Fibrinogen Synthesis, Distribution and Degradation

Abstract

Fibrinogen is a plasma protein of approximately 340,000 daltons containing everal per cent carbohydrate [169]. It is at least chiefly synthesized in the liver [156]. On exposure to thrombin it loses peptides [169] and forms long thin solid fibers [82]. These under the influence of fibrinase, Factor XIII [126,133], become markedly insoluble in the blood and tissue fluids, unless attacked by proteolytic enzymes such as plasmin [225]. Collections of intertwined fibers block holes in vessels thereby inhibiting blood loss, sometimes block the lumen of vessels thereby causing thrombosis, sometimes circulate in the blood stream till they lodge in vessels to cause emboli [72] and probably form a matrix for cell growth as in wound healing [7,278] and neoplastic spread [4]. A number of the many recent reviews of various aspects of fibrinogen behavior are noted below. Particularly relevant to what follows are reviews of the molecular structure of fibrinogen [169], the effects of proteolytic enzymes on fibrinogen [137], the pathways of catabolism of fibrinogen [167], the polymerization of fibrin monomers [63], the plasma and tissue fibrinogenolytic and fibrinolytic enzyme systems [152] and the control of protein synthesis in metazoan cells [168,271,232]. This review attempts to describe the physiology and pathophysiology of fibrinogen as it is synthesized, distributed to the blood stream and tissue fluids and catabolized, and to relate its somewhat extraordinary behavior to a few relevant features of what is known about other proteins. This requires discussion of some recent methods for studying fibrinogen metabolism and presentation of a picture of the fibrinogen molecule in continual motion from the time during which it is synthesized till the time when it is broken down through one or other of its several possible catabolic pathways. Also, this requires, because of the resulting clarification-and perhaps some readers may think this unfortunate-the use of some elementary mathematics of rate processes, which we try to keep as simple as possible and the use of which is

Scale Reduction of a Systems Coagulation Model With an Application to Modeling Pharmacokinetic–Pharmacodynamic Data

“…With this in mind, the fifth state was therefore assumed to be dominated by factor II. The extraction of the ODEs of the simplified model from the ODEs of the original model resulted in reduction of the total number of parameters to 11…”

“…Brown snake envenomation results in VICC with depletion of fibrinogen, factor V and factor VIII. 1,6 The time course of changes in fibrinogen, from any cause, is poorly understood, [8][9][10][11][12] making this an ideal setting to investigate the hypofibrinogenaemic states. An established mathematical model of the coagulation network 6 is described by 62 ordinary differential equations (ODEs) and 178 parameters.…”

“…Brown snake envenomation results in VICC with depletion of fibrinogen, factor V and factor VIII. 1 , 6 The time course of changes in fibrinogen, from any cause, is poorly understood, 8 , 9 , 10 , 11 , 12 making this an ideal setting to investigate the hypofibrinogenaemic states.…”

Population pharmacokinetic modelling of fibrinogen in patients with congenital or acquired—chronic or acute—hypofibrinogenaemia

“…Fibrinogen is a plasma‐soluble protein synthesized by the liver 1 . It is the key substrate for plasma blood coagulation, reaching a critically low plasma concentration earlier than other coagulation factors in case of bleeding 2 …”

Association of plasma fibrinogen and development of complications in type 2 diabetes mellitus

“…The formation of fibrinogen rises by about 20 times during strong inflammatory triggers, as it is an acute inflammatory phase reactant. 8,9 During acute inflammation, interleukin-6 acts as a key mediator for increased fibrinogen synthesis. 10 Moreover elevated fibrinogen level may be considered as a marker of low grade inflammation in vascular disease.…”