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 A(2)-depl eted rabbit (FXIII-DR). Plasma Factor XIIIA(2) (FXIIIA(2)) was depleted by infusion of the mono-specific goat anti-rabbit FXIIIA, IgG. Generalized Shw artzman reaction (GSR) was induced by priming and challenged by i.v. inject ion of LPS and local Shwartzman reaction (LSR) was primed by intradermal in jection of LPS and challenged by i.v. injection of LPS. Histological examin ation of the GSR animals showed, extensive thrombi accumulation in renal tu bules and bilateral cortical necrosis of kidney in 8 out of 10 rabbits but none in the FXIII-DR. Fibrinogen levels were elevated to 3 similar to4 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 cutaneou s vascular thrombosis, purpura, and secondary hemorrhagic necrosis whereas neither fibrin deposit nor necrosis of tissue were detected in FXIII-DR des pite 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 b ut not affected at all in FXIII-DR. These results suggest that during the s evere inflammatory conditions such as sepsis, the fibrinolytic system is fu nctionally sufficient to dissipate the pathogenic accumulation of dissemina ted intravascular clots and exudated fibrin clots if those clots were preve nted from getting crosslinked in plasma.