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Background <p>The coagulation system is closely linked to the inflammatory response and kinin system activation in sepsis, but its contribution to sepsis-associated capillary leak syndrome (SACLS) remains elusive. This study explored the underlying role of the coagulation system in SACLS.</p> Methods <p>Patients with sepsis were recruited to evaluate the early predictive potential of coagulation function-related indicators for capillary leakage. Patients with hemorrhagic fever with renal syndrome (HFRS) and scrub typhus, conditions featuring SACLS as a typical manifestation, were selected to validate the predictive value of coagulation-related indicators in SACLS. The levels of coagulation factors in patients with sepsis were analyzed to elucidate the altered mechanisms in the coagulation system. Additionally, rat SACLS models were established <i>via</i> an intravenous injection of lipopolysaccharide to corroborate the changes and potential effects of the coagulation system during SACLS.</p> Results <p>Prothrombin time (PT) and activated partial thromboplastin time (APTT) exhibited predictive potential for diagnosing capillary leak syndrome in patients with sepsis. APTT displayed higher sensitivity than PT in detecting SACLS at an early stage. Compared with the findings in patients with sepsis and normal APTT, the activities of coagulation factor Ⅺ (FXI) and FXII in plasma and levels of complement 3 and 4 in serum were significantly decreased in patients with APTT prolongation (all <i>P</i> &lt; 0.05) and negatively correlated with APTT prolongation (all <i>P</i> &lt; 0.05). FXI and FXII activities were decreased in the plasma of SACLS model rats (<i>P</i> &lt; 0.001). Conversely, FXII and complement levels were elevated in the lungs (both <i>P</i> &lt; 0.05), accompanied by elevated bradykinin levels (<i>P</i> &lt; 0.001).</p> Conclusions <p>APTT is a sensitive indicator for predicting SACLS. APTT prolongation in plasma might be attributable to the enrichment of FXII in the microcirculation. The microcirculatory enrichment of FXII might activate the kinin and complement systems, contributing to the process of capillary leakage.</p>

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Capillary leak syndrome in sepsis: the role of intrinsic coagulation pathway activation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月24日

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  • Li Shu,
  • Jin-Lian Jiang,
  • Yun-Fen Chen,
  • Ya Chen,
  • Huan Chen,
  • Ying-Hua Chen,
  • Wei-Wei Zhong,
  • Zhong-Qin Pan,
  • Xue Xiao,
  • Yi-Huai He

摘要

Background

The coagulation system is closely linked to the inflammatory response and kinin system activation in sepsis, but its contribution to sepsis-associated capillary leak syndrome (SACLS) remains elusive. This study explored the underlying role of the coagulation system in SACLS.

Methods

Patients with sepsis were recruited to evaluate the early predictive potential of coagulation function-related indicators for capillary leakage. Patients with hemorrhagic fever with renal syndrome (HFRS) and scrub typhus, conditions featuring SACLS as a typical manifestation, were selected to validate the predictive value of coagulation-related indicators in SACLS. The levels of coagulation factors in patients with sepsis were analyzed to elucidate the altered mechanisms in the coagulation system. Additionally, rat SACLS models were established via an intravenous injection of lipopolysaccharide to corroborate the changes and potential effects of the coagulation system during SACLS.

Results

Prothrombin time (PT) and activated partial thromboplastin time (APTT) exhibited predictive potential for diagnosing capillary leak syndrome in patients with sepsis. APTT displayed higher sensitivity than PT in detecting SACLS at an early stage. Compared with the findings in patients with sepsis and normal APTT, the activities of coagulation factor Ⅺ (FXI) and FXII in plasma and levels of complement 3 and 4 in serum were significantly decreased in patients with APTT prolongation (all P < 0.05) and negatively correlated with APTT prolongation (all P < 0.05). FXI and FXII activities were decreased in the plasma of SACLS model rats (P < 0.001). Conversely, FXII and complement levels were elevated in the lungs (both P < 0.05), accompanied by elevated bradykinin levels (P < 0.001).

Conclusions

APTT is a sensitive indicator for predicting SACLS. APTT prolongation in plasma might be attributable to the enrichment of FXII in the microcirculation. The microcirculatory enrichment of FXII might activate the kinin and complement systems, contributing to the process of capillary leakage.