INCREASED PRODUCTION OF PROCOAGULANT ACTIVITY BY PERIPHERAL BLOOD MONOCYTES IN HUMAN AND EXPERIMENTAL OBSTRUCTIVE JAUNDICE
Fibrin formation and subsequent microvascular thrombosis are important pathogenetic factors in renal failure associated with severe obstructive jaundice (OJ) particularly after surgery, but the mechanism of blood clotting activation is poorly understood. We have studied the procoagulant activity (PCA) of peripheral blood monocytes (M) in 35 patients with severe OJ (serum bilirubin > 8 mg% ) and in 27 nonjaundiced control patients, using a one-stage clotting assay. Monocytes from jaundiced patients, tested immediately after isolation, expressed low levels of PCA (7.3 ± 2.0 u/ 105 M) which was, however, significantly higher than in cells from controls (2.5 ± 0.4 u; p<0.05). In addition, following incubation in short-term cultures with and without endotoxin, they generated significantly more PCA than did control cells (p< 0.005) No significant difference in PCA was found between patients with and without malignancy in either group. In rabbits made icteric by bile duct ligation (15 days), the endotoxin-induced monocyte PCA was markedly increased as compared to sham-operated animals ( p<0.05). In all instances PCA was identified as tissue factor. When related to the clinical outcome of the disease, PCA was about 3-fold higher in the jaundiced patients who died than in the survivors (p<0.01). All patients with a fatal evolution had more than 500 u of endotoxin-induced PCA/105 M; such high levels of PCA were found only in 26% of icteric, uncomplicated patients and in 4% of controls (all without complications). The increased capacity of mononuclear phagocytes to produce PCA might help explain activation of blood coagulation in severe 0J. The association between exceedingly high levels of PCA and lethal outcome suggests that PCA may have a prognostic significance.