http://dx.doi.org/10.1136/bcr-2018-225910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169622PMC
September 2018
2 Reads

The Risk of Clonal Evolution of Granulocyte Colony-Stimulating Factor for Acquired Aplastic Anemia: A Systematic Review and Meta-Analysis.

Acta Haematol 2018 25;140(3):141-145. Epub 2018 Sep 25.

Tianjin Medical University General Hospital, Tianjin, China.

Objectives: This meta-analysis aimed to evaluate the risk of clonal evolution of granulocyte colony-stimulating factor (G-CSF) in acquired aplastic anemia (AA), and whether the use of G-CSF increases the occurrence of secondary malignant neoplasms, mainly myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) or paroxysmal nocturnal hemoglobinuria (PNH).

Methods: Data were gathered from randomized controlled trials (RCTs) to evaluate the effect of G-CSF versus no G-CSF at the risk of developing the clonal complications of acquired AA. Electronic searches in PubMed, Embase, and the Cochrane Library were performed to identify studies up to 1 January 2017. Read More

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http://dx.doi.org/10.1159/000491816DOI Listing
September 2018
12 Reads

How we treat paroxysmal nocturnal hemoglobinuria: A consensus statement of the Canadian PNH Network and review of the national registry.

Eur J Haematol 2019 Jan 25;102(1):36-52. Epub 2018 Oct 25.

Division of Hematology & Thromboembolism, McMaster University, Hamilton, Ontario, Canada.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disease characterized by intravascular hemolysis, thrombophilia, and marrow failure. Its phenotype is due to absent or reduced expression of GPI-linked complement regulators and subsequent sensitivity of hematopoietic cells to complement-mediated damage and lysis. Introduction of the terminal complement inhibitor eculizumab drastically improved outcomes in PNH patients; however, despite this improvement, there remain several challenges faced by PNH patients and physicians who care for them. Read More

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http://dx.doi.org/10.1111/ejh.13176DOI Listing
January 2019
10 Reads

Preoperative administration of eculizumab to prevent surgery-triggered hemolysis during cesarean section with paroxysmal nocturnal hemoglobinuria.

Clin Case Rep 2018 Sep 25;6(9):1807-1809. Epub 2018 Jul 25.

Perinatal and Maternal Center of Saitama Medical Center Jichi Medical University Saitama Japan.

Eculizumab in pregnancy has been reported to be effective in improving outcomes in patients with paroxysmal nocturnal hemoglobinuria. However, a cesarean section may result in surgery-triggered hemolysis. An additional dose of eculizumab just prior to delivery is an appropriate choice to prevent postoperative hemolysis. Read More

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http://dx.doi.org/10.1002/ccr3.1707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132156PMC
September 2018
3 Reads

Therapeutic challenges in pregnant women with paroxysmal nocturnal hemoglobinuria: A case report.

Medicine (Baltimore) 2018 Sep;97(36):e12155

Scientific Writing Office, EMESCAM.

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disease, arising from the mutation of clonal hematopoietic stem cells, with an estimated incidence of 1 to 5 cases per million individuals. In pregnant women, adequate information regarding the prevalence of PNH is lacking, and its management has been a challenge because of the significant complications in this group. The condition is diagnosed based on clinical findings and laboratory tests. Read More

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http://dx.doi.org/10.1097/MD.0000000000012155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133426PMC
September 2018
3 Reads

The Role of Whole-Body Magnetic Resonance Imaging (WB-MRI) in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH).

Sci Rep 2018 Sep 7;8(1):13458. Epub 2018 Sep 7.

Department of Hematology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

In PNH thromboembolic events (TEs) represent the leading cause of morbidity and mortality. Between Dec 2013 and Jan 2016 37 PNH patients (pts) (23 PNH, 14 AA/PNH; 51% (19/37) females; median age 44 years, median D-dimer levels 0.22 mg/l) were examined with a whole-body magnetic resonance imaging (WB-MRI) scan at 1. Read More

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http://www.nature.com/articles/s41598-018-31547-7
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http://dx.doi.org/10.1038/s41598-018-31547-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128936PMC
September 2018
7 Reads

Autoimmune hemolytic anemia.

Vnitr Lek 2018 ;64(5):514-519

Autoimmune hemolytic anemia (AIHA) is caused by auto-antibodies directed against self red blood cell (RBC) surface antigens. A consequence may be an intravascular hemolysis mediated by activated complement or extravascular hemolysis caused by destruction of complex of RBC with autoantibody in spleen and liver. The basic classification subdivides AIHA in primary/idiopathic and secondary with known underlying disease. Read More

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January 2018
4 Reads

Paroxysmal nocturnal hemoglobinuria.

Vnitr Lek 2018 ;64(5):508-513

Paroxysmal nocturnal hemoglobinuria (PNH) results from a deficiency in inhibitors of activated complement. This lack leads to complement mediated intravascular hemolysis, to activation of coagulation system with increased risk of thrombotic complications and to various degree of bone marrow failure. A molecular basis of PNH is a somatic mutation of PIGA gene causing a lack of glycosyl phosphatidyl inositol which binds many important antigens to cell surface membrane including inhibitors of activated complement CD59 and CD55 antigens. Read More

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January 2018
7 Reads

[Paroxysmal nocturnal hemoglobinuria and thrombosis in the era of eculizumab].

Rinsho Ketsueki 2018;59(8):1042-1047

Osaka University Graduate School of Medicine, Department of Hematology and Oncology.

Paroxysmal nocturnal hemoglobinuria (PNH) arises as a consequence of clonal expansion of hematopoietic stem cells that have acquired a somatic mutation in the PIGA gene. The resulting hematopoietic cells have deficiencies in the GPI-anchored complement regulatory proteins CD55 and CD59, which account for the intravascular hemolysis that is the primary clinical manifestation of PNH. Thromboembolism is a major cause of morbidity and mortality in PNH, particularly in Caucasian patients. Read More

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http://dx.doi.org/10.11406/rinketsu.59.1042DOI Listing
January 2018
5 Reads

Diagnosis and management of PNH: Review and recommendations from a Belgian expert panel.

Eur J Haematol 2018 Dec 23;101(6):737-749. Epub 2018 Oct 23.

Department of Haematology, CHU UCL Namur, Université catholique de Louvain, Yvoir, Belgium.

Despite its considerable morbidity and mortality, paroxysmal nocturnal haemoglobinuria (PNH) is still underdiagnosed. Patients with PNH can suffer from cardiovascular, gastrointestinal, neurological or haematological symptoms and refer to several specialists. The aim of this paper is to review the diagnosis and the management of PNH patients, with the primary focus on identifying high-risk groups. Read More

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http://dx.doi.org/10.1111/ejh.13166DOI Listing
December 2018
5 Reads

Ravulizumab (ALXN1210) in patients with paroxysmal nocturnal hemoglobinuria: results of 2 phase 1b/2 studies.

Blood Adv 2018 Sep;2(17):2176-2185

Department of Hematology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Ravulizumab (ALXN1210), a humanized monoclonal antibody to complement component C5, was engineered from eculizumab to have a substantially longer terminal half-life, permitting longer dosing intervals for paroxysmal nocturnal hemoglobinuria (PNH) treatment. Two phase 1b/2 multicenter open-label studies evaluated efficacy and safety of multiple doses and regimens of ravulizumab in PNH patients naive to complement-inhibitor treatment. Patients in study 103 (n = 13) received ravulizumab 900 mg (lower trough exposure) or 1800 mg every 4 weeks (higher trough exposure); those in study 201 (n = 26) received 1000 mg every 4, 1600 mg every 6, 2400 mg every 8, or 5400 mg every 12 weeks. Read More

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http://www.bloodadvances.org/lookup/doi/10.1182/bloodadvance
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http://dx.doi.org/10.1182/bloodadvances.2018020644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134221PMC
September 2018
60 Reads

Antiphosphatidylserine Antibody as a Cause of Multiple Dural Venous Sinus Thromboses and ST-Elevation Myocardial Infarction.

Am J Case Rep 2018 Aug 31;19:1042-1046. Epub 2018 Aug 31.

Senior Attending Physician, Abington Hematology Oncology Associates, Philadelphia, PA, USA.

BACKGROUND Antiphospholipid syndrome (APS) is an autoimmune disease characterized by antibodies directed against phospholipids on plasma membranes. Through unclear mechanisms, APS confers hypercoagulability. APS may cause recurrent thromboses in the arterial and venous vasculature. Read More

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https://www.amjcaserep.com/abstract/index/idArt/909698
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http://dx.doi.org/10.12659/AJCR.909698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128181PMC
August 2018
10 Reads

Eculizumab in pregnancy: a narrative overview.

J Nephrol 2019 Feb 29;32(1):17-25. Epub 2018 Aug 29.

Department of Public Health, University Federico II, Via Pansini 5, 80131, Naples, Italy.

Pregnancy can be a dangerous trigger for patients with paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), or hemolysis, elevated liver enzymes and low platelet (HELLP) syndrome. Due to the possibility of several serious complications, pregnancy is somewhat discouraged in the presence of the above diseases. Eculizumab is a humanized antibody that may dramatically change the clinical course of PNH, aHUS and HELLP syndrome. Read More

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http://dx.doi.org/10.1007/s40620-018-0517-zDOI Listing
February 2019
5 Reads

Eculizumab application during pregnancy in a patient with paroxysmal nocturnal hemoglobinuria: A case report with review of the literature.

Clin Case Rep 2018 Aug 27;6(8):1582-1587. Epub 2018 Jun 27.

Department of Obstetrics University Hospital of Zurich Zurich Switzerland.

Eculizumab is highly effective in inhibiting complement activation and has successfully shown to prevent complications and to improve quality of life in patients with paroxysmal nocturnal hemoglobinuria (PNH). Its application during pregnancy showed favorable fetal and maternal outcome in the presented case and has proven to be effective without raising safety concerns. Read More

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http://dx.doi.org/10.1002/ccr3.1634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099006PMC
August 2018
4 Reads

Be on Target: Strategies of Targeting Alternative and Lectin Pathway Components in Complement-Mediated Diseases.

Front Immunol 2018 8;9:1851. Epub 2018 Aug 8.

Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.

The complement system has moved into the focus of drug development efforts in the last decade, since its inappropriate or uncontrolled activation has been recognized in many diseases. Some of them are primarily complement-mediated rare diseases, such as paroxysmal nocturnal hemoglobinuria, C3 glomerulonephritis, and atypical hemolytic uremic syndrome. Complement also plays a role in various multifactorial diseases that affect millions of people worldwide, such as ischemia reperfusion injury (myocardial infarction, stroke), age-related macular degeneration, and several neurodegenerative disorders. Read More

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http://dx.doi.org/10.3389/fimmu.2018.01851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092519PMC
August 2018
7 Reads

Utility of dynamic contrast-enhanced MRI to assess small bowel perfusion in paroxysmal nocturnal hemoglobinuria before and after eculizumab.

Eur J Intern Med 2018 11 17;57:e25-e27. Epub 2018 Aug 17.

Department of Radiology, Centre for Experimental Imaging, San Raffaele Scientific Institute, Vita-Salute University, Milan, Italy.

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http://dx.doi.org/10.1016/j.ejim.2018.08.005DOI Listing
November 2018
5 Reads

Spontaneous Remission in Paroxysmal Nocturnal Hemoglobinuria-Return to Health or Transition Into Malignancy?

Front Immunol 2018 2;9:1749. Epub 2018 Aug 2.

Immunobiology Research Program, Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired syndrome characterized by intravascular hemolysis, thrombosis, and bone marrow failure. The disease is caused by a mutation in the gene that leads to the lack of glycosylphosphatidylinositol-anchored complement regulatory molecules CD55 and CD59 on affected blood cell surfaces. In previous studies, spontaneous clinical remissions have been described. Read More

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http://dx.doi.org/10.3389/fimmu.2018.01749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082924PMC
August 2018
9 Reads

Impairment of Nitric Oxide Pathway by Intravascular Hemolysis Plays a Major Role in Mice Esophageal Hypercontractility: Reversion by Soluble Guanylyl Cyclase Stimulator.

J Pharmacol Exp Ther 2018 Nov 14;367(2):194-202. Epub 2018 Aug 14.

Hematology and Hemotherapy Center (F.H.S., K.Y.F., C.F.F.-P., F.F.C.) and Department of Pharmacology, Faculty of Medical Sciences (E.C.A., F.B.C.), University of Campinas, Campinas, São Paulo, Brazil; and Division of Hematology, University of Washington, Seattle, Washington (K.Y.F.).

Paroxysmal nocturnal hemoglobinuria (PNH) patients display exaggerated intravascular hemolysis and esophageal disorders. Since excess hemoglobin in the plasma causes reduced nitric oxide (NO) bioavailability and oxidative stress, we hypothesized that esophageal contraction may be impaired by intravascular hemolysis. This study aimed to analyze the alterations of the esophagus contractile mechanisms in a murine model of exaggerated intravascular hemolysis induced by phenylhydrazine (PHZ). Read More

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http://dx.doi.org/10.1124/jpet.118.249581DOI Listing
November 2018
27 Reads