Coagulation systems

Factors I, II, III, V, VII, VIII, IX, X, XI, XII, and XIII, Protein C, and Protein S are synthesized in the Hver. Factor III is present in many different organs throughout the body. Factor IV is the divalent cation calcium. The concentration of calcium required for normal function of the blood coagulation system is much less than required for normal physiologic function of many organs in the body, eg, myocardium. 

In contrast to heparin, the coumarinic acid anticoagulants are inactive in vitw ]6k.e heparin they are active in vivo. The phenylindanedione-type compounds (7) (36) and warfarin (2) produce their in vivo inhibitory effect on the coagulation system by competitively antagonizing the normal activity of vitamin (8) (37—44). 

Food. Food-grade calcium chloride is used in cheese making to aid in rennet coagulation and to replace calcium lost in pasteurization. In the canning iadustry it is used to firm the skin of fmit such as tomatoes, cucumbers, and jalapenos. It acts as a control in many flocculation, coagulation systems (37). Food-grade calcium chloride is used in the brewing iadustry both to control the mineral salt characteristics of the water and as a basic component of certain beers (see Beer). 

Coagulation summarizes the mechanisms involved in stopping bleeding due to an injured or defective vessel wall. Coagulation is characterized by procoagulatory and anticoagulatory factors that are in balance under normal conditions. Vessel injuries are occluded by the coagulation system and spontaneous vessel occlusions dissolved by the fibrinolytic cascade. 

Basic aspects of the proteins of the blood coagulation system and of fibrinolysis are described in this chapter. Some fundamental aspects of platelet biology are also presented. Hemorrhagic and thrombotic states can cause serious medical emergencies, and thromboses in the coronary and cerebral arteries are major causes of death in many parts of the world. Rational management of these conditions requires a clear understanding of the bases of blood clotting and fibrinolysis. 

Histamine Serotonin Platelet-activating factor (PAF) Eicosanoids (various prostaglandins and leukotrienes) C3a, C4a, and C5a from the complement system Bradykinin and fibrin split products from the coagulation system... 

Early studies indicate that combined GP Ilb/IIIa inhibition with rt-PA thrombolysis may improve clinical and MRI outcomes after acute ischemic stroke, with an acceptable safety prohle. The dual targeting of platelets and hbrin by combination therapy may provide synergistic benefits, including increased arterial recanalization, reduced microvascular thrombosis, reduced arterial reocclusion, and less rt-PA-mediated blood-brain barrier injury and secondary activation of the coagulation system. 

Three types of coagulation were considered. The glucono(5)lactone (GDL)-induced coagulation system (GDL system) was prepared by acidification with 1.75 g/L GDL (Roquette, Lestrem, France). The rermet-induced coagulation system (rennet system) was prepared by the addition of calf rennet (SKW, Baupte, France) at 25.6/rg/L of milk. The GDL-I-rermet-induced coagulation system (mixed system) was prepared by acidification with 0.45 g/L GDL for 2h followed by the addition of rennet at 15.4/ig/L of milk. The experimental conditions for each system were selected in order to achieve gelation without syneresis. Coagulation kinetics were performed at 30°C. 

Define the role of an atherosclerotic plaque, platelets, and coagulation system in an acute coronary syndrome. 

Generally, the major adverse effects associated with colloids are fluid overload, dilutional coagulopathy, and anaphy-lactoid/anaphylactic reactions.24,32 Although derived from pooled human plasma, there is no risk of disease transmission from commercially available albumin or PPF products since they are heated and sterilized by ultrafiltration prior to distribution.24 Because of direct effects on the coagulation system with the hydroxyethyl starch and dextran products, they should be used cautiously in hemorrhagic shock patients. This is another reason why crystalloids maybe preferred in hemorrhagic shock. Furthermore, hetastarch can result in an increase in amylase not associated with pancreatitis. As such, the adverse-effect profiles of the various fluid types should also be considered when selecting a resuscitation fluid. 

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). 

The inflammatory process in sepsis is linked to the coagulation system. Pro-inflammatory mediators maybe procoagulant and antifibrinolytic, whereas anti-inflammatory mediators may be fibrinolytic. A key factor in the inflammation of sepsis is activated protein C, which enhances fibrinolysis and inhibits inflammation. Protein C levels are decreased in septic patients. 

Septic shock is frequently complicated by massive activation of the coagulation system. This can occur concomitantly with biphasic change in the fibrinolytic system, involving both activation and inhibition of plasminogen activation. The net result of the altered hemostatic state in sepsis is widespread microvascular trom-bosis. The early events leading to these disturbances are incompletely understood,... 

The Role of Plasma Cascade Systems in Sepsis 4.1.1. The Coagulation System... 

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

At present, the activation of the extrinsic coagulation system is considered to be of more importance in the initiation of DIC than the activation of the contact system (LI2, Cl 3). The activation of the extrinsic system starts with the release of tissue factor (TF) from endothelial cells. TF is a macromolecule, composed of a protein and a lipid fraction, that is synthesized by endothelial cells and monocytes. TF... 

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.

There are various inhibitors within the coagulation system that counterregulate activation of the coagulation cascade. Among them, antithrombin III (AT-III) and protein C (PC) are the most important (SI). AT-III binds in the presence of heparin the activated factors F-IXa, F-Xa, and F-IIa (thrombin). PC is activated by a complex formed between thrombin and thrombomodulin, a surface protein of endothelial cells. Once activated, PC in the presence of protein S (PS) specifically degrades activated factors F-Va and F-VIIIa. PC decreases in the course of sepsis in relation to the severity of the condition (L15). Experimental studies have... 

The first aspect of biocompatibility is a natural immune response. When a foreign object enters the blood stream, it can be attacked by the body s defense system. The first step is protein adsorption on an object surface. It is believed that the amount and type of protein adsorption is one of the most important steps determining whether the object is tolerated or rejected by the body. The next step is cell adhesion, which may cause aggregation and activation of platelets and triggering of the blood coagulation system with resulting thrombus formation. It may not only lead to sensor failure via surface blocking but directly threatens the patient s health. 

Hirudin is a leech-derived anticoagulant that functions by directly inhibiting thrombin. A range of blood-sucking animals contain substances in their saliva that specifically inhibit some element of the blood coagulation system (Table 12.4). 

Thrombin is a serine protease and is one of the key enzymes in the blood coagulation system. It plays fundamental roles in the human body, but the major interest is in the control of throm-... 

The heterogeneity of Lp(a) is related to ultrastructural motifs in the molecule, strongly resembling the so-called kringles found in both plasminogen and other plasma proteins, such as proteases of the coagulation system (tissue type plasminogen activator and prothrombin) (Fig. 2). 

---