Factor VII-phospholipid Complex Research Articles

Levels of plasma factor VII and factor VII activated forms as a function of plasma triglyceride levels

It has been shown that triglyceride levels are one of the determinants of factor VII levels. In this study we have simultaneously evaluated, in a group of 102 healthy individuals, the different forms of factor VII, namely factor VII mass, factor VII coagulant activity, activated factor VII double-chain form and factor VII-phospholipid complex, in relation to triglyceridaemia. The data showed a highly significant correlation of factor VII mass, factor VII coagulant activity and factor VII-phospholipid complex with triglycerides. No correlation was observed between the activated factor VII double-chain form and triglycerides. These data, together with analysis of the linear and orthogonal regression slopes, suggest that increase of plasma factor VII coagulant activity as a function of plasma triglyceride levels is attributable to an increase in both mass and activity of factor VII and that the increase in activity is dependent on an increase of factor VII-phospholipid complex rather than activated factor VII double-chain form. The ratio between the slopes of the regression straight line of factor VII mass and factor VII-phospholipid complex in relation to triglycerides was 2.23 (95% confidence limits 1.74–2.50), thus indicating that the contribution of factor VII mass is prevalent over that of the factor VII-phospholipid complex.

The influence of dietary change on hemostatic risk variables.

In the 1970s in the Diet-Antismoking Trial, of the Oslo Study, colleagues and I found that the majority of high-risk men with elevated serum cholesterol and elevated triglyceride concentrations had impaired fibrinolytic capacity. Later on, both our group and others found a similar negative correlation between serum triglyceride levels and fibrinolytic capacity. Furthermore, in a prospective study of dietary intervention in individuals with both elevated cholesterol and triglyceride levels, we found that dietary lowering of serum triglyceride levels was significantly and positively correlated with an improvement in fibrinolytic capacity. In another study, we made the same observation for the coagulation factor VII-phospholipid complex: the more the triglycerides were reduced by diet, the greater was the change in factor VII complex. This correlation was highly significant and independent of changes in serum cholesterol. Platelet function is also influenced by dietary habits, but except for the effects of a fish oil-enriched diet, few data are available about the dietary effects on platelet function. It seems, however, that in individuals with elevated lipid levels and elevated blood pressure, increased platelet reactivity is a highly prevalent finding. Many of the hemostatic risk variables are associated with the so-called "metabolic risk syndrome" characterized by an increase in serum insulin level, together with increased relative body weight, mild hypertension, hyperlipidemia, and physical inactivity. This syndrome can often be influenced favorably by life-style changes. A controlled study with interventions in diet and activity level has just been started by our group.

Withdrawal of chronic beta- adrenoceptorblockade: Effects on haemodynamics, blood lipids and haemostatic variables

The effect of cessation of chronic beta-adrenoceptorblockade on heart rate, blood pressure, blood lipids and selected haemostatic factors have been measured in 22 patients recovering from myocardial infarction. Clinical examination and blood tests were performed before and 12 weeks after withdrawal of beta-adrenoceptor-blockade, which had lasted for an average of 3 y. No effect was found on blood pressure. There was a significant increase in heart rate of 12%. Total cholesterol declined by 9%, high density lipoprotein (HDL-cholesterol) increased by 12%, and triglycerides decreased by 6%. The triglyceride dependent factors, plasminogen activator inhibitor (PAI-1) and factor VII-phospholipid complex, were not affected.

Increased Activity of Factor VII and Factor VII-Phospholipid Complex Measured Using a Normotest System in Subjects with Hyperlipidemia

Coagulation factor VII and factor VII-phospholipid complex (factor VIIpl), an activated form of factor VII, were measured using a Normotest system in 128 patients with various types of hyperlipoproteinemias and in 45 control subjects. A positive correlation was found between both factors VII (p less than 0.001) and VIIpl (p less than 0.0001) and serum triglycerides. Similar correlations were established with very low density lipoproteins. A positive correlation was also observed between factor VIIpl and total cholesterol, whereas inverse correlations were found with high-density lipoproteins for both factors VII and VIIpl. No positive correlation could be found between low-density lipoproteins and factors VII and VIIpl. This study has shown that patients with hyperlipoproteinemias associated with high serum triglyceride levels, with or without high cholesterol levels, have increased activity of factors VII and VIIpl, both previously associated with an increased risk of coronary heart disease.

Effects of Gemfibrozil on Lipids and Haemostasis after Myocardial Infarction

The effects of gemfibrozil on haemostatic variables were studied in 43 survivors of myocardial infarction with serum triglycerides (TG) greater than or equal to 2 mmol/l 2 weeks prior to randomization. The study was double-blind, placebo-controlled and stratified for chronic betablockade. Twenty-two individuals were given gemfibrozil 600 mg twice daily and 21 individuals received matching placebo. After 8 weeks the TG level was unchanged in the placebo group, whereas a 44% reduction was noted in the gemfibrozil group (p less than 0.001). Fibrinogen increased in both groups, while bleeding time and platelet count were unchanged. Clotting factor VII-phospholipid complex decreased in both groups, but the change was more marked and attained statistical significance only in the gemfibrozil group (60% reduction, p less than 0.01). By DDAVP-stimulated D-Dimer agglutination test 8 in 21 patients in the placebo group (38%) still had reduced fibronolytic capacity versus none in the gemfibrozil group (p = 0.001). Thus, in this study, gemfibrozil improved reduced fibrinolytic capacity and may have reduced hypercoagulability by lowering the clotting factor VII-phospholipid complex.

Phospholipase C‐Sensitive Factor Vii Actiy in Normal Pregnancy

We have previously reported the existence of a phospholipase C-sensitive form of factor VII-probably a factor VII-phospholipid complex in normal pregnancy. By bivariate regression analysis, the level of this complex shows highly significant positive correlations with serum triglycerides (r = 0.90, p less than 0.0001) and blood platelet count (r = 0.067, p = 0.0004). This high degree of correlation was verified by stepwise multiple regression analysis. It is presently not known how this factor VII complex formes.

The effect of phospholipase C on plasma factor VII

The proposed link between a circulating factor VII-phospholipid complex and the risk of cardiovascular disease (CVD) has stimulated us to investigate the effect of phospholipase C (PLC) on the factor VII (FVII) activity in plasma from healthy individuals. PLC caused a rapid fall in FVII activity which was larger with heparinized than with citrated plasma. EDTA inhibited the PLC effect so emphasizing the involvement of divalent cations. PLC dependent loss of FVII activity varied widely between individuals, showed a highly significant correlation with plasma triglyceride concentrations, and was always greater in post-prandial compared to fasting plasma samples. Experiments using pure recombinant FVIIa and plasma depleted of FVII by adsorption indicated that loss of FVII activity only occurred in the simultaneous presence of absorbed plasma, FVIIa and PLC. Preincubation of PLC with adsorbed plasma before adding FVIIa did not lead to loss of FVII activity. It appears that PLC may act on lipoproteins already bound to FVII, in order to inhibit FVII activity. Other results indicated that competition between different plasma components (lipoproteins) in binding to FVII may govern the extent of the PLC dependent reduction in FVII activity.

Influence of highly concentrated n-3 fatty acids on serum lipids and hemostatic variables in survivors of myocardial infarction receiving either oral anticoagulants or matching placebo

Forty patients with previous myocardial infarction were given 4 capsules with 1 g concentrated fish oil preparation daily for 4 weeks. No special diet was applied. The supplementation was equivalent to 3.4 grams of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) daily. Twenty-two of the 40 subjects received concomitant treatment with long-term oral anticoagulants (OAC). The fatty acid composition of serum after the supplementation period showed a significant increase in the proportion of EPA and DHA, while arachidonic acid (AA) remained essentially constant. This resulted in a rise of the EPA/AA ratio from 0.59 to 1.49 (p<0.001), confirming satisfying absorption of the concentrate. Blood lipids showed an overall decrease of triglycerides (TG) by 25% (p=0.02), while total cholesterol rose by 5% (p=0.03) and HDL-cholesterol was unaffected. Blood glucose and the TG associated factors plasminogen activator inhibitor and factor VII-phospholipid complex revealed trends towards reduction. Ivy bleeding time showed a significant prolongation, the median increasing from 240 to 270 seconds. A significant increase of fibrinogen was seen, as was a decrease of clotting time in the combined prothrombin test in patients receiving concomitant OAC. Thus, given for 4 weeks, the investigated concentrate of n-3 fatty acids exerts not merely beneficial effects as far as the risk profile for atherosclerotic disease is concerned. The results also point towards interactions with OAC that may be of clinical relevance.

Studies on coagulation, fibrinolysis, kallikrein-kinin and complement activation in systemic and pulmonary circulation during hip arthroplasty with acrylic cement

This study was designed to evaluate the contribution of the plasma cascade systems to the cardiopulmonary complications, occasionally leading to sudden death during hip arthroplasty using acrylic cement. The intraoperative pattern following uneventful surgery was therefore investigated in 8 patients with osteoarthrosis with frequent sampling from the radial and pulmonary arteries. The following general findings emerged: A gradual consumption of coagulation factors (platelets, fibrinogen, factor VII, antithrombin III), fibrinolytic components (plasminogen, alpha-2-antiplasmin), kallikrein-kinin factors (prekallikrein, kallikrein inhibitor) and complement factors (C3c, C4) was observed. Some intrapulmonary proteolytic inhibition was noticed as evidenced by lower arterial than mixed venous blood levels of alpha-2-antiplasmin and kallikrein inhibitor. Insignificant changes occurred for factor VII-phospholipid complex. A rapid, massive and transient increase in fibrinopeptide A (FPA) values in the radial artery, as opposed to the moderate increase in the pulmonary artery, was found immediately after reaming and broaching of bone. This probably reflected intrapulmonary fibrinogen to fibrin conversion, reaching a maximum 15–20 minutes before the femoral implantation. As estimated from the FPA arterial peak values and the fall in fibrinogen concentrations, approximately 5–10% of the circulating fibrinogen molecules were devoided of EPA during this intraoperative phase. The marked a-9 difference in FPA level supports earlier findings of intrapulmonary fibrin formation and deposition. This process, however preceded the critical period of cardiorespiratory collapse (CRC) by at least 15 minutes, and may thus predispose to this complication.

A simple method for determination of the factor VII-phospholipid complex using normotest

We report here a highly significant positive correlation observed when the factor VII-phospholipid complex (the phospholipase-C sensitive component of factor VII) in plasma was tested in a specific factor VII system and in Normotest (p<0,0001). The Normotest system, which is sensitive to variations in coagulation activity within the normal range, was not influenced by phospholipase C when the enzyme was added immediately before the start of the coagulation assay. Normotest is well suited for determination of the factor VII-phospholipid complex in plasma.

Factor VII-phospholipid complex in male survivors of acute myocardial infarction.

The presence of an activated form of coagulation factor VII--a factor VII-phospholipid complex--in male survivors of myocardial infarction is described. The level of this complex did not correlate with age or level of conventional risk factor score, but showed a highly significant positive correlation with serum triglycerides in all the subgroups as well as in the whole study population (r = 0.88, p less than 0.0001). Measurement of this form of activated factor VII may constitute a simple and promising method for additional screening of men at risk for cardiovascular disease.

A new form of coagulation factor VII in plasma.

We have reported the existence of a novel form of coagulation factor VII - probably a factor VII-phospholipid complex - in plasma from pregnant women and men at risk for cardiovascular disease. We report here further observations on the presence and characteristics of this complex. Some apparently healthy individuals who, on testing by standard methods, have normal levels of factor VII activity achieve such levels by means of a phospholipase C-sensitive modification of (some of) their factor VII molecules. Their residual factor VII activity after phospholipase C treatment of plasma may be as low as 10-20 U/ml. Antiserum to the protein component of thromboplastin (apoprotein III) had no effect on the factor VII activity, whereas antiserum to factor VII effectively blocked both the total factor VII activity and the residual activity of factor VII after treatment of plasma with phospholipase C. These factor VII complexes precipitate with the VLDL/LDL fraction in lipoprotein precipitations.