A model of in vivo human venous thrombosis that confirms changes in the release of specific soluble cell adhesion molecules in experimental venous thrombogenesis.
OBJECTIVE
The mechanisms of venous thrombogenesis have been studied by using animal models and cells in culture. The results from these systems may not, however, be relevant to the human condition. The aim of this study was to develop a method by which thrombus could be safely produced in a human vein in vivo. The model that was developed was used as a means of studying the changes in soluble adhesion molecule expression in human venous thrombogenesis.


METHODS
An autologous thrombin extract was used to generate experimental thrombi in the disconnected portion of the long saphenous veins of 30 patients who were undergoing routine bilateral varicose vein surgery. The contralateral vein was perfused with thrombin extract diluent buffer to act as the control. The concentration of soluble P-, E- and L-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule-1 were measured by means of specific enzyme-linked immunosorbent assays in samples of blood taken from veins in which thrombus had formed and in contralateral control veins.


RESULTS
Thrombosis invariably formed when at least 100 IU of thrombin activity was administered. Thrombus formation was independent of the time that the thrombin extract was allowed to remain within the emptied vessel. Thrombosis never developed in control vessels that were similarly treated with the buffer used to dilute the thrombin extract. Experimental thrombi were composed mainly of red cells, with layers of fibrin next to platelet and leukocyte packages. These findings are similar to those observed in samples of established human venous thrombi. There were small but significantly higher levels of the adhesion molecules, soluble P-selectin, and vascular cell adhesion molecule-1 in blood taken from veins in which experimental thrombi had formed, compared with controls (P =.015 and.007, respectively; Wilcoxon signed rank test). Serum levels of soluble L-selectin, E-selectin, and ICAM-1 were not affected by thrombosis.


CONCLUSIONS
This model is safe and reproducible. It produces thrombi with a morphology similar to that described for established human deep venous thrombi. The model may be appropriate for the study of the early changes that occur during human venous thrombogenesis and may also be of value in testing the efficacy of novel antithrombotic agents.
Department of Surgery, GKT Medical School, St Thomas Hospital, London, UK.
J
J
Quarmby
A
A
Smith
M
M
Collins
S
S
Cederholm-Williams
K
K
Burnand
D015815:Cell Adhesion Molecules / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008855:Microscopy, Electron, Scanning; D015203:Reproducibility of Results; D012501:Saphenous Vein; D013917:Thrombin / Q000494:pharmacology*; D014648:Varicose Veins / Q000601:surgery; D020246:Venous Thrombosis / Q000209:etiology / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D013917:Thrombin