Пароксизмална нощна хемоглобинурия – диагноза, клинична картина и нови терапевтични възможности
Keywords:
хемоглобинурия, пароксизмална, комплемент инактивиращи агенти
Abstract
Пароксизмалната нощна хемоглобинурия (ПНХ) е хронично мултисистемно, прогресивно и животозастрашаващо заболяване, което се характеризира с вътресъдова хемолиза, тромботични инциденти, тежки инфекции и костно-мозъчна недостатъчност. ПНХ е рядко заболяване с очаквана болестност по данни за Orphanet 2/100 000.
Парадигмата в лечението на ПНХ се променя с въвеждането на комплементна блокада посредством анти-С5 антитела и инхибитори на проксимални компоненти на комплемента. Блокадата на комплемента постига значима редукция на тромботичните усложнения, стабилно ниво на хемоглобин, контрол на хемолизата и подобряване качеството на живот при пациентите с ПНХ. Лечението с комплементни инхибитори подобрява свързаните с ПНХ органни усложнения като бъбречна недостатъчност и пулмонална хипертония.
В настоящия обзор са обобщени и представени актуални насоки за лечение на ПНХ, публикувани от международни и европейски национални дружества по хематология, както и са сравнени индикации за започване и преустановяване на терапия с анти-С5 инхибитори според ПНХ работни групи в редица европейски държави.
References
Brodsky RA. Paroxysmal nocturnal hemoglobinuria. Blood. 2014 Oct 30;124(18):2804–11.
Takeda J, Miyata T, Kawagoe K, et al. Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria. Cell. 1993 May 21;73(4):703–11.
Bessler M, Mason PJ, Hillmen P, et al. Paroxysmal nocturnal haemoglobinuria (PNH) is caused by somatic mutations in the PIG-A gene. EMBO J. 1994 Jan 1;13(1):110–7.
Miyata T, Takeda J, Iida Y, et al. The cloning of PIG-A, a component in the early step of GPI-anchor biosynthesis. Science. 1993 Feb 26;259(5099):1318–20.
Kinoshita T, Inoue N, Takeda J. Defective Glycosyl Phosphatidylinositol Anchor Synthesis and Paroxysmal Nocturnal Hemoglobinuria. In: Dixon FJ, editor. Advances in Immunology [Internet]. Academic Press; 1995 [cited 2023 Jul 20]. p. 57–103. Available from: https://www.sciencedirect.com/science/article/pii/S0065277608605842
Rollins SA, Sims PJ. The complement-inhibitory activity of CD59 resides in its capacity to block incorporation of C9 into membrane C5b-9. The Journal of Immunology. 1990 May 1;144(9):3478–83.
Lublin DM, Atkinson JP. Decay-Accelerating Factor: Biochemistry, Molecular Biology, and Function. Annual Review of Immunology. 1989;7(1):35–58.
Borowitz MJ, Craig FE, DiGiuseppe JA, et al. Guidelines for the diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria and related disorders by flow cytometry. Cytometry Part B: Clinical Cytometry. 2010;78B(4):211–30.
Dezern AE, Borowitz MJ. ICCS/ESCCA Consensus Guidelines to detect GPI-deficient cells in Paroxysmal Nocturnal Hemoglobinuria (PNH) and related Disorders Part 1 – Clinical Utility. Cytometry Part B: Clinical Cytometry. 2018;94(1):16–22.
Brodsky RA. How I treat paroxysmal nocturnal hemoglobinuria. Blood. 2009 Jun 25;113(26):6522–7.
Brodsky RA, Mukhina GL, Li S, et al. Improved detection and characterization of paroxysmal nocturnal hemoglobinuria using fluorescent aerolysin. Am J Clin Pathol. 2000 Sep;114(3):459–66.
Sutherland DR, Keeney M, Illingworth A. Practical guidelines for the high-sensitivity detection and monitoring of paroxysmal nocturnal hemoglobinuria clones by flow cytometry. Cytometry Part B: Clinical Cytometry. 2012;82B(4):195–208.
Parker C, Omine M, Richards S, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005 Dec 1;106(12):3699–709.
Morgan BP, Harris CL. Complement, a target for therapy in inflammatory and degenerative diseases. Nat Rev Drug Discov. 2015 Dec;14(12):857–77.
Lee JW, Sicre de Fontbrune F, Wong Lee Lee L, et al. Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study. Blood. 2019 Feb 7;133(6):530-539.
Hillmen P, Muus P, Röth A, et al. Long-term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria. Br J Haematol. 2013 Jul;162(1):62–73.
Terriou L, Patriquin CJ, Griffin M, et al. Long-Term Survival Benefit of Eculizumab Treatment in Patients with Paroxysmal Nocturnal Hemoglobinuria: Data from the International PNH Registry. Blood. 2021 Nov 5;138(Supplement 1):2188.
Mullard A. First approval of a complement C3 inhibitor opens up autoimmune and inflammatory opportunities. Nature Reviews Drug Discovery. 2021 May 26;20(7):496–496.
Prevalence of rare diseases: Bibliographic data , Orphanet Report Series, Rare Diseases collection, Janvier 2022, Number 1: Diseases listed in alphabetical order [Internet]. Available from: http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf
Richards SJ, Painter D, Dickinson AJ, et al. The incidence and prevalence of patients with paroxysmal nocturnal haemoglobinuria and aplastic anaemia PNH syndrome: A retrospective analysis of the UK’s population-based haematological malignancy research network 2004-2018. Eur J Haematol. 2021 Aug;107(2):211–8.
Jalbert JJ, Chaudhari U, Zhang H, et al. Epidemiology of PNH and Real-World Treatment Patterns Following an Incident PNH Diagnosis in the US. Blood. 2019 Nov 13;134:3407.
Goren Sahin D, Akay OM, Keklik M, et al. Clinical characteristics and therapeutic outcomes of paroxysmal nocturnal hemoglobinuria patients in Turkey: a multicenter experience. Ann Hematol. 2021 Jul;100(7):1667–75.
Du Y, Yang Y, Yang C, et al. Clinical characteristics of 512 eculizumab-naive paroxysmal nocturnal hemoglobinuria patients in China: a single-center observational study. Hematology. 2022 Dec;27(1):113–21.
Peffault De La Tour R, Sicre de Fontbrune F, Socié G. Paroxysmal nocturnal hemoglobinuria. Orphanet encyclopedia for professionals. [Internet]. Orphanet; 2017. Available from: https://www.orpha.net/consor/www/cgi-bin/OC_Exp.php?lng=FR&Expert=447
Hill A, Kelly RJ, Hillmen P. Thrombosis in paroxysmal nocturnal hemoglobinuria. Blood. 2013 Jun 20;121(25):4985–96; quiz 5105.
de Latour RP, Mary JY, Salanoubat C, et al.; French Society of Hematology; French Association of Young Hematologists. Paroxysmal nocturnal hemoglobinuria: natural history of disease subcategories. Blood. 2008 Oct 15;112(8):3099-106.
Hillmen P, Muus P, Dührsen U, et al. Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood. 2007 Dec 1;110(12):4123–8.
Kulasekararaj AG, Hill A, Rottinghaus ST, et al. Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study. Blood. 2019 Feb 7;133(6):540–9.
Brodsky RA, Young NS, Antonioli E, et al. Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Blood. 2008 Feb 15;111(4):1840–7.
Hillmen P, Young NS, Schubert J, et al. The Complement Inhibitor Eculizumab in Paroxysmal Nocturnal Hemoglobinuria. N Engl J Med. 2006 Sep 21;355(12):1233–43.
Brodsky RA, Peffault de Latour R, Rottinghaus ST, et al. Characterization of breakthrough hemolysis events observed in the phase 3 randomized studies of ravulizumab versus eculizumab in adults with paroxysmal nocturnal hemoglobinuria. Haematologica. 2021 Jan 1;106(1):230–7.
Hillmen P, Elebute M, Kelly R, et al. Long-term effect of the complement inhibitor eculizumab on kidney function in patients with paroxysmal nocturnal hemoglobinuria. Am J Hematol. 2010 Aug;85(8):553–9.
Rondeau E, Scully M, Ariceta G, et al. The long-acting C5 inhibitor, Ravulizumab, is effective and safe in adult patients with atypical hemolytic uremic syndrome naïve to complement inhibitor treatment. Kidney International. 2020 Jun 1;97(6):1287–96.
Hill A, Rother RP, Wang X, et al. Effect of eculizumab on haemolysis-associated nitric oxide depletion, dyspnoea, and measures of pulmonary hypertension in patients with paroxysmal nocturnal haemoglobinuria. Br J Haematol. 2010 May;149(3):414–25.
Hill A, Sapsford RJ, Scally A, et al. Under-recognized complications in patients with paroxysmal nocturnal haemoglobinuria: raised pulmonary pressure and reduced right ventricular function. Br J Haematol. 2012 Aug;158(3):409–14.
Fieni S, Bonfanti L, Gramellini D, et al. Clinical management of paroxysmal nocturnal hemoglobinuria in pregnancy: a case report and updated review. Obstet Gynecol Surv. 2006 Sep;61(9):593–601.
Kelly R, Arnold L, Richards S, et al. The management of pregnancy in paroxysmal nocturnal haemoglobinuria on long term eculizumab. British Journal of Haematology. 2010;149(3):446–50.
Cançado RD, Araújo A da S, Sandes AF, et al. Consensus statement for diagnosis and treatment of paroxysmal nocturnal haemoglobinuria. Hematol Transfus Cell Ther. 2021;43(3):341–8.
Onkopedia [Internet]. [cited 2023 Jul 24]. Paroxysmale nächtliche Hämoglobinurie (PNH). Available from: https://www.onkopedia.com/de/onkopedia/guidelines/paroxysmale-naechtliche-haemoglobinurie-pnh
Peffault de Latour R, Schrezenmeier H, Bacigalupo A, et al. Allogeneic stem cell transplantation in paroxysmal nocturnal hemoglobinuria. Haematologica. 2012 Nov;97(11):1666–73.
Devos T, Meers S, Boeckx N, et al. Diagnosis and management of PNH: Review and recommendations from a Belgian expert panel. European Journal of Haematology. 2018;101(6):737–49.
The Red Book. Treatment and procedures in hematology 2023. Chapter 23. [Internet]. 2023. Available from: https://www.hematology.cz/cervena-kniha-lecebne-postupy-v-hematologii/
Killick SB, Bown N, Cavenagh J, et al. Guidelines for the diagnosis and management of adult aplastic anaemia. British Journal of Haematology. 2016;172(2):187–207.
Sahin F, Akay OM, Ayer M, et al. Pesg PNH diagnosis, follow-up and treatment guidelines. Am J Blood Res. 2016;6(2):19–27.
Villegas A, Arrizabalaga B, Bonanad S, et al. [Spanish consensus statement for diagnosis and treatment of paroxysmal nocturnal haemoglobinuria]. Med Clin (Barc). 2016 Mar 18;146(6):278.e1-7.
Protocole national de diagnostic et de soins (PNDS) APLASIES MEDULLAIRES ACQUISES ET CONSTITUTIONNELLES [Internet]. 2023. Available from: https://hpnfrance.com/2023/05/31/mai-2023-mise-a-jour-du-pnds/
Johansson, Alsenhed J, Arvanitakis A, et al. Paroxysmal nokturn hemoglobinuri (PNH). Nationella rekommendationer för diagnostik, behandling och uppföljning. 2021.
Armstrong E, Jarva H, Korkama ES, et al. National recommendation: a statement prepared by hematology specialists (the PNH group) on the diagnosis, treatment and follow-up of PNH in Finland [Internet]. Suomen Hematologiyhdistys (Finnish Association of Hematology ); 2022. Available from: https://hematology.fi/hoito-ohjeet/hoito-ohje-1/pnh/
Dansk guidelines for behandling af patienter med paroxystisk nokturn hæmoglobinuria. [Internet]. Dansk Haematologisk Selskab (Danish Society of Hematology); 2013. Available from: https://hematology.dk/index.php/vejledninger/kliniske/2012-11-06-06-19-26
Bodó I, Amine I, Boban A, et al. Complement Inhibition in Paroxysmal Nocturnal Hemoglobinuria (PNH): A Systematic Review and Expert Opinion from Central Europe on Special Patient Populations. Adv Ther. 2023 Jun;40(6):2752–72.
Risitano AM, Marotta S, Ricci P, et al. Anti-complement Treatment for Paroxysmal Nocturnal Hemoglobinuria: Time for Proximal Complement Inhibition? A Position Paper From the SAAWP of the EBMT. Front Immunol. 2019;10:1157.
Lee JW, Kulasekararaj AG. Ravulizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Expert Opinion on Biological Therapy. 2020 Mar 3;20(3):227–37.
Bozio CH, Isenhour C, McNamara LA. Characteristics of and meningococcal disease prevention strategies for commercially insured persons receiving eculizumab in the United States. PLoS One. 2020;15(11):e0241989.
Hillmen P, Szer J, Weitz I, et al. Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria. N Engl J Med. 2021 Mar 18;384(11):1028–37.
de Castro C, Grossi F, Weitz IC, et al. C3 inhibition with pegcetacoplan in subjects with paroxysmal nocturnal hemoglobinuria treated with eculizumab. American Journal of Hematology. 2020;95(11):1334–43.
Takeda J, Miyata T, Kawagoe K, et al. Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria. Cell. 1993 May 21;73(4):703–11.
Bessler M, Mason PJ, Hillmen P, et al. Paroxysmal nocturnal haemoglobinuria (PNH) is caused by somatic mutations in the PIG-A gene. EMBO J. 1994 Jan 1;13(1):110–7.
Miyata T, Takeda J, Iida Y, et al. The cloning of PIG-A, a component in the early step of GPI-anchor biosynthesis. Science. 1993 Feb 26;259(5099):1318–20.
Kinoshita T, Inoue N, Takeda J. Defective Glycosyl Phosphatidylinositol Anchor Synthesis and Paroxysmal Nocturnal Hemoglobinuria. In: Dixon FJ, editor. Advances in Immunology [Internet]. Academic Press; 1995 [cited 2023 Jul 20]. p. 57–103. Available from: https://www.sciencedirect.com/science/article/pii/S0065277608605842
Rollins SA, Sims PJ. The complement-inhibitory activity of CD59 resides in its capacity to block incorporation of C9 into membrane C5b-9. The Journal of Immunology. 1990 May 1;144(9):3478–83.
Lublin DM, Atkinson JP. Decay-Accelerating Factor: Biochemistry, Molecular Biology, and Function. Annual Review of Immunology. 1989;7(1):35–58.
Borowitz MJ, Craig FE, DiGiuseppe JA, et al. Guidelines for the diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria and related disorders by flow cytometry. Cytometry Part B: Clinical Cytometry. 2010;78B(4):211–30.
Dezern AE, Borowitz MJ. ICCS/ESCCA Consensus Guidelines to detect GPI-deficient cells in Paroxysmal Nocturnal Hemoglobinuria (PNH) and related Disorders Part 1 – Clinical Utility. Cytometry Part B: Clinical Cytometry. 2018;94(1):16–22.
Brodsky RA. How I treat paroxysmal nocturnal hemoglobinuria. Blood. 2009 Jun 25;113(26):6522–7.
Brodsky RA, Mukhina GL, Li S, et al. Improved detection and characterization of paroxysmal nocturnal hemoglobinuria using fluorescent aerolysin. Am J Clin Pathol. 2000 Sep;114(3):459–66.
Sutherland DR, Keeney M, Illingworth A. Practical guidelines for the high-sensitivity detection and monitoring of paroxysmal nocturnal hemoglobinuria clones by flow cytometry. Cytometry Part B: Clinical Cytometry. 2012;82B(4):195–208.
Parker C, Omine M, Richards S, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005 Dec 1;106(12):3699–709.
Morgan BP, Harris CL. Complement, a target for therapy in inflammatory and degenerative diseases. Nat Rev Drug Discov. 2015 Dec;14(12):857–77.
Lee JW, Sicre de Fontbrune F, Wong Lee Lee L, et al. Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study. Blood. 2019 Feb 7;133(6):530-539.
Hillmen P, Muus P, Röth A, et al. Long-term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria. Br J Haematol. 2013 Jul;162(1):62–73.
Terriou L, Patriquin CJ, Griffin M, et al. Long-Term Survival Benefit of Eculizumab Treatment in Patients with Paroxysmal Nocturnal Hemoglobinuria: Data from the International PNH Registry. Blood. 2021 Nov 5;138(Supplement 1):2188.
Mullard A. First approval of a complement C3 inhibitor opens up autoimmune and inflammatory opportunities. Nature Reviews Drug Discovery. 2021 May 26;20(7):496–496.
Prevalence of rare diseases: Bibliographic data , Orphanet Report Series, Rare Diseases collection, Janvier 2022, Number 1: Diseases listed in alphabetical order [Internet]. Available from: http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf
Richards SJ, Painter D, Dickinson AJ, et al. The incidence and prevalence of patients with paroxysmal nocturnal haemoglobinuria and aplastic anaemia PNH syndrome: A retrospective analysis of the UK’s population-based haematological malignancy research network 2004-2018. Eur J Haematol. 2021 Aug;107(2):211–8.
Jalbert JJ, Chaudhari U, Zhang H, et al. Epidemiology of PNH and Real-World Treatment Patterns Following an Incident PNH Diagnosis in the US. Blood. 2019 Nov 13;134:3407.
Goren Sahin D, Akay OM, Keklik M, et al. Clinical characteristics and therapeutic outcomes of paroxysmal nocturnal hemoglobinuria patients in Turkey: a multicenter experience. Ann Hematol. 2021 Jul;100(7):1667–75.
Du Y, Yang Y, Yang C, et al. Clinical characteristics of 512 eculizumab-naive paroxysmal nocturnal hemoglobinuria patients in China: a single-center observational study. Hematology. 2022 Dec;27(1):113–21.
Peffault De La Tour R, Sicre de Fontbrune F, Socié G. Paroxysmal nocturnal hemoglobinuria. Orphanet encyclopedia for professionals. [Internet]. Orphanet; 2017. Available from: https://www.orpha.net/consor/www/cgi-bin/OC_Exp.php?lng=FR&Expert=447
Hill A, Kelly RJ, Hillmen P. Thrombosis in paroxysmal nocturnal hemoglobinuria. Blood. 2013 Jun 20;121(25):4985–96; quiz 5105.
de Latour RP, Mary JY, Salanoubat C, et al.; French Society of Hematology; French Association of Young Hematologists. Paroxysmal nocturnal hemoglobinuria: natural history of disease subcategories. Blood. 2008 Oct 15;112(8):3099-106.
Hillmen P, Muus P, Dührsen U, et al. Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood. 2007 Dec 1;110(12):4123–8.
Kulasekararaj AG, Hill A, Rottinghaus ST, et al. Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study. Blood. 2019 Feb 7;133(6):540–9.
Brodsky RA, Young NS, Antonioli E, et al. Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Blood. 2008 Feb 15;111(4):1840–7.
Hillmen P, Young NS, Schubert J, et al. The Complement Inhibitor Eculizumab in Paroxysmal Nocturnal Hemoglobinuria. N Engl J Med. 2006 Sep 21;355(12):1233–43.
Brodsky RA, Peffault de Latour R, Rottinghaus ST, et al. Characterization of breakthrough hemolysis events observed in the phase 3 randomized studies of ravulizumab versus eculizumab in adults with paroxysmal nocturnal hemoglobinuria. Haematologica. 2021 Jan 1;106(1):230–7.
Hillmen P, Elebute M, Kelly R, et al. Long-term effect of the complement inhibitor eculizumab on kidney function in patients with paroxysmal nocturnal hemoglobinuria. Am J Hematol. 2010 Aug;85(8):553–9.
Rondeau E, Scully M, Ariceta G, et al. The long-acting C5 inhibitor, Ravulizumab, is effective and safe in adult patients with atypical hemolytic uremic syndrome naïve to complement inhibitor treatment. Kidney International. 2020 Jun 1;97(6):1287–96.
Hill A, Rother RP, Wang X, et al. Effect of eculizumab on haemolysis-associated nitric oxide depletion, dyspnoea, and measures of pulmonary hypertension in patients with paroxysmal nocturnal haemoglobinuria. Br J Haematol. 2010 May;149(3):414–25.
Hill A, Sapsford RJ, Scally A, et al. Under-recognized complications in patients with paroxysmal nocturnal haemoglobinuria: raised pulmonary pressure and reduced right ventricular function. Br J Haematol. 2012 Aug;158(3):409–14.
Fieni S, Bonfanti L, Gramellini D, et al. Clinical management of paroxysmal nocturnal hemoglobinuria in pregnancy: a case report and updated review. Obstet Gynecol Surv. 2006 Sep;61(9):593–601.
Kelly R, Arnold L, Richards S, et al. The management of pregnancy in paroxysmal nocturnal haemoglobinuria on long term eculizumab. British Journal of Haematology. 2010;149(3):446–50.
Cançado RD, Araújo A da S, Sandes AF, et al. Consensus statement for diagnosis and treatment of paroxysmal nocturnal haemoglobinuria. Hematol Transfus Cell Ther. 2021;43(3):341–8.
Onkopedia [Internet]. [cited 2023 Jul 24]. Paroxysmale nächtliche Hämoglobinurie (PNH). Available from: https://www.onkopedia.com/de/onkopedia/guidelines/paroxysmale-naechtliche-haemoglobinurie-pnh
Peffault de Latour R, Schrezenmeier H, Bacigalupo A, et al. Allogeneic stem cell transplantation in paroxysmal nocturnal hemoglobinuria. Haematologica. 2012 Nov;97(11):1666–73.
Devos T, Meers S, Boeckx N, et al. Diagnosis and management of PNH: Review and recommendations from a Belgian expert panel. European Journal of Haematology. 2018;101(6):737–49.
The Red Book. Treatment and procedures in hematology 2023. Chapter 23. [Internet]. 2023. Available from: https://www.hematology.cz/cervena-kniha-lecebne-postupy-v-hematologii/
Killick SB, Bown N, Cavenagh J, et al. Guidelines for the diagnosis and management of adult aplastic anaemia. British Journal of Haematology. 2016;172(2):187–207.
Sahin F, Akay OM, Ayer M, et al. Pesg PNH diagnosis, follow-up and treatment guidelines. Am J Blood Res. 2016;6(2):19–27.
Villegas A, Arrizabalaga B, Bonanad S, et al. [Spanish consensus statement for diagnosis and treatment of paroxysmal nocturnal haemoglobinuria]. Med Clin (Barc). 2016 Mar 18;146(6):278.e1-7.
Protocole national de diagnostic et de soins (PNDS) APLASIES MEDULLAIRES ACQUISES ET CONSTITUTIONNELLES [Internet]. 2023. Available from: https://hpnfrance.com/2023/05/31/mai-2023-mise-a-jour-du-pnds/
Johansson, Alsenhed J, Arvanitakis A, et al. Paroxysmal nokturn hemoglobinuri (PNH). Nationella rekommendationer för diagnostik, behandling och uppföljning. 2021.
Armstrong E, Jarva H, Korkama ES, et al. National recommendation: a statement prepared by hematology specialists (the PNH group) on the diagnosis, treatment and follow-up of PNH in Finland [Internet]. Suomen Hematologiyhdistys (Finnish Association of Hematology ); 2022. Available from: https://hematology.fi/hoito-ohjeet/hoito-ohje-1/pnh/
Dansk guidelines for behandling af patienter med paroxystisk nokturn hæmoglobinuria. [Internet]. Dansk Haematologisk Selskab (Danish Society of Hematology); 2013. Available from: https://hematology.dk/index.php/vejledninger/kliniske/2012-11-06-06-19-26
Bodó I, Amine I, Boban A, et al. Complement Inhibition in Paroxysmal Nocturnal Hemoglobinuria (PNH): A Systematic Review and Expert Opinion from Central Europe on Special Patient Populations. Adv Ther. 2023 Jun;40(6):2752–72.
Risitano AM, Marotta S, Ricci P, et al. Anti-complement Treatment for Paroxysmal Nocturnal Hemoglobinuria: Time for Proximal Complement Inhibition? A Position Paper From the SAAWP of the EBMT. Front Immunol. 2019;10:1157.
Lee JW, Kulasekararaj AG. Ravulizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Expert Opinion on Biological Therapy. 2020 Mar 3;20(3):227–37.
Bozio CH, Isenhour C, McNamara LA. Characteristics of and meningococcal disease prevention strategies for commercially insured persons receiving eculizumab in the United States. PLoS One. 2020;15(11):e0241989.
Hillmen P, Szer J, Weitz I, et al. Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria. N Engl J Med. 2021 Mar 18;384(11):1028–37.
de Castro C, Grossi F, Weitz IC, et al. C3 inhibition with pegcetacoplan in subjects with paroxysmal nocturnal hemoglobinuria treated with eculizumab. American Journal of Hematology. 2020;95(11):1334–43.
Published
2024-02-09
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Белева Е. Пароксизмална нощна хемоглобинурия – диагноза, клинична картина и нови терапевтични възможности. Редки болести и лекарства сираци [Internet]. 2024Feb.9 [cited 2024May2];14(3-4):10-9. Available from: https://journal.raredis.org/index.php/RBLS/article/view/189
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