Crovalimab: First Approval

Drugs, Год журнала: 2024, Номер 84(6), С. 707 - 716

Опубликована: Май 14, 2024

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Multisite Thrombosis in a Patient with Paroxysmal Nocturnal Hemoglobinuria

Hämostaseologie, Год журнала: 2024, Номер unknown

Опубликована: Фев. 9, 2024

Abstract Case: Paroxysmal nocturnal hemoglobinuria (PNH) is an extremely rare bone marrow disorder caused by acquired mutations in the phosphatidylinositol glycan class A gene, which lead to a partial or total loss of cellular complement regulators CD55 and CD59.1 In addition complement-mediated hemolysis cytopenia, venous arterial thromboses at multiple and/or unusual sites are common complication occur up 44% patients historic PNH cohorts.1 2

Язык: Английский

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Thrombosis at Unusual Sites: Focus on Myeloproliferative Neoplasms and Paroxysmal Nocturnal Hemoglobinuria

Hämostaseologie, Год журнала: 2025, Номер unknown

Опубликована: Фев. 3, 2025

Abstract Patients with thrombosis at an unusual site will need to be explored for rare causes of thrombosis. Two these include myeloproliferative neoplasms (MPNs) and paroxysmal nocturnal hemoglobinuria (PNH). It is important not overlook causes, since they require specific management, in addition antithrombotic treatment (anticoagulants, antiplatelet agents). Unusual sites venous upper extremity veins, splanchnic cerebral retinal arterial renal, adrenal, splenic mesenteric arteries, intracardiac aortal locations. Suspicion MPN PNH should raised if there are concomitant abnormalities, such as elevated or decreased blood cell counts splenomegaly. Diagnosis JAK2V617F mutational screening well flow cytometric assessment GPI-anchored proteins the peripheral blood, respectively. Specific treatments may phlebotomy cytoreductive drugs hydroxyurea, anagrelide, pegylated interferon-alpha, Janus kinase inhibitors. Drugs used terminal complement inhibitors, eculizumab ravulizumab, proximally acting inhibitors pegcetacoplan iptacopan. high risk during their entire lifetime thus followed by specialists experienced care diseases.

Язык: Английский

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Dose Adjustments of Pegcetacoplan in a Patient With Paroxysmal Nocturnal Hemoglobinuria Undergoing Surgery: A Case Report

Cureus, Год журнала: 2025, Номер unknown

Опубликована: Март 25, 2025

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hemolytic anemia mediated by complement that may present with thrombosis and bone marrow failure. Treatments inhibiting component 5, such as eculizumab, improve intravascular hemolysis decrease the risk of thrombosis. However, persists in some patients because extravascular hemolysis. In this context, pegcetacoplan, a pegylated 3 inhibitor, valuable treatment option for PNH, it inhibits both hemolysis, improving anemia. Infections surgery trigger activation, dose adjustments treatments inhibit components be necessary these situations to avoid episodes breakthrough Here, we case 67-year-old male PNH who, after initiating pegcetacoplan 2022, underwent three scheduled surgeries one emergency surgery. We report successful use close monitoring prevent during perioperative periods.

Язык: Английский

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Health-related quality of life and influencing factors of patients with paroxysmal nocturnal hemoglobinuria in China

Orphanet Journal of Rare Diseases, Год журнала: 2024, Номер 19(1)

Опубликована: Май 3, 2024

Abstract Background Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder, leading to various complications and impairments in patients’ health-related quality of life (HRQOL). Limited research has been conducted evaluate the HRQOL Chinese patients with PNH. Understanding this specific population crucial for providing effective healthcare interventions improving patient’ health outcomes. This study aimed assess PNH, identify key determinants. Methods A cross-sectional was during 2022 recruit PNH China. The recruited from China, one largest public welfare patient mutual aid organization Data were collected via an online questionnaire including EQ-5D-5L (5L), social-demographic clinical characteristics. Descriptive statistics employed summarize characteristics participants their HRQOL. Multiple linear logistic regression analyses adopted explore factors affecting Results total 329 valid questionnaires collected. mean (SD) age 35.3 (10.0) years, 52.3% them being male. reported more problems Anxiety/Depression (81.5%) Pain/Discomfort (69.9%) dimensions compared other three 5L dimensions. utility score (HUS) EQ-VAS 0.76 (0.21) 62.61 (19.20), respectively. According multiple regression, initial symptoms (i.e., Anemia [fatigue, tachycardia, shortness breath, headache] back pain) complication thrombosis significant influencing HUS. Total personal income past year, symptom significantly VAS score. Social-demographic characteristics, such as gender, income, thrombosis, also found be related certain well. Conclusion Our manifested China markedly compromised, especially two mental-health dimensions, revealed several socio-demographic These findings could used empirical evidence enhancing

Язык: Английский

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CD59: Biological function and its potential for drug target action

Gene Reports, Год журнала: 2023, Номер 31, С. 101772 - 101772

Опубликована: Апрель 3, 2023

Язык: Английский

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Paroxysmal nocturnal haemoglobinuria - a rare entity in pancytopenia: a case report

International Journal of Advances in Medicine, Год журнала: 2024, Номер 11(5), С. 535 - 537

Опубликована: Авг. 27, 2024

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematologic disorder characterized by hemolysis, bone marrow failure, and thrombosis. This case report details 22-year-old male diagnosed with subclinical PNH, who presented symptoms of fatigue dyspnea on exertion. The classical were not seen in our patient. Laboratory evaluation revealed pancytopenia, macrocytosis low reticulocyte count. Serum B12 levels iron studies normal. Flow cytometry identified deficient expression glycosylphosphatidylinositol (GPI)-anchored proteins the patient’s erythrocytes, confirming diagnosis PNH. As patient was stage, he responded to conservative therapy. Avoidance stressors lead significant clinical improvement. highlights importance considering PNH young adults unexplained hematuria or venous thrombosis provides insights into management this challenging condition. Financial constraints use eculizumab developing countries like India, may present as therapeutic challenge. However, response transplantation underscores its efficacy controlling hemolysis improving quality life patients develop aplastic anemia.

Язык: Английский

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Complement inhibition in medicine: Hematology and beyond; complement inhibition in hematology: PNH and beyond

American Journal of Hematology, Год журнала: 2023, Номер 98(S4)

Опубликована: Март 14, 2023

This special issue of the American Journal Hematology is devoted to complement inhibition in treatment various human disorders. It was made possible by support from Apellis. Eight articles these issues cover complex cascade system its description last update most recent targeted therapies, at terminal and proximal levels. The part innate immunity. has always remained very difficult apprehend for many generations hematologists, similar “coagulation cascade”. And this appears even more true nowadays, since extreme sub-specialization moved apart immunology hematology, while they have been embedded when our masters dissected biology immune mechanism. aims put together clinical processes with biological mechanisms underlying findings. Dr Duval & Fremeaux-Bacchi «Complement hematologist»1 nicely (and comprehensively) describe robust efficient proteolytic cascades resulting opsonization lysis pathogen, as well generation inflammatory response. authors also how an increased activation or a loss regulation fine-tuned involved variety hematological diseases (as others). Among complement-mediated disorders, paroxysmal nocturnal hemoglobinuria (PNH) still remains prototypic model dysregulation disease. Dr. Panse «Paroxysmal Nocturnal Hemoglobinuria: where we stand»2 describes anti-C5 therapies revolutionized management prognosis PNH 2 decades. As discussed article, demonstrating control intravascular hemolysis, thrombosis protection, eventually overall survival improvement, hematologists learned use eculizumab (Soliris) manage patients receiving inhibition. A plethora new drugs interfering are under development Kulasekararaj going».3 first “proof-of-principle” inhibitor targeting C3 approved 2021 (Pecgetacoplan; Aspavelli) detail, novel agents, such factor B D inhibitors, study moment but promising results. All agents advanced field therapeutics that pathway may be effectively inhibited, making quite broader potential applications medicine. Beyond PNH, overactivation alternative drives pathogenesis primary atypical hemolytic uremic syndrome (aHUS). Leon et al. «Complement-driven syndrome»4 elegantly genetically-determined acquired aHUS, pregnancy-related (HUS), severe hypertension-associated HUS. complicated not clear) physiopathology those disorders largely addressed, approach. Transplant-associated thrombotic microangiopathy (TA-TMA) challenging situation clinicians, which reviewed Jodele Salbuski «Reeling Complement Transplant-Associated Thrombotic Microangiopathy: You're Going Need Bigger Boat».5 current understanding pathophysiology TA-TMA presented discussed, particularly it pertains activation, endothelial injury, management. Novel complement-blocking currently investigation addressed. We remark both HUS should considered hematological, multi-organ diseases; thus, considerations two conditions extended number additional affect kidneys other organs. Indeed, key player protective immunity against pathogens, excessive deregulated result collateral tissue injury. thus surprise central COVID-19 pandemic. Calado «Hyper-inflammation COVID-19»6 participation worsening symptoms during COVID infection. pathophysiology, trials, single observations using approach, summarized. data here paved way broad involvement different systemic, hyper-inflammatory conditions, include complications infectious (mostly viral), iatrogenic (e.g., cytokine storms appearing after cell-or antibody-based therapies). At end supplement, deal optimization therapeutic perspectives. Lamers «Complement-Targeted Therapeutics: An Emerging Field Enabled Academic Drug Discovery»7 recall difficulties researchers had face pioneer then develop inhibitors. Concerns about safety complement-targeted interventions, large high plasma concentrations target proteins, complexity system's engagement among factors kept off drug-discovery radar In their paper, document extraordinary examples aim venture some predictions headed to. manuscript, highlight challenges coming interaction between academic scientists for-profit entities, drive candidate shape actual successful translation. Finally, Prof. Luzzatto «closing remarks»8 takes advantage his long-lasting contribution share vision future recalls old concepts diseases, describing all achievements hematology discusses peculiarities introducing question whether best strategy intercept multiple well-chosen check points. Should absolute blockage several compounds patient trying find best, convenient, agent? And, addition anti-complement provides sharp comments pertain any medicine: believe informative, especially younger physicians. Several questions open fascinating field. do hope AJH readers will eight instructive clinically relevant daily practice. Our can inspire further advance field, appeared gold mine investors) few Régis Peffault de Latour received research Alexion, Novartis, Pfizer, Amgen; lecture fees Apellis/SOBI; served member advisory/investigator board Apellis/SOBI, Biocryst, Roche, Samsung; consultant Antonio M. Risitano Alnylam, Rapharma; Achillion, Samsung, Sanofi; Amyndas, Omeros.

Язык: Английский

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Functional Analysis of a Novel Complement C5a Receptor 1-Blocking Monoclonal Antibody

Journal of Innate Immunity, Год журнала: 2023, Номер 15(1), С. 836 - 849

Опубликована: Янв. 1, 2023

The complement system anaphylatoxin C5a is a critical player in inflammation. By binding to receptor 1 (C5aR1/CD88), regulates many cellular functions, mainly as potent pro-inflammatory inducer. We describe the generation and selection of antagonistic C5aR1 mouse monoclonal antibody (mAb).Initial hybridoma clone was performed with cell-binding study human whole blood. In-house mAb assessment for inhibition done via iLite® assay. specificity investigated on C5aR1his- C5aR2his-expressing Flp-In™-CHO cells. Physiological assessed C5a-driven calcium flux assay stimulation based isolated polymorphonuclear leukocytes (PMNs) blood model stimulated Escherichia coli.The supernatant clones targeting N-terminal section displayed efficient blood, which confirmed purified mAbs. 18-41-6 selected following in-house mAbs specific C5aR1. Full-size and/or F(ab')2 preparations were found efficiently abrogate C5a-induced neutrophils significantly reduce upregulation activation markers CD11b (neutrophils, monocytes) CD66b (neutrophils).Our results demonstrate that valuable tool investigating C5a-C5aR1 axis potential therapeutic candidate inflammatory disease treatment.

Язык: Английский

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An Interesting Case of Paroxysmal Nocturnal Hemoglobinuria With Renal Involvement

Cureus, Год журнала: 2024, Номер unknown

Опубликована: Июль 5, 2024

Paroxysmal nocturnal hemoglobinuria (PNH) is an uncommon genetic disorder that affects red blood cell production, causing symptoms like fatigue, abdominal pain, and shortness of breath. This condition can also result in dark urine increased risk infections. Diagnosis PNH involves testing flow cytometry, which confirm the presence condition. Once a diagnosis confirmed, personalized treatment plans should be developed to effectively manage improve patient's quality life. Treatment options for may include bone marrow transplantation, transfusions, use recombinant monoclonal antibody, eculizumab. Regular monitoring essential identify any complications arise due this With proper management treatment, patients with lead healthy fulfilling In case study, we present young adult male who suffers from renal failure, highlighting importance care ongoing complex

Язык: Английский

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