Activation of factor

Thrombin, the two-chain derivative of the prothrombin molecule, has a molecular weight of approximately 37,000 daltons. Its proteolytic properties induce the conversion of fibrinogen to fibrin to produce the initial visible manifestation of coagulation, the soluble fibrin clot. In addition, thrombin influences the activity of Factors V, VIII, and XIII and plasmin. Thrombin affects platelet function by inducing viscous metamorphosis and the release reaction with subsequent aggregation. 

Factor VII. This is a vitamin K-dependent serine protease that functions in the extrinsic coagulation pathway and catalyzes the activation of Factors IX and X. Factor VII is present constitutively in the surface membrane of pericytes and fibroblasts in the adventitia of blood vessels, vascular endothehum, and monocytes. It is a single-chain glycoprotein of approximately 50,000 daltons. 

HK it can interact with surface-bound factor XII on an adjacent particle thereby disseminating the reaction [25, 28]. As a result the effective kallikrein/factor XII ratio is increased in the presence of HK [25], Finally, in plasma, HK can displace other adhesive glycoproteins such as fibrinogen from binding to the surface [29]. In this sense, HK, like factor XII and prekallikrein, is also a coagulation cofactor because it is required for the generation of kalUkrein (a factor XII activator) as well as the activation of factor XI. 

Factor Xlla converts prekallikrein to kallikrein and kallikrein cleaves HK to generate bradykinin. There is also an important positive feedback in the system in which the kallikrein generated rapidly converts unactivated factor XII to activated factor XII, and the rate of this reaction is hundreds of times faster than the rate of autoactivation [11]. Therefore, much of the unactivated factor XII can be cleaved and activated by kallikrein. Cl inhibitor inhibits all functions of factor Xlla and it is one of two major plasma kallikrein inhibitors. Thus all functions of kallikrein are also inhibited, including the feedback activation of factor XII, the cleavage of HK, and the activation of plasma pro-urokinase [66] to lead to plasmin formation. Cl inhibitor also inhibits the fibrinolytic enzyme plasmin, although it is a relatively minor inhibitor compared to a2-antiplasmin or a2-macroglobulin. 

Activation of factor XII and cleavage of high molecular weight kininogen during acute attacks in hereditary and acquired Cl-inhibitor deficiencies. Immunopharmacology 1996 33 361-364. 

Activated by thrombin factor Villa is a cofactor in the activation of factor X by factor IXa. 

The Extrinsic Pathway Also Leads to Activation of Factor X But by a Different Mechanism... 

Four naturally occurring thrombin inhibitors exist in normal plasma. The most important is antithrombin III (often called simply antithrombin), which contributes approximately 75% of the antithrombin activity. Antithrombin III can also inhibit the activities of factors IXa, Xa, XIa, Xlla, and Vila complexed with tissue factor. a2-Macroglobulin contributes most of the remainder of the antithrombin activity, with heparin cofactor II and aj-antitrypsin acting as minor inhibitors under physiologic conditions. 

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). 

Vitamin K is a fat-soluble vitamin cofactor for the activation of factors II, VII, IX, and X in the liver. Almost all neonates are vitamin K-deficient at as a result of (1) insignificant transplacental vitamin K crossover, (2) lack of colonization of the colon by vitamin K-producing bacteria, and (3) inadequate dietary vitamin K intake (especially in breast-fed infants because human milk contains less vitamin K than infant formula or cow s milk). Vitamin K-deficiency bleeding (VKDB) refers to bleeding attributable to vitamin K deficiency within first 6 months of life. It occurs in three general time frames early (0-24 hours), classic (1-7 days), and late (2-12 weeks). Early onset occurs rarely and usually is associated with maternal ingestion of anticonvulsants, rifampin, isoniazid, and warfarin. Classic vitamin K-dependent bleeding usually results from the lack of prophylactic vitamin K administration in... 

The activity of factor Vila is enhanced astronomically (10 millionfold) upon binding to tissue factor. The VII or VHa-tissue factor complex activates factors IX and X and autoactivates factor VII. Although the activity of the tissue factor-factor VII complex is expressed without the presence of the negatively charged phosphatidylserine, the activity can be enhanced by its presence (9). 

A specific immunoassay for measuring two-chain factor VIIa levels in plasma has been developed to identify activation of factor VII in patients with acute coronary syndromes suchs as myocardial infarction and unstable angina (12). Because regulation of factor VIIa is believed to be mediated by tissue factor pathway inhibitor (TFPI), its measurement is also useful in assessing thombotic and cardio-vasular disorders. Because TFPI is released by heparin, its measurement is also useful in assessing the efficacy of heparin and endothelial cell function (93). 

Factors II, VII, and X are stable in plasma maintained under refrigeration for up to 6 hours. Plasma refrigerated for 6 hours and subsequently frozen at — 20°C and at -70°C showed no deterioration in the levels of these factors for up to 14 days. Factor V was stable for 6 hours when plasma was stored at 4°C. However, 20% of the activity of factor V was lost in plasma stored frozen at -20°C for over 7 days (104). Even in samples stored frozen at - 70°C, 10% of the activity of factor V was lost after 7 days (104). 

Von dem Borne P. A. K., Meijers J. C. M., Bouma B. N. Feedback activation of factor XI by thrombin in plasma results in additional formation of thrombin that protects fibrin clots from fibrinolysis. Blood 1995 86, 3035 -42. 

Activated factor XII leads to the activation of factor XI in turn, activated factor XI, along with Ca++ ions and factor IV, leads to activation of factor IX. Activated factor IX, along with Ca++ ions, factor VIII, and PF3, leads to the activation of factor X. From the point of factor X activation, the extrinsic and intrinsic mechanisms follow the same pathway to fibrin formation. 

IV Calcium ions Both Required for activation of factor XIII and stabilizes some factors... 

Factor XIa, in turn, activates factor IX. Factor IXa then promotes the activation of factor X, but only when it (i.e. IXa) is associated with factor Villa. Factor Villa is formed by the direct action of thrombin on factor VIII. The thrombin will be present at this stage because of prior activation of the intrinsic pathway. 

Intact factor VIII, as usually purified from the blood, consists of two distinct gene products factor VIII and (multiple copies of) von Willebrand s factor (vWF Figure 12.6). This complex displays a molecular mass ranging from 1 to 2 MDa, of which up to 15 per cent is carbohydrate. The fully intact factor VIII complex is required to enhance the rate of activation of factor IX of the intrinsic system. 

Active thrombin not only converts fibrinogen into fibrin, but also indirectly promotes its own synthesis by catalyzing the activation of factors V and Vlll. In addition, it catalyzes the activation of factor Xlll and thereby triggers the cross-linking of the fibrin. 

Thrombin, a serine protease, cleaves fibrinogen into fibrin to create a fibrous plug and also amplifies its own production through the activation of factor XI and cofactors V and Vlll. Thrombin also plays a crucial role in the activation of platelets through the cleavage of the protease-activated receptors on the platelet surface. Antagonists of G-protein-coupled protease-activated receptor PARi have been synthesised to study the role of thrombin PARi receptor in thrombosis and vascular injury. Thrombosis is the most common cause of death in the industrialised world and, whether through venous thromboembolism, myocardial infarction or stroke, ultimately involves the inappropriate activity of... 

This complex catalyzes the activation of factor IX or factor X as a part of the overall coagulation cascade. 

Intrinsic pathway All the protein factors necessary for coagulation are present in circulating blood. Clot formation may take several minutes and is initiated by activation of factor XII. 

The statistical evaluation by means of fhe four-point parallel line assay resulted for the Aronal forte toothpaste in a significant higher activity of factor 1.11 (C.l. 1.03-1.19 p = 0.05) in comparison to the dental gel standard. The evaluation carried out on the quality of the experiment... 

Sheiman B, Osadchaya O, Boyarskaya G et al (2007) Influence of enterosorption on functional activity of factors of antimicrobial resistance in patients with severe bums. Klinichna Imunologiya, Aleigologiya, Infectologiya 4 61-63 (In Russian)... 

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