Prognostic value of serum high mobility group box 1 protein and histone H3 levels in patients with disseminated intravascular coagulation: a multicenter prospective cohort study

Hirotaka Mori; Yuki Kataoka; Kayo Harada-Shirado; Noriaki Kawano; Mineji Hayakawa; Yoshinobu Seki; Toshimasa Uchiyama; Kazuma Yamakawa; Hiroyasu Ishikura; Yuhei Irie; Kenji Nishio; Noritaka Yada; Kohji Okamoto; Shingo Yamada; Takayuki Ikezoe

doi:10.1186/s12959-022-00390-2

Prognostic value of serum high mobility group box 1 protein and histone H3 levels in patients with disseminated intravascular coagulation: a multicenter prospective cohort study

Thromb J. 2022 Jun 13;20(1):33. doi: 10.1186/s12959-022-00390-2.

Authors

Hirotaka Mori^{1

2}, Yuki Kataoka^{2

3

4

5}, Kayo Harada-Shirado¹, Noriaki Kawano⁶, Mineji Hayakawa⁷, Yoshinobu Seki⁸, Toshimasa Uchiyama⁹, Kazuma Yamakawa¹⁰, Hiroyasu Ishikura¹¹, Yuhei Irie¹¹, Kenji Nishio¹², Noritaka Yada¹², Kohji Okamoto¹³, Shingo Yamada¹⁴, Takayuki Ikezoe¹⁵

Affiliations

¹ Department of Hematology, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
² Scientific Research Works Peer Support Group (SRWS-PSG), Osaka, Japan.
³ Department of Internal Medicine, Kyoto Min-Iren Asukai Hospital, 89 Tanaka Asukai-cho, Kyoto, 606-8226, Japan.
⁴ Section of Clinical Epidemiology, Department of Community Medicine, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, 606-8501, Japan.
⁵ Department of Healthcare Epidemiology, Kyoto University Graduate School of Medicine/Public Health, Sakyo-ku, Kyoto, 606-8501, Japan.
⁶ Department of Hematology, Miyazaki Prefectural Miyazaki Hospital, 5-30 Kita Takamatsu-machi, Miyazaki, 880-8510, Japan.
⁷ Department of Emergency Medicine, Hokkaido University Hospital, Kita-ku, Sapporo, Hokkaido, N14W5060-8648, Japan.
⁸ Department of Hematology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, 4132 Urasa, Minamiuonuma-shi, Niigata, 949-7302, Japan.
⁹ Department of Laboratory Medicine, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan.
¹⁰ Department of Emergency Medicine, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.
¹¹ Department of Emergency and Critical Care Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma Jonan-ku, Fukuoka, 814-0180, Japan.
¹² Department of General Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan.
¹³ Department of Surgery, Kitakyushu City Yahata Hospital, 2-6-2 Ogura Yahatahigashi-ku, Kitakyushu, Fukuoka, 805-8534, Japan.
¹⁴ Shino-Test Corporation, R&D Center, Sagamihara, 252-0331, Japan.
¹⁵ Department of Hematology, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960-1295, Japan. ikezoet@fmu.ac.jp.

Abstract

Background: We compared the prognostic value of serum high mobility group box 1 protein (HMGB1) and histone H3 levels with the International Society on Thrombosis and Haemostasis (ISTH) disseminated intravascular coagulation (DIC) scores for 28-day in-hospital mortality in patients with DIC caused by various underlying diseases.

Methods: We conducted a multicenter prospective cohort study including two hematology departments, four emergency departments, and one general medicine department in Japan, between August 2017 and July 2021. We included patients diagnosed with DIC by the ISTH DIC scoring system.

Results: Overall, 104 patients were included: 50 with hematopoietic disorders, 41 with infections, and 13 with the other diseases. The 28-day in-hospital mortality rate was 21%. The receiver operator characteristic (ROC) curve showed that a DIC score of 6 points, serum HMGB1 level of 8 ng/mL, and serum histone H3 level of 2 ng/mL were the optimal cutoff points. The odds ratios of more than these optimal cutoff points of the DIC score, serum HMGB1, and histone H3 levels were 1.58 (95% confidence interval [CI]: 0.60 to 4.17, p = 0.36), 5.47 (95% CI: 1.70 to 17.6, p = 0.004), and 9.07 (95% CI: 2.00 to 41.3, p = 0.004), respectively. The area under the ROC curve of HMGB1 (0.74, 95% CI: 0.63 to 0.85) was better than that of the ISTH DIC scores (0.55, 95% CI: 0.43 to 0.67, p = 0.03), whereas that of histone H3 was not (0.71, 95% CI: 0.60 to 0.82, p = 0.07). Calibration and net reclassification plots of HMGB1 identified some high-risk patients, whereas the ISTH DIC scores and histone H3 did not. The category-free net reclassification improvement of HMGB1 was 0.45 (95% CI: 0.01 to 0.90, p = 0.04) and that of histone H3 was 0.37 (95% CI: - 0.05 to 0.78, p = 0.08).

Conclusions: Serum HMGB1 levels have a prognostic value for mortality in patients with DIC. This finding may help physicians develop treatment strategies.

Keywords: Calibration; Discrimination; Disseminated intravascular coagulation; High mobility group box 1 protein; Histone H3; Net reclassification improvement; Prognosis.