The Relation of Factors XII, XI, and IX to Hypercoagulable States

Abstract

SummaryEvidence has been obtained in rabbits that the reduction of the silicone whole blood clotting time to the normal glass range reflects a hypercoagulable state attributable to circulating activated factors XII and XI. The potential clinical implications of these findings are discussed.

Stasis Thrombi Induced by Bacterial Endotoxin

“…We have previously suggested that an increased tendency to thrombus formation, coupled with silicone clotting times in the glass range, represents a hypercoagulable state. 3 The finding of diarrhea and hyperemic intestines suggested the possibility that these rabbits were suffering from a naturally acquired enteritis, which was associated with abnormally shortened clotting times. Evans et al 10 have described a disease of young rabbits characterized by the frequent association of enteritis and polyagglutinable red cells.…”

“…Endotoxin derived from Escherichia coli 0111:B4 was generously supplied to us by Dr. Herbert A. Ravin, 3 and an endotoxin prepared from Salmonella newington was kindly provided by Dr. P. W. Robbins.…”

“…3 Subsequent to these determinations, 10 rabbits with diarrhea and hyperemic intestines, presumably due to an enteric infection in the rabbit colony, were found to have markedly shortened clotting times, with a loss of the normal glass-silicone differential. In these animals the control clotting times in glass and silicone tubes were identical, with a mean of 8.0 minutes in glass and silicone (range 5 to 13 minutes).…”

“…It has been shown previously that such reductions do not occur with the infusion of isotonic saline or 1% human albumin. 3 To determine whether the endotoxin-treated rabbits were in a hypercoagulable state, E. coli endotoxin was injected into 19 rabbits in doses of 0.25 and 0.75 mg/kg (table 2). After 10 minutes of stasis 12 rabbits showed no thrombi, while 7 showed partial thrombi (1 to 2-f-).…”

The role of the liver in serum-induced hypercoagulability.

“…The infusion of normal human serum into animals engenders a transient period of hypercoagulability characterized by profound shortening of the whole blood clotting time in both glass and silicone-coated tubes (2). During this period of hypercoagulability, blood trapped in isolated venous segments rapidly coagulates, forming a thrombotic cast of the isolated venous segment (3).…”