Haemostatic function in precocious myocardial infarction and vein graft occlusion after coronary artery bypass grafting

Sammanfattning: Haemostatic function in precocious myocardial infarction and early vein graft occlusion after coronary artery bypass grafting Elisabeth Moor The Cardiology Unit and the King Gustaf V Research Institute, Department of Medicine, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden The present study examined the role of blood coagulation and fibrinolytic function in patients with coronary heart disease in two settings; in patients with precocious myocardial infarction in whom thrombosis is considered to constitute an important pathogenic mechanism and in unselected patients undergoing coronary artery bypass grafting (CABG) in whom early thrombotic occlusion of vein grafts is a considerable problem. Particular attention was paid to coagulation factor Vll and the tissue factor pathway inhibitor (TFPI) in the young postinfarction patients. Factor Vll coagulant activity (Vllc) has been associated with the risk of future fatal coronary events in initially healthy middle-aged men. Tissue factor pathway inhibitor (TFPI) regulates the tissue factor-induced blood coagulation through binding to the factor Vlla/tissue factor(TF) complex. The present studies were conducted to assess the role of coagulation factor Vll in patients with myocardial infarction at a young age and to examine the relations between plasma lipoproteins, factor Vll genotype, and factor Vll mass and activity. We also quantified the TFPI activity and examined the relationships between TFPI activity, plasma lipoproteins and coagulation factor Vll. The plasma level of factor Vll antigen (Vllag) was higher in patients than in controls, the difference being accounted for by the patients with hypertriglyceridaemic lipoprotein phenotypes. In contrast, the plasma concentration of the fully active, two-chain factor Vll molecule (Vlla) was similar in patients and controls. Patients and controls with factor Vll Arg/Arg genotype had higher factor Vll levels (both protein and activity). The polymorphism also affected the relation between VLDL and Vllag, The similar plasma concentrations of Vlla in patients and controls speak against a role of factor Vll as a nsk factor for precocious myocardial infarction. TFPI activity, on the other hand, was higher in patients than in controls. This difference was accounted for by the patients with type llb hyperlipoproteinaemia. A weak correlation was present between TFPI activity and Vllag concentration in the patients, but not in the controls. The elevated TFPI activity in the patients was closely associated with the plasma level of dense low density lipoprotein(LDL) particles and with the plasma concentration of the small, dense high density lipoprotein (HDL) subspecies HDL3b. Thus, TFPI activity was raised in the individuals who had elevated levels of the lipoproteins that carry TFPI. Elevated TFPI levels were also accompanied by elevated levels of factor Vll protein amongst the patients. In a pilot-study conducted to characterise perioperative perturbations of the haemostatie system, a marked postoperative activation of the coagulation and fibrinolytic systems was seen in connection with CABG. The degree of activation of the two systems in response to surgery differed widely between individuals. Also the acute-phase response differed between the patients but could only partly explain the pronounced activation of the coagulation cascade. Based on this pilot-study it seemed resonable to assume that hypercoagulability and impaired fibrinolytic function might be implicated in early saphenous vein graft occlusion after CABG. In a larger-scale study conducted to identify haemostatic predictors of early saphenous vein graft occlusion after CABG, pre- and postoperative determinations of haemostatic faetors and inhibitors were related to the presence of graft occlusion at three months after surgery in 100 consecutive male patients . The percentage increase in plasma PAI-I activity on the first postoperative day was significantly higher in the 23 patients who had graft occlusion compared with the patients with patent grafts. Otherwise, no pre- or postoperative haemostatic measurements predicted early vein graft closure. The factor V (Arg 506-Gln) mutation confers an increased risk of deep vein thrombosis, whereas its role in myocardial infarction and graft closure after CABG remains unclear. Therefore, genoyping for the factor V mutation was performed in the patients with myoeardial infarction at a young age and in the CABG patients. The mutation did not appear to increase the risk of myocardial infarction at a young age. As expected, the factor V mutation had a strong effect on pre- and postoperative activated protein C ratios in patients undergoing CABG. Heterozygotes for the mutation amongst the controls had significantly higher prothrombin fragment 1+2 levels, a marker of thrombin generation, compared with subjects lacking the mutant allele. There were no differences in APC ratios between patients with or without saphenous vein graft occlusion. However, presence of the factor V mutation was found to be associated with early vein graft occlusion. ISBN 91-628-2368-X