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The aim of this study was to assess the effects of aerobic exercise on resting and 24-hour blood pressure (BP), left ventricular mass (LVM), plasma fibrinogen and factor VII (FVII). For this purpose 14 sedentary subjects with untreated diastolic BP between 90 and 104 mm Hg completed a 12-week supervised exercise program. At the end of this period, 8 subjects resumed a sedentary life-style and were reexamined 2 months later (detraining). Baseline, posttraining and postdetraining examinations included resting BP assessment, ambulatory BP monitoring, cardiopulmonary stress test, echocardiography and measurements of plasma fibrinogen and FVII. Exercise-mediated increase in aerobic fitness (VO2 max + 24%) was associated with a significant reduction in resting systolic and diastolic BP (p < 0.01), mean systolic and diastolic 24-hour BP (p < 0.001) and LVM index. As for the coagulation parameters only the concentration of fibrinogen significantly decreased (p < 0.01) whereas FVII remained unchanged. The 8 subjects that resumed a sedentary life-style were reexamined 2 months later: their resting BP, 24-hour BP and fibrinogen concentration returned to baseline values; only the effect on LVM was conserved. Our study underlines the usefulness and safety of regular physical exercise in mild hypertension. Most of the patients (11 of 14) had their BP normalized and a significant reduction in LVM and fibrinogen concentration was observed, leading to an overall improvement in coronary risk profile.

Localised extravascular initiation of mammalian haemostasis is achieved by the anatomical localization of tissue factor (TF) around blood vessels and at organ surfaces. TF avidly binds factor VII from outflowing blood following vascular injury, forming the tissue factor/factor VII (TF.VII) complex. This is rapidly converted to TF.VIIa, the active initiator of blood coagulation. Structural studies have revealed that the extracellular region of TF consists of two C2-type immunoglobulin-like modules rigidly held at an angle of 125 degrees by an extensive buried interface. The regions of TF involved in binding factor VII extend from the binding finger of the domain interface across quite a wide surface of the distal (N-terminal) module. Solution scattering studies show that both TF and factor VII adopt an extended conformation in solution and that the complex is formed by a compact side by side alignment of the two proteins along their long axes.

Extrinsic pathway inhibitor (EPI) is a Kunitz type serine protease inhibitor. EPI is a potent inhibitor of the factor VIIa/thromboplastin (TP) complex in the presence of factor Xa and is also a direct inhibitor of factor Xa. The inhibitory mechanism is complex and is currently thought to involve, in a first step, the formation of a EPI-factor Xa complex, and, in a second step, the formation a quaternary EPI-factor Xa-factor VIIa-TP complex. In the blood vessels, EPI is confined to three different pools. A major pool of EPI is bound to the endothelial surface, and this fraction may be released by heparin. Plasma contains a second, but smaller pool of EPI (approximately 10-50% of the endothelial surface pool) at a concentration of 50-100 ng/ml. This pool consists mostly of EPI-lipoprotein complexes and only less than 10% is carrier-free EPI. A third pool of EPI is confined to platelets (less than 10% of the plasma pool). The biological role of these pools has not yet been clarified, but some evidence suggest that the carrier-free EPI is biologically most active. In patients, disseminated intravascular coagulation may continue despite normal or even elevated EPI levels. However, evidence has now been provided to indicate that EPI can inhibit factor VIIa/TP complexes formed in vivo to prevent the effect of limited amounts of TP. Taken together, the present knowledge of EPI indicates that EPI functions as a key inhibitor to feedback control of blood coagulation initiated by TP.

A brief review of the interactions of the intrinsic and extrinsic coagulation pathway is given. The complex of thromboplastin and factor VII may well be the most important trigger in both pathways.

Factor VII, a single-chain zymogen, has sufficient proteolytic activity to initiate blood coagulation. The reason that coagulation does not occur continuously is that the zymogen like its 2-chain derivative enzyme, factor VIIa, absolutely requires tissue factor. The latter, a lipid-dependent glycoprotein, is not normally present in the blood. Upon tissue injury, however, coagulation is initiated by the activation of factors IX and X. The relationship of these events to the possibility that hemophilia A and B are tissue factor-dependent diseases is discussed.

Two patients with factor VII Padua abnormality were studied during prophylactic administration of factor VII concentrates for tooth extractions. The amounts administered were 15.8 and 17.2 units/kg body weight in 30 and 20 min, respectively. The end infusion factor VII activity levels were 55 and 64%, respectively. Survival times of the exogenous components were 6.5 and 6 h, respectively. Satisfactory hemolstasis was obtained in both instances.

A short review about the place of coagulation factor VII in the initial phase of blood coagulation is given. A theoretical model describing the relationship between the half-life times of vitamin K-dependent coagulation factors and the control frequency of oral anti-coagulation therapy is presented. The constraints that control frequency imposes on the type of determination to be carried out are discussed.