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Tissue factor pathway inhibitor (TFPI), a kunitztype inhibitor of the extrinsic coagulation pathway, factor VII coagulant (FVIIc), FVIIa, and the fibrinolytic factors plasminogen activator inhibitor-1 (PA1-1) and tissue plasminogen activator (TPA) have been studied in various hyperlipidemias. Compared with a normal lipidic group, mean TFPI activity was 70% higher (P < .001) and 36% higher (P < .001) in type IIa and IIb hyperlipidemias, respectively, and was lower by 13% in type IV hyperlipidemia (P = .05). TFPI was correlated with LDL cholesterol (P < .001), total cholesterol (P < .001), HDL cholesterol (P < .01), apolipoproteins (apo) AI (P < .001) and B (P < .001) and lipoprotein a (P < .01). TFPI was negatively correlated with the triglyceride level (P < .05); the correlation was dependent on LDL cholesterol and HDL cholesterol levels, which were decreased in type IV hyperlipidemia. FVIIc activity (P < .001) was increased by 30% in both type IV and type IIb hyperlipidemia and was correlated with triglyceride levels. FVIIa was not significantly increased in any group compared with control group. FVIIc was correlated with triglyceride level (P < .001), while FVIIa was not. Interestingly, FVIIa was correlated with FVIIc (r = .5, P < .001) in the control group as well as in the hyperlipidemic groups (r = .32, P < .01). These results favor the hypothesis that higher FVIIc concentrations in hyperlipidemic patients are likely due to enhancement of synthesis of FVII and that a part of this FVII circulates in an activated chemical form. Compared with the control group, PAI-1 activity was twofold higher (P < .08) in type IIa hyperlipidemia, threefold higher (P < .001) in type IIb hyperlipidemia, and fourfold higher in type IV hyperlipidemia (P < .001). PAI-1 activity correlated with triglyceride levels (P < .001), apoB levels (P < .001) and total cholesterol levels (P < .05). These correlations were dependent on apoB and probably reflect the correlation between PAI-1 and VLDL. In contrast, TPA level was normal in the different hyperlipidemias. No correlation was found between TFPI, FVIIc, and PAI-1. Variation of TFPI activity appears to be related to the variations of its main lipoprotein carriers: LDL, HDL, and Lp (a). The association in hypertriglycemic patients of hypercoagulability (increased FVIIc and decreased TFPI) and hypofibrinolysis (increased PAI-1) may explain thrombosis predisposition of some of these patients. However, it would be interesting to study the increased levels of endothelium-derived TFPI in plasma induced by the injection of heparin.

SummarySeveral studies have suggested a dose-response relation between the oestrogen content of oral contraceptive (OC) and the risk of both venous thrombosis and arterial disease, when oestrogen doses were higher than 50 μg. However, there is no clear epidemiological evidence for a decrease in thrombotic risk with formulations containing less than 50μg oestrogen. Therefore, we investigated haemostatic variables in users of OC containing either 30 μg (35 women) or 50μg (29 women) ethinyl estradiol as compared with non users (64 women) matched for age and smoking status. Mean values of antithrombin activity were significantly lower in 30 γg or 50 μg oestrogen users than in non users (96% and 98% vs 105%, respectively, p<0.001), but they were not significantly different between the two groups of OC users. There was a significant increase in mean values of factor VII antigen in women taking either 30μg or 50μg oestrogen as compared with non users (96% and 101% vs 85%, respectively, p<0.005). Although the difference between both groups of OC users was not significant, a positive linear trend in factor VII levels was observed within the 0-50μg oestrogen range (p <0.001). Mean levels of fibrinogen were slightly higher in 30μg or 50μg oestrogen users than in non users (2.71, 2.66 g/l vs 2.55 g/l, respectively,), but there was no significant difference between the three groups. Mean values of PAI-1 activity were significantly lower in both groups of OC users than in non users (4.89 and 4.63 AU/ml vs 6.47 AU/ml, respectively, p <0.02), but this decrease was not dose-dependent. There was no significant difference in haemostatic variables between 30 μg oestrogen preparations containing either 100μg (13 women), 150μg (3 women) or 200μg (19 women) levonorgestrel. In 50μg oestrogen preparations, the wide range of different types of progestogens did not allow valid assessment of proge- stogens effect. These data provide further evidence for an alteration of blood coagulation and fibrinolysis in OC users within the 30μg-50μg oestrogen range. However, despite a possible dose-dependent effect of oestrogen on factor VII, our results suggest no substantial change in PAI-1 activity and other markers of thrombogenic risk when oestrogen content of combined OC is decreased from 50μg to 30μg. The potential role of progestogens in haemostatic system needs further investigations.

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