The coagulation cascade

Davie E W, Fu]lkawa K and KIslel W 1991 The coagulation cascade Initiation, maintenance and regulation 1991 Bioohemistry 30 10 363-10 370... 

Factor V. High in sialic acid content. Factor V is a large asymmetric single-chain glycoprotein that becomes an active participant in the coagulation cascade when it is converted to its active form by a-thrombin. Approximately 25% of human Factor V is found in the whole blood associated with platelets. Factor V is an essential cofactor along with Factor Xa plus phosphohpid plus Ca " in the conversion of prothrombin to thrombin. 

During activation of the coagulation cascade, coagulation factors form multimolecular (often trimolecular)... 

Primary hemostasis is the first phase of hemostasis consisting of platelet plug formation at the site of injury. It occurs within seconds and stops blood loss from capillaries, arterioles, and venules. Secondary hemostasis, in contrast, requires several minutes to be complete and involves the formation of fibrin through the coagulation cascade. 

Binding calcium ions (Ca2+) is a prerequisite for the activation of seven clotting factors in the coagulation cascade that are dependent on vitamin K. The term cascade indicates, that the factois involved depend from... 

Besides the changes in wettability, they found that the hemocompatibility was significantly affected by plasma treatment. Treatment of PDMS with both Ar and O2 induced a decrease in hemocompatibility, leading to shorter clotting times. The N2 and NH3 treatments had a significantly beneficial effect on the activation of the coagulation cascade. 

Figure 51-1. The pathways of blood coagulation. The intrinsic and extrinsic pathways are indicated. The events depicted below factor Xa are designated the final common pathway, culminating in the formation of cross-linked fibrin. New observations (dotted arrow) include the finding that complexes of tissue factor and factor Vila activate not only factor X (in the classic extrinsic pathway) but also factor IX in the intrinsic pathway, in addition, thrombin and factor Xa feedback-activate at the two sites indicated (dashed arrows). (PK, prekallikrein HK, HMW kininogen PL, phospholipids.) (Reproduced, with permission, from Roberts HR, Lozier JN New perspectives on the coagulation cascade. Hosp Pract [Off Ed] 1992Jan 27 97.)...

Activated platelets, besides forming a platelet aggregate, are required, via newly expressed anionic phospholipids on the membrane surface, for acceleration of the activation of factors X and II in the coagulation cascade (Figure 51—1). 

Roberts HR, Lozier JN New perspectives on the coagulation cascade. Hosp Pract (Off Ed) 1992 27 97. 

The multiple effects of UFH on the coagulation cascade may increase its potential to cause hemorrhage." Anticoagulants with more specific sites of action may confer a better safety profile. Two such anticoagulants are low-molecular-weight heparin (LMWH) and heparinoids. 

PCCs contain the vitamin K-dependent factors II, VII, IX, and X. These agents represent another attempt to bypass the factor at which the antibody is directed (see Fig. 64-2). However, PCCs carry the risk of serious thrombotic complications. Porcine factor VIII is most useful when the inhibitor titer is less than 50 BU (see Fig. 64-2 for dose and frequency). Owing to its similarity to human factor VIII, porcine factor VIII participates in the coagulation cascade. However, most inhibitors have very weak neutralizing activity against it. Porcine factor VIII is a third-line agent (only after factor Vila and a PCC have failed) owing to a 15% incidence of cross-reactivity.15... 

Thromboplastin A substance that triggers the coagulation cascade. Tissue factor is a naturally-occurring thromboplastin and is used in the prothrombin time test. 

The fluidity of blood is a result of the inhibition of a complex series of enzymic reactions in the coagulation cascade (see Fig. 10). When triggered either intrinsically (by contact with foreign surfaces ), or extrinsically (by tissue factors from damaged cells), inactive proenzymes (factors XII, XI, IX, and X) are transformed into activated pro-teinases (XHa, XIa, IXa, and Xa, respectively). Each proteinase catalyzes the activation of the following proenzyme in the sequence, up to formation of thrombin (Factor Ha), another proteinase that catalyzes partial... 

Fig. 10. — Simplified Representation of the Coagulation Cascade. [AT denotes Antithrombin segments represent exogenous heparin, where — is a segment...

The concept that different structural domains on the heparin chains are principally involved for optimal activity in the foregoing interactions could not be perceived in early work on structure-activity correlations, because the activity of heparin has been most frequently evaluated only with whole-blood-clotting tests (such as the U.S.P. assay). Development of assays for specific clotting-factors (especially Factor Xa and thrombin) has permitted a better insight into the mechanism of action of heparin at different levels of the coagulation cascade. 

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... 

---