Thrombosis-related characteristics of pregnant women with antithrombin deficiency, protein C deficiency and protein S deficiency in Japan

Takao Kobayashi; Kazuko Sugiura; Toshiyuki Ojima; Mariko Serizawa; Kyuya Hirai; Eriko Morishita

doi:10.1186/s12959-024-00581-z

Thrombosis-related characteristics of pregnant women with antithrombin deficiency, protein C deficiency and protein S deficiency in Japan

Thromb J. 2024 Feb 8;22(1):18. doi: 10.1186/s12959-024-00581-z.

Authors

Takao Kobayashi^#¹, Kazuko Sugiura^#², Toshiyuki Ojima³, Mariko Serizawa⁴, Kyuya Hirai⁵, Eriko Morishita⁶

Affiliations

¹ Department of Obstetrics and Gynecology, Hamamatsu Medical Center, 328 Tomitsuka-Cho, Chuo-Ku, Hamamatsu, Shizuoka, 432-8580, Japan. tkoba@hmedc.or.jp.
² Faculty of Nursing, Department of Women's Health, Nursing and Midwifery, Fukuoka Prefectural University, 4395 Ita, Tagawa, Fukuoka, 825-8585, Japan.
³ Department of Community Health and Preventive Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-Ku, Hamamatsu, Shizuoka, 431-3192, Japan.
⁴ Department of Obstetrics and Gynecology, Hamamatsu Medical Center, 328 Tomitsuka-Cho, Chuo-Ku, Hamamatsu, Shizuoka, 432-8580, Japan.
⁵ Department of Obstetrics, Gynecology and Family Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-Ku, Hamamatsu, Shizuoka, 431-3192, Japan.
⁶ Department of Laboratory Sciences, College of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa, 920-0942, Japan. eriko86@staff.kanazawa-u.ac.jp.

^# Contributed equally.

Abstract

Background: We previously conducted a primary survey of pregnant women with hereditary thrombophilia based on national surveillance in Japan, but did not examine their thrombosis-related characteristics. Antithrombin (AT) deficiency, protein C (PC) deficiency and protein S (PS) deficiency are the major types of hereditary thrombophilia in Japan.

Methods: We examined their detailed information related to thrombosis, and evaluated peripartum outcomes in comparison with control data obtained from the Japan Society of Obstetrics and Gynecology.

Results: Definite or probable AT deficiency, PC deficiency and PS deficiency were observed in 80, 50, and 317 pregnancies, respectively, from 2014 to 2018 in Japan, with prevalence rates among total deliveries of 0.011%, 0.007%, 0.044%. The number of pregnancies with AT, PC and PS deficiency might have been as many as 27, 17 and 108 every year if complete answers had been provided. In the peripartum period of current pregnancies, 27.5% of women with AT deficiency, 28.0% with PC deficiency and 13.2% with PS deficiency developed thrombosis (p < 0.001 vs. control). Pregnant women with AT and PC deficiency were more susceptible to thrombosis than those with PS deficiency (P < 0.01). Of the thromboses, 92.3% occurred during pregnancy, 62.8% at less than 15 gestational weeks. The earliest onset of thrombosis was 5 gestational weeks. Prophylactic anticoagulation significantly prevented the onset of both antepartum and postpartum thrombosis (p < 0.0001). The rate of recurrent pregnancy loss in women with low PC or PS activities was significantly higher than in controls (p < 0.0001); however, it is unknown whether recurrent pregnancy loss is related to hereditary PS deficiency. There seem to have been few serious maternal or fetal/neonatal complications due to placental insufficiency related to a hypercoagulable state other than growth restriction.

Conclusions: This survey revealed the thrombosis-related characteristics of pregnant women with hereditary thrombophilia in Japan. We suggest prophylactic anticoagulation to prevent maternal or fetal/neonatal complications.

Keywords: Antithrombin deficiency; Pregnant women; Protein C deficiency; Protein S deficiency; Thrombophilia.