Abstract
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.
Highlights
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematologic disorder caused by somatic mutations of the PIGA gene in hematopoietic stem cells [1]
C3b initiates the terminal complement cascade by the formation of the C5 convertase, which cleaves C5 and thereafter C6, C7, C8, and C9. This results in the formation of the terminal membrane attack complex (MAC), which forms pores in the membrane of erythrocytes promoting cell lysis
Once the diagnosis of DAT-negative intravascular hemolytic anemia is made, PNH diagnosis is established through a flow cytometry
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematologic disorder caused by somatic mutations of the PIGA gene in hematopoietic stem cells [1] Such mutations result in impaired production of glycosyl phosphatidyl inositol (GPI), an anchor molecule for many different cellular membrane proteins. The latter include CD55 ( named decay accelerating factor, DAF) and CD59 (membrane inhibitor of reactive lysis, MIRL), which are natural complement inhibitors and are lost on the membrane of PNH cells. We describe old and new clinical and therapeutic aspects of PNH through the presentation of some instructive clinical vignettes. We 2 ofof describe old and new clinical and therapeutic aspects of PNH through the presentation some instructive clinical vignettes
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