Depletion of plasma factor XIII prevents disseminated intravascular coagulation-induced organ damage.
The impact of clot stability affecting the vasculopathy and tissue necrosis in Shwartzman reaction was investigated using plasma Factor XIII A2-depleted rabbit (FXIII-DR). Plasma Factor XIIIA2 (FXIIIA2) was depleted by infusion of the mono-specific goat anti-rabbit FXIIIA2 IgG. Generalized Shwartzman reaction (GSR) was induced by priming and challenged by i.v. injection of LPS and local Shwartzman reaction (LSR) was primed by intradermal injection of LPS and challenged by i.v. injection of LPS. Histological examination of the GSR animals showed, extensive thrombi accumulation in renal tubules and bilateral cortical necrosis of kidney in 8 out of 10 rabbits but none in the FXIII-DR. Fibrinogen levels were elevated to 3 approximately 4 fold at 24 h and lowered at 48 h whereas a steady rise was seen in the FXIII-DR. FDP levels in GSR animals were significantly elevated at 24 h and further increased at 48 h but only slightly elevated in the FXIII-DR. Examination of the LSR tissues after 48 h showed an acute onset of progressive cutaneous vascular thrombosis, purpura, and secondary hemorrhagic necrosis whereas neither fibrin deposit nor necrosis of tissue were detected in FXIII-DR despite of an early edema formation. Fibrinogen levels were also increased two fold at 24 h but returned to basal levels at 48 h in control LSR animals but not affected at all in FXIII-DR. These results suggest that during the severe inflammatory conditions such as sepsis, the fibrinolytic system is functionally sufficient to dissipate the pathogenic accumulation of disseminated intravascular clots and exudated fibrin clots if those clots were prevented from getting crosslinked in plasma.
Lee
S Y
SY
The Catholic University of Korea, Department of Natural Sciences, College of Medicine, Seoul.
Chang
S K
SK
Lee
I H
IH
Kim
Y M
YM
Chung
S I
SI
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation / Q000150:complications* / Q000517:prevention & control; D005176:Factor XIII / Q000276:immunology / Q000494:pharmacology*; D005177:Factor XIII Deficiency / Q000150:complications / Q000503:physiopathology; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology; D009336:Necrosis; D010958:Plasminogen / Q000187:drug effects; D011817:Rabbits; D018805:Sepsis; D012790:Shwartzman Phenomenon / Q000097:blood / Q000139:chemically induced; D012867:Skin / Q000187:drug effects / Q000473:pathology; D012871:Skin Diseases / Q000209:etiology / Q000517:prevention & control
D000911:Antibodies, Monoclonal; D008070:Lipopolysaccharides; D005337:Fibrin; D005340:Fibrinogen; D010958:Plasminogen; D005176:Factor XIII