Demographics, clinical profile and treatment landscape of patients with haemophilia B in China

Dear Editor, Haemophilia B (HB) is a rare inherited bleeding disorder resulting from mutations in the F9 gene encoding clotting factor IX (FIX) responsible for blood clotting. Severe HB is characterized by recurrent and spontaneous bleeding typically into joints, muscles, and soft tissues. Delays in treatmentmay lead to crippling arthropathy, and bleeding into vital organs could be life-threatening.1 The current status of patients with HB in China is poorly understood. This letter reports a real-world cohort of HB patients in China with a focus on their demographic profiles, clinical characteristics, and treatment strategies. We included all 3782 patients with a confirmed diagnosis of HB registered in the Haemophilia Treatment Centre Collaboration Network of China (HTCCNC) Registry from January 1, 2007 to March 25, 2021(data cutoff date). Demographics, clinical characteristics, and management were obtained through electronic medical records from the contributing hospitals. Paediatric patients (children) are defined as patients<18 years age at the time of data cutoff, adults being ≥18 years. Joint bleeding is defined as any symptom of the elbow, knee, or ankle requiring infusion of clotting factors. Joint deformity is defined as angulation and/or displacement of articulating bones. All statistical analyses were conducted using SPSS software version 26.0 (SPSS Inc., Chicago, IL, USA). The study was approved by the hospital-based ethic committee. The demographic characteristics of the studied population are shown in Table 1. All but two patients are male. Of the two female patient, one was 11 years old with severe haemophilia and another 26 years old with mild haemophilia. Paediatric patients accounted for 43.5%.Aclear family historywas reported in27.1% (n=1024) patients. Of these 3258 patients with records of disease severity, 744 were severe (FIX:C<1%), 1945 were moderate (FIX:C 1–5%), and 569 were mild (FIX:C 5–40%). As shown in Table 2, among the 1443 patients with records showing diagnostic delay (age at diagnosis minus age at first bleeding symptom), the mean (±SD) delay was 2.46 (±7.03) years for all patients, 2.13 (±5.72) years for severe, 2.61 (±7.37) years for moderate, 3.15 (±8.94) years for mild patients; and 3.91 (±8.99) years for all adults, .58 (±1.70) years for all children. Of the 1266 patients with records allowing for calculation of delays in initial treatment (age at first treatment minus age at first bleeding symptom), the mean (±SD) delay was 3.24 (±7.78) years for all HB patients, 3.17 (±6.71) for the severe, 3.13 (±7.69) for moderate, 4.00 (±10.18) for mild patients; and 5.01 (±9.67) years for all adults, and .74 (±1.82) years for all children. Bleeding events and deformities were most common in the knees, followed by the ankles and elbows. Joint bleeding events were recorded in 880 (71.7%) patients at time of registration with the mean (±SD) number of different joints having had bleeding being 4.31 (±3.08) for the total HB population, 4.84 (±3.08) for the severe, 4.28 (±3.05) for the moderate, 2.97 (±2.19) for themild patients; and 4.81 (±3.20) for all adults, and 3.43 (±2.65) for all children. The mean (±SD) annual joint bleeding frequency for all 214 patientswith informationwas 16.53 (±22.03), being 19.72 (±23.50) for adult patients, and 10.75 (±17.81) for paediatric patients. In addition, 526 (42.9%) patients had deformed joints, mean (±SD) number being2.44 (±1.87) for allHBpatients, 2.63 (±1.88) for the severe, 2.38 (±1.95) for themoderate, 2.22 (±1.60) for themild patients. The number of deformed jointswas 2.59 (±1.96) for all adults, and 1.75 (±1.22) for all children. Among 823 patients with treatment information, most (n = 702 patients, 85.3%) received on-demand therapy, of whom 17% (n = 121) patients received treatment only for severe bleeding and 10.4% (n = 73) patients received on-demand with periodic prophylaxis. Only 89 (10.8%) patients received prophylaxis treatment (including primary, secondary, and tertiary prophylaxis), 58 (65.2%) of whom children. Thirty-two (3.9%) patients received no treatment. FIX Inhibitor information was available in 1101 patients. Inhibitors were present in 26 (2.4%), absent in 450 (40.9%) patients and unknown for the remaining patients. Of the 26 HB patients with inhibitors, 21 had severe and five hadmoderate disease. The HTCCNC established in 2004 has made important achievement in promoting care of haemophilia in China, and in haemophilia information registration.2 Our study is significant in that it is the first population-based nationwide study of the Chinese HB population. The number of patients with HB registered at the HTCCNC network was only 3782, much lower than the estimated 6000–7000 based on the prevalence according to WFH.3 Understanding the prevalence of HB in China is important for us to plan future haemophilia care. The data will facilitate our development of more efforts to improve the awareness of haemophilia among our health careworkers particularly to recognize the disease, tomake early diagnosis and to initiate treatment as early as possible. It is notable that the number of patients withmoderate haemophilia in this study was more than twice that of severe haemophilia, and that the bleeding phenotype of both groups were similar suggesting some of the moderate patients actually had severe haemophilia. The factor levels were done at local laboratories and not in a central lab and may