Abstract
Extract: Human adult and umbilical cord-derived leukocytes were shown to be capable of generating tissue factor activity on exposure to endotoxin and to reduced pH. Blood for leukocyte separation was collected from normal adults and from newly delivered sections of umbilical cord and mixed leukocyte preparations were obtained by separation over methyl cellulose Hypaque. The coagulant activity of the cell suspension was assayed using a one-stage or two-stage method. Cord-derived leukocytes were shown to develop greater coagulant activity than adult-derived leukocytes when stimulated by endotoxin in vitro at 2,000 cells/mm3. This response to endotoxin was partially inhibited by prior exposure of the cells to prostaglandin (PG) E1 and to L-epinephrine. Acetylcholine stimulated the production of coagulant activity in the absence of endotoxin. Both cord and adult-derived leukocytes (20,000/mm3 developed coagulant activity when exposed to pH reduction by lactic or hydrochloric acids and this activity was shown to be tissue factor.
Speculation: TF production by leukocytes (monocytes) after endotoxin stimulation may explain the frequently encountered association of disseminated intravascular coagulation (DIC) with gram-negative septicemia in the newborn infant. The effect of pH reduction in association with hypoxia in the perinatal period, by causing tissue factor (TF) activity to become available, may be the trigger mechanism for the coagulation changes of varying degrees of DIC seen in these situations. Necrotizing enterocolitis could be the result of endotoxin penetration of the bowel mucosa which induces monocyte chemotaxis and local TF production by these cells; this would cause local intravascular coagulation with platelet consumption and necrotic sequelae. It remains to be established whether inhibition of in vivo endotoxin-induced monocyte TF production can be achieved with PGE1, and whether such therapy might improve the outcome in gram-negative septicemia.
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Rivers, R., Hathaway, W. Studies on Tissue Factor Activity and Production by Leukocytes of Human Umbilical Cord and Adult Origin. Pediatr Res 9, 167–171 (1975). https://doi.org/10.1203/00006450-197504000-00005
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DOI: https://doi.org/10.1203/00006450-197504000-00005
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