Thromboplastic Activity of Human Arterial Walls and its Interaction with the Plasmatic Coagulation System

Abstract

Intact arterial vessel wall is not thrombogenic. Disorders of the endothelium in connection with pathological conditions such as atherosclerosis, hyperlipidaemia, hypertension and hyperuricemia induce interaction of surfaces of high thromboplastic activity with the blood stream. In such situations local formation of thrombin will take place immediately. Evidence is presented for the essential and unique activation of the extrinsic pathway of the plasmatic coagulation system. The local formation of thrombin at pathologically altered arterial wall seems to be an important trigger for arterial thrombosis and haemostasis. It could be that in vivo the initial step of thrombogenesis depends upon the formation of the activator complex between tissue-thromboplastin and factor VII.

Half-Life Time and Control Frequency of Vitamin K-Dependent Coagulation Factors

“…However, one thing emerges very clearly: fac tor VII must play a central and important role in the initial phase of blood coagulation. This idea is further supported by the fact that contrary to the other vitamin K-dependent coagulation factor zymogens, factor VII has relatively strong esterase activity in its native (one-chain) form [Zaugg, 1980;Zur and Ne merson, 1980;Radcliffe and Nemerson, 1975], Finally the in vitro occurrence of coldpromoted activation, the fact that factor VIIa in plasma stored at 4 °C is stable for several days [Seligsohn et al, 1978a, b], the persis tence of activated factor VII in circulation for several hours (t' /z = 144 min) after transfu sion of factor IX concentrates [Seligsohn et al, 1979a, b] and the observation that anti thrombin III does not inactivate factor VIIa [Osterud et al. 1976;Jesty, 1978] all point to the special place factor VII takes among the serine esterase enzymes of the coagulation cascade.…”

How to Measure Factor VII and Factor VII Activation

“…Factor VII is the only coagulation factor in the circulating blood which has relatively strong esterase activity in its native form [28,29]. This factor VII alone is a poor activator of factor X or factor IX.…”

“…On exposure to weak tissue thrombo plastin this activated form of factor VII, aVlla, has a tremendous effect when present in blood since the generation of thrombin is then highly accelerated. However, under physiological conditions tissue thromboplas tin is probably only exposed to the blood dur ing vessel wall injury or when monocytes are disrupted or stimulated to produce tissue thromboplastin [11,12,16,28]. Due to the persistence of factor a-VIIa in the circulation it would seem important to explore whether it could lead to a significant generation of thrombin even in the absence of tissue thromboplastin, and thus play a role as a thrombogenic factor in cardiovascular dis eases.…”

Increased Thrombin Activity During Thrombolysis

“…There may be several reasons for this observation. The infarct vessel is likely to expose its thrombogenic surface again after removal of the thrombus (4). Moreover, thromboplastic material may be washed out from the reperfused ischemic myocardium.…”