Activation of the tissue factor pathway occurs during continuous venovenous hemofiltration.
BACKGROUND
Activation of the tissue factor pathway occurs during continuous venovenous hemofiltration (CVVH). Despite adequate exogenous anticoagulation, the occlusion of CVVH circuits can occur within minutes to a few hours of use and is associated with evidence of thrombin generation. Having found no evidence of activation of the contact factor (intrinsic coagulation) pathway during CVVH, we sought to examine the effect of the first episode of CVVH on the tissue factor (extrinsic) pathway of coagulation and thrombin generation.


METHODS
Twelve critically ill patients were studied prior to the commencement of hemofiltration and at regular intervals thereafter until the filter clotted.


RESULTS
Prior to hemofiltration, most patients had increased levels of plasma tissue factor, thrombin-antithrombin (TAT) complexes, and tissue factor pathway inhibitor (TFPI); during hemofiltration, further generation of TAT complexes occurred. Initially, levels of activated factor VII (FVIIa) fell and TFPI increased, but during the course of hemofiltration, the levels of TFPI fell and FVIIa increased. Levels of tissue factor increased during CVVH in some patients, but this was not related to the generation of FVIIa.


CONCLUSIONS
These data indicate that activation of FVII occurred during CVVH, which was related to levels of TFPI, but not tissue factor, and was coincidental to thrombin generation.
Cardigan
R A
RA
Department of Haematology, University College London Medical School, London, England, United Kingdom.
McGloin
H
H
Mackie
I J
IJ
Machin
S J
SJ
Singer
M
M
D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000097:blood / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects; D005167:Factor VII / Q000378:metabolism; D015942:Factor VIIa / Q000378:metabolism; D065427:Factor Xa Inhibitors; D005260:Female; D006440:Hemofiltration / Q000009:adverse effects*; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D013917:Thrombin / Q000096:biosynthesis; D013925:Thromboplastin / Q000378:metabolism*; D013997:Time Factors
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D005167:Factor VII; D006493:Heparin; D013925:Thromboplastin; D015942:Factor VIIa; D013917:Thrombin