Intrinsic coagulation system, activation

Fig. 2. The intrinsic and extinsic cascade coagulation systems. activation -I, inhibition HMK, high molecular kininogen Cl-inh., complement-1 esterase inhibitor AT-III, antithrombin HI a 1 -PI, alpha-1 protein inhibitor pf-3, platelet factor 3.

The role of Ca in bovine factor IX structure and activation has been examined. Although several cations effectively interact with factor IX, there appears to be a rigid specificity for the cation in the activation of this proenzyme by the intrinsic coagulation system. The lack of co-operative interactions in the binding... 

The platelets subsequently release adenosine diphosphate (ADP) which results in the cohesion of additional platelets thus forming the nucleus around which fibrin is formed (by activation of the intrinsic coagulation system). Entrapment of red and white blood cells follows and a full-blown throndOus results. 

The coagulation system that generates thrombin consists of intrinsic and extrinsic pathways. Both pathways are composed of a series of enzymatic reactions eventually producing thrombin, fibrin, and a stable clot. In parallel with the coagulation, the fibrinolytic system is activated locally. Plasminogen is converted to plasmin, which dissolves the fibrin mesh1 2 3 (Fig. 64—1). 

Activation of the coagulation system may start after activation of the contact factors (intrinsic system) or after release of tissue factor (extrinsic system). 

The sequence of reactions which take place by the activation of the coagulation system at the blood/biomaterial interface are summarized in Fig. 3. The competitive adsorption behavior of proteins at the biomaterial surface determines the pathway and the extent of intrinsic coagulation and adhesion of platelets. Predictions about the interactions between the biomaterial surface and the adsorbed proteins can only be formulated by having an exact knowledge of the structure of the biomaterial s surface and the conformation of the adsorbed proteins. These interactions are determined both by the hydrophobic/hydrophilic, charged/uncharged, and polar/non-polar parts of the proteins and the nature of the polymer surface [25-27]. A commonly accepted fact is that decreasing sur-... 

The contact of biomaterial surfaces with the biological system blood provokes, with different intensity, activation of the intrinsic coagulation pathway at the blood/biomaterial interface. Clinically important and reproducible investigation methods are carried out to evaluate blood compatibility. The following coagulation parameters, obtained after the contact of the foreign surface with native, non-anticoagulant human whole blood in a modified Bowry blood chamber [93] and compared to the initial citrate plasma values, are evaluated ... 

Platelets and blood coagulation are also influenced by lipids and fatty acids. Saturated fatty acids are activators of the "contact factor" in the intrinsic clotting system and exert an influence on the activation of platelets, as do prostaglandins (E.F. Lxischer). Phospholipids of red blood cells and phospholipids and fatty acids of platelets may differ in nutritionally different areas (Cincinnati, Ohio Milan and Palermo, Italy) and the lipid composition of platelets may have an effect on their function the nutritional state may predispose to thrombogenic phenomena (J.M. lacono et al.). 

The intrinsic and extrinsic system paths advance independendy through their initial interactions but eventually follow a common course. The activity of both pathways are important m vivo. The concept of separate systems provides a practical means of evaluating laboratory and clinical coagulation abnormalities. 

An overview of the coagulation cascade and sites of action for coumarins and heparin is shown in A. There are two ways to initiate the cascade (B) 1) conversion of factor XII into its active form (Xlla, intrinsic system) at intravascular sites denuded of endothelium 2) conversion of factor VII into Vila (extrinsic system) under the influence of a tissue-derived lipoprotein (tissue thromboplastin). Both mechanisms converge via factor X into a common final pathway. 

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