Clinical Manifestation and Errors in the Diagnosis of Classical Paroxysmal Nocturnal Hemoglobinuria: A clinical case series of 150 patients

• Main Authors: AD Kulagin, OU Klimova, AV Dobronravov, MO Ivanova, TA Rudakova, EV Babenko, VA Dobronravov, BV Afanas’ev
• Format: Article
• Language: Russian
• Published: Practical Medicine Publishing House 2017-07-01
• Series: Kliničeskaâ onkogematologiâ
• Subjects: paroxysmal nocturnal hemoglobinurea; PNH clone; cytopenia; clinical manifestation; diagnostic errors
• Online Access: http://bloodjournal.ru/wp-content/uploads/2017/09/5.pdf

Background. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disease of the blood system, characterized by intravascular hemolysis, cytopenia and thrombosis. Diagnostic errors with delayed diagnosis of PNH are often due to the variety of the clinical presentation and the lack of awareness of the doctors of this rare disease. Aim. The aim of the study was to characterize the options for clinical manifestation and the complexity of diagnosis of classical PNH. Materials & Methods. The research included 150 patients with PNH. The inclusion criteria were: 1) clinical and laboratory signs of intravascular hemolysis; 2) verification of the diagnosis using standard flow cytometry; 3) absence of aplastic anemia, myelodysplastic syndrome and primary myelofibrosis. The patients were of 13 to 72 years old (median age 34 years). The study population consisted of 89 (59 %) women and 61 (41 %) men. Results. The time before the diagnosis ranged from 0 to 455 months (median 33 months). The median size of the PNH clone among granulocytes and erythrocytes was 95 % and 41 %, respectively. The median of the lactic dehydrogenase was 7.2 times the upper limit of normal (ULN). Cytopenia occurred in 65 % of patients, including a combination of thrombocytopenia and neutropenia in 29 % of cases. Weakness and fatigue (99 %), hemoglobinuria (57 %), pain (52 %), icterus (46 %), dysphagia (37 %) and infection/fever (23 %) were the most common symptoms on the onset of the disease. Before the diagnosis of PNH, thrombosis or acute kidney injury was found in 22 % and 18 % of patients, respectively. Only 22 % of patients were initially diagnosed with PNH. In the remaining patients, the primary diagnosis was inadequate. Conclusion. The clinical manifestation of PNH is characterised by the presence of hemoglobinuria, cytopenia and early thrombosis in 57 %, 65 % and 22 % of patients, respectively. Errors of the primary diagnosis reach 78 % and lead to inadequate treatment. The results of the research showed the need for multidisciplinary approach and strict adherence to diagnostic algorithms of PNH in the risk groups, according to current recommendations.