Monocyte tissue factor expression, cell activation, and thrombin formation during cardiopulmonary bypass: a clinical study.
OBJECTIVE
Cardiopulmonary bypass is associated with extensive thrombin generation and cell activation. Our main hypothesis in this study was that the expression of tissue factor on circulating monocytes contributes to the formation of thrombin.


METHODS
Markers of activation of the coagulation cascade and cell activation were measured in 26 patients undergoing elective heart operations randomized to the use of heparin-coated (Duraflo II, n = 13) or standard cardiopulmonary bypass circuits (n = 13).


RESULTS
Thrombin generation, measured as the thrombin-antithrombin complex, increased considerably during cardiopulmonary bypass with peak levels 3 hours afterward and with remaining elevation 20 hours later. Despite increased monocyte and granulocyte activation and increased levels of monocyte chemotactic protein-1, which upregulates monocyte tissue factor expression in vitro, monocyte tissue factor expression was not increased at the end of cardiopulmonary bypass. Furthermore, at this time the monocytes were less sensitive to in vitro stimulation by endotoxin. These results might be explained by simultaneous enhanced levels of interleukin-10, which effectively downregulates monocyte tissue factor expression in vitro. Twenty hours after cardiopulmonary bypass was discontinued, the tissue factor expression on freshly isolated monocytes and on monocytes stimulated by endotoxin was significantly increased compared with preoperative levels. At this time increased activation markers of granulocytes, monocytes, and lymphocytes were also recorded. None of the measured parameters was found to be different between the groups.


CONCLUSIONS
The tissue factor expression on circulating monocytes is upregulated the day after heart operations. The clinical relevance and the regulatory mechanism behind the enhanced expression, however, are not fully elucidated.
Ernofsson
M
M
Department of Clinical Chemistry, University Hospital, Uppsala, Sweden.
Thelin
S
S
Siegbahn
A
A
D000368:Aged; D000990:Antithrombin III / Q000032:analysis; D001779:Blood Coagulation Factors / Q000378:metabolism; D002315:Cardiopulmonary Bypass; D018932:Chemokine CCL2 / Q000032:analysis; D005260:Female; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000032:analysis; D013925:Thromboplastin / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology*
D001779:Blood Coagulation Factors; D018932:Chemokine CCL2; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D006493:Heparin; D013925:Thromboplastin; D010447:Peptide Hydrolases