PubMed · 11363862
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1996-09-20. Settlement accepted.. https://pubmed.ncbi.nlm.nih.gov/11363862/
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Circulating monocytes as well as resident monocyte-derived macrophages (MDMs) in the atherosclerotic plaque express tissue factor. We tested the hypothesis that differentiation of monocytes into macrophages increases their tissue factor expression. This was done by isolating monocytes from human blood and culturing them for 24 h or allowing their differentiation into macrophages for 8 days before assay. Tissue factor procoagulant activity was assessed by recalcification clotting assay while Western blotting quantitated tissue factor protein. Immunocytochemistry was applied to localize antigenic tissue factor in cells. The results showed that freshly-isolated monocytes expressed low baseline procoagulant activity (0.0004+/-0.0003 ng rhTF/10(6) cells) which increased 100-fold in 24-h cultured monocytes (0.04+/-0.01 ng/10(6) cells, P<0.0001) and was associated with detectable tissue factor protein by Western blotting. Furthermore, MDMs expressed 25-fold higher procoagulant activity (1.0+/-0.5 ng/10(6) cells, P<0.04) and increased tissue factor protein content compared with 24-h monocytes as corroborated by immunocytochemistry. LPS stimulation increased baseline binding activity of transcription factor kappaB three-fold (P<0.03) and 2.6-fold (P<0.09) in monocytes and in macrophages, respectively. The results demonstrate that differentiation of human monocytes into macrophages in culture enhances their tissue factor expression. The observed tissue factor increase that can be further stimulated by LPS may contribute to thrombogenicity of macrophage-rich atheroma. Activation of the TF-kappaB transduction pathway suggests its potential role in the transcriptional regulation of TF gene in response to acute stimulation in these cells. This cell-culture model may provide the opportunity to evaluate the effect of various interventions on macrophage procoagulant activity.
OBJECTIVE: Thromboembolic events in patients who have undergone the Fontan operation have been reported to be as high as 20% to 33%. A hypercoagulable state with deficiencies in proteins C and S has been implicated. Using age-matched control subjects, we evaluated whether an altered coagulation state is present earlier in the course of staged single-ventricle repair. METHODS: After informed consent had been obtained, coagulation factors were assayed in 36 infants (mean age, 7.7 +/- 3.6 months) with single-ventricle cardiac defects immediately before undergoing the bidirectional Glenn procedure; 34 infants (mean age, 8.4 +/- 2.6 months) without cardiac disease were assayed as control subjects. Concentration of factors II, V, VII, VIII, IX, and X; antithrombin III; plasminogen; proteins C and S; fibrinogen; serum albumin; and liver enzymes were measured. Normal reference intervals on the basis of the control subjects were determined by using 95% confidence limits. Patient demographic and hemodynamic variables were evaluated as possible predictors of coagulation abnormalities. RESULTS: Concentrations of protein C; factors II, V, VII, IX, and X; plasminogen; fibrinogen; and antithrombin III were significantly lower in the pre-Glenn infants compared with the age-matched control subjects (all P <.001, Student t test). On the basis of multiple logistic regression, no specific hemodynamic variables were predictive of a procoagulant or anticoagulant deficiency. Ventricular dysfunction did predict the presence of multiple coagulation abnormalities (P <.001). CONCLUSION: Procoagulant and anticoagulant factor abnormalities occur early in the course of single-ventricle repair and precede the cavopulmonary connection.