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Capillary leak syndrome in sepsis: the role of intrinsic coagulation pathway activation
Li Shu1,2, Jin-Lian Jiang2, Yun-Fen Chen2
1Department of Infectious Diseases, Suining Central Hospital, Suining, Sichuan Province, 629000, China.
Insights
Activated partial thromboplastin time (APTT) is a sensitive indicator for predicting sepsis-associated capillary leak syndrome (SACLS). APTT prolongation may result from Factor XII enrichment, activating kinin and complement systems, leading to capillary leakage.
Area of Science:
- Coagulation and Thrombosis
- Sepsis Pathophysiology
- Complement System
Background:
- Sepsis involves complex interactions between coagulation, inflammation, and kinin systems.
- The precise role of coagulation in sepsis-associated capillary leak syndrome (SACLS) requires further elucidation.
- Understanding these links is crucial for managing sepsis complications.
Purpose of the Study:
- To investigate the predictive value of coagulation indicators for capillary leakage in sepsis.
- To explore the mechanisms of the coagulation system in SACLS.
- To validate coagulation markers in conditions with SACLS, such as HFRS and scrub typhus.
Main Methods:
- Recruited sepsis patients to assess coagulation indicators for capillary leakage prediction.
- Included patients with HFRS and scrub typhus to validate markers in SACLS.
- Analyzed coagulation factor levels in sepsis patients and utilized rat SACLS models induced by lipopolysaccharide.
Main Results:
- Prothrombin time (PT) and activated partial thromboplastin time (APTT) showed predictive potential for capillary leak syndrome in sepsis.
- APTT demonstrated higher sensitivity than PT for early SACLS detection.
- APTT prolongation correlated with decreased plasma FXI and FXII activities and serum complement levels, and elevated lung FXII, complement, and bradykinin in rat models.
Conclusions:
- APTT serves as a sensitive biomarker for predicting SACLS.
- APTT prolongation in plasma is likely due to Factor XII (FXII) enrichment in the microcirculation.
- Microcirculatory FXII enrichment may trigger kinin and complement systems, driving capillary leakage in SACLS.
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.
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