Difficult Cases of Paroxysmal Nocturnal Hemoglobinuria: Diagnosis and Therapeutic Novelties
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 cy...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-03-01
|
| Series: | Journal of Clinical Medicine |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2077-0383/10/5/948 |
| _version_ | 1797416531634683904 |
|---|---|
| author | Bruno Fattizzo Fabio Serpenti Juri Alessandro Giannotta Wilma Barcellini |
| author_facet | Bruno Fattizzo Fabio Serpenti Juri Alessandro Giannotta Wilma Barcellini |
| author_sort | Bruno Fattizzo |
| collection | DOAJ |
| description | 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. Particularly, the clinical significance of small PNH clones in patients with bone marrow failures, including aplastic anemia and myelodysplastic syndromes, as well as in uncommon associations, such as myeloproliferative disorders, is still largely unknown. Besides current treatment with the anti-C5 eculizumab, which reduced PNH-related morbidity and mortality, new complement inhibitors will likely fulfill unmet clinical needs in terms of patients’ quality of life and better response rates (i.e., responses in subjects with C5 polymorphisms; reduction of extravascular hemolysis and breakthrough hemolysis episodes). Still, unanswered questions remain for these agents regarding their use in mono- or combination therapy, when to treat, and which drug is the best for which patient. Lastly, long-term safety needs to be assessed in real-life studies. In this review, we describe some clinical vignettes illustrating practical aspects of PNH diagnosis and management; moreover, we discuss recent advances in PNH diagnostic and therapeutic approaches. |
| first_indexed | 2024-03-09T06:04:32Z |
| format | Article |
| id | doaj.art-9df89ffe3c444d5b9e3b260d973daa82 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-09T06:04:32Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-9df89ffe3c444d5b9e3b260d973daa822023-12-03T12:05:06ZengMDPI AGJournal of Clinical Medicine2077-03832021-03-0110594810.3390/jcm10050948Difficult Cases of Paroxysmal Nocturnal Hemoglobinuria: Diagnosis and Therapeutic NoveltiesBruno Fattizzo0Fabio Serpenti1Juri Alessandro Giannotta2Wilma Barcellini3Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, 20122 Milan, ItalyFondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, 20122 Milan, ItalyFondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, 20122 Milan, ItalyFondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, 20122 Milan, ItalyParoxysmal 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. Particularly, the clinical significance of small PNH clones in patients with bone marrow failures, including aplastic anemia and myelodysplastic syndromes, as well as in uncommon associations, such as myeloproliferative disorders, is still largely unknown. Besides current treatment with the anti-C5 eculizumab, which reduced PNH-related morbidity and mortality, new complement inhibitors will likely fulfill unmet clinical needs in terms of patients’ quality of life and better response rates (i.e., responses in subjects with C5 polymorphisms; reduction of extravascular hemolysis and breakthrough hemolysis episodes). Still, unanswered questions remain for these agents regarding their use in mono- or combination therapy, when to treat, and which drug is the best for which patient. Lastly, long-term safety needs to be assessed in real-life studies. In this review, we describe some clinical vignettes illustrating practical aspects of PNH diagnosis and management; moreover, we discuss recent advances in PNH diagnostic and therapeutic approaches.https://www.mdpi.com/2077-0383/10/5/948paroxysmal nocturnal hemoglobinuriaeculizumabcomplement inhibitorsbone marrow failuresmyelodysplastic syndromes |
| spellingShingle | Bruno Fattizzo Fabio Serpenti Juri Alessandro Giannotta Wilma Barcellini Difficult Cases of Paroxysmal Nocturnal Hemoglobinuria: Diagnosis and Therapeutic Novelties Journal of Clinical Medicine paroxysmal nocturnal hemoglobinuria eculizumab complement inhibitors bone marrow failures myelodysplastic syndromes |
| title | Difficult Cases of Paroxysmal Nocturnal Hemoglobinuria: Diagnosis and Therapeutic Novelties |
| title_full | Difficult Cases of Paroxysmal Nocturnal Hemoglobinuria: Diagnosis and Therapeutic Novelties |
| title_fullStr | Difficult Cases of Paroxysmal Nocturnal Hemoglobinuria: Diagnosis and Therapeutic Novelties |
| title_full_unstemmed | Difficult Cases of Paroxysmal Nocturnal Hemoglobinuria: Diagnosis and Therapeutic Novelties |
| title_short | Difficult Cases of Paroxysmal Nocturnal Hemoglobinuria: Diagnosis and Therapeutic Novelties |
| title_sort | difficult cases of paroxysmal nocturnal hemoglobinuria diagnosis and therapeutic novelties |
| topic | paroxysmal nocturnal hemoglobinuria eculizumab complement inhibitors bone marrow failures myelodysplastic syndromes |
| url | https://www.mdpi.com/2077-0383/10/5/948 |
| work_keys_str_mv | AT brunofattizzo difficultcasesofparoxysmalnocturnalhemoglobinuriadiagnosisandtherapeuticnovelties AT fabioserpenti difficultcasesofparoxysmalnocturnalhemoglobinuriadiagnosisandtherapeuticnovelties AT jurialessandrogiannotta difficultcasesofparoxysmalnocturnalhemoglobinuriadiagnosisandtherapeuticnovelties AT wilmabarcellini difficultcasesofparoxysmalnocturnalhemoglobinuriadiagnosisandtherapeuticnovelties |