ECLIPSE: a French Study Concerning the Diagnosis of Paroxysmal Nocturnal Hemoglobinuria (PNH)
Authors: Petropoulou Anna D. , Lamy Thierry , Michallet Mauricette , Amoura Zahir , de Latour Regis Peffault , Socié Gérard 
Published: October 2019

Abstract 5134

Aim:

PNH is a rare disease with prevalence between 7.3 and 15.9 cases/million. PNH is a life-threatening disease that affects mostly young adults with median age at diagnosis being 33 years. Diagnosis is difficult and often delayed because of the clinical polymorphism of the disease. ECLIPSE is a French study which aimed to evaluate the delay between the onset of PNH symptoms and the date of diagnosis, to identify the clinical signs leading to diagnosis and to determine which medical specialists are seen first by PNH patients (pts).

Patients and Methods:

4920 physicians were asked to participate in the study: 992 haematologists, 1638 internists, 1155 gastroenterologists, 697 nephrologists, 438 neurovascular physicians. Physicians were divided into 3 groups: (a) physicians having diagnosed PNH at least once, (b) having suspected a PNH without having confirmed the diagnosis, (c) neither having suspected nor diagnosed a PNH. The response rate was analysed by medical speciality and was defined by the number of physicians responding divided by the number of physicians invited to participate.

Results:

528 physicians accepted to participate in the study (overall response rate: 10.7%). In total, 507 answers were analysed. Among the 507 physicians, 108 (21 %) had diagnosed PNH at least once (group a), 213 (42 %) had suspected PNH without confirming the diagnosis (group b) and 186 (37 %, CI95% [32.49 % - 41.05 %]) neither had suspected nor diagnosed PNH (group c). In group (a), the clinical signs and symptoms which led to diagnosis were: pancytopenia 44%, anaemia 37%, haemolysis 23%, peripheral venous thrombosis 18%, hepatic vein thrombosis 14% and hemoglobinuria 14%. The physicians of group (a) were also asked to describe the clinical situations which raised the suspicion for PNH diagnosis: unexplained thrombosis (86%), hemoglobinuria (84%), aplastic anaemia (83%), Coombs negative anaemia (80%), cytopenias (71%) were the most frequent symptoms triggering the test for PNH. Physicians of group (a) were also asked to describe the circumstances of their latest PNH diagnosis. The patient was referred to the physician most frequently by the Emergencies (23%), a haematologist (22%) or by an internist (21%). The most frequent functional symptoms of their latest diagnosed pts were: fatigue (39%), anaemia (24%), abdominal pain (20%) and thrombosis (14%). Seven percent of PNH pts did not report any functional symptom before diagnosis. PNH diagnosis was confirmed in a mean time of 9.32±11.46 months after the onset of symptoms, and a maximum delay between first symptoms and diagnosis being 60 months. Biological signs which raised the suspicion for a PNH were: anaemia (80%), increase of LDH (60%), increase of biluribin (44%), thrombocytopenia (41%) and/or neutropenia (28%). Confirmation of PNH diagnosis was made by flow cytometry in 87% of the cases. Two hundred and thirteen physicians belong to group (b), having at least once suspected PNH without confirming diagnosis. Half of them (50%) had suspected at least 5 times a PNH diagnosis, without confirmation. Clinical and biological signs which prompted physicians of group (b) to suspect PNH were: Coombs negative anaemia (48%), pancytopenia (42%) and/or aplastic anaemia (38.5%), myelodysplastic syndrome (18%), hemoglobinuria (15.5%), increase level of LDH associated with venous or arterial thrombosis (15%), abdominal pain (14%), dark urine (12%) or jaundice (11%). Finally, 186 physicians declared having neither suspected nor diagnosed any PNH pts. Furthermore, 6.5% of physicians have never heard about PNH.

Conclusions:

PNH diagnosis is usually difficult and delayed as its signs and symptoms are diverse and non-specific. The ECLIPSE study aimed to better understand the diagnostic procedures for PNH, to evaluate the delay between onset of symptoms and diagnosis and to determine the medical specialists involved in the diagnosis and management of PNH pts. PNH is mainly diagnosed by hematologists. Frequent symptoms leading to diagnosis were unexplained thrombosis, hemoglobinuria, Coombs negative anaemia, but also aplastic anaemia, unexplained cytopenias and myelodysplastic syndrome. Flow cytometry, the gold standard for PNH testing, was only used in 87% of cases. Diagnosis was usually delayed with a maximum of 5 years between onset of PNH symptoms and diagnosis. Fatigue and abdominal pain were commonly reported symptoms and should therefore be more routinely assessed.

Disclosures:

No relevant conflicts of interest to declare.