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

Abstract

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. One of the most important is increasing awareness of the heterogeneity with which patients can present, which can lead to significant delays in recognition. Data from the Canadian PNH Registry are presented to demonstrate the variety of presenting symptoms. In Canada, geography precludes consolidation of care to just a few centers, so management is distributed across academic hospitals, linked together as the Canadian PNH Network. The Network over the last several years has developed educational programs and clinical checklists and has worked to standardize access to diagnostics across the country. Herein, we address some of the common diagnostic and therapeutic challenges faced by PNH physicians and give our recommendations.Gaps in knowledge are also addressed, and where appropriate, consensus opinion is provided. K E Y W O R D Saplastic anemia and bone marrow failure, bone marrow transplantation, coagulation disorders, red cell disorders | 37 PATRIQUIN eT Al.

Paroxysmal Nocturnal Hemoglobinuria: An Underestimated Cause of Pediatric Thromboembolism

“…In accordance with our findings, Patriquin et al recently published a review article proposing that the diagnosis of PNH should be considered in five clinical scenarios, abbreviated by the acronym CATCH: cytopenia, aplastic anemia/ myelodysplasia, thrombosis, Coombs'-negative hemolysis, and hemoglobinuria. 17 Both, our case presentation and retrospective single-center study show that in all children with thrombosis, intravascular hemolysis, and cytopenia, it is worth considering PNH as underlying disease to prevent delayed diagnosis and to initiate the appropriate treatment including eculizumab. Note: All patients were suspicious (>3 criteria for PNH) for, but not diagnosed with PNH.…”

Development of a patient-reported outcome questionnaire for aplastic anemia and paroxysmal nocturnal hemoglobinuria (PRO-AA/PNH)

“…tremor and ataxia, paresthesia, muscle spasms and cramps, impairment of family time). We assumed that our nal symptom list was still not complete considering that the limited number of participating patients (n = 24) and medical experts (n = 7) cannot capture all aspects of this ultra-rare disease. This led us to add one open question in our nal PRO questionnaire ("Did you have any other symptoms/problems, which were not queried above?"))…”

“…Case reports/series covered further 304 patients (AA n = 187, PNH n = 110, AA-PNH n = 7). Partial overlap of the cohorts was found in seven studies of the PNH international registry or national PNH registries [2,[21][22][23][24][25][26], as well as in three studies by Hillmen et al [27][28][29] with the SHEPHERD [30] and one of the TRIUMPH trials [31].…”

Development of a patient-reported outcome questionnaire for aplastic anemia and paroxysmal nocturnal hemoglobinuria (PRO-AA/PNH)

“…Case reports/series covered further 304 patients (AA n = 187, PNH n = 110, AA-PNH n = 7). Partial overlap of the cohorts was found in seven studies of the PNH international registry or national PNH registries [2, [21][22][23][24][25][26], as well as in three studies by Hillmen et al [27][28][29] with the SHEPHERD [30] and one of the TRIUMPH trials [31].…”