Causes and consequences of coagulation activation in sepsis: an evolutionary medicine perspective

Fiusa, Maiara Marx Luz; Carvalho-Filho, Marco Antonio; Annichino-Bizzacchi, Joyce M; De Paula, Erich V

doi:10.1186/s12916-015-0327-2

Table 1 Effect of coagulation factor deficiencies in animal models of sepsis

From: Causes and consequences of coagulation activation in sepsis: an evolutionary medicine perspective

Model (genetic alteration)	Effect on hemostasis*	Sepsis/infection model	Effect on pathogen clearance/sepsis severity
EPCR deficiency	↑	Pneumococcal sepsis	↓ bacterial dissemination [81]
		Melioidosis**	Unaltered [82]
		Endotoxemia	↑ mortality [83]
α2-antiplasmin deficiency	↓	Melioidosis**	↑ mortality, ↑ bacterial dissemination [59]
Overexpression of EPCR	↓	Pneumococcal sepsis	↑ bacterial dissemination [81]
Overexpression of EPCR	↓	Melioidosis**	↑ bacterial dissemination [82]
t-PA deficiency	↑	Melioidosis**	↓ mortality, ↓ bacterial dissemination [56]
t-PA deficiency	↑	Septic peritonitis	↑ mortality, ↑ bacterial dissemination [84]
Factor XI deficiency	↓	Y. enterocolitica (ip)	Unaltered [51]
		Peritoneal sepsis	↓ mortality [71]
		Listeriosis	↓ mortality, ↓ bacterial dissemination [70]
Factor VIII deficiency	↓	Endotoxemia	Unaltered [85]
Factor VIII deficiency	↓	E. coli (ip)	↑ bacterial growth, ↔ survival [86]
Factor IX deficiency	↓	Endotoxemia	Unaltered [85]
PAI-1 deficiency	↓	Melioidosis**	↑ mortality, ↑ bacterial dissemination [57]
		H. influenza infection	↑ bacterial dissemination [58]
		Klebsiella pneumonia	↑ mortality, ↑ bacterial dissemination [87]
Fibrinogen deficiency	↓	Y. enterocolitica (ip)	↑ mortality, ↑ bacterial dissemination [51]
		Group A streptococci	↑ mortality [52]
		Listeriosis	↑ mortality, ↑ bacterial dissemination [50]
Factor V deficiency	↓	Group A streptococci	↑ mortality [52]
Tissue factor deficiency	↓	S. aureus sepsis	Unaltered [72]
		Y. enterocolitica (ip)	↑ mortality [51]
		Endotoxemia	↓ inflammation [88]
		Endotoxemia	↓ mortality, ↓ inflammation [31]
PAI-1 + TAFI double deficiency	↓	Y. enterocolitica (ip)	↑ mortality [51]
Factor II deficiency	↓	S. aureus sepsis	↓ mortality [72]
Factor XIII deficiency	↓	S. aureus sepsis	Unaltered [72]
Factor XIII deficiency	↓	S. pyogenes (skin)	↑ bacterial dissemination [15]
Protein C deficiency (het)	↑	Endotoxemia	↑ mortality [89]
TAFI deficiency	↓	E. coli (ip)	Transient ↑ bacterial outgrowth [90]
Factor VII deficiency	↓	Endotoxemia	↓ mortality, ↓ inflammation [32]
Factor V leiden	↑	Septic peritonitis	Unaltered [91]
Factor V leiden	↑	Endotoxemia	↓ mortality [76]***

*The global effect of each genetic deficiency on hemostasis was defined based on current knowledge about hemostatic mechanisms. **Respiratory sepsis by intranasal instillation of Gram-negative Burkholderia pseudomallei. ***Lower mortality observed only in heterozygous mice. EPCR: endothelial protein C receptor. t-PA: tissue-type plasminogen activator; PAI-1: plasminogen activator inhibitor-1; TAFI: thrombin-activatable fibrinolysis inhibitor; ip: intraperitoneal; het: heterozygous.

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ISSN: 1741-7015

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