Direct activation of factor X by monocytes occurs during cardiopulmonary bypass.
We hypothesized that monocyte procoagulant activity, which includes up-regulation of tissue factor and direct activation of factor X by CD11b. is an activator of coagulation during cardiopulmonary bypass (CPB), because recent studies have cast doubt on the presumption that the surfaces of CPB activate the intrinsic pathway. Sequential samples were taken from 17 patients undergoing cardiac surgery. During CPB a significant increase in thrombin-antithrombin complexes occurred (P < 0.0005). Factor XIIa levels increased (P < 0.005) but remained within the normal range. Total monocyte procoagulant activity was measured and a functional assay was developed to detect direct activation of factor X alone. There was a significant increase in total procoagulant activity on circulating monocytes from the start of CPB (P < 0.005) to which direct factor X activation was a major contributor (P < 0.005). Direct activation of factor X was inhibited by CD11b blocking peptides. Using flow cytometry, up-regulation of monocyte CD11b (P < 0.0005). but not up-regulation of tissue factor, was found on circulating monocytes. Monocytes adherent on the oxygenator fibres showed increased CD11b expression (P < 0.0001), but no tissue factor when assessed by fluorescent image analysis. In conclusion, direct activation of factor X through monocyte CD11b occurs during CPB and appears to contribute to thrombin generation during CPB.
Parratt
R
R
Department of Cardiothoracic Surgery, Imperial College School of Medicine at The National Heart and Lung Institute, Heart Science Centre, Harefield Hospital, Middlesex.
Hunt
B J
BJ
D000328:Adult; D000368:Aged; D000990:Antithrombin III / Q000378:metabolism; D001777:Blood Coagulation / Q000502:physiology*; D002315:Cardiopulmonary Bypass; D004797:Enzyme-Linked Immunosorbent Assay; D015956:Factor XIIa / Q000502:physiology; D015951:Factor Xa / Q000502:physiology*; D005260:Female; D006801:Humans; D016177:Macrophage-1 Antigen / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology*; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism
D016177:Macrophage-1 Antigen; D000990:Antithrombin III; D013925:Thromboplastin; D015956:Factor XIIa; D013917:Thrombin; D015951:Factor Xa