Paroxysmal nocturnal hemoglobinuria: clinical cases and diagnostic difficulties

Анотація

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder caused by the PIGA gene mutation. The major clinical manifestations include hemolytic anemia, signs of bone marrow dysfunction, and the presence of thrombosis, especially in atypical locations. PNH is classified by 3 types: classical, on the background of another blood disease, and subclinical. Making the diagnosis of PNH can be a difficult task due to the presence of clinical signs that are also characteristic of hemolytic and aplastic anemias, nephrotic syndrome, etc., which prolongs the time until the patient receives the appropriate treatment. The authors of the publication conducted a general review of the literature and an analysis of clinical cases of PNH in order to increase the awareness of specialists of various profiles in the diagnostics of rare diseases using the example of PNH. The article presents 3 clinical cases of different types of PNH. Patient A. was not finally examined and did not receive full treatment for 10 years, he was previously diagnosed with aplastic anemia, myelodysplastic syndrome, mesangial glomerulonephritis, received immunosuppressive therapy with partial effect. According to the data of the immunocytological study, the PNH clone was found, which made up 64.80% of erythrocytes, 94.73% of monocytes, and 97.82% of neutrophils. Reticulocytes made up 60‰, lactate dehydrogenase level was 1630 Units/L, there were no episodes of thrombosis. Patient G. was observed with a diagnosis of myelo­dysplastic syndrome: refractory anemia for 4 years, was examined for PNH after the loss of effect of erythropoietin therapy and the appearance of manifestations of hemolysis, which became more significant during the last year. A PNH clone was detected, which made up 17.83% of erythrocytes, 96.72% of monocytes, and 96.28% of neutrophils. Reticulocytes made up 127‰, bilirubin level – 28.74 mmol/l, lactate dehydrogenase – 1081.5 Units/L. Patient M. has been ill for several months with a pronounced cytopenic syndrome, and according to the bone marrow trepanobiopsy the hypocellular bone marrow was found out. According to the data of the immunocytological study, a reduction of CD55 and C59 expression was found out, which corresponds to PNH, as well as immunocytological signs of myelodysplastic syndrome. The final diagnosis of PNH was confirmed by molecular genetic study: a mutation in the PIGA gene was detected. The level of reticulocytes in this patient was 17‰, the level of bilirubin was 13.3 mmol/l, the level of lactate dehydrogenase was 232.2 Units/L, and there were no episodes of thrombosis. Conclusions. Patients A. and G. can be classified as patients with type 2 PNH. Patient M. can be classified as a patient with type 3 PNH due to the absence of signs of hemolysis and thrombosis in the presence of mutation in the PIGA gene on the background of MDS. The presented cases of PNH demonstrate the existing problems of diagnosing this rare disease. The variability of clinical manifestations, the lack of specific diagnostic criteria leads to late establishment of the correct diagnosis and, as a result, untimely treatment.