Zhong, Xin, Wenqiong Du, Zhaowen Zong, Renqing Jiang, Yijun Jia, Zhao Ye, and Haoyang Yang. Features of coagulo-fibrinolytic derangement due to bleeding in nonacclimatized rabbits acutely exposed to high altitude. High Alt Med Biol. 24:68-75, 2023. Background: The present study aimed to observe the time course of coagulo-fibrinolytic derangement due to bleeding in rabbits acutely exposed to high altitude (HA). Materials and Methods: Forty-eight rabbits were randomly divided into four groups and were subjected to minor bleeding at low altitude, major bleeding at low altitude, minor bleeding after acute exposure to HA, and major bleeding after acute exposure to HA. To produce minor and major bleeding, 10% and 30% of the total blood volume was removed, respectively. At designated time points, samples were taken for laboratory examination. Results: While minor bleeding at low altitude led to minor coagulo-fibrinolytic derangements, it led to complicated derangements at HA, which presented as an early hypercoagulable state and transition to hypocoagulable and hyperfibrinolytic states with lower clot firmness. Major bleeding at HA resulted in greater derangements of the R time, K values, the D-dimer concentration, the alpha angle, maximum amplitude, and the concentration of fibrinogen than were observed at low altitude. Conclusions: The extent of coagulo-fibrinolytic derangements due to bleeding in rabbits after acute exposure to HA was more severe and complicated than that at low altitude. Therefore, proper resuscitation should be applied based on these changes.