SURVEY-BASED HEMATOLOGIST VIEW OF PAROXYSMAL NOCTURNAL HEMOGLOBINURIA: AN OPPORTUNITY FOR IMPROVEMENT OF DIAGNOSIS AND MANAGEMENT

Sborník

Background. Paroxysmal nocturnal hemoglobinuria (PNH) is a genetic, progressive, life-threatening disorder characterized by chronic, uncontrolled terminal complement activation and hemolysis. The disease has a prevalence of 2. 0-15. 9 cases/million and a median age of onset of 33 years. Early diagnosis and intervention is critical; however, PNH is associated with diverse symptoms that often make diagnosis difficult to establish (average delay in diagnosis is 2. 5-3 years). 35% of patients with PNH die within 5 years of diagnosis. Aims. To assess clinicians’ awareness of PNH, identify causes of delay in PNH diagnosis, determine the signs and symptoms that prompt clinicians to test for PNH, and gain insight into how PNH is managed in different regions. Methods. A survey comprising 43 questions was distributed to hematologists involved in the management of PNH throughout the Middle-East, North Africa, and Central and Eastern Europe. Results. Of the 70 physicians who completed the questionnaire, 90% were hematologists, with 33% specializing in hematologic oncology. Responders were familiar with PNH (91%) and with syndromes associated with PNH (myelodysplastic syndromes [97%]; aplastic anemia [96%]). 59% were currently managing ≥1 patient with PNH and 64% had diagnosed the disease within the past 3 years. Median time from clinical presentation to diagnosis was 6-9 months (range 3 months to 3 years). In general, patients with symptoms indicative of PNH were tested for the disease: 74% of patients with aplastic anemia, 42% with myelodysplastic syndrome, 74% with hemoglobinuria, 53% with unexplained thrombosis, 59% with Coombs-negative hemolytic anemia, and 47% with unexplained cytopenia. Almost all responders (98%) used flow cytometry to confirm diagnosis of PNH and the majority (77%) were aware that both erythrocytes and granulocytes or monocytes should be tested by flow cytometry to confirm diagnosis. Of the palliative medications prescribed to patients with PNH, blood transfusion was the most common (90% of patients), followed by immunosuppressants (48%) and iron supplements (42%). Almost all responders (98%) were aware of eculizumab; however, only 28% of patients were prescribed eculizumab. 17. 5% of patients underwent bone marrow transplantation (Middle-East and North Africa, 25%; Central and Eastern Europe, 10%). Conclusions. Within a population of hematologists with experience of PNH, diagnosis may still take up to 3 years. The use of flow cytometry, the ‘gold standard’ for PNH diagnosis, is widespread, though greater awareness of the symptoms indicative of PNH is required. Palliative medications (immunosuppressants and iron supplements) are widely used despite having no impact on PNH1. Bone marrow transplantation is still used, particularly in the Middle-East and North Africa. This is despite its risk for substantial morbidities and mortality, and despite being indicated only for those patients with signs of bone marrow failure2. In spite of increased awareness of eculizumab effectiveness and its ability to reduce hemolysis and normalize survival3, its use is not yet widespread in these regions.

Survey funded by Alexion. Authors received no financial support

Haematologica, 2012; 97(s1):  585