Publication Number: 4843

 

Abstract Title : Cardiovascular disease risk assessment in Japanese adults with hemophilia: Interim results of a multicenter study

 

Category: 300s - Hemostasis, Thrombosis and Vascular Wall Biology

 

Review Category: 322. Hemophilia A and B: Clinical and Epidemiological

 

Authors

 

Yushi Chikasawa¹, Hisanori Kosuge², Azusa Nagao³, Tomoko Yamaguchi⁴, Masato Bingo¹, Mio Ishikura¹, Toshiki Osaki¹, Shun Kaneko¹, Ryui Miyashita¹, Akito Ichiki¹, Takashi Muramatsu¹, Mihoko Yotsumoto¹, Kagehiro Amano¹, Satoshi Hida², Takeshi Hagiwara⁴, Kazuhiro Satomi², Ei Kinai¹

 

¹ Tokyo Medical University, Department of Laboratory Medicine, Tokyo, Japan, ² Tokyo Medical University, Department of Cardiology, Tokyo, Japan, ³ Kansai Medical University, Division of Hematology and Oncology, Osaka, Japan, ⁴ Ogikubo Hospital, Department of Blood Coagulation, Tokyo, Japan

 

Abstract  Body

 

Background

 

Although patients with hemophilia have historically been considered at low risk for cardiovascular disease (CVD), recent studies report increasing CVD incidence in this population. Ischemic heart disease incidence is reported lower in Japanese hemophilia patients (~0.3%) compared to Western populations. On the other hand, a Japanese study also reported that approximately 25% of HIV-positive patients with hemophilia exhibited moderate-to-severe coronary atherosclerosis, suggesting a more complex and unclear clinical picture. There is no significant difference in mortality CVD between patients with hemophilia and the general population. However, in patients with hemophilia, the use of anticoagulant or antiplatelet therapy is complex, high-risk, and costly; therefore, identifying CVD risk factors and implementing preventive strategies is essential.

 

 

Objective

 

To investigate the prevalence and risk factors for CVD among adult hemophilia patients without chest symptoms and inform preventative strategies.

 

 

Methods

 

Between April 2022 and March 2025, hemophilia patients aged ≥30 years who attended participating institutions and provided written informed consent underwent coronary computed tomography (CT) scanning. Health-related quality of life was assessed using the SF-36® v2 questionnaire. Vascular inflammation markers, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and high-sensitivity C-reactive protein (hs-CRP), were measured from blood samples. Pulse wave velocity (PWV) testing was also conducted. An interim analysis was performed on cases for which complete data were available as of June 2025. Univariate analyses were conducted to evaluate the association between individual clinical and laboratory parameters and moderate-to-high CVD risk, as determined by coronary CT findings. Statistical analyses were performed using SPSS software. Categorical and continuous variables were compared using the chi-square test and Mann– Whitney U test, respectively. A p-value of <0.05 was considered statistically significant.

 

 

Results

 

A total of 126 patients (hemophilia A: 109, hemophilia B: 17) underwent coronary CT. Among those with hemophilia A, 69 (63.3%) were severe, 24 (22.0%) moderate, and 15 (11.9%) mild; 1 had inhibitors. In hemophilia B, 15 (88.2%) were severe and 2 (11.8%) were moderate, with inhibitors in 2 patients. Treatment regimens for hemophilia A included emicizumab (n=26), prophylaxis with extended half-life factor VIII (EHL-FVIII; n=41), prophylaxis with standard half-life FVIII (SHL-FVIII; n=18), and on-demand therapy (n=24). For hemophilia B: prophylaxis with EHL-FIX (n=11), prophylaxis with SHL-FIX (n=1), on-demand therapy (n=3), and regular bypassing agent use (n=2). Median age of all patients was 54.0 years (IQR: 45.0–61.0). Prevalence of CVD risk factors among all patients included hypertension (41.3%), dyslipidemia (28.6%), diabetes (13.5%), chronic kidney disease (12.7%), current smoking (16.7%), and HIV infection (26.2%).

 

 

Patients were stratified by Agatston score into low-risk (<100; n=97) and moderate-to-high-risk (≥100; n=29) groups. The moderate-to-high-risk group was significantly older and had higher rates of hypertension, dyslipidemia, and diabetes. TNF-α levels and baPWV were significantly elevated in this group. No significant differences were observed in SF-36®v2 scores. All 29 moderate-to-high-risk patients were recommended for cardiology referral; however, only 9 underwent coronary angiography. All of 3 patients underwent coronary angiography in the high-risk subgroup (Agatston ≥400; n=9) showed moderate or greater coronary stenosis; one started antiplatelet therapy. In the moderate-risk subgroup (Agatston 100–399; n=20), 3 of 6 patients received coronary angiography had moderate or greater stenosis, with one requiring coronary artery bypass grafting.

 

 

Conclusion

 

In this study, the risk of CVD in Japanese patients with hemophilia appeared comparable to that of the general population. Aging, hypertension, dyslipidemia, and diabetes were identified as major risk factors for CVD. Additionally, TNF-α and baPWV emerged as potential markers for identifying individuals at moderate or higher risk of coronary artery disease, warranting further investigation.

 

 

 

Keywords: Research

 

Disclosure : Yushi Chikasawa: Bayer yakuhin, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, KM Biologics, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, CSL-Behring, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Takeda Pharmaceutical, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: Yes, Current equity holder in private company: No, Honoraria: No, Fujimoto Pharmaceuticals, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Sanofi, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Novo Nordisc Pharma, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Japan Blood Products Organization, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: Yes, Current equity holder in private company: No, Honoraria: No, Chugai Pharmaceuticals, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Pfizer, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Hisanori Kosuge: None declared, Azusa Nagao: Sekisui Medical Co, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Takeda Pharmaceutical, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: Yes, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, KM Biologics, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Chugai Pharmaceutical, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: Yes, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Sanofi, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Bayer yakuhin, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: Yes, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Fujimoto Pharmaceutical, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Novo Nordisk Pharma, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, CSL-Behring, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Japan Blood Products Organization, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Pfizer, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Tomoko Yamaguchi: Takeda Pharmaceutical, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, CSL-Behring, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Novo Nordisk, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Sanofi, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Chugai Pharmaceutical, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Fujimoto Pharmaceutical, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Bayer, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Masato Bingo: Sanofi, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Takeda Pharmaceutical, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, CSL Behring, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Novo Nordisk Pharma, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Bayer, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, CHUGAI pharmaceutical, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: Yes, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Fujimoto Pharmaceutical, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Mio Ishikura: None declared, Toshiki Osaki: Chugai Pharmaceuticals, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Shun Kaneko: Chugai Pharmaceuticals, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Ryui Miyashita: Bayer, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, CSLBehring, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Sanofi, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Chugai Pharmaceuticals, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Takeda Pharmaceutical, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Akito Ichiki: Takeda Pharmaceutical, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Bayer yakuhin, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Takashi Muramatsu: None declared, Mihoko Yotsumoto: None declared, Kagehiro Amano: Pfizer, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Bayer, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Chugai Pharmaceutical, Consultancy (Includes expert testimony): Yes, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Takeda Pharmaceutical, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Sanofi, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, CSL Behring, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Sekisui Medical Co., Ltd., Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Fujimoto Pharmaceutical, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, KM biologics, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Novo Nordisk Pharma, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Satoshi Hida: None declared, Takeshi Hagiwara: Japan Blood Products Organization, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, KM Biologics, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Takeda Pharmaceutical, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Pfizer, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, CSL-Behring, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Chugai Pharmaceuticals, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Bayer, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Novo Nordisc Pharma, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Sanofi, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: Yes, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Kazuhiro Satomi: None declared, Ei Kinai: Bayer, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Novo Nordisk, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Pfizer, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Takeda Pharmaceutical, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, CSL-Behring, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Chugai Pharmaceuticals, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Fujimoto Pharmaceutical, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes, Sanofi Genzyme, Consultancy (Includes expert testimony): No, Patents & Royalties: No, Ended employment in the past 24 months: No, Research Funding: No, Divested equity in a private or publicly-traded company in the past 24 months: No, Current equity holder in publicly-traded company: No, Current Employment: No, Current holder of stock options in a privately-held company: No, Current equity holder in private company: No, Honoraria: Yes