Experimental thrombosis I: Relation with fibrinogen and other haemostatic parameters

Epidemiological studies have shown that the haemostatic parameters Fibrinog en (Fg), Factor VII (F VII), Factor VIII (F VIII), von Willebrand factor (V WF), Tissue Plasminogen Activator (L-PA), Plasminogen Activator Inhibitors (PAI) are risk factors/markers of ischemic cardiovascular disease, Ferritin (sFER) and Leukocytosis have also been implicated. In the present study we have followed the levels of fibrinogen, von Willebrand factor and thrombom odulin in relation to lipids, iron and the appearance of atherosclerotic le sions in New Zealand rabbits fed with a cholesterol enriched diet for a two -month period compared with a group of control rabbits. Hematocrit and whit e blood cell count (WBC) were measured in parallel. In hyperchlestorolemic rabbits the levels of fibrinogen and von Willebrand factor increased progre ssively, showing a positive correlation with the increasing cholesterol lev els, There was an increase in soluble thrombomodulin beginning at the eight h week of study, In addition, these animals showed gross intimal atheroscle rotic lesions in the whole extension of their aortas. Immunohistochemical s tudies showed the presence of fibrin(ogen) related antigen throughout the a rterial wall and in the central portions of the atheromas. In the control g roup there was no formation of atherosclerotic plaques and all haemostatic, haematological and biochemical parameters were within the normal range. WB C and sFER levels were unaffected in both groups. Our results show that inc reased levels of fibrinogen and von Willebrand factor, known coronary risk factors, are strongly associated with the formation of atherosclerotic plaq ues in rabbits. The plaques contain a considerable amount of fibrinogen rel ated antigen. (C) 2000 Elsevier Science Ltd. All rights reserved.