Editor's Note：The 5th Annual Meeting of Chinese Alliance for Societies of Hematology (2025 CASH) was held in Tianjin from January 3 to 5, under the theme “Comprehensive Hematology, Comprehensive Health, and Comprehensive Well-being.” Top hematology experts from China and abroad were invited to discuss the latest advancements and future trends in hematology.

During the conference, Dr. Rong Fu from Tianjin Medical University General Hospital delivered a presentation titled Interpretation of the PNH China Guidelines, offering valuable references and guidance for the standardized management and treatment of paroxysmal nocturnal hemoglobinuria (PNH). Hematology Frontier had the privilege of interviewing Professor Fu to further explore the topic.

Background of the Updated Guidelines

The China Guidelines for the Diagnosis and Treatment of Paroxysmal Nocturnal Hemoglobinuria (2024 Edition) were published in Chinese Journal of Hematology in August 2024. As the corresponding author and chief writer, Professor Fu explained the context behind the update.

PNH is a rare acquired clonal hematopoietic stem cell disorder characterized by intravascular hemolysis, bone marrow failure, and high-risk thrombosis. Although PNH is classified as a benign hemolytic disorder, severe cases can be life-threatening.

Despite its classification as a rare disease under China’s First National List of Rare Diseases, PNH remains significant due to China’s large population, with cases reported across all age groups, especially among young and middle-aged patients. This underscores the urgent need to enhance its management and treatment.

Recent years have witnessed significant advancements in PNH diagnosis and treatment, particularly in complement inhibitor therapies. To further standardize and improve PNH management in China, the China Guidelines for the Diagnosis and Treatment of Paroxysmal Nocturnal Hemoglobinuria (2024 Edition) were developed by the Red Cell Disease Group of the Hematology Branch of the Chinese Medical Association.

Diagnostic Updates

Compared to previous versions, the 2024 guidelines introduce several key updates in PNH diagnosis, significantly enhancing early detection and precision treatment.

The new guidelines refine diagnostic criteria and processes, update screening indications, and emphasize the pivotal role of high-sensitivity flow cytometry, which is now regarded as the “gold standard” for PNH diagnosis.

Key Diagnostic Updates

1. Standardized Nomenclature for PNH Clones The guidelines adopt the standardized nomenclature for PNH clones recommended by the International Clinical Cytometry Society (ICCS) and the European Society for Clinical Cell Analysis (ESCCA).

2. Expanded Screening Indications New indications for PNH clone screening include previously unexplained symptoms such as dyspnea, abdominal pain, headaches, back pain, dysphagia, erectile dysfunction, and weight loss.

3. Detailed Clinical Manifestations PNH-specific symptoms, including hemoglobinuria, fatigue, jaundice, hepatosplenomegaly, thrombosis, renal dysfunction, pulmonary hypertension, pancytopenia, and smooth muscle dysfunction (e.g., dysphagia and abdominal pain), are now explicitly outlined.

4. Updated Laboratory Tests In addition to routine tests, the guidelines now recommend assessing iron metabolism markers, immunoglobulin levels (IgG, IgA, IgM, C3, C4), and using flow cytometry for FLAER detection.

5. Enhanced Diagnostic Typing Flow cytometry’s high sensitivity enables precise detection of GPI-anchored protein deficiencies, PNH clone size quantification, and identification of small PNH clones. Based on flow cytometry, hemolysis indicators, and bone marrow cytology, PNH is categorized into three types: classic, PNH with bone marrow failure syndromes, and subclinical.

6. Expanded Differential Diagnosis To improve diagnostic accuracy, the guidelines add a differential diagnosis spectrum for distinguishing PNH from other acquired hemolytic disorders.

Treatment Strategies

The 2024 guidelines offer updated recommendations for PNH treatment, emphasizing individualized approaches based on clinical subtypes. Symptomatic and supportive care is no longer standard treatment for PNH.

For classic PNH, complement inhibitors such as C5 inhibitors and factor B inhibitors are recommended as first-line therapies. Subclinical PNH requires no direct treatment for PNH clones but focuses on managing underlying bone marrow failure with immunosuppressants. Patients with combined bone marrow failure and high PNH clone levels may benefit from immunosuppressants combined with complement inhibitors, while younger patients with suitable donors may consider allogeneic hematopoietic stem cell transplantation (allo-HSCT).

The guidelines also detail indications, treatment plans, adverse reaction management, and specific recommendations for complement inhibitors, immunosuppressive therapies, allo-HSCT, and other exploratory treatments. Furthermore, they highlight the importance of risk assessment, management of complications, pediatric PNH treatment, and follow-up monitoring.

Key Considerations

Before starting complement inhibitor therapy, patients must be vaccinated at least two weeks in advance to minimize infection risks. Persistent anemia during C5 inhibitor therapy should prompt evaluation for red blood cell C3 deposition-related extravascular hemolysis (EVH). For C5 inhibitor-related EVH, proximal complement inhibitors, corticosteroids, or clinical trials may be considered.

Long-Term Management and Quality of Life

Recognizing PNH as a chronic disease, the guidelines emphasize follow-up and quality of life improvements:

1. Symptom Monitoring Patients should monitor anemia, thrombosis, infections, and other symptoms such as fatigue, hematuria, dyspnea, and pain.
2. Regular Check-ups Patients receiving complement inhibitors require periodic monitoring of blood cell counts, PNH clone proportions, and complement activity. Plasma free C5 levels can indicate terminal complement activity, while flow cytometry or Coombs testing for C3 deposition evaluates EVH.
3. Allo-HSCT Monitoring Post-transplant patients should be monitored for blood cell counts, hemolysis, and PNH clone changes, along with signs of GVHD and infections.
4. Stable PNH Monitoring For stable PNH patients, annual monitoring suffices unless clinical or hematologic changes necessitate more frequent evaluations.

About Dr. Rong Fu

Dr. Rong Fu is a renowned hematologist at Tianjin Medical University General Hospital, where she serves as Vice President and Director of the Hematology Center. She holds a doctorate in medicine and is a professor, chief physician, and Ph.D. supervisor.

She is a member of numerous professional organizations, including:

• Standing Committee of the Hematology Branch, Chinese Medical Association
• Vice Leader of the Red Cell Group and PNH Collaboration Group, Hematology Branch, Chinese Medical Association
• President of the Red Cell Diseases Committee, Beijing Cancer Prevention Society
• Deputy Leader of the MDS/MPN Working Group, Hematological Oncology Professional Committee, Chinese Anti-Cancer Association

Professor Fu has authored Chinese Expert Consensus on Aplastic Anemia, PNH Expert Consensus, and Expert Consensus on Pure Red Cell Aplasia in China. She is a distinguished editorial board member of the Chinese Journal of Hematology and Journal of Clinical Laboratory Analysis.

Her research focuses on hematopoietic stem cell biology in disease states, regenerative hematopoiesis, and translational research. She has led over 20 national-level research projects and authored more than 60 publications.