Abstract: OBJECTIVES: Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare, life-threatening, acquired blood disorder characterized by hemolytic anemia, thrombosis, and bone marrow failure. The heterogeneous clinical presentation and disease limited awareness among physicians often delay the diagnosis, compromising patient clinical outcomes. The study aims to develop consensus-based recommendations for timely and accurate identification of PNH patients by different medical specialties in Greece who are likely to be involved in disease diagnosis and care coordination.
METHODS: A ten-member expert panel, comprising of four hematologists and six clinicians from different specialties (internist, nephrologist, gastroenterologist, hepatologist, urologist, and cardiologist), participated in a Delphi process. Based on a targeted literature review, the Steering Committee developed a structured questionnaire with evidence-based statements on PNH symptoms, diagnosis, and monitoring, along with six hypothetical patient cases of common signs, symptoms and potential confounding factors to capture the differential diagnosis. All panelists rated the statements on a five-point scale (from “strongly disagree” to “strongly agree”) in two Delphi rounds and suggested diagnostic, monitoring tests and specialist referrals. Consensus and strength were determined using predefined criteria.
RESULTS: All statements received very strong recommendation with ≥90% agreement after two rounds of Delphi voting. Consensus was achieved for 94.8% of the diagnostic tests and 88.8% of the medical referrals, supporting appropriate PNH screening and diagnosis. All hypothetical patient cases were appropriately referred to a hematologist, indicating strong alignment in recognizing PNH-related clinical features among diverse specialties. The Delphi consensus led to the development of a structured, evidence-based screening and diagnostic algorithm for PNH in Greece.
CONCLUSIONS: These standardized recommendations and actionable guidance for timely and accurate diagnosis across different specialties could enable earlier detection and timely referral to hematology care. The early diagnosis of this ultra-rare disease has the potential to significantly improve patient outcomes while reducing the clinical and economic burden of delayed or misdiagnosed cases.
