Effect of leukopenia induced by cyclophosphamide on the initial stage of arterial thrombosis in mice

Kee Ook Lee, Il Kwon, Hyo Suk Nam, Youngseon Park, Jayoung Kim, Yeseul Shim, Zolzaya Erdenebileg, Myoung Jin Cha, Hyun Jung Choi, Hye Yeon Choi, Jae Woo Song, Ji Hoe Heo

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2 Citations (Scopus)


Introduction: Leukocytes are found in organizing thrombi and are associated with thrombus growth. However, their role in the initial stage of thrombus formation is not well known. We investigated the role of leukocytes in the early stage of arterial thrombosis by inducing leukopenia. Methods: In this double-blind, randomized, placebo-controlled study, 72 Institute of Cancer Research mice were randomly treated with intraperitoneal 100 mg/kg cyclophosphamide or normal saline. The primary outcome was time to occlusion after FeCl3 treatment. We also compared thrombus size, histological composition, and association with peripheral blood cell counts between cyclophosphamide and control groups. Results: Cyclophosphamide treatment significantly decreased leukocyte counts by 82.8% compared to placebo (P < 0.001). The time to occlusion was significantly longer in the cyclophosphamide group (3.31 ± 1.59 min) than in the control group (2.30 ± 1.14 min; P = 0.003). The immunoreactivity for Ly6G-positive cells, intracellular histone H3, and released histone H3 in thrombi was significantly reduced in the cyclophosphamide group by 92.8%, 50.2%, and 34.3%, respectively. Time to occlusion had a moderate negative correlation with leukocyte count in peripheral blood (r = −0.326, P = 0.022) in the entire group. Conclusions: Cyclophosphamide-induced leukopenia attenuated thrombus formation during the early stage of arterial thrombosis. Our findings suggest the potential role of leukocytes in the initial stage of arterial thrombosis.

Original languageEnglish
Pages (from-to)111-119
Number of pages9
JournalThrombosis Research
Publication statusPublished - 2021 Oct

Bibliographical note

Funding Information:
This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), which is funded by the Ministry of Education ( NRF-2018R1A2A3074996 ).

Publisher Copyright:
© 2021

All Science Journal Classification (ASJC) codes

  • Hematology


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